63 results on '"Jinjun Shan"'
Search Results
2. An LC-MS/MS Method for the Pharmacokinetic and In Vitro Metabolism Studies of Praeruptorin A in Rat
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Mengmeng Song, Tong Xie, Jinjun Shan, Zhuicheng Xu, and An Kang
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Chromatography ,Pharmacokinetics ,Chemistry ,In vitro metabolism ,Lc ms ms ,Biophysics ,Pharmaceutical Science ,Molecular Medicine ,Praeruptorin A ,Biochemistry - Abstract
Objective: The study aims to investigate the pharmacokinetic profile of Praeruptorin A and khellactone and in vitro hydrolysis of praeruptorin A to khellactone in different biological samples. Methods: A LC-MS/MS method was established. Analytes and internal standard (IS) were isolated using the protein precipitation method and then separated on a Thermo BDS Hypersil C18 (2.1 mm×50 mm, 2.4μm) column using a mobile phase consisting of 0.05% formic acid solution and acetonitrile. Samples were analyzed in positive electrospray-ionization (ESI) mode using multiple reaction monitoring (MRM). Results: The calibration plots gave desirable linearity (r2>0.99) in the concentration range from 0.99-990.0 and 2.0-2000.0 ng/mL for Praeruptorin A and khellactone, respectively. In addition, the LOQs of these analytes were sufficient for vivo pharmacokinetic study and vitro hydrolysis study of Praeruptorin A. The intra-batch and inter-batch precision were all within 14.05%, and the accuracy was between 89.39% and 109.50%. The extraction efficiency of PA and khellactone ranged from 76.35 ~ 89.58%. The matrix effects of analytes and the IS were between 89.67% ~ 105.26%. Conclusion: The liver CYPs mediated by the metabolism of PA may contribute to the systemic exposure of its active metabolite, khellactone, in rats.
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- 2022
3. Metabolomic Study of Kidney Injury Induced by Antitubercular Drugs and Therapeutic Effect of Glutathione Based on Gas Chromatography-Mass Spectrometry
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Jinjun Shan, Linxiu Peng, and Tong Xie
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Creatinine ,Kidney ,010401 analytical chemistry ,Therapeutic effect ,Isoniazid ,02 engineering and technology ,Glutathione ,Pharmacology ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,Analytical Chemistry ,chemistry.chemical_compound ,medicine.anatomical_structure ,Metabolomics ,chemistry ,medicine ,Gas chromatography–mass spectrometry ,0210 nano-technology ,Rifampicin ,medicine.drug - Abstract
Histopathology and serum biochemical indicators (urea nitrogen and creatinine) were investigated to evaluate the kidney injury caused by the combination use of isoniazid (100 mg/(kg·d, ig)) and rifampicin (100 mg/(kg·d, ig) which were used as antitubercular drugs. The endogenous metabolites extracted from kidney tissue were evaluated based on gas chromatography-mass spectrometry coupled with partial least squares-discriminant analysis and other multidimensional, as well as unidimensional statistical methods. Glutathione, which was reported to protect tissue from damage caused by antitubercular drugs, was used to treat rats (250 mg/(kg·d, iv)) with kidney damage. Biochemical indicators showed that creatinine and urea nitrogen increased (p
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- 2020
4. Integrated Network Pharmacology and Lipidomics to Reveal the Inhibitory Effect of Qingfei Oral Liquid on Excessive Autophagy in RSV-Induced Lung Inflammation
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Tong Xie, Yuling Liu, Lu Feng, Shouchuan Wang, Hui Chen, Xiaorong Wang, Jinjun Shan, Chu Chu, Li An, Lili Lin, and Mengjiang Lu
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Pharmacology ,excessive autophagy ,Chemistry ,respiratory syncytial virus ,ATG5 ,Autophagy ,lipin-1 ,Inflammation ,RM1-950 ,qingfei oral liquid ,In vivo ,Lipidomics ,medicine ,network pharmacology ,lipidomics ,PI3K/AKT/mTOR ,Pharmacology (medical) ,Therapeutics. Pharmacology ,KEGG ,medicine.symptom ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Original Research - Abstract
Background: Respiratory syncytial virus (RSV) can cause varying degrees of lung inflammation in children. Qingfei Oral Liquid (QF) is effective in treating childhood RSV-induced lung inflammation (RSV-LI) in clinics, but its pharmacological profiles and mechanisms remain unclear.Methods: This study combined network Pharmacology, lipidomics, pharmacodynamics, and pathway validation to evaluate the therapeutic mechanisms of QF. Using Cytoscape (v3.8.2) and enrichment analyses from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), a global view of the putative compound-target-pathway network was created. The corresponding lipidomic profiles were then used to detect differently activated lipids, revealing the metabolic pathway, using ultra-high-performance liquid chromatography linked to hybrid Quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS). Meanwhile, the in vivo efficiency of QF, the enrichment pathway, and the excessive autophagy inhibition mechanisms were validated in RSV-infected mice models.Results: The network pharmacology results demonstrated 117 active compounds acted directly upon 101 core targets of QF against RSV-LI. The most significantly enriched pathway was the PI3K/Akt/mTOR signaling pathway (p < 0.05). In addition, untargeted lipidomics were performed, and it was revealed that higher lung levels of DAG 30:0, DAG 30:5, DAG 32:0, DAG 16:0_18:0, DAG 17:0_17:0, DAG 34:1, DAG 36:0, DAG 36:1 in the RSV-LI group were decreased after QF administration (FDR < 0.05, FC > 1.2). Lipin-1, a key enzyme in DAG synthesis, was increased in the RSV-LI mouse model. Animal experiments further validated that QF inhibited the PI3K/Akt/mTOR signaling pathway, with lower lung levels of phosphorylated PI3K, AKT and mTOR, as well as its related proteins of lipin-1 and VPS34 (p < 0.01). Finally, pharmacodynamic investigations indicated that QF reduced airway inflammation caused by excessive autophagy by decreasing lung levels of RSV F and G proteins, Beclin-1, Atg5, and LC3B II, IL-1 and TNF-α (p < 0.05).Conclusion: Lipidomic-based network pharmacology, along with experimental validation, may be effective approaches for illustrating the therapeutic mechanism of QF in the treatment of RSV-LI.
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- 2021
5. Effect of Kechuanting Acupoint Sticking Therapy On Asthma Control And Serum Metabolite Characteristics In Asthma Patients Treated With Long-Term Inhaled Corticosteroid-Formoterol
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Cong Zhang, Hong Li, Lanying Liu, Jun Hu, Hesheng Wang, Kuan Di, Shumei Zhao, Xiaoyan Gong, Kaiwen Ge, Qidong Huang, Jinjun Shan, and Puxi Zhang
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medicine.medical_specialty ,medicine.drug_class ,business.industry ,Metabolite ,medicine.disease ,Gastroenterology ,respiratory tract diseases ,chemistry.chemical_compound ,chemistry ,Asthma control ,Internal medicine ,medicine ,Corticosteroid ,Formoterol ,business ,medicine.drug ,Asthma - Abstract
Background: Despite the availability of inhaled corticosteroid-formoterol treatment, asthma in some patients is poorly controlled. Kechuanting acupoint sticking therapy may regulate immunological functions to improve asthma. In this study, we focused on the effect of Kechuanting acupoint sticking therapy on disease control and the characteristics of serum metabolites in asthma patients treated with long-term inhaled corticosteroid-formoterol. Methods: We enrolled healthy controls (n=30) and asthma patients treated with inhaled corticosteroid-formoterol for at least 6 months (n=30) and evaluated asthma control, lung function, and airway inflammation after treatment with Kechuanting acupoint sticking therapy (in asthma patients at baseline and week 6). Gas chromatography-mass spectrometry was used to analyze the serum samples of the two groups. Results: Asthma control test scores, forced expiratory volume in one second, and peak expiratory flow increased (PConclusions: Kechuanting acupoint sticking therapy improved asthma control in patients treated with long-term inhaled corticosteroid-formoterol, and the serum metabolomic pathway analysis demonstrated the association of Kechuanting acupoint sticking therapy with carbohydrate, glycerolipid, and amino acid metabolism.Trial registration: https://www.chictr.org.cn, ChiCTR1800016644.
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- 2021
6. Potential Therapeutic Applications of Pulmonary Surfactant Lipids in the Host Defence Against Respiratory Viral Infections
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Jianjian Ji, Xie Tong, Zichen Luo, Ying Zhang, Ling Sun, Wang Xianzheng, Jinjun Shan, and Yingzhao Liao
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respiratory viral infections ,ARDS ,Mini Review ,Immunology ,Antiviral Agents ,Microbiology ,chemistry.chemical_compound ,Immune system ,Pulmonary surfactant ,medicine ,Animals ,Humans ,therapeutic applications ,Immunology and Allergy ,Phosphatidylinositol ,Respiratory system ,Lung ,Phosphatidylglycerol ,SARS-CoV-2 ,pulmonary surfactant lipids ,Chemistry ,COVID-19 ,Pulmonary Surfactants ,RC581-607 ,medicine.disease ,Lipids ,COVID-19 Drug Treatment ,Surfactant protein A ,medicine.anatomical_structure ,Host-Pathogen Interactions ,lipids (amino acids, peptides, and proteins) ,Immunologic diseases. Allergy - Abstract
Pulmonary surfactant is a complex and highly surface-active material. It covers the alveolar epithelium and consists of 90% lipids and 10% proteins. Pulmonary surfactant lipids together with pulmonary surfactant proteins facilitate breathing by reducing surface tension of the air-water interface within the lungs, thereby preventing alveolar collapse and the mechanical work required to breathe. Moreover, pulmonary surfactant lipids, such as phosphatidylglycerol and phosphatidylinositol, and pulmonary surfactant proteins, such as surfactant protein A and D, participate in the pulmonary host defense and modify immune responses. Emerging data have shown that pulmonary surfactant lipids modulate the inflammatory response and antiviral effects in some respiratory viral infections, and pulmonary surfactant lipids have shown promise for therapeutic applications in some respiratory viral infections. Here, we briefly review the composition, antiviral properties, and potential therapeutic applications of pulmonary surfactant lipids in respiratory viral infections.
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- 2021
7. Plasma characteristic metabolites of pediatric community-acquired pneumonia in traditional Chinese medicine syndrome differentiation
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Tong Xie, Wensheng Zhai, Li An, Jinjun Shan, Ying Zhang, Cunsi Shen, Lili Lin, Shouchuan Wang, Wei-Wei Li, Lina Du, and Yan Yang
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medicine.medical_specialty ,Ceramide ,Histology ,Arginine ,Phenylalanine ,Traditional Chinese medicine ,chemistry.chemical_compound ,Community-acquired pneumonia ,Internal medicine ,Aspartic acid ,medicine ,Humans ,Metabolomics ,Medicine, Chinese Traditional ,Child ,Syndrome differentiation ,Ecology, Evolution, Behavior and Systematics ,Chromatography, High Pressure Liquid ,Chemistry ,Pneumonia ,medicine.disease ,Fold change ,Endocrinology ,Metabolome ,Anatomy ,Biomarkers ,Biotechnology ,Chromatography, Liquid - Abstract
Community-acquired pneumonia (CAP) is the leading cause of lower respiratory tract infections in children. Heat syndrome (HS) and cold syndrome (CS) are two main syndrome types of pediatric CAP in traditional Chinese medicine (TCM). This study aimed to identify plasma metabolic profiles in pediatric CAP and to further select potential biomarkers to distinguish between HS and CS. An ultra-performance liquid chromatography coupled with linear ion trap quadrupole-orbitrap mass spectrometry method was applied to plasma samples of 296 patients and 55 healthy controls (HC). The samples were divided into the discovery group (n = 213, HS = 160, CS = 23, HC = 30) and the validation group (n = 138, HS = 93, CS = 20, HC = 25). The orthogonal partial least-squares discriminant analysis, the value of fold change, and Kruskal-Wallis test with false discovery rate correction (q-value0.05) were applied to identify differential plasma metabolites. The area under the ROC curve (AUC) was used to evaluate the diagnostic performance of the screened metabolites. The results showed that the plasma levels of aspartic acid, phenylalanine, arginine, lysoPC20:1, lysoPE16:0, lysoPE18:0, and PE (16:0_22:6) were increased in CS compared with HC. The plasma levels of PC (18:1_18:1), PC (20:4_20:4), PE (16:0_18:2), lysoPE20:4, lysoPE18:2, and lysoPE22:6 were decreased, whereas, the plasma level of ceramide (d18:1_24:1) was increased in HS compared with HC. There were 13 differential metabolites in CS (AUC = 0.995) and 15 differential metabolites in HS (AUC = 0.954), compared with HC. A panel of seven biomarkers, including LysoPC20:1, lysoPE16:0, lysoPE18:2, lysoPE20:4, lysoPE22:6, PC (18:1_18:1), and PC (20:4_20:4) showed good discrimination between HS and CS with an AUC of 0.982. Altered plasma amino acids and lipids may provide an objective basis for TCM syndrome differentiation in pediatric CAP.社区获得性肺炎是儿童最常见的下呼吸道感染性疾病之一,其中医辨证分型可分为寒、热证两大类。本研究旨在建立寒、热证之间的血浆代谢图谱, 并找出区分二者的潜在生物标志物。采用超高效液相色谱联合线性离子阱四极轨道质谱技术检测 296 例患者和 55 例健康儿童血浆样品, 其中 213 例为筛选组(热证 = 160 例, 寒证 = 23 例, 健康对照 = 30 例), 138 例为验证组(热证 = 93 例, 寒证 = 20 例, 健康对照 = 25 例)。寒、热证之间的差异性代谢物筛选方法为正交偏最小二乘判别分析 (OPLS-DA)、差异倍数、Kruskal-Wallis检验结合 FDR 错误发现率校准 (q值 0.05)。ROC曲线下面积 (AUC) 评价潜在生物标志物的诊断准确性。与健康对照组相比, 寒证中天冬氨酸、苯丙氨酸、精氨酸、溶血性磷脂酰胆碱 20:1、溶血性磷脂酰乙醇胺 16:0、溶血性磷脂酰乙醇胺 18:0 和磷脂酰乙醇胺 (16:0_22:6)表达水平升高, 而热证中磷脂酰胆碱 (18:1_18:1)、磷脂酰胆碱 (20:4_20:4)、磷脂酰乙醇胺 (16:0_18:2)、溶血性磷脂酰乙醇胺 20:4、溶血性磷脂酰乙醇胺 18:2 和溶血性磷脂酰乙醇胺 22:6表达水平降低。神经酰胺 (d18:1_24:1)是热证中唯一上调的物质。13 个差异性代谢物组合, 其区分寒证与健康对照的 AUC 为 0.995, 15 个差异性代谢物组合, 其区分热证与健康对照之间的 AUC 为 0.954。7个脂质组成的代谢物群组, 包括溶血性磷脂酰胆碱 20:1, 溶血性磷脂酰乙醇胺 16:0, 溶血性磷脂酰乙醇胺 18:2, 溶血性磷脂酰乙醇胺 20:4, 溶血性磷脂酰乙醇胺 22:6, 磷脂酰胆碱 (18:1_18:1), 磷脂酰胆碱 (20:4_20:4), 其区分寒证与热证的 AUC 为 0.982, 呈现出极好的诊断价值, 可作为区分儿童社区获得性肺炎寒、热证的潜在生物标志物。综上所述, 血浆中代谢紊乱的氨基酸和脂质为中医儿科辨证客观化提供了一定的依据。.
