98 results on '"Wenyuan Gao"'
Search Results
2. Diosgenin alleviates nonalcoholic steatohepatitis through affecting liver-gut circulation
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Mengyao Yan, Shuli Man, Yueru Liang, Long Ma, Lanping Guo, Luqi Huang, and Wenyuan Gao
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Pharmacology - Abstract
Nonalcoholic steatohepatitis (NASH), as the aggressive form of nonalcoholic fatty liver disease (NAFLD), rapidly becomes the leading cause of end-stage liver disease or liver transplantation. Nowadays, there has no approved drug for NASH treatment. Diosgenin possesses multiple beneficial effects towards inhibition of lipid accumulation, cholesterol metabolism, fibrotic progression and inflammatory response. However, there has been no report concerning its effects on NASH so far. Using methionine and choline-deficient (MCD) feeding mice, we evaluated the anti-NASH effects of diosgenin. 16 S rDNA was used to investigate gut microbiota composition. Transcriptome sequencing, LC/MS and GC/MS analysis were used to evaluate bile acids (BAs) metabolism and their related pathway. Compared with the MCD group, diosgenin treatment improved the hepatic dysfunction, especially decreased the serum and hepatic TC, TG, ALT, AST and TBA to nearly 50%. Content of BAs, especially CA and TCA, were decreased from 59.30 and 26.00-39.71 and 11.48 ng/mg in liver and from 0.96 and 2.1-0.47 and 1.13 μg/mL in serum, and increased from 7.01 and 11.08-3.278 and 5.11 ng/mg in feces, respectively. Antibiotic and fecal microbiota transplantation (FMT) treatment further confirmed the therapeutic effect of diosgenin on gut microbiota, especially Clostridia (LDA score of 4.94), which regulated BAs metabolism through the hepatic FXR-SHP and intestinal FXR-FGF15 pathways. These data indicate that diosgenin prevents NASH by altering Clostridia and BAs metabolism. Our results shed light on the mechanisms of diosgenin in treating NASH, which pave way for the design of novel clinical therapeutic strategies.
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- 2022
3. Effects of the polysaccharides extracted from Chinese yam (Dioscorea opposita Thunb.) on cancer-related fatigue in mice
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Y.C. Liu, Shuli Man, Zhi-peng Huo, Yu Wang, Yiqian Zhang, Wenyuan Gao, Genbei Wang, and Yi He
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chemistry.chemical_classification ,Arabinose ,biology ,Rhamnose ,General Medicine ,Pharmacology ,urologic and male genital diseases ,Polysaccharide ,Malondialdehyde ,medicine.disease_cause ,Superoxide dismutase ,chemistry.chemical_compound ,chemistry ,Galactose ,biology.protein ,medicine ,Blood urea nitrogen ,Oxidative stress ,Food Science - Abstract
The aim of this study was to investigate the anti-fatigue activity of Chinese Yam polysaccharides (CYPs). The structural characterization of CYPs was conducted using Fourier transform-infrared spectroscopy, nuclear magnetic resonance spectroscopy, gel permeation chromatography-light scattering-refractive index, and ion chromatography. The weight-loaded swimming capability, behavior performance, tumor growth, content of adenosine triphosphate (ATP), and biochemical markers of CYP in a cancer-related fatigue mouse model were tested. The results showed that CYP is a mixture with an average Mw of 75.57 kDa and is mainly composed of rhamnose, glucuronic acid, glucose, galactose, and arabinose with a molar ratio of 0.01 : 0.06 : 1.00 : 0.17 : 0.01. CYP increased the exhausting swimming time, which was decreased in the cisplatin (DDP) control group and the model group. CYP also increased the content of ATP in musculus gastrocnemius, which was down-regulated by DDP; the DDP had significantly enhanced the contents of interleukin-1β (IL-lβ), malondialdehyde (MDA), blood urea nitrogen (BUN) and lactic dehydrogenase (LDH) and inhibited the activity of superoxide dismutase (SOD) in the muscle. Administration of CYP decreased the levels of IL-lβ, MDA, BUN and LDH, and up-regulated the SOD activity. The DDP + CYP group presented a decreased tumor volume and a lower tumor weight as compared with the model group. Moreover, the mice in the CYP or DDP + CYP groups had heavier body weights than the mice in the model group and DDP group. These results suggest that CYP should improve cancer-related fatigue via the regulation of inflammatory responses, oxidative stress and increase in energy supplementation.
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- 2021
4. Quality evaluation of different varieties of rhubarb based on multicomponents and bioactivity: Application to quality control in the production of rhubarb decoction pieces
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Wei Liang, Zhang Weimei, Yuan Chen, Jiachen Sun, Fengxia Guo, Jing Hu, Wenyuan Gao, and Xia Li
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Molecular Docking Simulation ,Quality Control ,Pharmacology ,Clinical Biochemistry ,Drug Discovery ,Discriminant Analysis ,General Medicine ,Rheum ,Molecular Biology ,Biochemistry ,Chromatography, High Pressure Liquid ,Analytical Chemistry - Abstract
In this work, we developed a novel HPLC method for the simultaneous determination of 16 bioactive components in rhubarb and used it to determine the contents. Through the determination of bioactive components and in vitro activity, we compared the differences between 18 batches of different varieties of rhubarb. The contents of 16 bioactive components in Rheum officinale Baill., Rheum tanguticum Maxim. ex Balf., and Rheum palmatum Linn. were 57.53-76.09, 98.88-130.61 and 36.18-48.66 mg/g, respectively. The average inhibition rates of alkaline phosphatase in R. tanguticum were the highest, reaching 79.53%. The average inhibition rates of thrombin and Na
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- 2022
5. Q-marker identification of Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz. in pulmonary metastasis of liver cancer mice
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Genbei Wang, Mengyao Yan, Ruijia Hao, Panpan Lv, Yu Wang, Shuli Man, and Wenyuan Gao
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Pharmacology ,Mice ,Tandem Mass Spectrometry ,Drug Discovery ,Liver Neoplasms ,Liliaceae ,Animals ,Saponins ,Melanthiaceae ,Rhizome ,Chromatography, Liquid - Abstract
Rhizoma Paridis saponins (RPS) as the mainly active components of Paris polyphylla var. yunnanensis (Franch.) Hand.-Mazz., possess tumor therapeutic potential. However, the anti-tumor material basis of RPS in liver cancer pulmonary metastasis remains poorly understood. The objective of this study was to identify the distribution and anti-cancer effects of RPS in liver cancer pulmonary metastatic model.In this study, a mouse liver cancer pulmonary metastasis model was established to determine the distribution of different saponins in the tissues by UPLC-MS and plasma protein binding rate.As a result, RPS prolonged the survival time and inhibited the pulmonary metastasis in H22 injected mice through its underlying mechanism. UPLC-MS identified saponins from RPS such as PVII, PH, PVI, PII, gracillin and PI in tissues, which may be regarded as the Q-markers in RPS. Surprisingly, the concentration of PI, PII and gracillin as diosgenyl saponins was higher than that of pennogenyl saponins in the liver and lung. Besides, plasma protein binding rate of PII was higher than that of PVII.These findings suggested that PVII, PH, PVI, PI, PII and gracillin are regarded as the Q-markers of RPS in liver cancer pulmonary metastasis. The concentration of PI, PII and gracillin as diosgenyl saponins was higher than that of pennogenyl saponins in the liver and lung. It would be helpful for understanding the importance of RPS with anticancer activities in the future.
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- 2022
6. Penicillium sp. YJM-2013 induces ginsenosides biosynthesis in Panax ginseng adventitious roots by inducing plant resistance responses
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Juan Wang, Lu Yao, Wenxia Liang, Shihui Wang, Wenyuan Gao, and Jun Lu
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Pharmacology ,Cell signaling ,Strain (chemistry) ,biology ,food and beverages ,Pathogenic fungus ,biology.organism_classification ,Microbiology ,chemistry.chemical_compound ,Ginseng ,Complementary and alternative medicine ,Biosynthesis ,chemistry ,Fusarium oxysporum ,Penicillium ,Pharmacology (medical) ,Transcription factor - Abstract
Objective Fusarium oxysporum is a common pathogenic fungus in ginseng cultivation. Both pathogens and antagonistic fungi have been reported to induce plant resistance responses, thereby promoting the accumulation of secondary metabolites. The purpose of this experiment is to compare the advantages of one of the two fungi, in order to screen out more effective elicitors. The mechanism of fungal elicitor-induced plant resistance response is supplemented. Methods A gradient dilution and the dural culture were carried out to screen strains. The test strain was identified by morphology and 18 s rDNA. The effect of different concentrations (0, 50, 100, 200, 400 mg/L) of Penicillium sp. YJM-2013 and F. oxysporum on fresh weight and ginsenosides accumulation were tested. Signal molecules transduction, expression of transcription factors and functional genes were investigated to study the induction mechanism of fungal elicitors. Results Antagonistic fungi of F. oxysporum was identified as Penicillium sp. YJM-2013, which reduced root biomass. The total ginsenosides content of Panax ginseng adventitious roots reached the maximum (48.95 ± 0.97 mg/g) treated with Penicillium sp. YJM-2013 at 200 mg/L, higher than control by 2.59-fold, in which protopanoxadiol-type ginsenosides (PPD) were increased by 4.57 times. Moreover, Penicillium sp. YJM-2013 activated defense signaling molecules, up-regulated the expression of PgWRKY 1, 2, 3, 5, 7, 9 and functional genes in ginsenosides synthesis. Conclusion Compared with the pathogenic fungi F. oxysporum, antagonistic fungi Penicillium sp. YJM-2013 was more conducive to the accumulation of ginsenosides in P. ginseng adventitious roots. Penicillium sp. YJM-2013 promoted the accumulation of ginsenosides by intensifying the generation of signal molecules, activating the expression of transcription factors and functional genes.
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- 2020
7. Demonstrating Analytical Similarity of Trastuzumab Biosimilar HLX02 to Herceptin® with a Panel of Sensitive and Orthogonal Methods Including a Novel FcγRIIIa Affinity Chromatography Technology
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Liqi Xie, Peilan Qin, Scott Liu, Yanpeng Xu, Wenyuan Gao, Lihong Lu, Linlin Wang, Sipeng Li, Weidong Jiang, Pengcheng Shen, Michael Hongwei Xie, and Erhui Zhang
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030203 arthritis & rheumatology ,Pharmacology ,Chemistry ,Fc gamma receptor IIIa ,Biosimilar ,General Medicine ,Computational biology ,Highly sensitive ,03 medical and health sciences ,Reference product ,0302 clinical medicine ,Affinity chromatography ,Similarity (network science) ,Trastuzumab ,030220 oncology & carcinogenesis ,medicine ,Pharmacology (medical) ,skin and connective tissue diseases ,Biotechnology ,medicine.drug - Abstract
A biosimilar needs to demonstrate its similarity to the originator reference product (RP) in terms of structural and functional properties as well as nonclinical and clinical outcomes. The aim was to assess the analytical similarity between the trastuzumab biosimilar HLX02 and Europe-sourced Herceptin® (EU-Herceptin®) and China-sourced Herceptin® (CN-Herceptin®) following a quality-by-design (QbD) quality study and tier-based quality attribute evaluation. A panel of highly sensitive and orthogonal methods, including a novel Fc gamma receptor IIIa (FcγRIIIa) affinity chromatography technique that enables quantitative comparison of glycan effects on effector function, was developed for the assessment. To ensure the full product variability was captured, ten batches of HLX02 were compared with 39 RP batches with expiry dates from August 2017 to March 2021. The extensive three-way similarity assessment demonstrated that HLX02 is highly similar to the RPs. Furthermore, the %afucose, %galactose, and FcγRIIIa affinity of the RPs were observed to first decrease and then return to the original level in relation to their expiry dates, and the RP batches can be subgrouped by their FcγRIIIa affinity chromatograms. HLX02 is demonstrated to be more similar to the RPs of the high FcγRIIIa affinity group. Besides having an overall high analytical similarity to both EU-Herceptin® and CN-Herceptin®, HLX02 is more similar to Herceptin® with high FcγRIIIa affinity, a result that demonstrates the power of the novel FcγRIIIa affinity chromatography technology in biosimilarity evaluation.
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- 2020
8. Rosmarinic acid potentiates and detoxifies tacrine in combination for Alzheimer's disease
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Mingjuan Yang, Xinyu Zhang, Ou Qiao, Haixia Ji, Yi Zhang, Xiaoying Han, Wenzhe Wang, Xia Li, Juan Wang, Lanping Guo, Luqi Huang, and Wenyuan Gao
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Pharmacology ,Complementary and alternative medicine ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
There is no doubt that Alzheimer's disease (AD) is one of the greatest threats facing mankind today. Within the next few decades, Acetylcholinesterase inhibitors (AChEIs) will be the most widely used treatment for Alzheimer's disease. The withdrawal of the first generation AChEIs drug Tacrine (TAC)/ Cognex from the market as a result of hepatotoxicity has always been an interesting case study. Rosmarinic acid (RA) is a natural compound of phenolic acids that has pharmacological activity for inhibiting Alzheimer's disease, as well as liver protection.In this study, we determined that RA can reduce the hepatotoxicity of TAC, and both of them act synergistically to inhibit the progression of AD in mice.In addition to the wild type mice (WT) group, the 6-month-old APP/PS1 (APPswe/PSEN1dE9) double-transgenic (Tg) mice were randomly divided into 6 groups: Tg group, TAC group, RA group, TAC+Silymarin (SIL) group, TAC+RA-L (Rosmarinic Acid Low Dose) goup and TAC+RA-H (Rosmarinic Acid High Dose) group. A series of experiments were carried out, including open field test, Morris water maze test, Hematoxylin - Eosin (HE) staining, Nissl staining, biochemical analysis, immunofluorescence analysis, western blotting analysis and so on.RA combined with TAC could enter the brain tissue of AD mice, and the combination of drugs could better improve the cognitive behavior and brain pathological damage of AD mice, reduce the expression of A β oligomer, inhibit the deposition of A β, inhibit the activity of AChE and enhance the level of Ach in hippocampus. Both in vivo and in vitro experiments showed that RA could alleviate the hepatotoxicity or liver injury induced by TAC. The Western blot analysis of the liver of AD mice showed that RA combined with TAC might inhibit the apoptosis of Bcl-2/Bax, reduce the programmed apoptosis mediated by caspase-3 and reduce the burden of liver induced by TAC, could inhibit the development of liver apoptosis by alleviating the hepatotoxicity of TAC and inhibiting the phosphorylation of JNK.The potential drug combination that combines rosmarinic acid with tacrine could reduce tacrine's hepatotoxicity as well as enhance its therapeutic effect on Alzheimer's disease.