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- 2021
8. An optimized analytical method for cellular targeted quantification of primary metabolites in tricarboxylic acid cycle and glycolysis using gas chromatography-tandem mass spectrometry and its application in three kinds of hepatic cell lines
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Li Feng, Jia Xu, Weifeng Yao, Jinjun Shan, Tong Xie, Li Zhang, and Yuanyuan Zhai
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Citric Acid Cycle ,Clinical Biochemistry ,Pharmaceutical Science ,Glycerophospholipids ,Gas Chromatography-Mass Spectrometry ,Analytical Chemistry ,Metabolomics ,Tandem Mass Spectrometry ,Drug Discovery ,Animals ,Humans ,Glycolysis ,Spectroscopy ,chemistry.chemical_classification ,Gas Chromatography/Tandem Mass Spectrometry ,Chemistry ,Selected reaction monitoring ,Tricarboxylic Acids ,Primary metabolite ,Hep G2 Cells ,Tricarboxylic acid ,Rats ,Citric acid cycle ,Metabolic pathway ,Glucose ,Biochemistry ,Hepatocytes ,Energy Metabolism - Abstract
Energy synthesis in aerobic organisms relies on two major metabolic pathways, i.e. tricarboxylic acid (TCA) cycle and glycolysis, the metabolites of which are highly affected by many diseases. Cells are the basic unit of the organism and have independent, ordered and self-controlled metabolic systems. Therefore, it is necessary to quantify intracellular metabolites in TCA cycle and glycolysis. In this study, we established a repeatable gas chromatography-tandem mass spectrometry (GC–MS/MS) method with selected reaction monitoring (SRM) mode for simultaneous quantification of several primary metabolites in these two pathways, including glucose, 3-phosphoglycerate, phosphoenolpyruvate (PEP), pyruvate, lactate, citrate, cis-aconitate, isocitrate, α-ketoglutarate, succinate, fumarate and malate. There are many solvents to extract the metabolites in these two pathways, however, which one is more effective still remains unclear. Sample pretreatment was optimized for solvent types and volumes to advance the extraction efficiency of metabolites. 500 μL of 75% methanol-methyl tert-butyl ether (MTBE) was finally selected for the extraction of targeted metabolites in cells due to its highest extraction efficiency. Activated carbon as an effective adsorbent was successfully applied to the removal of endogenous targeted metabolites in cells for getting the analyte-free surrogate matrices. A series of methodological studies verified the validity of this optimized approach which was applied to quantify and compare the targeted metabolites in three common hepatic cells. The developed GC–MS/MS method provided a better way to determine the metabolites of energy metabolism in cellular metabolomics, facilitating the application of targeted quantification metabolomics to precisely discover the metabolic alterations.
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- 2019
9. Urine metabolic profiles in paediatric asthma
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Lili Lin, Wei-Wei Li, Yan-Zhen Chen, Qigang Dai, Man Tian, Bin Yuan, Shouchuan Wang, Jia-Lei Tao, Jianjian Ji, and Jinjun Shan
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Male ,Pulmonary and Respiratory Medicine ,Metabolite ,Urine ,chemistry.chemical_compound ,Metabolomics ,Aspartic acid ,Humans ,Medicine ,Child ,Purine metabolism ,Asthma ,Inflammation ,business.industry ,medicine.disease ,chemistry ,Case-Control Studies ,Immunology ,Metabolome ,Uric acid ,Female ,Heptadecanoic acid ,business ,Biomarkers - Abstract
Asthma is a global problem and complex disease suited for metabolomic profiling. This study explored the candidate biomarkers specific to paediatric asthma and provided insights into asthmatic pathophysiology.Children (aged 6-11 years) meeting the criteria for healthy control (n = 29), uncontrolled asthma (n = 37) or controlled asthma (n = 43) were enrolled. Gas chromatography-mass spectrometry was performed on urine samples of the patients to explore the different types of metabolite profile in paediatric asthma. Additionally, we employed a comprehensive strategy to elucidate the relationship between significant metabolites and asthma-related genes.We identified 51 differential metabolites mainly related to dysfunctional amino acid, carbohydrate and purine metabolism. A combination of eight candidate metabolites, including uric acid, stearic acid, threitol, acetylgalactosamine, heptadecanoic acid, aspartic acid, xanthosine and hypoxanthine (adjusted P 0.05 and fold-change1.5 or0.67), showed excellent discriminatory performance for the presence of asthma and the differentiation of poor-controlled or well-controlled asthma, and area under the curve values were0.97 across groups. Enrichment analysis based on these targets revealed that the Fc receptor, intracellular steroid hormone receptor signalling pathway, DNA damage and fibroblast proliferation were involved in inflammation, immunity and stress-related biological progression of paediatric asthma.Metabolomic analysis of patient urine combined with network-biology approaches allowed discrimination of asthma profiles and subtypes according to the metabolic patterns. The results provided insight into the potential mechanism of paediatric asthma.
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- 2019
10. Glycyrrhizic acid improving the liver protective effect by restoring the composition of Lactobacillus
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Jinjun Shan, Letian Chen, Jing Wang, Liuqing Di, and Tianjie Yuan
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0301 basic medicine ,Cirrhosis ,Metabolite ,Medicine (miscellaneous) ,CCL4 ,Gut microbiota ,Pharmacology ,Phosphotransferase ,03 medical and health sciences ,chemistry.chemical_compound ,0404 agricultural biotechnology ,Lactobacillus ,Gene expression ,medicine ,Glycyrrhetinic acid ,TX341-641 ,Glycyrrhizic acid ,030109 nutrition & dietetics ,Nutrition and Dietetics ,biology ,Nutrition. Foods and food supply ,04 agricultural and veterinary sciences ,medicine.disease ,biology.organism_classification ,040401 food science ,Bioavailability ,16S rRNA sequencing ,chemistry ,Liver cirrhosis ,TLR4 ,Food Science - Abstract
Glycyrrhizic acid (GL) and its deglycosylated metabolite glycyrrhetinic acid (GA) have been recognized as effective drugs for liver diseases. However, the underlying molecular mechanism of GL and GA remains unclear. Here, CCl4 was used to induce the liver cirrhosis in rat, GL and GA both significantly alleviate the liver fibrosis by decreasing the ALT, AST level in serum. While, only GL was observed to significantly down-regulate the TLR4 and LBP gene expression, which indicated that GL could have direct impact on the intestinal flora. Additionally, 16S rRNA gene sequencing showed that GL especially restore the abundance of Lactobacillus compared with the model group, however, GA has no effect on the cirrhosis-induced gut dysbiosis. Furthermore, PICRUSt analysis showed that GL could improve the relative abundance of phosphotransferase systems and phosphor-glucosidases which may promote the bioavailability of GL. These results may provide novel strategies for prevention and treatment of liver cirrhosis.
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- 2019
11. In-silico-library-based method enables rapid and comprehensive annotation of cardiolipins and cardiolipin oxidation products using high resolution tandem mass spectrometer
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Binghuan Yuan, Yao Lu, Cunsi Shen, Yu He, Xia Zhao, Jianjian Ji, Tong Xie, Jinjun Shan, Lili Lin, and Jianya Xu
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Tandem ,Cardiolipins ,In silico ,High resolution ,Computational biology ,Mass spectrometry ,Biochemistry ,Analytical Chemistry ,Mitochondria ,chemistry.chemical_compound ,Annotation ,Mice ,Template ,chemistry ,Tandem Mass Spectrometry ,Cardiolipin ,Environmental Chemistry ,Animals ,Computer Simulation ,Oxidation-Reduction ,Spectroscopy - Abstract
Accumulated evidences suggest that cardiolipins (CLs) and cardiolipin oxidation products (oxCLs) are a class of essential molecules that play critical roles in many physiological functions. Diversity of four acyl chains leads to high structure complexity for cardiolipin species including CLs, monolysocardiolipins (MLCLs) and their oxCLs. The ability to rapidly identify CL species can be implemented by the match of mass spectrometry (MS)-based in-silico spectral database. In this study, after optimizing the chromatography conditions and MS detection, an in-silico library containing 377,754 simulated tandem mass spectra deducing from 31,578 CLs to 52,160 of MLCLs was successfully augmented based on LipidBlast templates. For the construction of the oxCLs' library, twenty-five fatty acyls oxidation products relating to nine oxidation types were permuted and combined. A total of 42,180 oxCL spectra were predicted based on the experimental measurements of oxCLs forming by artificially oxidation. Applying the in-silico database to murine mitochondria and cell samples enabled the sensitive and comprehensive annotation of 86 MLCLs, 307 CLs and 112 oxCLs with high annotation confidence. Compared to the conventional method, our proposed in-silico database provides a more comprehensive interpretation for CL species' characterization with high throughput and sensitivity in nontarget lipidomic study.
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- 2021
12. The gut microbiota during the progression of atherosclerosis in the perimenopausal period shows specific compositional changes and significant correlations with circulating lipid metabolites
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Qi Chen, Ying Chao, Qichun Zhang, Jinjun Shan, Meng-Hua Ma, Huimin Bian, Xichao Yu, Weiwei Zhang, Yu Li, Yunhui Bi, Peng Cheng, Tingting Ji, Yu Fu, Jun Li, and Qinghai Meng
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0301 basic medicine ,menopause ,Blood lipids ,RC799-869 ,Gut flora ,Feces ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Hyperlipidemia ,Estradiol ,lipid metabolomics ,Estrogen Replacement Therapy ,digestive, oral, and skin physiology ,Gastroenterology ,Diseases of the digestive system. Gastroenterology ,Fecal Microbiota Transplantation ,Lipids ,Infectious Diseases ,Disease Progression ,Ovariectomized rat ,Female ,lipids (amino acids, peptides, and proteins) ,030211 gastroenterology & hepatology ,Research Article ,Research Paper ,Microbiology (medical) ,medicine.medical_specialty ,Normal diet ,Ovariectomy ,Biology ,Diet, High-Fat ,Microbiology ,ApoE −/- mice ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Metabolomics ,gut microbiota ,Bacteria ,Cholesterol ,Lipid metabolism ,Atherosclerosis ,Lipid Metabolism ,biology.organism_classification ,medicine.disease ,Gastrointestinal Microbiome ,Perimenopause ,Mice, Inbred C57BL ,Transplantation ,030104 developmental biology ,Endocrinology ,chemistry - Abstract
Atherosclerosis (AS) is exacerbated in the perimenopausal period, which significantly increases the incidence rate of cardiovascular disease. The disruption of the gut microbiota has been associated with AS or menopause, but the specific changes of AS-associated gut microbiota in the perimenopausal period remain largely unknown. As lipid abnormalities are mainly responsible for AS, the relationship between lipid metabolism abnormalities and gut microbiota disruptions during menopause is rarely reported hitherto. In the present study, ApoE−/- mice fed with a high-fat diet (HFD) were subjected to ovariectomy and supplemented with estrogen. The ovariectomized HFD-fed ApoE−/- mice underwent significant AS damage, hepatic lipid damage, hyperlipidemia, and changes of lipid metabolism- and transport-related enzymes. There was significantly higher abundance of some lipid metabolites in the plasma of ovariectomized HFD-fed ApoE−/- mice than in non-ovariectomized ones, including cholesterol esters, triglycerides, phospholipids, and other types of lipids (free fatty acids, acylcarnitine, sphingomyelins, and ceramides). The administration of estrogen significantly reduced the contents of most lipid metabolites. The diversity and composition of gut microbiota evidently changed in ovariectomized HFD-fed ApoE−/- mice, compared to HFD-fed ApoE−/- mice without ovariectomy. In contrast, with estrogen supplementation, the diversity and composition of gut microbiota were restored to approach that of non-ovariectomized HFD-fed ApoE−/- mice, and the relative abundances of some bacteria were even like those of C57BL/6 mice fed with a normal diet. On the other hand, the transplantation of feces from C57BL/6 mice fed with normal diet to ovariectomized HFD-fed ApoE−/- mice was sufficient to correct the hyperlipidemia and AS damage, and to reverse the characteristics changing of lipid metabolomics in ovariectomized HFD-fed ApoE−/- mice. These phenomena were also been observed after transplantation of feces from estrogen-treated ovariectomized HFD-fed ApoE−/- mice to ovariectomized HFD-fed ApoE−/- mice. Moreover, the gut microbiota and lipid metabolites were significantly correlated, demonstrating that the changes of serum lipids may be associated with the gut microbiota disruptions in the perimenopausal period. In conclusion, the gut microbiota during the progression of AS in the perimenopausal period showed specific compositional changes and significant correlations with circulating lipid metabolites. Estrogen supplementation may exert beneficial effects on gut bacteria and lipid metabolism.
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- 2021
13. Citrus alkaline extracts prevent endoplasmic reticulum stress in type II alveolar epithelial cells to ameliorate pulmonary fibrosis via the ATF3/PINK1 pathway
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Xianmei Zhou, Jian-Xin Li, Wenpan Peng, Zhichao Wang, Hailang He, Jinjun Shan, Cheng Gu, Yong Xu, Jonathan Hrovat, Fanchao Feng, Ping Yang, Qi Wu, and Di Han
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Citrus ,Pulmonary Fibrosis ,Pharmaceutical Science ,03 medical and health sciences ,chemistry.chemical_compound ,Bleomycin ,Mice ,0302 clinical medicine ,In vivo ,Drug Discovery ,Pulmonary fibrosis ,medicine ,Animals ,030304 developmental biology ,Pharmacology ,A549 cell ,0303 health sciences ,Activating Transcription Factor 3 ,Plant Extracts ,Endoplasmic reticulum ,Tunicamycin ,respiratory system ,medicine.disease ,Endoplasmic Reticulum Stress ,In vitro ,Cell biology ,Blot ,Complementary and alternative medicine ,chemistry ,030220 oncology & carcinogenesis ,Alveolar Epithelial Cells ,Unfolded protein response ,Molecular Medicine ,Protein Kinases ,Signal Transduction - Abstract
Background Idiopathic pulmonary fibrosis is a chronic, progressive, fibrotic disease. Although the pathogenesis remains unclear, the effect of endoplasmic reticulum (ER) stress in type II alveolar epithelial cells (AEC IIs) is increasingly thought to be a critical mechanism. Purpose We investigated the effects of citrus alkaline extracts (CAE) on AEC IIs and elucidated the underlying mechanism for their possible use in ameliorating pulmonary fibrosis (PF). Methods A bleomycin-induced mouse model of PF, and an in vitro tunicamycin (TM) -induced ER stress model in A549 cells were successfully established. Accumulation of collagen in lung tissues in vivo was assessed using histological analysis and western blotting. The expression levels of the ER-stress marker BiP and other related proteins were assessed by western blotting and immunofluorescence staining. Mitochondrial membrane potential was assessed to evaluate mitochondrial homeostasis. Results CAE mitigated collagen deposition to ameliorate PF in vivo. CAE suppressed the bleomycin or TM-induced increases in ER-stress biomarker, BiP, and PERK pathway proteins, resulting in a decrease in ER stress in mouse lung tissues and A549 cells, respectively. Additionally, CAE treatment suppressed the bleomycin or TM-induced increase in the ER-stress downstream proteins, activating ATF3 and increased the levels of PINK1 in AEC IIs, both in vivo and in vitro. The reduced mitochondrial homeostasis induced by TM was restored by CAE-treatment in A549 cells. Furthermore, conditioned media from TM-treated A549 cells increased collagen deposition in MRC5 cells mainly via TGF-β1. The increased collagen deposition was not seen using conditioned media from CAE-treated A549 cells. Conclusion These results provide novel insights into the potential mechanism of CAE in inhibiting ER stress in AEC IIs, and suggests that it has great potential to ameliorate PF via the ATF3/PINK1 pathway.
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- 2020
14. A novel strategy based on targeted cellular metabolomics for quantitatively evaluating anti-aging effect and screening effective extracts of Erzhi Wan
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Weifeng Yao, Xin Li, Yuanyuan Zhai, Jinjun Shan, Li Zhang, Tong Xie, Mengting Gao, Anwei Ding, Li Feng, and Yifei Wang
- Subjects
Aging ,Chromatography ,Chemistry ,Clinical Biochemistry ,Curve analysis ,Cell Biology ,General Medicine ,Computational biology ,Biochemistry ,Analytical Chemistry ,Cell Line ,Rats ,Rats, Sprague-Dawley ,Metabolic pathway ,Metabolomics ,Tandem Mass Spectrometry ,Metabolome ,Animals ,Aging effect ,Multivariate statistical ,After treatment ,Drugs, Chinese Herbal - Abstract
The complexity of ingredients in traditional Chinese medicine (TCM) makes it challenging to clarify its efficacy in an acceptable and scientific approach. The present study was aimed to use quantification results from targeted cellular metabolomics to evaluate anti-aging efficacy of a famous Chinese medicine formula, Erzhi Wan (EZW), and screen possible effective extracts, depending on the developed strategy integrating multivariate receiver operating characteristic (ROC) curve and analytic hierarchy process (AHP). In this study, senescent NRK cells induced by D-galactose were treated with drug-containing serum of EZW and four kinds of extracts (petroleum ether, ethyl acetate, butanol and water). Intermediates of two major metabolic pathways for energy synthesis, tricarboxylic acid (TCA) cycle and glycolysis, were accurately quantified by GC-MS/MS to identify discriminate metabolites for clarifying therapeutic mechanism of EZW based on multivariate statistical analysis. Senescent and non-senescent cells were successfully distinguished using these metabolites by ROC curve analysis. Next, these metabolites were used as evaluation indexes to quantitatively reflect different effect of EZW and its extracts, according to the role of them in distinguishing groups and in conjunction with AHP. In vitro detection of senescence-associated β-galactosidase (SA-β-gal) activity was used to verify the reliability of evaluation results. The reversal after treatment of drug-containing serum of EZW and extracts was observed, and the petroleum ether extract might be the potential active extract responsible for the major anti-aging effect of EZW, which was in agreement with in vitro experiments. Altogether, metabolomics was a powerful approach for evaluation efficacy and elucidation action mechanisms of TCM. The integrated evaluation strategy in this paper with properties of high practicality, feasibility and effectivity was expected to provide a new insight into comprehensive and quantitative efficacy evaluation.
- Published
- 2020
15. Alisol B 23-acetate activates ABCG5/G8 in the jejunum via the LXRα/ACAT2 pathway to relieve atherosclerosis in ovariectomized ApoE
- Author
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Jun Li, Weiwei Zhang, Meng-Hua Ma, Xichao Yu, Huimin Bian, Jinjun Shan, Qi Chen, Yunhui Bi, Yuhan Zhang, Ying Chao, Qinghai Meng, Yu Fu, and Tingting Ji
- Subjects
Aging ,medicine.medical_specialty ,Mice, Knockout, ApoE ,Lipoproteins ,Ovariectomy ,Sterol O-acyltransferase ,Blood lipids ,Glycerophospholipids ,Diet, High-Fat ,Jejunum ,chemistry.chemical_compound ,Mice ,Internal medicine ,AB23A ,medicine ,Animals ,Humans ,exogenous cholesterol ,ATP Binding Cassette Transporter, Subfamily G, Member 5 ,Liver X receptor ,Aorta ,Cholestenones ,Triglycerides ,Liver X Receptors ,biology ,Cholesterol ,ATP Binding Cassette Transporter, Subfamily G, Member 8 ,Lipid metabolism ,LXRα-ACAT2 ,Cell Biology ,Lipid Droplets ,Atherosclerosis ,Lipid Metabolism ,Plaque, Atherosclerotic ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Ovariectomized rat ,ABCG5 ,biology.protein ,ABCG5/G8 ,Female ,Cholesterol Esters ,Caco-2 Cells ,lipid mass spectrometry ,Sterol O-Acyltransferase ,Research Paper - Abstract
Phytosterols have been shown to improve blood lipid levels and treat atherosclerosis. This research investigated the effects of phytosterol Alisol B 23-acetate (AB23A) on jejunum lipid metabolism and atherosclerosis. The results show that intragastric administration of AB23A can significantly reduce atherosclerotic plaque area and lipid accumulation in the jejunum of ovariectomized ApoE-/- mice fed a high-fat diet and can also improve the lipid mass spectra of the plasma and jejunum. In vitro studies have shown that AB23A can increase cholesterol outflow in Caco-2 cells exposed to high fat concentrations and increase the expression of ATP-binding cassette transfer proteins G5/G8 (ABCG5/G8), the liver X receptor α (LXRα). Furthermore, inhibition of LXRα can significantly eliminate the active effect of AB23A on decreasing intracellular lipid accumulation. We also confirmed that AB23A has a negative effect on Acyl-CoA cholesterol acyltransferase 2 (ACAT2) in Caco-2 cells cultured in the high concentrations of fat, and we found that AB23A further reduces ACAT2 expression in cells treated with the ACAT2 inhibitor pyripyropene or transfected with ACAT2 siRNA. In conclusion, we confirmed that AB23A can reduce the absorption of dietary lipids in the jejunum by affecting the LXRα-ACAT2-ABCG5/G8 pathway and ultimately exert an anti-atherosclerotic effect.
- Published
- 2020
16. A review of saponin intervention in metabolic syndrome suggests further study on intestinal microbiota
- Author
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Zichen Luo, Liuqing Di, Ying Zhang, Jinjun Shan, and Weichen Xu
- Subjects
0301 basic medicine ,Peroxisome proliferator-activated receptor ,Adipokine ,Gut flora ,Pharmacology ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,medicine ,Animals ,Humans ,Liver X receptor ,Hypolipidemic Agents ,chemistry.chemical_classification ,Metabolic Syndrome ,biology ,business.industry ,Saponins ,medicine.disease ,biology.organism_classification ,Lipid Metabolism ,Gastrointestinal Microbiome ,Intestines ,030104 developmental biology ,Treatment Outcome ,chemistry ,030220 oncology & carcinogenesis ,Steatosis ,Metabolic syndrome ,Insulin Resistance ,business ,Energy Intake ,Energy Metabolism ,Dyslipidemia ,Biomarkers - Abstract
Metabolic syndrome (MetS) is a series of symptoms including insulin resistance, obesity, dyslipidemia, elevated fasting blood glucose levels, and hepatic steatosis. As a key criterion in MetS, the onset of insulin resistance is related to abnormal levels of circulating free fatty acids and adipokines. It has been discovered in recent years that metabolites and pathogen-associated molecular patterns of intestinal/gut microbiota are also important factors that cause insulin resistance and MetS. Saponins are the main components of many botanicals and traditional Chinese medicines (TCMs), such as ginseng, platycodon, licorice, and alfalfa. They have poor bioavailability, but can be transformed into secondary glycosides and aglycones by intestinal microbiota, further being absorbed. Based on in vivo and in vitro data, we found that saponins and their secondary metabolites have a preventive effect on MetS, and the effective targets are distributed in the intestine and other organs in human body. Intestinal targets involve pancreatic lipase, dietary cholesterol, and intestinal microbiota. Other targets include central appetite, nuclear receptors such as PPAR and LXR, AMPK signaling pathway and adipokines levels, etc. In view of the poor bioavailability of saponins, it is inferred that targets for prototype-saponins to interfere with MetS is mainly located in the intestine, and the activation of other targets may be related to secondary glycosides and aglycones transformed from saponins by intestinal flora. We suggest that the role of intestinal microbiota in saponin intervention in MetS should be further investigated.
- Published
- 2020
17. Rhein Suppresses Lung Inflammatory Injury Induced by Human Respiratory Syncytial Virus Through Inhibiting NLRP3 Inflammasome Activation via NF-κB Pathway in Mice
- Author
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Tong Xie, Jianjian Ji, Xia Zhao, Shouchuan Wang, Qigang Dai, Lili Lin, Yingmei Dong, Cunsi Shen, Jing Yan, An Kang, Jinjun Shan, Jianya Xu, and Zhengguang Zhang
- Subjects
0301 basic medicine ,Inflammation ,rhein ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Immune system ,Western blot ,Medicine ,Pharmacology (medical) ,Original Research ,Pharmacology ,respiratory syncytial virus infection ,Lung ,medicine.diagnostic_test ,business.industry ,lcsh:RM1-950 ,lung inflammation ,tissue damage ,NF-κB ,Inflammasome ,respiratory system ,medicine.disease ,Pneumonia ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Therapeutics. Pharmacology ,chemistry ,pro-inflammatory cytokine ,030220 oncology & carcinogenesis ,Immunology ,medicine.symptom ,business ,medicine.drug ,Respiratory tract - Abstract
Rhein is one of active anthraquinone components in traditional Chinese herbal medicine Rheum palmatum L., possessing anti-inflammatory, antioxidant, antitumor, antiviral, and hepatoprotective activities. Human respiratory syncytial virus (RSV), a common virus, is able to result in pneumonia and bronchitis, which usually can be seen in infants. However, so far the effects of Rhein on RSV-induced pneumonia are still unknown. As the NLRP3 inflammasome is activated excessively, it is able to lead to inflammatory response and tissue injury in most viral infection process (including RSV infection) of respiratory tract. Therefore, we designed experiments to reveal whether Rhein can treat RSV-induced pneumonia by inhibiting NLRP3 inflammasome activation. In present research, we established the pneumonia model of BALB/C mice caused by RSV. First of all, the pathology of lung tissue and the weight of mice were evaluated, and the corresponding lung index was calculated. Additionally, the expression of pro-inflammatory mediators in serum and lung tissues, and related proteins (NLRP3, ASC and Caspase-1) of NLRP3 inflammasome and NF-κB pathway were detected by Enzyme-linked immunosorbent assay (ELISA), Real-time PCR (RT-PCR), Immunohistochemistry (IHC), and Western blot (WB), respectively. The determination of lung index and lung tissue pathological evaluation revealed that Rhein was able to alleviate lung infection and injury caused by RSV. The results of ELISA showed that Rhein was able to reduce the release of pro-inflammatory cytokines in the serum and lung tissues of RSV-induced BALB/c mice, including IL-1β, IL-6, TNF-α, IL-18, and IL-33. Additionally, it was revealed that Rhein inhibited the immune inflammatory response of RSV-infected mice, which was likely to be associated with the inhibition the NLRP3 inflammasome activation via NF-κB pathway. To sum up, our results indicated that Rhein may inhibit RSV-induced pulmonary inflammatory response effectively; meanwhile, it is emphasized that Rhein therapy is likely to be a promising treatment on the RSV-infected lung inflammation and avoidance of lung tissue damage.
- Published
- 2020
18. Interventional effects of the direct application of 'Sanse powder' on knee osteoarthritis in rats as determined from lipidomics via UPLC-Q-Exactive Orbitrap MS
- Author
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Wei Mei, Zhengquan Huang, Cunsi Shen, Peimin Wang, Nongshan Zhang, Songjiang Yin, Bo Xu, Jun Mao, Runlin Xing, Zichen Luo, Jinjun Shan, Peng Wu, and Yancheng Xiao
- Subjects
Osteoarthritis ,Pharmacology ,Orbitrap ,High-performance liquid chromatography ,LC–MS ,Prescription ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Western blot ,law ,Liquid chromatography–mass spectrometry ,Lipidomics ,Direct application “Sanse powder” therapy ,medicine ,030304 developmental biology ,030203 arthritis & rheumatology ,chemistry.chemical_classification ,0303 health sciences ,medicine.diagnostic_test ,Chemistry ,Research ,KOA lipidomics ,Fatty acid ,lcsh:Other systems of medicine ,medicine.disease ,lcsh:RZ201-999 ,Reverse transcription polymerase chain reaction ,Complementary and alternative medicine - Abstract
Background Our previous clinical evidence suggested that the direct application of “Sanse powder” the main ingredient of “Yiceng” might represent an alternative treatment for knee osteoarthritis. However, the mechanism underlying its effect is poorly understood. In this study, we investigated the mechanism of the effect of direct “Sanse powder” application for the treatment of knee osteoarthritis (KOA) in rats by using lipidomics. Methods KOA rats were established by cutting the anterior cruciate ligament, and the cold pain threshold and mechanical withdrawal threshold (MWT) of seven rats from each group were measured before modelling (0 days) and at 7, 14, 21 and 28 days after modelling. Histopathological evaluation of the synovial tissue was performed by haematoxylin and eosin (H&E) staining after modelling for 28 days. Interleukin-1β (IL-1β), pro-interleukin-1β (pro-IL-1β) and tumor necrosis factor-α (TNF-α) proteins in synovial tissue were measured by western blot, and the mRNA expression levels of IL-1β and TNF-α in synovial tissue were measured using Real-time reverse transcription polymerase chain reaction (qRT-PCR), the levels of IL-1β and TNF-α in rat serum were measured by enzyme-linked immunosorbent assay (ELISA), Serum lipid profiles were obtained by using ultra-performance liquid chromatography combined with quadrupole-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap MS). Results The results confirmed that the direct application of “Sanse powder” had a significant protective effect against KOA in rats. Treatment with “Sanse powder” not only attenuated synovial tissue inflammation but also increased the levels of the cold pain threshold and MWT. In addition, the lipidomics results showed that the levels of diacylglycerol (DAG), triacylglycerols (TAGs), lysophosphatidylcholine (LPC), phosphatidylcholine (PC), fatty acid esters of hydroxy fatty acids (FAHFAs), and phosphatidylethanolamine (PE) were restored almost to control levels following treatment. Conclusions Lipidomics provides a better understanding of the actions of direct application “Sanse powder” therapy for KOA.