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- 2023
9. Targeting adipokines: A new strategy for the treatment of myocardial fibrosis
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Xiaoying Han, Yi Zhang, Xinyu Zhang, Haixia Ji, Wenzhe Wang, Ou Qiao, Xia Li, Juan Wang, Changxiao Liu, Luqi Huang, and Wenyuan Gao
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Pharmacology ,Leptin ,Adipokines ,Adipose Tissue ,Endothelial Cells ,Humans ,Adiponectin ,Obesity ,Fibrosis - Abstract
Cardiac fibrosis is a pathogenic factor of many cardiovascular diseases (CVD), which seriously affects people's life and health, causing huge economic losses.Therefore, it is very significant to find an effective treatment for myocardial fibrosis. Adipokines are mainly derived from adipose tissue and have an prominent regulatory effect on glucose and lipid metabolism, inflammation, immune response and cardiovascular function. Adipose tissue is composed of a variety of cell types, including adipocytes, endothelial cells, macrophages and smooth muscle cells. Adipokines mainly include adiponectin, leptin, resistin, visfatin and omentin, which are synthesized and secreted by adipocytes. More and more evidence shows that adipokines can regulate the progress of cardiac fibrosis. This scientific review provides new ideas for targeting adipokines in the treatment of myocardial fibrosis and provides strategies for the development of new, safe, and effective pharmacological antagonists against myocardial fibrosis based on adipokines activity.
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- 2021
10. Combining network pharmacology with chromatographic fingerprinting and multicomponent quantitative analysis for the quality evaluation of Astragali Radix
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Xiaohuan Li, Xinhua Guo, Miao Sha, Wenyuan Gao, and Xia Li
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Pharmacology ,Clinical Biochemistry ,Drug Discovery ,General Medicine ,Astragalus Plant ,Astragalus propinquus ,Network Pharmacology ,Molecular Biology ,Biochemistry ,Chromatography, High Pressure Liquid ,Analytical Chemistry ,Drugs, Chinese Herbal - Abstract
Nowadays, cultivated variants and adulterants of Astragali Radix (AR) have flooded the market, causing the quality assurance of AR to be challenging. To address this issue, we combined network pharmacology with chromatographic fingerprinting and multicomponent quantitative analysis for the quality evaluation of AR. Specifically, through network pharmacology, a complete understanding of the active components and pharmacological activities of AR was established. In addition, establishing fingerprint profiles and multicomponent quantitation by high-performance liquid chromatography (HPLC) is convenient and comprehensive, and can more fully reflect the overall situation of the distribution of various chemical components. To evaluate and differentiate AR from different origins, hierarchical cluster analysis and principal component analysis were performed. The result showed that AR acts synergistically through multiple targets and pathways. The content of chemical components in AR from different origins varied significantly. Combining network pharmacology and multicomponent quantification results, astragaloside II and IV and formononetin can be used as quality markers for the quality control of AR. This study provides a comprehensive and reliable strategy for the quality evaluation of AR and identifies its quality markers to ensure the quality of the herb.
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- 2021
11. Proteomic Analysis Reveals the Protective Effects of Yiqi Fumai Lyophilized Injection on Chronic Heart Failure by Improving Myocardial Energy Metabolism
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Ou Qiao, Xiaoying Han, Wenzhe Wang, Wenyuan Gao, Aichun Ju, Changxiao Liu, Yi Zhang, Juan Wang, Xinyu Zhang, Haixia Ji, Dekun Li, and Xia Li
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Pharmacology ,chemistry.chemical_classification ,Yiqi Fumai lyophilized injection ,mitochondrial biogenesis ,Retinoid X receptor alpha ,medicine.diagnostic_test ,Chemistry ,oxidative phosphorylation ,Alpha (ethology) ,Peroxisome proliferator-activated receptor ,Oxidative phosphorylation ,RM1-950 ,medicine.disease ,perixisome proliferation-activated receptor alpha ,chronic heart failure ,Western blot ,Mitochondrial biogenesis ,Heart failure ,medicine ,Pharmacology (medical) ,Therapeutics. Pharmacology ,Receptor ,Original Research - Abstract
Yiqi Fumai lyophilized injection (YQFM) is the recombination of Sheng mai san (SMS).YQFM has been applied clinically to efficaciously and safely treat chronic heart failure (CHF). However, the mechanism of YQFM is still not fully elucidated. The purpose of our study was to investigate the protective mechanism of YQFM against abdominal aortic coarctation (AAC) in rats by proteomic methods. After YQFM treatment, the cardiac function were obviously meliorated. One hundred and fifty-seven important differentially expressed proteins (DEPs) were identified, including 109 in model rat compared with that in control rat (M:C) and 48 in YQFM-treated rat compared with that in model rat (T:M) by iTRAQ technology to analyze the proteomic characteristics of heart tissue. Bioinformatics analysis showed that DEPs was mainly involved in the body’s energy metabolism and was closely related to oxidative phosphorylation. YQFM had also displayed efficient mitochondrial dysfunction alleviation properties in hydrogen peroxide (H2O2)-induced cardiomyocyte damage by Transmission Electron Microscope (TEM), Metabolic assay, and Mitotracker staining. What’s more, the levels of total cardiomyocyte apoptosis were markedly reduced following YQFM treatment. Furthermore, Western blot analysis showed that the expressions of peroxisome proliferator activated receptor co-activator-1α(PGC-1α) (p < 0.01 or p < 0.001), perixisome proliferation-activated receptor alpha (PPAR-α) (p < 0.001)and retinoid X receptor alpha (RXR-α) were upregulated (p < 0.001), PGC-1α as well as its downstream effectors were also found to be upregulated in cardiomyocytes after YQFM treatment(p < 0.001).These results provided evidence that YQFM could enhance mitochondrial function of cardiomyocytes to play a role in the treatment of CHF by regulating mitochondrial biogenesis-related proteins.
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- 2021
12. Chemometric analysis of active compounds and antioxidant and α‐glucosidase inhibitory activities for the quality evaluation of licorice from different origins
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Xinhua Guo, Wenyuan Gao, Ping Zhao, Xue-Mei Zhang, Xuemin Zhang, and Xia Li
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Antioxidant ,DPPH ,medicine.medical_treatment ,Clinical Biochemistry ,Biochemistry ,High-performance liquid chromatography ,Antioxidants ,Mass Spectrometry ,Analytical Chemistry ,chemistry.chemical_compound ,Drug Discovery ,Glycyrrhiza ,medicine ,Glycoside Hydrolase Inhibitors ,Chemometrics ,Molecular Biology ,Chromatography, High Pressure Liquid ,Flavonoids ,Pharmacology ,Chromatography ,ABTS ,Plant Extracts ,Reproducibility of Results ,Biological activity ,General Medicine ,chemistry ,Liquiritigenin ,Isoliquiritigenin ,Liquiritin - Abstract
Contents of total flavonoids (TFc), total phenolics (TPc), and total crude polysaccharide (TCPc) in licorice from different origins were determined by optimized colorimetric methods, whereas five monomer ingredients (liquiritin [LQ], isoliquiritin [ILQ], liquiritigenin [LQG], isoliquiritigenin [ILQG], and glycyrrhizic acid [GA]) were simultaneously identified and quantified by HPLC-MS and HPLC. The results indicated that the contents of chemical compounds in licorice showed significant difference in different origins. Hierarchical cluster analysis and principal component analysis further proved that producing area indeed affected the quality including compounds and pharmacological activity in licorice. Licorice from Inner Mongolia exhibited the excellent DPPH assay, whereas samples from Gansu and Xinjiang showed high scavenging capacity to OH and ABTS free radicals. Meanwhile, α-Glu inhibitory activity of licorice samples was four times higher than the antioxidant activity. Correlation analysis made clear that TFc and TCPc both strongly contribute to DPPH scavenge capacity at P < 0.01 level, whereas TCPc contributed to α-Glu inhibitory activity at P < 0.05 level. This study would contribute to the comprehensive quality evaluation based on the compounds and pharmacological activity of licorice, and provide a reference for the choice of producing area to ensure the quality of licorice as a medicine.
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- 2021
13. New insights in drug development for Alzheimer's disease based on microglia function
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Xinyu Zhang, Haixia Ji, Luqi Huang, Ou Qiao, Na Liu, Changxiao Liu, Xueqian Zhang, Wenyuan Gao, and Yi Zhang
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0301 basic medicine ,Phagocytosis ,Disease ,RM1-950 ,Drug design ,03 medical and health sciences ,0302 clinical medicine ,Drug Development ,Neuroinflammation ,Alzheimer Disease ,Medicine ,Structure–activity relationship ,Animals ,Humans ,Pharmacology ,Amyloid beta-Peptides ,Low toxicity ,Microglia ,business.industry ,General Medicine ,Alzheimer's disease ,Structure-activity relationship ,030104 developmental biology ,medicine.anatomical_structure ,Neuroprotective Agents ,Drug development ,030220 oncology & carcinogenesis ,Therapeutics. Pharmacology ,business ,Neuroscience ,Function (biology) - Abstract
One of the biggest challenges in drug development for Alzheimer's disease (AD) is how to effectively remove deposits of amyloid-beta (Aβ). Recently, the relationship between microglia and Aβ has become a research hotspot. Emerging evidence suggests that Aβ-induced microglia-mediated neuroinflammation further aggravates the decline of cognitive function, while microglia are also involved in the process of Aβ clearance. Hence, microglia have become a potential therapeutic target for the treatment or prevention of AD. An in-depth understanding of the role played by microglia in the development of AD will help us to broaden therapeutic strategies for AD. In this review, we provide an overview of the dual roles of microglia in AD progression: the positive effect of phagocytosis of Aβ and its negative effect on neuroinflammation after over-activation. With the advantages of novel structure, high efficiency, and low toxicity, small-molecule compounds as modulators of microglial function have attracted considerable attention in the therapeutic areas of AD. In this review, we also summarize the therapeutic potential of small molecule compounds (SMCs) and their structure-activity relationship for AD treatment through modulating microglial phagocytosis and inhibiting neuroinflammation. For example, the position and number of phenolic hydroxyl groups on the B ring are the key to the activity of flavonoids, and the substitution of hydroxyl groups on the benzene ring enhances the anti-inflammatory activity of phenolic acids. This review is expected to be useful for developing effective modulators of microglial function from SMCs for the amelioration and treatment of AD.
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- 2021
14. The protective effects of Aquilariae Lignum Resinatum extract on 5-Fuorouracil-induced intestinal mucositis in mice
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Wenyuan Gao, Jingze Zhang, Jing Gao, Shuli Man, Hong Zheng, and Zhaoxiang Jin
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Diarrhea ,Male ,Mucositis ,Antimetabolites, Antineoplastic ,Enterocyte ,Pharmaceutical Science ,Ileum ,Pharmacology ,medicine.disease_cause ,Pathogenesis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Intestinal mucosa ,Drug Discovery ,medicine ,Animals ,Medicine, Chinese Traditional ,Rats, Wistar ,030304 developmental biology ,0303 health sciences ,Tumor Necrosis Factor-alpha ,business.industry ,medicine.disease ,Intestinal Diseases ,medicine.anatomical_structure ,Complementary and alternative medicine ,030220 oncology & carcinogenesis ,Molecular Medicine ,Tumor necrosis factor alpha ,Fluorouracil ,business ,Oxidative stress - Abstract
Background Aquilariae Lignum Resinatum as a traditional Chinese medicine is used in prescription for treatment of gastrointestinal diseases. Phytochemical investigations show that there are many anti-ulcer and anti-inflammatory ingredients in A. agallocha methanol extract (AEE). However, scarce data is available about the constituents absorbed into the blood, activity and mechanisms of AEE on intestinal mucositis. Hypothesis/Purpose To analyze the bioactive constituents of AEE absorbed in the blood, and further explore the potential mechanisms of the protection against chemotherapy-induced intestinal mucositis. Methods The serum pharmacochemistry using UHPLC-Q-TOF/MS was performed to screen the bioactive compounds of AEE absorbed in serum. The intestinal mucositis was induced by 5-Fuorouracil (5-Fu) and treated with AEE. The severity of intestinal mucositis was evaluated based on body weight, food-intake and diarrhea. Furthermore, the mechanism of AEE was investigated involved in the pathogenesis of mucositis on repairing injury of intestinal mucosa, immune functions, and inflammatory response. Results Altogether, 11 components were identified or tentatively characterized in dosed plasma. In pharmacodynamics study, intestinal mucositis caused by 5-Fu was effectively attenuated after AEE treatment. AEE treatment improved food-intake and injury of the intestinal mucosa, relieved body weight loss and severe diarrhea through up-regulating expression of proliferating cell nuclear antigen (PCNA) and inhibiting the levels of cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) in ileum segments. Conclusions AEE protected against 5-Fu-induced intestinal mucositis (IM) in mice through mechanisms that involved in promoting the enterocyte proliferative activity, maintaining the integrity of tight junction proteins, inhibiting oxidative stress and ameliorating the inflammatory disturbances. Accordingly, A. agallocha may be a promising therapeutic candidate used for the prevention of IM during cancer chemotherapy.