- Published
- 2020
19. Untargeted lipidomics reveals specific lipid abnormalities in Sjögren's syndrome
- Author
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Deshun Kong, Shijia Liu, Wei Ji, Jinjun Shan, Jiawei Lu, Mengying Ke, Xiangyu Lv, Yuhua Li, Lili Lin, Wenjuan Qian, Yan Lu, Lu Wang, Jue Wang, Ping Liu, Jinfeng Su, Qiuxiang Shen, Wenjun Chen, Yunke Guo, Pan Gao, and Youjuan Zhu
- Subjects
Male ,medicine.medical_specialty ,Sensitivity and Specificity ,Mass Spectrometry ,chemistry.chemical_compound ,Rheumatology ,Internal medicine ,Phosphatidylcholine ,Carnitine ,Lipidomics ,Medicine ,Humans ,Pharmacology (medical) ,Beta oxidation ,Chromatography, High Pressure Liquid ,Triglycerides ,Triglyceride ,Receiver operating characteristic analysis ,business.industry ,Discriminant Analysis ,Serum samples ,Biomarker (cell) ,Endocrinology ,Sjogren's Syndrome ,chemistry ,Case-Control Studies ,Phosphatidylcholines ,Female ,Sjogren s ,business ,Biomarkers - Abstract
Objective The relationship between serum lipid variations in SS and healthy controls was investigated to identify potential predictive lipid biomarkers. Methods Serum samples from 230 SS patients and 240 healthy controls were collected. The samples were analysed by ultrahigh-performance liquid chromatography coupled with Q Exactive™ spectrometry. Potential lipid biomarkers were screened through orthogonal projection to latent structures discriminant analysis and further evaluated by receiver operating characteristic analysis. Results A panel of three metabolites [phosphatidylcholine (18:0/22:5), triglyceride (16:0/18:0/18:1) and acylcarnitine (12:0)] was identified as a specific biomarker of SS. The receiver operating characteristic analysis showed that the panel had a sensitivity of 84.3% with a specificity of 74.8% in discriminating patients with SS from healthy controls. Conclusion Our approach successfully identified serum biomarkers associated with SS patients. The potential lipid biomarkers indicated that SS metabolic disturbance might be associated with oxidized lipids, fatty acid oxidation and energy metabolism.
- Published
- 2019
20. A two-step ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry with mass defect filtering method for rapid identification of analogues from known components of different chemical structure types in Fructus Gardeniae-Fructus Forsythiae herb pair extract and in rat’s blood
- Author
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Minxin Meng, Wei Zhou, and Jinjun Shan
- Subjects
Male ,Iridoid ,medicine.drug_class ,Decoction ,01 natural sciences ,Biochemistry ,Lignans ,Analytical Chemistry ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Glucuronides ,Tandem Mass Spectrometry ,medicine ,Caffeic acid ,Animals ,Humans ,Glycosides ,Oleanolic acid ,Chromatography, High Pressure Liquid ,Serum Albumin ,Binding Sites ,Chromatography ,Phillyrin ,Plant Extracts ,010405 organic chemistry ,Solid Phase Extraction ,010401 analytical chemistry ,Organic Chemistry ,General Medicine ,Phenylethanoid ,Gardenia ,Rats ,0104 chemical sciences ,Molecular Docking Simulation ,chemistry ,Fruit ,Quercetin ,Kaempferol ,Glucuronide ,Drugs, Chinese Herbal - Abstract
Fructus Gardeniae-Fructus Forsythiae herb pair is an herbal formula used extensively to treat inflammation and fever, but few systematic identification studies of the bioactive components have been reported. Herein, the unknown analogues in the first-step screening were rapidly identified from representative compounds in different structure types (geniposide as iridoid type, crocetin as crocetin type, jasminoside B as monocyclic monoterpene type, oleanolic acid as saponin type, 3-caffeoylquinic acid as organic acid type, forsythoside A as phenylethanoid type, phillyrin as lignan type and quercetin 3-rutinoside as flavonoid type) by UPLC-Q-Tof/MS combined with mass defect filtering (MDF), and further confirmed with reference standards and published literatures. Similarly, in the second step, other unknown components were rapidly discovered from the compounds identified in the first step by MDF. Using the two-step screening method, a total of 58 components were characterized in Fructus Gardeniae-Fructus Forsythiae (FG-FF) decoction. In rat's blood, 36 compounds in extract and 16 metabolites were unambiguously or tentatively identified. Besides, we found the principal metabolites were glucuronide conjugates, with the glucuronide conjugates of caffeic acid, quercetin and kaempferol confirmed as caffeic acid 3-glucuronide, quercetin 3-glucuronide and kaempferol 3-glucuronide by reference standards, respectively. Additionally, most of them bound more strongly to human serum albumin than their respective prototypes, predicted by Molecular Docking and Simulation, indicating that they had lower blood clearance in vivo and possibly more contribution to pharmacological effects. This study developed a novel two-step screening method in addressing how to comprehensively screen components in herbal medicine by UPLC-Q-Tof/MS with MDF.
- Published
- 2018
21. Gas chromatography-mass spectrometry based plasma metabolomics of H1N1-induced inflammation in mice and intervention with Flos Lonicerae Japonica-Fructus Forsythiae herb pair
- Author
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Jianjian Ji, Wenjuan Qian, Liuqing Di, Tong Xie, Wei Zhou, Linxiu Peng, An Kang, and Jinjun Shan
- Subjects
Male ,0301 basic medicine ,Clinical Biochemistry ,Flos ,Inflammation ,Pharmacology ,Lung injury ,Biochemistry ,Gas Chromatography-Mass Spectrometry ,Analytical Chemistry ,Mice ,03 medical and health sciences ,Influenza A Virus, H1N1 Subtype ,Metabolomics ,Orthomyxoviridae Infections ,Oral administration ,medicine ,Animals ,Forsythia ,Chromatography ,biology ,Plant Extracts ,Chemistry ,Cell Biology ,General Medicine ,biology.organism_classification ,medicine.disease ,Mice, Inbred C57BL ,Lonicera ,Metabolic pathway ,030104 developmental biology ,Fruit ,Viral pneumonia ,Host-Pathogen Interactions ,Metabolome ,Female ,Gas chromatography–mass spectrometry ,medicine.symptom ,Drugs, Chinese Herbal - Abstract
Flos Lonicerae Japonica-Fructus Forsythiae herb pair (Yin-Qiao in Chinese, YQ), is used clinically for the treatment of viral pneumonia due to its heat-clearing and detoxifying functions. In the present work, the effect of YQ in H1N1-induced inflammation in mice was investigated by metabolomics based on GC-MS. Body weight and histological results were used to assess the lung injury, while the levels of IL-6 and TNF-α in plasma were used to evaluate the extent of inflammation. The acquired GC-MS data were further subjected to multivariate data analysis, and the significantly altered metabolites identified. After statistical and pathway analysis, 17 significantly altered metabolites and 3 possible metabolic pathways were found in plasma between normal and H1N1-induced pneumonia mice, while 17 significant differential metabolites were identified when YQ treatment group was compared with model group. This work indicates that oral administration of YQ could protect mice from H1N1-induced inflammation partially by ameliorating the associated metabolic disturbances.
- Published
- 2018
22. Simultaneous determination of sulfur compounds from the sulfur pathway in rat plasma by liquid chromatography tandem mass spectrometry: application to the study of the effect of Shao Fu Zhu Yu decoction
- Author
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Ruilin Su, Yilin Song, Armaan Basheer Shaikh, Xi Chen, Shulan Su, An Kang, Jinjun Shan, Yumei Chi, Yue Zhang, Li Yu, Hongmei Wen, Haishan Deng, Tong Xie, Le Shi, and Shuying Han
- Subjects
0301 basic medicine ,Analyte ,Formic acid ,Drug Evaluation, Preclinical ,chemistry.chemical_element ,Decoction ,Mass spectrometry ,01 natural sciences ,Biochemistry ,Antioxidants ,Analytical Chemistry ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Limit of Detection ,Tandem Mass Spectrometry ,Liquid chromatography–mass spectrometry ,Animals ,Derivatization ,Chromatography, High Pressure Liquid ,Detection limit ,Chromatography ,Sulfur Compounds ,Chemistry ,010401 analytical chemistry ,Sulfur ,Rats ,0104 chemical sciences ,Oxidative Stress ,030104 developmental biology ,Female ,Metabolic Networks and Pathways ,Drugs, Chinese Herbal - Abstract
A sensitive, accurate, and time-saving approach was developed for the simultaneous quantification of eight sulfur compounds in the sulfur pathway, which could reflect the status of an organism, including oxidative stress, signal transduction, enzyme reaction, and so on. In order to overcome the instability of highly reactive sulfhydryl compounds, N-ethylmaleimide derivatization was adopted to effectively protect sulfhydryl-containing samples. Using isotope-labeled glutathione (GSH-13C2, 15N), the validated method was demonstrated to offer satisfactory linearity, accuracy, and precision. Separation was done by UHPLC, using a BEH amide column. Accordingly, 0.1% formic acid acetonitrile was selected as the precipitant. A tandem mass spectrometer was coupled to the chromatographic system and afforded a detection limit of 0.2 ng/mL. Good linearity was maintained over a wide concentration range (r2 > 0.994), and the accuracy was in the range of 86.6–114% for all the studied compounds. The precision, expressed in RSD%, ranged from 1.1% to 9.4% as intraday variability and less than 13% as interday precision for all of the analytes. The approach was applied to study the potential therapeutic mechanism of a well-known traditional Chinese medicine, Shao Fu Zhu Yu decoction. The results suggested that Shao Fu Zhu Yu decoction might protect against oxidative damage by increasing the concentrations of sulfhydryl compounds.
- Published
- 2018
23. Regulatory Effect of Xiaofeng Xuanqiao Decoction on Spleen Metabolites in Allergic Rhinitis Mice Based on Gas Chromatography Mass Spectrometry
- Author
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Mingchen Jiang, Xie Tong, Jinjun Shan, Jialei Tao, and Shouchuan Wang
- Subjects
medicine.anatomical_structure ,Chromatography ,Chemistry ,Applied Mathematics ,General Mathematics ,medicine ,Spleen ,Decoction ,Gas chromatography–mass spectrometry - Published
- 2018
24. Clinical lipidomics analysis reveals biomarkers of lipid peroxidation in serum from patients with rheumatoid arthritis
- Author
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Jiawei Lu, Jue Wang, Qiuxiang Shen, Shijia Liu, Jinjun Shan, Tingting Xu, Guisheng Zhou, Wenjun Chen, Youjuan Zhu, Yan Lu, and Mengying Ke
- Subjects
medicine.medical_specialty ,Receiver operating characteristic ,Triglyceride ,medicine.diagnostic_test ,business.industry ,medicine.disease ,Gastroenterology ,Analytical Chemistry ,Pathogenesis ,Lipid peroxidation ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Rheumatoid arthritis ,Lipidomics ,medicine ,Differential diagnosis ,business ,Lipid profile ,Spectroscopy - Abstract
Rheumatoid arthritis (RA) is a common chronic inflammatory disorder characterized by inflammation of the synovium which causes joint damage, chronic pain, and disability. Changes in lipid profile are seen before overt RA disease manifestations suggesting that lipids contribute to the inflammation-driven metabolic changes in tumor necrosis factor. Currently, the pathogenesis of RA is unclear. Moreover, it is important to search for lipids biomarkers for early diagnosis of the disease. Herein, we compared the lipid profile of healthy individuals and RA patients to provide evidence for the diagnosis and management of persons with RA. Serum samples were collected from 511 RA patients and 396 health controls (HC). The samples were analyzed by ultra-performance liquid chromatography Q-Exactive mass spectrometry. Potential lipid biomarkers were screened and validated using the partial least squares discriminant analysis (PLS-DA), orthogonal partial least squares-discriminant analysis (OPLS-DA), random forest, binary logistic regression (BLR), receiver operating characteristic (ROC) and counter propagation artificial neural network (CP-ANN) analysis. A total of 36 differential lipid metabolites were identified, including phosphatidylethanolamine (PE), triglyceride (TG), acylcarnitine (ACar) and phosphatidylcholine (PC). Among them, PE 16:0-18:2, TG 18:0-18:1-18:2 and PE 18:2-18:2 were identified as specific biomarkers for differential diagnosis of RA. ROC analysis showed that the biomarkers had a sensitivity of 68% with a specificity of 63% in discriminating RA from HC individuals. The resulting CP-ANN can be used to identify unknown RA samples with predictive accuracy of 97% as determined through cross validation. The external validation accuracy of CP-ANN was 100% in all evaluated cases. The three lipid serum biomarkers were associated with the disease activity in RA. These lipid biomarkers showed that lipid peroxidation is disrupted in RA.
- Published
- 2021
25. A post processing strategy to score and rank the annotation confidence of saponins in natural products by integrating MS2 spectral similarity and fragment interpretation
- Author
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Jinjun Shan, Tong Xie, Xia Zhao, Yu He, Jun Jiang, and Wenjun Tong
- Subjects
Chemistry ,business.industry ,Clinical Biochemistry ,Rank (computer programming) ,Cosine similarity ,Pharmaceutical Science ,Pattern recognition ,Spectral similarity ,Analytical Chemistry ,Interpretation (model theory) ,Market fragmentation ,Annotation ,Fragment (logic) ,Drug Discovery ,Artificial intelligence ,business ,Spectroscopy ,Statistic - Abstract
Tandem mass spectrometry-spectra-based annotation in natural products challenges a lot because of ambiguous structural characterization. It still lacks an efficiency method to score and rank the annotation confidence. Herein, we develop a novel approach to rank the annotation confidences of saponins. Annotations were accomplished according to fragmentation patterns. The corresponding diagnostic fragments and their abundances were recorded. Average abundances were taken as a reference spectrum, and the cosine similarity score (CSS) was calculated to measure how well the spectral matched. According to CSS values, statistic description for confidence levels can be effectively provided. Next, the fragment interpretation score (FIS) was proposed to investigate the deviators' characteristic fragmentation. FIS offset the effect from the deviators' unique fragments. Suspicious annotations involving low CSS and high FIS, may derived from the MS2 spectral background interferences or co-elution. Annotations with low CSS and FIS rank as low confidences, as these annotations need more attention. Using this method, novel saccharide sequences, specific fragmentation preferences, undistinguished precursors, even new structures can also be well traced. By proposed new scoring system, confidence evaluations can be ranked, resulting in significantly enhanced annotation reliability.