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- 2019
15. Spasmolytic activity of Aquilariae Lignum Resinatum extract on gastrointestinal motility involves muscarinic receptors, calcium channels and NO release
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Jingze Zhang, Wenyuan Gao, Huimin Li, Jiawei Zhang, and Yanfei Qu
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Wei-Chang-An pill ,Pharmaceutical Science ,interstitial cells of Cajal ,Pharmacology ,chemistry.chemical_compound ,Mice ,Random Allocation ,0302 clinical medicine ,Drug Discovery ,Muscarinic acetylcholine receptor ,Cholinergic ,Voltage-dependent calcium channel ,Chemistry ,General Medicine ,Calcium Channel Blockers ,Receptors, Muscarinic ,Thymelaeaceae ,030220 oncology & carcinogenesis ,symbols ,Molecular Medicine ,Ca2+ channels ,medicine.drug ,Research Article ,Motility ,Context (language use) ,Muscarinic Antagonists ,Nitric oxide ,03 medical and health sciences ,symbols.namesake ,Organ Culture Techniques ,nitric oxide ,medicine ,Animals ,Rats, Wistar ,Dose-Response Relationship, Drug ,Plant Extracts ,lcsh:RM1-950 ,neostigmine ,Parasympatholytics ,Interstitial cell of Cajal ,Neostigmine ,Rats ,lcsh:Therapeutics. Pharmacology ,Complementary and alternative medicine ,Gastric Emptying ,Calcium Channels ,Gastrointestinal Motility ,030217 neurology & neurosurgery - Abstract
Context: Aquilariae Lignum Resinatum (ALR), the dry rhizome of Aquilaria agallocha R. (Thymelaeaeeae), has been widely used to treat emesis, stomachache and gastrointestinal dysfunction. Objective: This study evaluates the effects of ALR methanol extract on gastrointestinal motility (GIM) and possible mechanisms of the action involved. Materials and methods: In vivo, the study evaluated the effects of ALR (200–800 mg/kg) on gastric emptying and small intestinal motility in normal and neostigmine-induced adult KM mice. The in vitro effects of ALR (0.2–1.6 mg/mL) on GIM were performed on isolated jejunum of Wistar rats, pretreated with acetylcholine (ACh), KCl, CaCl2, and pre-incubation with l-NAME (a selective inhibitor of the nitric oxide synthase). Results: In vivo, ALR (800 mg/kg) decreased gastric emptying (70.82 ± 9.81%, p
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- 2018
16. Cerebralcare Granule® enhances memantine hydrochloride efficacy in APP/PS1 mice by ameliorating amyloid pathology and cognitive functions
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Yi Zhang, Xiaoying Han, Wenzhe Wang, Wenyuan Gao, Zhi Li, Xinyu Zhang, Changxiao Liu, Ou Qiao, Haixia Ji, Xia Li, and Juan Wang
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Cerebralcare Granule® ,Pharmacology ,Memantine hydrochloride ,Synaptic plasticity ,Other systems of medicine ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Amyloid precursor protein ,Medicine ,Cognitive decline ,Neuroinflammation ,030304 developmental biology ,0303 health sciences ,biology ,business.industry ,Research ,Complementary and alternative medicine ,biology.protein ,Synaptophysin ,Alkaline phosphatase ,business ,Aβ plaque accumulation ,Alzheimer’s disease ,RZ201-999 ,030217 neurology & neurosurgery ,TBIL ,Cognitive impairments ,Complementary medicine - Abstract
Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory deficits and cognitive decline. Current drugs can only relieve symptoms, but cannot really cure AD. Cerebralcare Granule® (CG) is a Traditional Chinese medicine (TCM) containing a variety of biologically active compounds. In our previous studies, CG has shown a beneficial effect against memory impairment in mice caused by d-galactose. However, whether CG can be used as a complementary medicine for the treatment of AD remains unexplored. Here, we use a combination of CG and memantine hydrochloride (Mm) to treat Alzheimer-like pathology and investigate the effects and mechanisms in vivo. Methods The histology of brain was examined with Hematoxylin–eosin (HE) staining, Golgi staining and Thioflavin S staining. ELISA was applied to assess the expression levels or activities of CAT, SOD, GSH-Px, MDA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL) in serum, as well as the levels of IL-6, IL-1β, and TNF-α in the mice brain. Western blotting was used to assess the expression of β-secretase (BACE1), amyloid precursor protein (APP), APPβ, APPα, synaptophysin (SYN), growth-associated protein 43 (GAP43), and postsynaptic density 95 (PSD95). Results In the present study, the combination group (CG + Mm) significantly attenuated Alzheimer-like behavior without adverse effects in APP/PS1 mice, indicating its high degree of safety and efficacy after long-term treatment. CG + Mm reduced AD pathological biomarker Aβ plaque accumulation by inhibiting BACE1 and APP expression (P P P P Conclusions Taken together, these data supported the notion that CG combined with Mm might ameliorate the cognitive impairment through multiple pathways, suggesting that CG could play a role as complementary medicine to increase anti-AD effect of chemical drugs by reducing Aβ deposition, neuroinflammation, oxidative damage, and improving synaptic plasticity.