- Published
- 2021
26. Suppressive Effect of Ginsenoside Rg3 against Lipopolysaccharide-Induced Depression-Like Behavior and Neuroinflammation in Mice
- Author
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An Kang, Tong Xie, Dong Zhu, Jinjun Shan, Liuqing Di, and Xiao Zheng
- Subjects
Lipopolysaccharides ,Male ,0301 basic medicine ,medicine.medical_specialty ,Ginsenosides ,Lipopolysaccharide ,Panax ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Humans ,Neuroinflammation ,Mice, Inbred ICR ,Behavior, Animal ,Microglia ,Depression ,Interleukin-6 ,Plant Extracts ,Tumor Necrosis Factor-alpha ,Brain ,General Chemistry ,Tail suspension test ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Ginsenoside ,Tumor necrosis factor alpha ,Serotonin ,General Agricultural and Biological Sciences ,030217 neurology & neurosurgery ,Behavioural despair test - Abstract
Ginsenoside Rg3 (Rg3), a major active ingredient enriched in red ginseng, possesses well-confirmed immunoregulatory effects. Immune disturbance is a common trigger and aggravating factor of depression. The aim of this study was to explore the effects of Rg3 on lipopolysaccharide (LPS)-induced depression-like behavior in mice and the involvement of immune regulation. Pretreatment with Rg3 (i.g., 20 and 40 mg/kg) effectively ameliorated LPS (i.p., 0.83 mg/kg) induced body weight loss, anorexia, and immobility time in both the tail suspension test and the forced swimming test. Rg3 attenuated the disturbed turnover of tryptophan and serotonin in the hippocampus, accompanied by decreased mRNA expression of pro-inflammatory cytokines and indoleamine-2,3-dioxygenase (IDO). These central benefits were partially linked to the regulation of microglia activation and nuclear factor kappa B (NF-κB) pathway. In addition, Rg3 significantly reduced LPS-induced elevation of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in plasma, and restored the systemic balance of tryptophan-kynurenine metabolism. Taken together, our results demonstrated that Rg3 was effective in ameliorating depressive-like behavior induced by immune activation, adding new evidence to support its health benefits by immunoregulation.
- Published
- 2017
27. Tanshinone IIA Can Inhibit Angiotensin II-Induced Proliferation and Autophagy of Vascular Smooth Muscle Cells via Regulating the MAPK Signaling Pathway
- Author
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Ning Liu, Pei Wang, Yao Ding, Jingping Lu, and Jinjun Shan
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Cell signaling ,Vascular smooth muscle ,MAP Kinase Signaling System ,Primary Cell Culture ,Pharmaceutical Science ,p38 Mitogen-Activated Protein Kinases ,Muscle, Smooth, Vascular ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Western blot ,medicine ,Autophagy ,Animals ,Phosphorylation ,Protein kinase A ,Cells, Cultured ,Cell Proliferation ,Pharmacology ,medicine.diagnostic_test ,Chemistry ,Angiotensin II ,General Medicine ,Cell biology ,Rats ,030104 developmental biology ,Apoptosis ,030220 oncology & carcinogenesis ,Abietanes ,cardiovascular system - Abstract
To examine the effect of tanshinone IIA on Angiotensin II (Ang II)-induced proliferation and autophagy in vascular smooth muscle cells (VSMCs) and the related mechanism. VSMCs were treated with Ang II with or without tanshinone IIA (1, 5 and 10 µg/mL), and the proliferation, apoptosis in cells with different treatment were examined by methylthiazolyl tetrazolium (MTT) and flow cytometry methods. Moreover, the expression of autophagy related proteins and mitogen-activated protein kinase (MAPK) signaling molecules were examined by RT-quantitative (q)PCR and Western blot methods. Ang II induced significantly increase in the proliferation and autophagy of VSMCs, and the MAPK signaling was activated. Tanshinone IIA can attenuate Ang II-induced effects via down-regulating the MAPK signaling pathway. Tanshinone IIA can inhibit Ang II-induced proliferation and autophagy of VSMCs via regulating the MAPK signaling pathway.
- Published
- 2019
28. Talin promotes integrin activation accompanied by generation of tension in talin and an increase in osmotic pressure in neurite outgrowth
- Author
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Yunfeng Hu, Jun Guo, Jinjun Shan, Yiqian Zhai, Jilai Tian, Yifan Wang, and Xiaolong Zhang
- Subjects
0301 basic medicine ,Talin ,Integrins ,animal structures ,Neurite ,Integrin ,Neuronal Outgrowth ,macromolecular substances ,Microfilament ,environment and public health ,Biochemistry ,Mechanotransduction, Cellular ,PC12 Cells ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Osmotic Pressure ,Cell Line, Tumor ,Genetics ,Osmotic pressure ,Animals ,Humans ,Aggrecans ,Nerve Growth Factors ,Molecular Biology ,Aggrecan ,Cells, Cultured ,Neurons ,biology ,Chemistry ,RNA-Binding Proteins ,Rats ,DNA-Binding Proteins ,Mice, Inbred C57BL ,Actin Cytoskeleton ,030104 developmental biology ,Förster resonance energy transfer ,Nerve growth factor ,embryonic structures ,Biophysics ,biology.protein ,biological phenomena, cell phenomena, and immunity ,030217 neurology & neurosurgery ,Intracellular ,Biotechnology - Abstract
Neuronal polarization depends on the interaction of intracellular chemical and mechanical activities in which the cytoplasmic protein, talin, plays a pivotal role during neurite growth. To better understand the mechanism underlying talin function in neuronal polarization, we overexpressed several truncated forms of talin and found that the presence of the rod domain within the overexpressed talin is required for its positive effect on neurite elongation because the neurite number only increased when the talin head region was overexpressed. The tension in the talin rod was recognized using a Forster resonance energy transfer-based tension probe. Nerve growth factor treatment resulted in inward tension of talin elicited by microfilament force and outward osmotic pressure. By contrast, the glial scar-inhibitor aggrecan weakened these forces, suggesting that interactions between inward pull forces in the talin rod and outward osmotic pressure participate in neuronal polarization. Integrin activation is also involved in up-regulation of talin tension and osmotic pressure. Aggrecan stimuli resulted in up-regulation of docking protein 1 (DOK1), leading to the down-regulation of integrin activity and attenuation of the intracellular mechanical force. Our study suggests interactions between the intracellular inward tension in talin and the outward osmotic pressure as the effective channel for promoting neurite outgrowth, which can be up-regulated by integrin activation and down-regulated by DOK1.-Wang, Y., Zhang, X., Tian, J., Shan, J., Hu, Y., Zhai, Y., Guo, J. Talin promotes integrin activation accompanied by generation of tension in talin and an increase in osmotic pressure in neurite outgrowth.
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- 2019
29. Vector analysis of steerable mechanical tension across nuclear lamina
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Zhao H, Chen T, Jinjun Shan, HuiWen Wu, Jianming Guo, Junqiang Zhang, and Wang Yuxuan
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biology ,Chemistry ,Microtubule ,Biophysics ,biology.protein ,Osmotic pressure ,Nuclear lamina ,Stathmin ,Cofilin ,Cytoskeleton ,Intermediate filament ,Microfilament - Abstract
SUMMARYThe nucleus is the most prominent organelle in eukaryotic cells, and its deformation depends on interactions between the nuclear lamina (NL) and cytoskeleton structural tensions. The structural tensions can be quantified at a pico-Newton (pN) level using a genetically encoded optical probe. In living cells, NL tensions countered the 4.26pN resting strain imposed competitively by cytoskeletal tension. The depolymerization of microfilaments or microtubules drove an aberrant increase in outward osmotic pressure through the production of mass protein-nanoparticles. The osmotic pressure also served as a directional converter of inward cytoskeletal force, and contributed to the outward expansion of NL via the passive pull of intermediate filaments (IFs). The NL, but not IFs, can remotely detect extracellular osmosis pressure alterations, which are closely associated with highly polarized microfilament and microtubule structures and their directional force activities. The oxidative-induced increase of NL tension results from intracellular hyper-osmosis, associated closely with protein-nanoparticles production elicited by cofilin and stathmin activation. These data reveal that intracellular steerable forces interact direction-dependently to control NL tension in terms of their magnitude and vectors.
- Published
- 2018
30. Development of a multiple reaction monitoring (MRM) method based on high performance liquid chromatography/tandem mass spectrometry to analyze in vivo exposure profiles of complex herbal components independent of standards
- Author
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Cunsi Shen, Shouchuan Wang, Liuqing Di, Jianya Xu, An Kang, Jinjun Shan, Xia Zhao, and Tong Xie
- Subjects
0301 basic medicine ,Chromatography ,biology ,Chemistry ,Schisandra chinensis ,General Chemical Engineering ,010401 analytical chemistry ,Selected reaction monitoring ,High resolution ,Improved method ,General Chemistry ,biology.organism_classification ,Tandem mass spectrometry ,01 natural sciences ,High-performance liquid chromatography ,0104 chemical sciences ,03 medical and health sciences ,030104 developmental biology ,In vivo ,Tripterygium wilfordii - Abstract
Exposure profiles of herbal components in vivo play pivotal roles in pharmacodynamic evaluation. Herein, we report the development of a universal multiple reaction monitoring (MRM) method for the sensitive and accurate identification of in vivo exposure profiles of complex herbal systems, including exposure components, exposure times, and relative exposure levels. The method integrated multiple scan monitoring types based on high performance liquid chromatography/tandem mass spectrometry (HPLC/MS-MS), and mainly consisted of four steps: (a) analyzing herbal extract samples by high resolution mass spectrometry, (b) refining S-lens and CE voltages to develop the MRM method, (c) detecting exposure components, and (d) evaluating exposure times and levels. We applied this developed method step-by-step to delineate the flavonoid profiles of a Schisandra chinensis extract, detecting 22 exposure flavonoids of which 19 were defined as long-term exposure components. Using a “relative exposure approach”, relative exposure levels in vivo were further elucidated. Compared with the general method based on high resolution MS-based HPLC/linear trap quadrupole (LTQ)-Orbitrap, the improved method provided more comprehensive detection. Furthermore, we demonstrated the utility of this approach in the investigation of exposure profiles of pyridine alkaloids in a Tripterygium wilfordii Hook.F. extract. Of 55 MRM transitions, 39 exposure components were detected. The results of this study suggested that the improved method might provide an excellent foundation for sufficient, sensitive, and accurate monitoring of exposure profiles in complex herbal systems or homologous compounds in vivo.
- Published
- 2016
31. A metabolomics approach to studying the effects of Jinxin oral liquid on RSV-infected mice using UPLC/LTQ-Orbitrap mass spectrometry
- Author
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Shouchuan Wang, An Kang, Jinjun Shan, Liuqing Di, Jianya Xu, Tong Xie, and Li-na Du
- Subjects
viruses ,Administration, Oral ,Respiratory Syncytial Virus Infections ,Mass Spectrometry ,Virus ,Cell Line ,Mice ,chemistry.chemical_compound ,Metabolomics ,Tandem Mass Spectrometry ,Liquid chromatography–mass spectrometry ,Drug Discovery ,medicine ,Animals ,Humans ,Respiratory system ,Chromatography, High Pressure Liquid ,Pharmacology ,Mice, Inbred BALB C ,Ribavirin ,respiratory system ,medicine.disease ,Respiratory Syncytial Viruses ,Pharmaceutical Solutions ,Pneumonia ,chemistry ,Viral pneumonia ,Immunology ,Bronchitis ,Female ,Chromatography, Liquid ,Drugs, Chinese Herbal - Abstract
Ethnopharmacological relevance Jinxin oral liquid (JOL) is a traditional Chinese medicine (TCM) formula modified from ma-xing-shi-gan-tang, an ancient formula widely used in the treatment of respiratory diseases such as bronchitis, pneumonia, and asthma. In our previous studies, JOL was shown to safely and effectively treat viral pneumonia, especially that involving respiratory syncytial virus (RSV). Aim of the study To investigate the mechanism of the effect of JOL in RSV infected mice, using a metabolomics approach based on ultra-performance liquid chromatography coupled with linear ion trap quadrupole-Orbitrap mass spectrometry (UPLC/LTQ-Orbitrap–MS). Materials and methods BALB/c mice were divided into four groups, the control group (saline inoculation/no treatment), RSV group (RSV inoculation/saline treatment), RSV+JOL group (RSV inoculation/JOL treatment), and RSV+Riba group (RSV inoculation/ribavirin treatment). Plasma and lung tissue samples were collected 7 days after the inoculation/treatment protocols, and UPLC/LTQ-Orbitrap-MS method based on metabolomics was developed. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were utilized to identify biomarkers potentially associated with the anti-RSV activity of JOL. Results JOL was associated with reduced inflammatory responses in RSV-infected lung tissue. The combination of PCA and OPLS-DA revealed deviations in 11 biomarkers in plasma, and 16 biomarkers in lung tissue induced by RSV that were corrected with JOL treatment. These biomarkers were primarily components of metabolic pathways involving glycerophosphocholines, sphingolipids, and glycerolipids. JOL was able to restore the abnormal levels of these biomarkers detected in the plasma and lung tissue of RSV-infected mice to approximately normal levels. Conclusions This study suggested that JOL can treat RSV pneumonia effectively, partially by ameliorating the associated disturbances to lipid metabolism. The results provided insight into the anti-RSV mechanism of JOL, and also demonstrated that metabolomics is a valuable tool for investigating the efficacy of TCM treatment for RSV pneumonia, and the associated biomarkers involved.
- Published
- 2015
32. Application of untargeted lipidomics based on UHPLC-high resolution tandem MS analysis to profile the lipid metabolic disturbances in the heart of diabetic cardiomyopathy mice
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Jianping Li, Jianming Guo, Jinjun Shan, Yu He, Xuejun Xu, and Zichen Luo
- Subjects
medicine.medical_specialty ,Ceramide ,Lipid Metabolism Disorder ,Heart disease ,Diabetic Cardiomyopathies ,Clinical Biochemistry ,Pharmaceutical Science ,01 natural sciences ,Analytical Chemistry ,Mice ,chemistry.chemical_compound ,Insulin resistance ,Internal medicine ,Diabetic cardiomyopathy ,Drug Discovery ,Lipidomics ,Diabetes Mellitus ,medicine ,Animals ,cardiovascular diseases ,Chromatography, High Pressure Liquid ,Spectroscopy ,010405 organic chemistry ,Chemistry ,010401 analytical chemistry ,Heart ,musculoskeletal system ,medicine.disease ,Lipids ,0104 chemical sciences ,Endocrinology ,Lipotoxicity ,cardiovascular system ,lipids (amino acids, peptides, and proteins) ,Sphingomyelin - Abstract
Diabetic cardiomyopathy (DCM) is a distinct form of heart disease caused by diabetes. Lipid accumulation has been reported to present in the hearts of DCM animals, however characterization of disordered lipids, and their roles in the etiology and progress of DCM remain largely undefined. In present study, an untargeted lipidomics based on ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometers was established for global detection of lipids in the hearts of DCM mice. DCM mice showed significant cardiac dysfunction with decreased left ventricular fractional shortening (FS) and ratio of peak early filling velocity to atrial filling velocity (MV E/A). Histological lesion, fibrosis, hypertrophy, and lipid accumulation were also observed in the heart of DCM mice. By lipidomics analysis, a total of 244 lipids were identified, of which 89 lipids were significantly changed. The disordered metabolic profile of lipids in DCM mice heart were characterized by the accumulation of triacylglycerol, glycerophospholipid, cholesterol-sulfate, ceramide and sphingomyelin, as well as by the loss of glycerophospholipid. The lipid alterations in the heart were correlated with the development of cardiac dysfunction, lipotoxicity, inflammation and insulin resistance. Correlations between lipid metabolism disorders and DCM progress should be further explored.