- Published
- 2021
17. Treatment for liver cancer: From sorafenib to natural products
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Wenyuan Gao, Ganggang Zhao, Chen Luo, Shuli Man, Mengyao Yan, and Long Ma
- Subjects
Sorafenib ,Oncology ,medicine.medical_specialty ,Ginsenosides ,medicine.medical_treatment ,Antineoplastic Agents ,Liver transplantation ,Protein Serine-Threonine Kinases ,Chronic liver disease ,Targeted therapy ,Immediate-Early Proteins ,chemistry.chemical_compound ,Internal medicine ,Regorafenib ,Drug Discovery ,medicine ,Humans ,Pharmacology ,Flavonoids ,Biological Products ,Organic Chemistry ,Liver Neoplasms ,Cancer ,General Medicine ,medicine.disease ,chemistry ,Resveratrol ,Neoplastic Stem Cells ,Lenvatinib ,Liver cancer ,medicine.drug - Abstract
Liver cancer most commonly develops in patients with chronic liver disease, the etiology of which includes viral hepatitis (B and C), alcohol, obesity, dietary carcinogens, and so forth. The current treatment modalities, including surgical resection and liver transplantation, have been found far from effective. Hence, there is an obvious critical need to develop alternative strategies for the treatment of it. In this review, we discuss the formation process and therapeutic targets of liver cancer. Currently, targeted therapy is limited to sorafenib, lenvatinib, regorafenib, ramucirumab and cabozantinib which leads to a survival benefit in patients, but on the other hand is hampered by the occurrence of drug resistance. Pleasingly and importantly, there are multiple natural products undergoing clinical evaluation in liver cancer, such as polyphenols like icaritin, resveratrol, and silybin, saponins including ginsenoside Rg3 and glycyrrhizinate, alkaloid containing irinotecan and berberine and inorganic compound arsenic trioxide at present. Preclinical and clinical studies have shown that these compounds inhibit liver cancer formation owing to the influence on the anti-viral, anti-inflammation, anti-oxidant, anti-angiogenesis and anti-metastasis activity. Furthermore, a series of small molecule derivatives inspired by the aforementioned compounds are designed and synthesized according to structure-activity relationship studies. Drug combination and novel type of drug-targeted delivery system thereof have been well developed. This article is ended by a perspective remark of futuristic development of natural product-based therapeutic regimen for liver cancer treatment. We expect that this review is an account for current status of natural products as promising anti-liver cancer treatments and should contribute to its understanding.
- Published
- 2021
18. Pharmacokinetics profiles of polyphyllin II and polyphyllin VII in rats by liquid chromatography with tandem mass spectrometry
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Wenyuan Gao, Yu Wang, Shuli Man, Genbei Wang, Chen Luo, and Ruijia Hao
- Subjects
Male ,Clinical Biochemistry ,Antineoplastic Agents ,Urine ,Tandem mass spectrometry ,030226 pharmacology & pharmacy ,01 natural sciences ,Biochemistry ,Sensitivity and Specificity ,Analytical Chemistry ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacokinetics ,In vivo ,Tandem Mass Spectrometry ,Drug Discovery ,Animals ,Tissue Distribution ,Molecular Biology ,Chromatography, High Pressure Liquid ,Pharmacology ,Chromatography ,biology ,fungi ,010401 analytical chemistry ,Paris polyphylla ,Reproducibility of Results ,General Medicine ,Polyphyllin VII ,Saponins ,biology.organism_classification ,In vitro ,0104 chemical sciences ,Rats ,chemistry ,Ginsenoside ,Administration, Intravenous ,Female ,Steroids - Abstract
Polyphyllin II (PII) and polyphyllin VII (PVII) were the main active ingredients in Paris Polyphylla with an excellent antitumor effect in vitro and in vivo. In this study, a rapid and precise LC-MS/MS method was developed and validated for the separation and simultaneous determination of PII and PVII in rat plasma, tissues, feces and urine using ginsenoside Rg3 as the internal standard. A positive linearity ranged from 1 to 1000 ng/mL in samples. At the same time, intra- and inter-day precision were in range of 1.8% to 12.0%. The accuracy was ranged from 95.9% to 100.8%. Mean extraction recovery of PII and PVII were ranged from 86.6% to 96.4%. The analytical method has been successfully applied to the pharmacokinetic studies of PII and PVII in rats after their intravenous administration. After entering systemic circulation, PII and PVII were rapidly distributed in organs, mainly including liver, lung and spleen. Their elimination rate was slow. All these data provided a theoretical basis for the application of PII and PVII in the treatment of liver and lung related diseases.
- Published
- 2021
19. p53: A double-edged sword in tumor ferroptosis
- Author
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Xinyu Zhang, Xia Li, Haixia Ji, Changxiao Liu, Xiaoying Han, Wenzhe Wang, Juan Wang, Luqi Huang, and Wenyuan Gao
- Subjects
Pharmacology ,Programmed cell death ,Autophagy ,Apoptosis ,Cell cycle ,Cell biology ,Lipid peroxidation ,chemistry.chemical_compound ,chemistry ,Neoplasms ,Ferroptosis ,Humans ,Lipid Peroxidation ,Tumor Suppressor Protein p53 ,Signal transduction ,Transcription factor ,NADP ,Nicotinamide adenine dinucleotide phosphate - Abstract
Ferroptosis is a type of lipid peroxidation-induced cell death that can be regulated in various ways, from changing the activity of antioxidant enzymes to the levels of transcription factors. The p53 tumor suppressor gene is the "guardian of the genome" and is involved in controlling cell survival and division under various pressures. In addition to its effects on apoptosis, autophagy, and cell cycle, p53, through the way of transcription dependent or independent two-way, also regulates the biological processes of tumor cell sensitivity to ferroptosis, including the metabolism of amino acids, nicotinamide adenine dinucleotide phosphate, and lipid peroxidation, as well as the biosynthesis of glutathione, phospholipids, NADPH and coenzyme Q10.As reviewed here, we summarized the metabolic network of p53 and its signaling pathway in regulating ferroptosis and elucidated possible factors and potential clinical application of p53 regulating ferroptosis. This review will provide a basis for further understanding the role of p53 in tumor ferroptosis and new strategies for cancer therapeutic avenues.
- Published
- 2022
20. Tissue distribution, metabolism and absorption of Rhizoma Paridis Saponins in the rats
- Author
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Yu Wang, Shuli Man, Gen-Bei Wang, Yu Liu, Ruijia Hao, and Wenyuan Gao
- Subjects
Administration, Oral ,Spleen ,Pharmacology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacokinetics ,Oral administration ,Drug Discovery ,medicine ,Distribution (pharmacology) ,Animals ,Humans ,030304 developmental biology ,0303 health sciences ,biology ,Molecular Structure ,Plant Extracts ,Paris polyphylla ,Diosgenin ,Metabolism ,Saponins ,biology.organism_classification ,Rats ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Efflux ,Caco-2 Cells ,Melanthiaceae - Abstract
Ethnopharmacological relevance Paris polyphylla var yunnanensis as a traditional Chinese medicine has been used in the treatment of liver disease for thousands of years. Rhizoma Paridis saponins (RPS) were the main active ingredients in Paris polyphylla with an excellent antitumor effect. However, metabolic and distribution of RPS has not been known. Aim of the study: The objective of this study was to research metabolic and distribution of RPS. Materials and methods In this study, the separation and simultaneous determination of RPS in rat plasma and tissues were developed and validated by LC–MS/MS. The permeability and recovery of RPS were tested by Caco-2. S9 assay suggested the metabolic mode of RPS in rats. Results After oral administration of RPS, the metabolic compound like diosgenin was detected in different tissues although there was none in RPS. The concentration of PI, PII, PVI, PVII, PH and gracillin in the spleen was the highest among these organs. The content of diosgenin were the highest in lung and brain. Caco-2 test indicated that PI, PII, PVI and PVII were low permeability and low recovery. Efflux ratio indicated that PVI should be a potential P-gp substrate. Potential P-gp substrate may be PVI. S9 assay suggested that RPS possess slow metabolic and moderate metabolic compounds. Conclusions Integrated LC–MS/MS analysis of serum samples, together with Caco-2 and S9 assays provided a theoretical basis for the application of RPS in the future.