- Published
- 2020
33. Integrated Serum and Fecal Metabolomics Study of Collagen-Induced Arthritis Rats and the Therapeutic Effects of the Zushima Tablet
- Author
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Jinjun Shan, Linxiu Peng, Wenjuan Qian, Tong Xie, An Kang, Bei Gao, and Liuqing Di
- Subjects
rheumatoid arthritis ,0301 basic medicine ,Arthritis ,Butyrate ,Gut flora ,Pharmacology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Metabolomics ,medicine ,Pharmacology (medical) ,Original Research ,030203 arthritis & rheumatology ,Chinese medicine ,gut microbiota ,biology ,Fatty acid metabolism ,lcsh:RM1-950 ,Cholic acid ,Metabolism ,biology.organism_classification ,medicine.disease ,metabolomics ,gas chromatography-mass spectrometry ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,chemistry ,Pyruvic acid - Abstract
The Zushima tablet (ZT) has been used for decades in the clinical treatment of rheumatoid arthritis (RA) in China. However, its therapeutic mechanism is unclear. In this study, we aimed to explore the distinctive metabolic patterns in collagen-induced arthritis (CIA) rats and evaluate the therapeutic effects of ZT on RA using untargeted serum and fecal metabolomics approaches based on gas chromatography coupled with mass spectrometry. Body weight, hind paw swelling, TNF-α and IL-1β levels, arthritis scores, and histopathological parameters were assessed. In the metabolomics study, 31 altered metabolites in the serum and 30 in the feces were identified by comparing the model with the control group using statistical processing. These altered metabolites revealed that the tricarboxylic acid cycle, glycolysis metabolism, fatty acid metabolism, and purine metabolism were disturbed in CIA rats, and most of these altered metabolites including l-isoleucine, l-aspartic acid, pyruvic acid, cholic acid, and hypoxanthine, were rectified by ZT. Furthermore, short-chain fatty acids in feces were quantitatively determined, and the results showed that ZT could regulate the levels of propionate, butyrate, and valerate in CIA rats. Then, gut microbiota were analyzed by 16S rRNA analysis. Our results showed that Firmicutes and Bacteroidetes were the most abundant bacteria in rats. The levels of 19 types of bacteria at the family level were altered in RA rats, and most of them could be regulated by ZT. This study demonstrated that metabolomics analysis is a powerful tool for providing novel insight into RA and for elucidating the potential mechanism of ZT.
- Published
- 2018
34. Lipid profile perturbations in the plasma and lungs of mice with LPS-induced acute lung injury revealed by UHPLC-ESI-Q Exactive HF MS analysis
- Author
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Pingxi Xiao, Liuqing Di, Linxiu Peng, Wenjuan Qian, Jinjun Shan, Tong Xie, An Kang, Wei Zhou, and Lili Lin
- Subjects
Lipopolysaccharides ,Male ,Spectrometry, Mass, Electrospray Ionization ,Lipopolysaccharide ,Clinical Biochemistry ,Acute Lung Injury ,Pharmaceutical Science ,Inflammation ,Pharmacology ,Lung injury ,Analytical Chemistry ,chemistry.chemical_compound ,Drug Discovery ,Lipidomics ,medicine ,Animals ,Metabolomics ,Lung ,Spectroscopy ,Chromatography, High Pressure Liquid ,Mice, Inbred BALB C ,medicine.diagnostic_test ,Metabolism ,Lipids ,Disease Models, Animal ,medicine.anatomical_structure ,chemistry ,lipids (amino acids, peptides, and proteins) ,Nasal administration ,medicine.symptom ,Inflammation Mediators ,Lipid profile ,Biomarkers - Abstract
An UHPLC-ESI-Q Exactive HF MS-based lipidomics method was successfully applied to profile various lipids from the plasma and lungs of mice intranasally challenged with lipopolysaccaride (LPS). Response trends of lipids to LPS were graphically represented by variable importance in projection (VIP) plot, heat map, and bar plot. As a result, 77 differential lipids in the lung and 13 differential lipids in the plasma were identified by comparison between healthy and LPS- induced mice. These results revealed the correlation between inflammation and lipids metabolism. The differentially regulated lipids could also be potentially used as biomarkers for inflammation.
- Published
- 2018
35. Liquid Chromatography Coupled with Linear Ion Trap Hybrid OrbitrapMass Spectrometry for Determination of Alkaloids in Sinomeniumacutum
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Cunsi Shen, Xia Zhao, Jianya Xu, Jinjun Shan, Tong Xie, Jianjian Ji, Wenjun Tong, and Shouchuan Wang
- Subjects
Morphinan ,Formic acid ,Sinomenium acutum ,Pharmaceutical Science ,Protonation ,Aporphines ,Mass spectrometry ,alkaloids ,01 natural sciences ,Dissociation (chemistry) ,Analytical Chemistry ,lcsh:QD241-441 ,chemistry.chemical_compound ,Fragmentation (mass spectrometry) ,lcsh:Organic chemistry ,Drug Discovery ,heterocyclic compounds ,Physical and Theoretical Chemistry ,Quadrupole ion trap ,Chromatography ,010405 organic chemistry ,Chemistry ,010401 analytical chemistry ,Organic Chemistry ,fragmentation pattern ,0104 chemical sciences ,Chemistry (miscellaneous) ,Molecular Medicine ,morphinan - Abstract
The characterization of alkaloids is challenging because of the diversity of structures and the complicated fragmentation of collision induced structural dissociation in mass spectrometry. In this study, we analyzed the alkaloids in Sinomenium acutum (Thunb.) Rehderet Wil by high resolution mass spectrometry. Chromatographic separation was achieved on a Phenomenex Kinetex C18 (2.1 mm ×, 100 mm, 2.6 &mu, m) column with a mobile phase consisting of acetonitrile and water (0.1% formic acid) under gradient elution. A total of 52 alkaloids were well separated and 45 of them were structurally characterized, including morphinans, aporphines, benzylisoquinolines, and protoberberines. Specially, mass spectrometric study of the morphinan alkaloids were explicitly investigated. Electrostatic potential plot from simulation was calculated for determination of protonation sites. Further fragmentation analysis suggested that the C3H7N, CH4O, and H2O elimination was displayed in MS2 spectrum. These fragmentation pathways are universal for morphinan alkaloids having methoxy substituted cyclohexenone or cyclohexadienone moieties. Additionally, for nitrogen oxides, an ion-neutral complex intermediate is involved in the fragmentation process, generating additional oxygenated ions. All these results provided the universal rules of fragmentation used for detection of alkaloids, and will be expected to be highly useful for comprehensive study of multi-components in the herbal medicine analysis.
- Published
- 2018
36. Vector Analysis of Cytoskeletal Structural Tension and the Mechanisms that Underpin Spectrin-Related Forces in Pyroptosis
- Author
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Jinjun Shan, JiaRui Zhang, Xiaoguang Margaret Liu, Xu Shen, Guo Jun, Chen Tingting, and Yichen Guo
- Subjects
0301 basic medicine ,Osmosis ,Physiology ,Clinical Biochemistry ,Breast Neoplasms ,Microfilament ,Biochemistry ,Microtubules ,Cell membrane ,03 medical and health sciences ,Mice ,Microtubule ,medicine ,Pyroptosis ,Animals ,Humans ,Spectrin ,Cytoskeleton ,Molecular Biology ,General Environmental Science ,Calcium signaling ,030102 biochemistry & molecular biology ,Chemistry ,Cell Membrane ,Cell Biology ,Actin Cytoskeleton ,030104 developmental biology ,medicine.anatomical_structure ,Biophysics ,MCF-7 Cells ,General Earth and Planetary Sciences ,Female ,Intracellular ,Neoplasm Transplantation - Abstract
Aims: Pyroptotic cells are characterized by plasma swelling, membrane blebbing, and disintegration of the cell membrane mediated by spectrin-based membrane skeleton and intercellular competitive tension activities. The spectrin-based membrane skeleton is involved in membrane organization through the regulation of intercellular tension. Using genetically encoded tension sensors to attain noninvasive force measurements in structural proteins, we investigated how cytoskeletal structural tension influences changes in plasma morphology during pyroptosis and the regulatory mechanism of cytoskeletal structural tension that underpins pyroptosis. Results: The results indicate that increasing spectrin tension is caused by osmotic swelling. Hightened tension of spectrin was closely associated with the shrink tension transmitted synergistically by microfilaments (MFs) and microtubules (MTs). However, the increment of spectrin tension in pyroptotic cells was controlled antagonistically by MF and MT forces. Different from MF tension, outward MT forces participated in the formation of membrane blebs. Spectrin tension caused by inward MF forces resisted pyroptosis swelling. Stabilization of MF and MT structure had little influence on intracellular tension and pyroptosis deformation. Pyroptosis-induced cytoskeletal structural tension was highly dependent on calcium signaling and reactive oxygen species generation. Blocking of membrane pores, nonselective ion flux, or elimination of caspase-1 cleavage resulted in the remission of structural forces associated with pyroptosis failure. Innovation and Conclusions: The data suggest that subcellular tension, in terms of magnitude and vector, is integral to pyroptosis through the mediation of swelling and blebbing and the elimination of structural tension, especially MT forces, may result in pyroptosis inhibition.
- Published
- 2018
37. A Comparative Pharmacokinetic Study by UHPLC-MS/MS of Main Active Compounds after Oral Administration of Zushima-Gancao Extract in Normal and Adjuvant-Induced Arthritis Rats
- Author
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Linxiu Peng, Chen Lianghui, Liuqing Di, Wenjuan Qian, Jinjun Shan, Tong Xie, and An Kang
- Subjects
Male ,rheumatoid arthritis ,Phytochemicals ,Pharmaceutical Science ,Tandem mass spectrometry ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Stability ,Pharmacokinetics ,lcsh:Organic chemistry ,Tandem Mass Spectrometry ,Drug Discovery ,Daphnoretin ,Animals ,Physical and Theoretical Chemistry ,Glycyrrhizin ,Chromatography, High Pressure Liquid ,030203 arthritis & rheumatology ,Chromatography ,Molecular Structure ,Organic Chemistry ,Reproducibility of Results ,Zushima-Gancao extract ,UHPLC-MS/MS ,pharmacokinetics ,Arthritis, Experimental ,Rats ,chemistry ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,Molecular Medicine ,Liquiritigenin ,Quantitative analysis (chemistry) ,Isoliquiritigenin ,Liquiritin ,Drugs, Chinese Herbal - Abstract
A sensitive and rapid ultra high-performance liquid-chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been applied to investigate the influence of rheumatoid arthritis (RA) on the pharmacokinetics of nine analytes (daphnetin, daphnoretin, 7-hydroxycoumarin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizin, and glycyrrhetinic acid), which are major active components in Zushima-Gancao extract. The analytes and internal standard (IS) were separated in a Hypersil Gold C18 column and detected on a triple-stage quadrupole mass spectrometer using the validated method. All analytes exhibited good linearities (R2 > 0.98), and the lower limit of quantification (LLOQs) were sufficient for quantitative analysis. Intra- and inter-batch precision were all within 14.96% while the accuracy of nine analytes ranged from −17.99 to 14.48%, and these results were all within acceptance criteria. The extraction recoveries, matrix effects, and stabilities were all satisfactory. Main pharmacokinetic parameters of each compound were compared, and significant differences were found in parameters of daphnetin, daphnoretin, liquiritin, isoliquiritin, isoliquiritigenin, glycyrrhizin, and glycyrrhetinic acid, especially the last one, between the two groups. Therefore, adjuvant-induced arthritis has different effects on the pharmacokinetics of ingredients in Zushima-Gancao extract. The comparative pharmacokinetic study between normal and adjuvant-induced arthritis rats might provide more comprehensive information to guide the clinical usage of Zushima-Gancao extract for treating RA.
- Published
- 2018
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38. Effects of Gancao on pharmacokinetic profiles of platycodin D and deapio-platycodin D in Jiegeng
- Author
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Jiashuang Zou, Wei Zhou, An Kang, Jinjun Shan, Cunsi Shen, Shouchuan Wang, Li-na Du, Jianya Xu, Liuqing Di, and Tong Xie
- Subjects
Male ,Platycodon ,Cmax ,Pharmacology ,Plant Roots ,Intestinal absorption ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Pharmacokinetics ,Tandem Mass Spectrometry ,Liquid chromatography–mass spectrometry ,Drug Discovery ,Glycyrrhiza ,Animals ,Humans ,Analysis software ,Chromatography ,Plant Extracts ,Chemistry ,Platycodin D ,Metabolism ,Saponins ,Triterpenes ,In vitro ,Rats ,Intestinal Absorption ,Area Under Curve ,Caco-2 Cells ,Rhizome ,Chromatography, Liquid ,Drugs, Chinese Herbal ,Half-Life - Abstract
Ethnopharmacological relevance Jiegeng (Radix Platycodi), the dried root of Platycodon grandiflorum A. DC (Campanulaceae), has been used to treat cough, sore throat, bronchitis, and bronchial asthma for thousands of years. It is commonly prescribed with Gancao (Radix et Rhizoma Glycyrrhizae) as a herbal combination in traditional Chinese medicine (TCM) to produce synergistic effects. Aim of the study To elucidate the herbaceous compatibility of Jiegeng and Gancao, we investigated the comparative pharmacokinetics, intestinal absorption, and microbial metabolism of platycodin D (PD) and deapio-platycodin D (DPD), the platycodins contained in Jiegeng. Materials and methods In the comparative pharmacokinetic study, the concentrations of PD and DPD in Jiegeng extract (JE) and the Jiegeng–Gancao herb pair (JGHP) were determined in rat plasma using liquid chromatography–tandem mass spectrometry (LC–MS/MS). In addition, the main pharmacokinetic parameters were calculated using data analysis software (DAS). Furthermore, in vitro studies using Caco-2 cells and fecal lysates were performed to contradistinguish the intestinal absorption and microbial metabolism of PD and DPD in JE from those in JGHP. Results The peak concentration (Cmax) and area under the plasma concentration curve (AUC) of PD in rats orally administrated JGHP significantly increased compared to that in rats treated with JE. In addition, the time to reach peak concentration (Tmax) and half-life (t1/2) of PD and DPD in combination with JGHP were all prolonged compared with those of JE. There was no significant difference in the absorption of PD between JE and JGHP in Caco-2 cells. However, the hydrolysis of both PD and DPD in JGHP were weaker than that in JE after a 2-h incubation in fecal lysate which might be responsible for the different pharmacokinetic profiles of the platycodins in JE and JGHP. Conclusion In this study, we discovered that Gancao might influence the pharmacokinetic profiles of PD and DPD in Jiegeng. Furthermore, the difference in profiles may be attributable to the inequable microbial metabolism rather than intestinal absorption of the platycodins in JE and JGHP. The results of this study elucidated the pharmacokinetic compatibility and rationale for the use of JGHP.