- Published
- 2020
21. Shunaoxin pills improve the antihypertensive effect of nifedipine and alleviate its renal lipotoxicity in spontaneous hypertension rats
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Xuanshuo Liu, Changxiao Liu, Yan Liu, Yu Liu, Shuli Man, Chen Luo, and Wenyuan Gao
- Subjects
Male ,China ,Nifedipine ,Health, Toxicology and Mutagenesis ,Renal function ,Blood Pressure ,010501 environmental sciences ,Management, Monitoring, Policy and Law ,Pharmacology ,Toxicology ,Kidney ,01 natural sciences ,03 medical and health sciences ,0302 clinical medicine ,Rats, Inbred SHR ,Medicine ,Animals ,Antihypertensive Agents ,0105 earth and related environmental sciences ,business.industry ,Lipid metabolism ,General Medicine ,medicine.disease ,Lipid Metabolism ,Rats ,Blood pressure ,medicine.anatomical_structure ,Lipotoxicity ,Adipogenesis ,030220 oncology & carcinogenesis ,Hypertension ,business ,Dyslipidemia ,medicine.drug ,Drugs, Chinese Herbal - Abstract
Shunaoxin pills (SNX) have been used to treat cerebrovascular diseases in China since 2005. Hypertension is a major risk factor for cerebrovascular disease. This study aimed to explore the synergistic antihypertensive effect of SNX and nifedipine and whether SNX could alleviate nifedipine-induced renal lipotoxicity. During administration, systolic blood pressure was measured weekly. After 5 weeks administration, we examined pathological changes of kidney, renal function, the lipid metabolism index, and adipogenesis genes expression in the kidney tissues, and explored its underlying mechanism. Finally, network pharmacology was used for supplement and verification. As a result, SNX improved the antihypertensive effect of nifedipine and apparently improved nifedipine-induced renal pathological changes, dyslipidemia and the levels of adipogenesis gene expression in kidney tissues. SNX reduced the levels of interleukin-6 and interleukin-1β in renal tissues, down-regulated the production of malondialdehyde, and increased superoxide dismutase activity and the protein expression of heme oxygenase-1 in kidney tissues. Network pharmacology also showed that SNX could improve nifedipine-induced renal lipotoxicity. The combination of SNX and nifedipine had certain benefits in the treatment of hypertension.
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- 2020
22. Antihypertensive and renal protective effect of Shunaoxin pill combined with captopril on spontaneous hypertension rats
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Shuli Man, Li Yang, Changxiao Liu, Wenyuan Gao, Hao Xiang, Guanyu Lu, and Yijia Wang
- Subjects
0301 basic medicine ,Captopril ,Bradykinin ,Vasodilation ,RM1-950 ,Pharmacology ,Nitric Oxide ,Antihypertension ,03 medical and health sciences ,chemistry.chemical_compound ,Random Allocation ,0302 clinical medicine ,Fibrosis ,Rats, Inbred SHR ,medicine ,Animals ,Antihypertensive Agents ,Aorta ,Kidney ,Endothelin-1 ,business.industry ,Angiotensin II ,Combinatorial treatment ,Renoprotection ,General Medicine ,medicine.disease ,Lipid Metabolism ,Endothelin 1 ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Blood pressure ,chemistry ,Gene Expression Regulation ,Shunaoxin pill ,030220 oncology & carcinogenesis ,Hypertension ,Drug Therapy, Combination ,Kidney Diseases ,Therapeutics. Pharmacology ,Nitric Oxide Synthase ,business ,Dyslipidemia ,medicine.drug ,Drugs, Chinese Herbal - Abstract
Introduction According to previous reports, hypertension has become the most common chronic disease in the world. Captopril, an angiotensin-converting enzyme inhibitor, has been widely used for the therapy of arterial hypertension and cardiovascular diseases therapy. Besides, Shunaoxin pill (SNX) as a traditional Chinese prescription showed antihypertensive effect in our previous research. Objective This study means to investigate whether SNX combining with captopril could show antihypertensive and renal protective effects on spontaneous hypertension rats (SHRs). Methods SHRs were randomly assigned to four treatment groups, including non-treated group, captopril, SNX, and captopril + SNX-treated groups. Their body weight and systolic blood pressure (SBP) were measured weekly. Histopathological examination was analyzed through Masson staining and hematoxylin and eosin staining. Biochemical analyses, ELISA, and western blot were used to analyze their combining mechanism. Results In this experiment, this combinatorial therapy significantly reduced aortic wall thickness, increased the content of NO, NOS and eNOS, decreased the content of bradykinin and endothelin 1(ET-1), and regulated the levels of TG, TC and HDLC back to normal, which suggested they could induce vasodilation and lower blood pressure. Meanwhile, histological examination alleviated that captopril + SNX remarkably inhibited renal injury, including tubular disorder, inflammatory cell infiltration and fibrosis. They down-regulated the serum levels of BUN and Cr, protein expression of IL-1β, NF-κB, Bax, Cyt c, caspase 3, 8 and 9 in kidney tissues and significantly increased the levels of Bcl-2 in kidney tissues compared with monotherapy group. Conclusion The combinatorial treatment of SNX and captopril lowered blood pressure through adjusting NO/NOS, ET-1 and dyslipidemia profile. Furthermore, this treatment alleviated the kidney damage via reducing the release of inflammatory factors and the expression of apoptotic markers. Therefore, these results provided a rationale for future clinical use of SNX combined with captopril in antihypertensive and protecting renal functions in hypertension.
- Published
- 2020
23. Pharmacokinetics and Bioavailability of the Isoflavones Formononetin and Ononin and Their in Vitro Absorption in Ussing Chamber and Caco-2 Cell Models
- Author
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Hai-Yu Zhao, Li-Yu Luo, Miao-Xuan Fan, Wenyuan Gao, Xu Wu, and Mingxing Li
- Subjects
Male ,0301 basic medicine ,Metabolite ,Biological Availability ,Pharmacology ,Models, Biological ,Permeability ,Intestinal absorption ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Glucosides ,Pharmacokinetics ,Animals ,Humans ,Formononetin ,Intestinal Mucosa ,Ononin ,Ussing chamber ,Plant Extracts ,Biological Transport ,General Chemistry ,Isoflavones ,Rats ,Bioavailability ,Intestines ,030104 developmental biology ,Intestinal Absorption ,chemistry ,030220 oncology & carcinogenesis ,Caco-2 Cells ,General Agricultural and Biological Sciences - Abstract
Formononetin and its glycoside ononin are bioactive isoflavones widely present in legumes. The present study investigated the pharmacokinetics, bioavailability, and in vitro absorption of formononetin and ononin. After an oral administration to rats, formononetin showed a higher systemic exposure over ononin. The oral bioavailability of formononetin and ononin were 21.8% and 7.3%, respectively. Ononin was more bioavailable than perceived, and its bioavailability reached 21.7% when its metabolite formononetin was taken into account. Both formononetin and ononin exhibited better absorption in large intestine segments than that in small intestine segments. Formononetin displayed a better permeability in all intestinal segments over ononin. Transport of formononetin across Caco-2 cell monolayer was mainly through passive diffusion, while ononin was actively pumped out by MRP2 but not P-gp. The results provide evidence for better understanding of the pharmacological actions of formononetin and ononin, which advocates more in vivo evaluations or human trials.