- Published
- 2015
39. Simultaneous determination of twenty-six components of Flos Lonicerae japonicae–Fructus Forsythiae herb couple using UPLC-ESI-MS/MS: application to its preparations
- Author
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Shouchuan Wang, Minxin Meng, Wenzheng Ju, Baochang Cai, Liuqing Di, Wei Zhou, and Jinjun Shan
- Subjects
Chromatography ,Neochlorogenic acid ,biology ,Phillyrin ,Loganin ,General Chemical Engineering ,General Engineering ,Arctiin ,Hyperoside ,Flos ,biology.organism_classification ,Analytical Chemistry ,chemistry.chemical_compound ,chemistry ,Chlorogenic acid ,Caffeic acid - Abstract
In this study, we developed a method using UPLC-ESI-MS/MS to simultaneously determine the contents of forsythoside B, loganin, macranthoidin B, dipsacoside B, rutin, arctiin, phillyrin, pinoresinol-β-D-glucoside, 3,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, isoquercitrin, hyperoside, astragalin, luteoloside, genistin, arctigenin, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, quercetin, luteolin, genistein, quinic acid, caffeic acid, isoforsythoside and forsythoside A in Flos Lonicerae japonicae–Fructus Forsythiae herb couple with a run time of only 8 min. The separation was performed on an Acquity UPLC HSS T3 C18 column (100 mm × 2.1 mm, 1.8 μm) at a flow rate of 0.4 mL min−1, and acetonitrile/methanol (4 : 1, v/v) – 0.4% formic acid was used as the mobile phase. Variations in the intra- and inter-day precision of all analytes were below 5.00%; the matrix effect of all the analytes was found to be within the acceptable range; and the accuracy was evaluated by a recovery test within the range of 95.63–103.10%. The method successfully quantified the twenty-six compounds in the Flos Lonicerae japonicae–Fructus Forsythiae herb couple. Moreover, it transpired through hierarchical cluster analysis and principal component analysis that the consistency of the Flos Lonicerae japonicae–Fructus Forsythiae herb couple as the two important herbs in Flos Lonicerae japonicae–Fructus Forsythiae herb couple preparations (Shuang-Huang-Lian oral liquid, Yin-Qiao-Jie-Du tablet and Fufang Qin-Lan oral liquid), except that in Qin-Re-Jie-Du oral liquid was relatively good. The results showed that the method was accurate, sensitive and reliable.
- Published
- 2015
40. Transepithelial transport of phenolic acids in Flos Lonicerae Japonicae in intestinal Caco-2 cell monolayers
- Author
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Wei Zhou, Shouchuan Wang, Liuqing Di, Baochang Cai, and Jinjun Shan
- Subjects
Flos ,Models, Biological ,Flavones ,chemistry.chemical_compound ,Hydroxybenzoates ,Humans ,ATP Binding Cassette Transporter, Subfamily B, Member 1 ,Intestinal Mucosa ,chemistry.chemical_classification ,Chromatography ,biology ,Multidrug resistance-associated protein 2 ,food and beverages ,Biological Transport ,Epithelial Cells ,General Medicine ,Propolis ,biology.organism_classification ,Multidrug Resistance-Associated Protein 2 ,Intestines ,Kinetics ,Lonicera ,chemistry ,Caco-2 ,Paracellular transport ,Efflux ,Caco-2 Cells ,Multidrug Resistance-Associated Proteins ,Luteolin ,Drugs, Chinese Herbal ,Food Science - Abstract
The oral bioavailabilities of phenolic acids in Flos Lonicerae Japonicae beverage were low. The observation from an in vitro Caco-2 cell model showed that the absorptions of phenolic acids were mainly permeated via paracellular diffusion, and influenced by P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). Besides, the Papp (AP→BL) values in Flos Lonicerae Japonicae were significantly higher than those of monomers, which was attributed to the decrease of efflux ratios (
- Published
- 2015
41. Simultaneous determination of seven catechins in rat plasma by ultra-high performance liquid chromatography tandem mass spectrometry and its application to a pharmacokinetics study
- Author
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Xiaochun Wan, Junsong Li, Yuhong Liang, Shihua Zhang, Liang Zhang, Jinjun Shan, Liwei Xu, and Yuhui Han
- Subjects
Chromatography ,Chemistry ,Formic acid ,General Chemical Engineering ,Selected reaction monitoring ,Extraction (chemistry) ,General Engineering ,Ethyl acetate ,Gallate ,Analytical Chemistry ,chemistry.chemical_compound ,Pharmacokinetics ,Liquid chromatography–mass spectrometry ,Polyphenol - Abstract
A rapid, sensitive and selective ultra-high performance liquid chromatography tandem mass spectrometry method was developed and validated for the determination and pharmacokinetic investigation of seven catechins in rat plasma. The rat plasma was extracted with simple liquid–liquid extraction using ethyl acetate. Plasma sample was separated by UHPLC on a Hypersil GOLD C18 column (1.9 μm, 50 × 2.1 mm) using a mobile phase consisting of methanol–0.05% formic acid in water with gradient elution. The total run time was 10.5 min and seven catechins were efficiently separated. The detection was performed on a selected reaction monitoring using the respective transitions m/z 289.070 → 109.010 for (−)-epicatechin/(+)-catechin, 305.089 → 125.228 for (−)-epigallocatechin/(−)-gallocatechin and 441.150 → 169.325 for (−)-epicatechin gallate and 456.840 → 169.257 for (−)-epigallocatechin gallate/(−)-gallocatechin gallate. Mean recovery of seven catechins was in the range of 84.92–102.18%. The intra- and inter-day precisions (RSD) of these analytes were all less than 6.17% and 5.84%. This method was successfully applied in the pharmacokinetic study of seven catechins in the plasma of rats after oral administration of 700 mg kg−1 tea polyphenols.
- Published
- 2015
42. Influence of Jiegeng on Pharmacokinetic Properties of Flavonoids and Saponins in Gancao
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Jianya Xu, Tong Xie, Cunsi Shen, Jianjian Ji, Yan-Cao Mao, An Kang, Hao Wu, Liuqing Di, Linxiu Peng, and Jinjun Shan
- Subjects
Radix platycodonis ,Glycyrrhiza uralensis Fisch ,pharmacokinetics ,absorption ,metabolism ,Pharmaceutical Science ,Decoction ,Pharmacology ,01 natural sciences ,Article ,Analytical Chemistry ,lcsh:QD241-441 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Chalcone ,Pharmacokinetics ,Glucosides ,lcsh:Organic chemistry ,Drug Discovery ,Humans ,Glycyrrhiza uralensis ,Physical and Theoretical Chemistry ,Glycyrrhizin ,Flavonoids ,Platycodin D ,Organic Chemistry ,Saponins ,Triterpenes ,0104 chemical sciences ,Bioavailability ,010404 medicinal & biomolecular chemistry ,chemistry ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,Flavanones ,Molecular Medicine ,Liquiritigenin ,Caco-2 Cells ,Isoliquiritigenin ,Liquiritin - Abstract
Jiegeng Gancao decoction, which is composed of Jiegeng and Gancao at a weight ratio of 1:2, was widely used for treating pharyngalgia and cough for thousands of years. Our previous work indicated that Gancao could increase the systemic exposure of platycodin D and deapio-platycodin D, two main components in Jiegeng. However, whether Jiegeng could alter the pharmacokinetics of the main compounds in Gancao is still unknown. Thus, the purpose of this study was to compare the oral pharmacokinetics of flavonoids and saponins from Gancao alone vs. after co-administration with Jiegeng. Furthermore, Caco-2 cell transport and fecal hydrolysis were investigated to explain the altered pharmacokinetic properties. Pharmacokinetics results suggested that the bioavailability of liquiritin, isoliquiritin, glycyrrhizin and its metabolite, glycyrrhetinic acid, could be improved while bioavailability of liquiritigenin and isoliquiritigenin deteriorated when co-administered with Jiegeng. The Caco-2 transport study showed no significant difference of the Papp values of the main components in Jiegeng Gancao decoction when compared with those in Gancao decoction (p > 0.05). The in vitro metabolism study suggested that saponins and flavonoids glycosides in Gancao were influenced and the metabolic characteristics of most ingredients were consistent with pharmacokinetic results, such as liquiritin and glycyrrhetinic acid. The hydrolysis of liquiritigenin and glycyrrhizin observed with fecal lysate in vitro appeared consistent with the oral pharmacokinetics. Based on experiments, the pharmacokinetic profiles of six components in Gancao were influenced by Jiegeng. The metabolic process might partially contribute to the altered pharmacokinetic behavior. The metabolism of some components of Gancao appeared to be inhibited when coadministered with Jiegeng, possibly by the Jiegeng constituent platycodin.
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- 2017
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- View/download PDF
43. Bu-shen-zhu-yun decoction promotes synthesis and secretion of FSHβ and LHβ in anterior pituitary cells in vitro
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Bei Liu, Huifang Zhou, Mingqing Shi, Xiao-fei Jiang, Jinjun Shan, Jianya Xu, Yizhen Yuan, Tong Xie, and Bo-ru Zhou
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0301 basic medicine ,medicine.medical_specialty ,Synaptosomal-Associated Protein 25 ,Estrogen receptor ,Gonadotropin-releasing hormone ,Luteal phase ,Gonadotropin-Releasing Hormone ,Rats, Sprague-Dawley ,03 medical and health sciences ,Munc18 Proteins ,Anterior pituitary ,Pituitary Gland, Anterior ,Internal medicine ,Cell Line, Tumor ,Progesterone receptor ,medicine ,Animals ,RNA, Messenger ,Chromatography, High Pressure Liquid ,Early Growth Response Protein 1 ,Pharmacology ,Estrous cycle ,Cell Nucleus ,Chemistry ,GNRHR ,General Medicine ,Luteinizing Hormone, beta Subunit ,Up-Regulation ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Follicle Stimulating Hormone, beta Subunit ,Female ,Receptors, LHRH ,Hormone ,Drugs, Chinese Herbal ,Transcription Factors - Abstract
Luteal phase defects (LPD) are an important etiology of infertility which has increased in recent years. Studies have shown that bu-shen-zhu-yun decoction (BSZY-D) can lower the expression of estrogen receptor and progesterone receptor, in rats endometrium of embryonic implantation period, which upregulated by mifepristone, and improve uterine receptivity. The aim of present study was to determine the effect of BSZY-D on the synthesis and secretion of gonadotropic hormones in the anterior pituitary cells of rats. Rats were treated with saline (control) or BSZY-D two times/day for three estrous cycles by gavage. The cerebrospinal fluid (CSF) were collected for further cell treatment. The components in BSZY-D, serum and CSF were analysed by High Performance Liquid Chromatography (HPLC). Cells were either pretreated with normal CSF or BSZY-D/CSF before being stimulated with or without cetrorelix. The mRNA and proteins levels of receptors, hormones, and transcription factors were detected by RT-PCR, western blot analysis and immunostaining. We show that non-toxic concentrations of cetrorelix, a GnRH antagonist, can reduce the mRNA and protein levels of GnRHR, LH, and FSH. This effect could be reversed by the addition of BSZY-D/CSF. We also show decreased mRNA and protein expression of transcription factors, such as CREB, and Egr-1 and secretory vescicles, including SNAP-25 and Munc-18 upon treatment with cetrorelix could be reversed post co-treatment with BSZY-D/CSF. These results indicate that BSZY-D/CSF treatment led to increased levels of GnRHR, transcription factors, and secretory vesicles leading to increased secretion of FSH and LH. Thus, BSZY-D presents a promising candidate to treat luteal phase defects and infertility.
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- 2017
44. Fluorescent ligand fishing combination with in-situ imaging and characterizing to screen Hsp 90 inhibitors from Curcuma longa L. based on InP/ZnS quantum dots embedded mesoporous nanoparticles
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Jinjun Shan, Wei Li, An Kang, Yue Hu, Dong Zhu, Zhaoyi Miao, Xiao-Jing Zhang, Tianlin Wang, and Anchen Fu
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0301 basic medicine ,In situ ,Phosphines ,Protein Conformation ,Drug Evaluation, Preclinical ,Nanoparticle ,Nanotechnology ,Sulfides ,Mass spectrometry ,Ligands ,Indium ,Analytical Chemistry ,HeLa ,03 medical and health sciences ,0302 clinical medicine ,Curcuma ,Quantum Dots ,Humans ,MTT assay ,HSP90 Heat-Shock Proteins ,biology ,Ligand ,Chemistry ,Plant Extracts ,Optical Imaging ,biology.organism_classification ,Combinatorial chemistry ,Fluorescence ,Molecular Docking Simulation ,030104 developmental biology ,Zinc Compounds ,030220 oncology & carcinogenesis ,Mesoporous material ,Porosity ,HeLa Cells - Abstract
Although ligand fishing has been shown to be an efficient technique for the identification of bioactive components from complex mixtures such as natural products, it cannot be applied to biomedical image processing. Herein, a specific fluorescent ligand fishing combined with in situ imaging approach is presented for the identification of heat shock protein 90 (Hsp 90) inhibitors from complex matrixes, Curcuma longa L., using N-terminus immobilized Hsp 90α functionalized InP/ZnS quantum dots embedded mesoporous nanoparticles (i.e. Hsp 90α (NT)-FQDNs) as extraction sorbents and fluorescent tracer. The fished ligands were identified by liquid chromatography time-of-flight/mass spectrometry (LC-TOF/MS) and gas chromatography-mass spectrometry (GC-MS). Moreover, in situ imaging by confocal laser scanning microscopy (CLSM) was applied for evaluating the effect of fished-ligands on bioactivity-induced apoptosis morphologically in HeLa cells. MTT assay verified the bioactivity of the ligands and molecular docking results further provided convincing information to verify the feasible binding mode between ligands and protein. Twelve ligands as potential Hsp 90 inhibitors were ultimately fished and identified from Curcuma longa L. crude extracts. The proposed approach based on Hsp 90α functionalized nanocomposites is superior in the combination of highly specific screening efficiency and concurrent visual in situ imaging, which could have great promise for the development of other plant-derived Hsp 90 inhibitors, and providing a rapid and reliable platform for discovering biologically active molecules in natural products.
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- 2017
45. Effect of chito-oligosaccharide on the oral absorptions of phenolic acids of Flos Lonicerae extract
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Liuqing Di, Jiashuang Zou, Baochang Cai, Wei Zhou, Ailing Yin, Jinjun Shan, and Xiaobin Tan
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Absorption (pharmacology) ,Antioxidant ,Phenolic acids ,medicine.medical_treatment ,Administration, Oral ,Biological Availability ,Oligosaccharides ,Pharmaceutical Science ,Flos ,Flowers ,Flavones ,Article ,Intestinal absorption ,Rats, Sprague-Dawley ,Phenols ,Pharmacokinetics ,Drug Discovery ,Hydroxybenzoates ,medicine ,Animals ,Humans ,Food science ,Antiviral activity ,Tight junction ,ComputingMethodologies_COMPUTERGRAPHICS ,Pharmacology ,chemistry.chemical_classification ,Chitosan ,Chromatography ,Dose-Response Relationship, Drug ,biology ,Plant Extracts ,Chito-oligosaccharide ,Oligosaccharide ,biology.organism_classification ,Rats ,Bioavailability ,Lonicera ,Intestinal Absorption ,Complementary and alternative medicine ,chemistry ,Flos Lonicerae extract ,Molecular Medicine ,Caco-2 Cells - Abstract
Graphical abstract, Phenolic acids, the main active ingredients in Flos Lonicerae extract possess strong antibacterial, antioxidant and antiviral effects, and their contents was higher largely than that of other ingredients such as flavones, but the absolute bioavailability orally was significantly low, which is significant low influencing clinical efficacies of its oral preparations. In the present study, in vitro Caco-2 cell, in situ single-pass intestinal perfusion and in vivo pharmacokinetics study were performed to investigate the effects of COS on the intestinal absorption of phenolic acids. The pharmacological effects such as antiviral activity improvement by COS were verified by MDCK cell damage inhibition rate after influenza virus propagation. The observations from in vitro Caco-2 cell showed that the absorption of phenolic acids in Flos Lonicerae extract could be improved by COS. Meanwhile, COS at the same low, medium and high concentrations caused a significant, concentration-dependent increase in the Papp-value for phenolic acids compared to the control group (p
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- 2014
46. Surfactant Lipidomics of Alveolar Lavage Fluid in Mice Based on Ultra-High-Performance Liquid Chromatography Coupled to Hybrid Quadrupole-Exactive Orbitrap Mass Spectrometry
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Linxiu Peng, Jinjun Shan, Ying Zhang, Rui Yang, Jia Xu, Tong Xie, Jianjian Ji, Lili Lin, Xiuqin Zhan, and Wenjuan Qian
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0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,lcsh:QR1-502 ,Lung injury ,Orbitrap ,01 natural sciences ,Biochemistry ,Article ,lcsh:Microbiology ,law.invention ,03 medical and health sciences ,chemistry.chemical_compound ,law ,Phosphatidylcholine ,Lipidomics ,medicine ,surfactant lipidomics ,high-resolution mass spectrometry ,Molecular Biology ,Phosphatidylglycerol ,bronchoalveolar lavage fluid ,Chromatography ,medicine.diagnostic_test ,Chemistry ,lipopolysaccharide ,010401 analytical chemistry ,Lipid metabolism ,respiratory system ,Lipidome ,respiratory tract diseases ,0104 chemical sciences ,030104 developmental biology ,Bronchoalveolar lavage ,acute lung injury ,lipids (amino acids, peptides, and proteins) - Abstract
Surfactant lipid metabolism is closely related to pulmonary diseases. Lipid metabolism disorder can cause lung diseases, vice versa. With this rationale, a useful method was established in this study to determine the lipidome in bronchoalveolar lavage fluid (BALF) of mice. The lipid components in BALF were extracted by liquid&ndash, liquid extraction (methanol and methyl tert-butyl ether, and water). Ultra-high-performance liquid chromatography coupled to hybrid Quadrupole-Exactive Orbitrap mass spectrometry was used to analyze the extracted samples, which showed a broad scanning range of 215&ndash, 1800 m/z. With MS-DIAL software and built-in LipidBlast database, we identified 38 lipids in positive, and 31 lipids in negative, ion mode, including lysophosphatidylcholine (lysoPC), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), etc. Then, the changes of lipids in BALF of mice with acute lung injury (ALI) induced by lipopolysaccharide (LPS) was investigated, which may contribute to further exploration of the pathogenesis of ALI.
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- 2019
47. A rapid and sensitive LC-MS/MS method for the determination of osthole in rat plasma: application to pharmacokinetic study
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Xiao-Li Zhao, Jinjun Shan, Fei Yun, Xiao-lin Bi, An Kang, and Liuqing Di
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Pharmacology ,Detection limit ,Analyte ,Chromatography ,biology ,Imperatorin ,Electrospray ionization ,Clinical Biochemistry ,Selected reaction monitoring ,Ethyl acetate ,General Medicine ,biology.organism_classification ,Biochemistry ,Analytical Chemistry ,chemistry.chemical_compound ,Cnidium monnieri ,chemistry ,Drug Discovery ,Sample preparation ,Molecular Biology - Abstract
Osthole, a major component isolated from the fruit of Cnidium monnieri (L.) Cusson, has been widely used in traditional Chinese medicine. We developed and validated a rapid and sensitive LC-MS/MS method for the quantification of osthole in rat plasma. Sample preparation involved simple liquid-liquid extraction by ethyl acetate after addition of imperatorin as internal standard (IS). The analyte was separated using a C(18) column with the mobile phase of methanol-0.1% formic acid (80:20, v/v) at a flow rate of 0.4 mL/min. The elutes were detected under positive electrospray ionization in multiple reaction monitoring mode. The method was sensitive with 0.5 ng/mL as the lower limit of detection. Good linearity was obtained over the range of 1.0-500.0 ng/mL. The intra and inter-batch accuracy for osthole in rat plasma samples ranged from 99.5 to 108.1% and the variation was
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- 2013
48. Comparative pharmacokinetic study of pyranocoumarins and khellactone in normal and acute lung injury rats after oral administration of Peucedanum praeruptorum Dunn extracts using a rapid and sensitive liquid chromatography-tandem mass spectrometry method
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Dong Zhu, Hongmei Wen, Liuqing Di, An Kang, Tong Xie, Yu Dong, Yuqiong Pei, and Jinjun Shan
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0301 basic medicine ,Male ,Metabolite ,Clinical Biochemistry ,Acute Lung Injury ,Administration, Oral ,Lung injury ,Pharmacology ,Biochemistry ,Pyranocoumarins ,Analytical Chemistry ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Pharmacokinetics ,Liquid chromatography–mass spectrometry ,Oral administration ,Coumarins ,Limit of Detection ,Tandem Mass Spectrometry ,Drug Discovery ,Animals ,Molecular Biology ,Lung ,Chromatography ,Reproducibility of Results ,General Medicine ,Rats ,Peucedanum praeruptorum ,030104 developmental biology ,chemistry ,Linear Models ,Quantitative analysis (chemistry) ,Chromatography, Liquid ,Drugs, Chinese Herbal - Abstract
Pyranocoumarins are the main constitutes in Peucedanum praeruptorum Dunn and possess various biological activities. In this article, we developed and validated a rapid and sensitive liquid chromatography-tandem mass spectrometry method for the targeted quantification of the pyranocoumarins, praeruptorin A, praeruptorin B and praeruptorin E, and khellactone, which is a common metabolite of these pyranocoumarins in rat plasma samples. We then performed a comparative pharmacokinetic study of these pyranocoumarins and khellactone in normal and lipopolysaccharide-induced acute lung injury (ALI) in rats following oral administration of P. praeruptorum Dunn extracts. Calibration curves gave desirable linearity (r > 0.99) and the lower limit of quantifications were sufficient for quantitative analysis. The precision and accuracy were assessed by intra-batch and inter-batch assays, and the relative standard deviations were all within 10.23% and the accuracy (relative error) was between -5.52% and 8.68%. The extraction recoveries, matrix effects and stability were also acceptable. The pharmacokinetic study revealed that the area under the concentration-time curve (0-t) of khellactone in ALI rats was significantly decreased compared with the normal rats. Meanwhile, the systemic exposures of these pyranocoumarins were slightly higher in the ALI rats than those in normal rats were. The pharmacokinetic study in the pathological state might provide information that was more comprehensive to guide the clinical usage of P. praeruptorum Dunn.
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- 2016
49. Gut microbiota in the pharmacokinetics and colonic deglycosylation metabolism of ginsenoside Rb1 in rats: Contrary effects of antimicrobials treatment and restraint stress
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Hongmei Wen, Jinjun Shan, Dong Zhu, An Kang, Yu Dong, Tong Xie, Shengjie Zhang, and Liuqing Di
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Male ,Restraint, Physical ,Glycosylation ,Ginsenosides ,Colon ,Administration, Oral ,Pharmacology ,Gut flora ,Toxicology ,030226 pharmacology & pharmacy ,Rats, Sprague-Dawley ,03 medical and health sciences ,Ginseng ,Feces ,0302 clinical medicine ,Pharmacokinetics ,Anti-Infective Agents ,Oral administration ,Stress, Physiological ,medicine ,Metabolome ,Animals ,biology ,Chemistry ,Body Weight ,Reproducibility of Results ,General Medicine ,Metabolism ,medicine.disease ,biology.organism_classification ,beta-Galactosidase ,eye diseases ,Gastrointestinal Microbiome ,Disease Models, Animal ,Dysbiosis ,030217 neurology & neurosurgery - Abstract
Ginsenoside Rb1, an active ingredient in Panax ginseng, was widely used for its various biological activities. To clarify the role of the gut microbiota in pharmacokinetics and metabolism of Rb1, a comprehensive and comparative study of colonic deglycosylation metabolism and systemic exposure of ginsenoside Rb1 in normal rats, antimicrobials (ATMs) treated rats, and restraint stressed rats was conducted. ATMs treated rats received oral administration of non-absorbable antimicrobial mixtures for 7 consecutive days. Restraint stressed rats were subjected to repeated restraint stress for a period of 2 h once daily for 7 days. Plasma concentration dynamics, urine and fecal excretion of Rb1 and its deglycosylation metabolites (Rd, F2, and C-K) were studied. Moreover, the in vitro metabolism of Rb1 in fecal suspension and the fecal β-d-glucosidase activity were profiled. Systemic exposure of the deglycosylation metabolites of ginsenoside Rb1 (F2, C-K) were significantly higher in restraint stressed rats, but ATMs treated rats exhibited a decreased plasma levels of F2 and C-K, compared with normal rats. Further studies illustrated that altered systemic Rb1 and its deglycosylation metabolites exposure in restraint-stressed rats and ATMs treated rats may be partially attributed to alternations in cumulative fecal excretion. The distinguishing fecal β-d-glucosidase, in vitro elimination of Rb1, and formation of these deglycosylation metabolites afforded further evidence for the in vivo data. In conclusion, the dys-regulated fecal β-d-glucosidase activity and deglycosylation metabolism may contribute to the altered pharmacokinetic of ginsenoside Rb1 and its hydrolysis metabolites after ATMs treatment or restraint stress exposure. Our results may offer valuable insights into the pharmacological changes of bioactive ginsenosides in dys-regulated gut microbiota statue.
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- 2016
50. Metabolomics analysis of Tripterygium wilfordii formulation based on theory of detoxicity compatibility
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Jinjun Shan, Li-Li Lin, Cunsi Shen, Zhe Feng, Lingling Zhou, Tong Xie, Xueping Zhou, and Jianya Xu
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Male ,0301 basic medicine ,Tripterygium ,Drug Compounding ,Branched-chain amino acid ,Gas Chromatography-Mass Spectrometry ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Metabolomics ,Animals ,Pharmacology (medical) ,Panax notoginseng ,Amino Acids ,General Pharmacology, Toxicology and Pharmaceutics ,chemistry.chemical_classification ,biology ,biology.organism_classification ,Rehmannia glutinosa ,Rats ,Lactic acid ,Amino acid ,Glutamine ,030104 developmental biology ,Liver ,Complementary and alternative medicine ,Biochemistry ,chemistry ,Tripterygium wilfordii ,Energy Metabolism ,Drugs, Chinese Herbal - Abstract
Tripterygium wilfordii Hook. f. induced-hepatotoxicity was the main limitation for its usage in clinic. Qingluo Tongbi formulation showed obvious attenuation for hepatotoxicity in clinic and fundamental research in vivo. To explore the potential mechanism of the attenuation, we conducted a study on the plasma metabolomic profiles of T. wilfordii and Qingluo Tongbi formulation in rats by a sensitive gas chromatography-mass spectrometry (GC-MS/MS) method. In plasma samples, a total of 72 compounds were analyzed by EI source MS, and were successfully identified by matching NIST database. The semi-quantification results were then calculated by OPLS-DA model with SIMCA-P 13.0 software. The three groups were clearly distinguished in OPLS-DA score plot. In addition, the observation values of Qingluo Tongbi formulation showed the obvious trend towards the control levels, suggesting the detoxicity effect of the formulation. Variation metabolites were further analyzed by VIP and One Way ANOVAs, and the results showed a significant increase in compounds of glycogenic amino acids, such as alanine, proline, serine and glutamine after the administration of T. wilfordii, indicated that the tissue proteins were decomposed and amino acids were leakage into blood. Qingluo Tongbi formulation could reverse the amino acids into normal level. On the contrary, the levels of glucose, lactic acid and hydroxy butyrate decrease, and the formulation can relieve the disorder in the levels of lactic acid, suggesting the regulation of the energy metabolism. Additionally, the level of branched chain amino acid was decreased, suggested the toxicity was induced, but the formulation cannot increase it into the normal levels. Nevertheless, all the above results suggested that the classical Qingluo Tongbi formulation displayed the liver protection effect by adjusting the amino acid levels and regulating the energy metabolism. Qingluo Tongbi formulation was developed based on traditional Chinese medicine theory "detoxicity compatibility", and contained Panax notoginseng (Burk.) F. H. Chen to nourish blood and absorb clots. Modern pharmacology suggested that its liver protection effect was correlated with the promotion of protein synthesis. Another important herb is Rehmannia glutinosa Libosch., which can regulate the energy metabolism. Both were consistent with the metabolomic results in this study, which explained the potential mechanism of "detoxicity compatibility" theory. Therefore, the currently developed metabolomic approach and the obtained results would be highly useful for the comprehensive toxicity studies for other herbal medicines and various complex deoxicity formulations.
- Published
- 2016
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