- Published
- 2018
24. Shunaoxin dropping pill, a Chinese herb compound preparation, attenuates memory impairment in <scp>d</scp>-galactose-induced aging mice
- Author
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Bingjie Jiang, Jingze Zhang, Zhuo Qu, Changxiao Liu, Hong Zhou, and Wenyuan Gao
- Subjects
0301 basic medicine ,Programmed cell death ,Chemistry ,General Chemical Engineering ,Neurotoxicity ,Hippocampus ,General Chemistry ,Pharmacology ,medicine.disease ,medicine.disease_cause ,Neuroprotection ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,In vivo ,Apoptosis ,medicine ,030217 neurology & neurosurgery ,Neuroinflammation ,Oxidative stress - Abstract
The Shunaoxin dropping pill (SNX) is derived from a traditional recipe. It has been used to treat cerebrovascular diseases in China since 2005 (approval number Z20050041). In this study, we used an in vitro H2O2-induced PC12 cell oxidative damage model and an in vivo D-gal-induced mouse memory impairment model to investigate whether SNX had neuroprotective effects. In vitro, prior to exposure to 100 μM H2O2 for 2 h, PC12 cells were pre-treated with SNX 50 μg mL−1 for 24 h. Hoechst 33258 staining was used to confirm the effect of SNX on apoptosis in the PC12 cells. Our results demonstrate that H2O2 suppresses the proliferation of PC12 cells and induces cell death. Pretreatment with SNX attenuates H2O2-induced apoptosis in PC12 cells. In vivo, D-gal was administered (100 mg kg−1, subcutaneously (s.c.)) once daily for 8 weeks to induce memory deficit and neurotoxicity in the brain of an aging mouse. Then, SNX (320 mg kg−1) was simultaneously administered orally. The present study demonstrates that SNX can alleviate aging in the mouse brain induced by D-gal via improving behavioral performance, alleviating oxidative stress, inhibiting neuroinflammation, and reducing brain cell damage in the hippocampus. Overall, these data clearly demonstrate the neuroprotective effect of SNX from the in vitro and in vivo results. SNX may be considered a novel agent for easing aging and/or age-related neurodegenerative diseases.
- Published
- 2018
25. Yiqi Fumai lyophilized injection attenuates doxorubicin-induced cardiotoxicity, hepatotoxicity and nephrotoxicity in rats by inhibition of oxidative stress, inflammation and apoptosis
- Author
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Yue Gu, Changxiao Liu, Aichun Ju, Wenyuan Gao, Bingjie Jiang, Jingze Zhang, and Shuli Man
- Subjects
0301 basic medicine ,chemistry.chemical_classification ,Cardiotoxicity ,Reactive oxygen species ,business.industry ,General Chemical Engineering ,medicine.medical_treatment ,Glutathione peroxidase ,Intraperitoneal injection ,General Chemistry ,Pharmacology ,medicine.disease_cause ,Nephrotoxicity ,Lipid peroxidation ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Toxicity ,Medicine ,business ,Oxidative stress - Abstract
Doxorubicin (DOX) is one of the most effective antineoplastic drugs, however, its organ toxicity inhibits the clinical utility. This study was aimed at investigating the protective effects of Yiqi Fumai lyophilized injection (YQFM) against DOX-induced tissue injury and exploring the mechanisms which mediated reactive oxygen species (ROS), inflammation and apoptosis. The experiment was as follows: rats were subjected to an intraperitoneal injection (i.p.) of YQFM (0.481 g kg−1, i.p.) for 12 days; DOX (5 mg kg−1, i.p.) was administered on the 4th, 8th and 12th days to achieve a cumulative dose of 15 mg kg−1. Pretreatment of YQFM significantly ameliorated intracellular damage and dysfunction of the heart, liver and kidneys via decreasing activities of injury indexes. The levels of lipid peroxidation and glutathione depletion were clearly reduced following YQFM pretreatment, meanwhile the activities of glutathione peroxidase, superoxide dismutase, and catalase were elevated. Additionally administering YQFM could mitigate the cardiotoxicity, hepatotoxicity and nephrotoxicity via reducing levels of inflammatory factors and decreasing apoptosis. Accordingly, this study indicated that YQFM attenuated DOX-induced toxicity by ameliorating organ function, decreasing ROS production, and preventing excessive inflammation and apoptosis.
- Published
- 2018
26. Effect of Rhizoma Paridis saponin on the pain behavior in a mouse model of cancer pain
- Author
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Yu Wang, Genbei Wang, Y.C. Liu, and Wenyuan Gao
- Subjects
0301 basic medicine ,business.industry ,General Chemical Engineering ,General Chemistry ,(+)-Naloxone ,Pharmacology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Nociception ,Blood serum ,Opioid ,Medicine ,Serotonin ,Prostaglandin E2 ,Cancer pain ,business ,Receptor ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Rhizoma Paridis saponins (RPS) as active parts of P. polyphylla Smith var. yunnanensis has been used as an anti-cancer drug in traditional Chinese medicine. In this study, RPS was first found to demonstrate a potent effect on markedly reducing the pain induced by cancer. Therefore, the aim of this study was to further explore the analgesic effect of RPS and its possible reaction pathway on H22 hepatocarcinoma cells inoculated in the hind right paw of mice. Cancer-induced pain model mice were randomly divided into 5 groups (n = 10) and orally administered with RPS (50–200 mg kg−1) for 2 weeks. On the last day of treatment, the pain behavior of mice was measured using hot-plate test and open field test, and brain tissues were sampled for detection of biochemical indices, malondialdehyde (MDA), superoxide dismutase (SOD), prostaglandin E2 (PGE2), serotonin (5-HT) and β-endorphin (β-EP). Moreover, the concentrations of NF-κB and IL-1β in the blood serum were measured by ELISA reagent kits. In addition, naloxone, the non-selective antagonist of opioid receptors, was used to identify the opioid receptors involved in RPS's action. It has been found that RPS alleviates cancer pain mainly via the suppression of inflammatory pain induced by oxidative damage, such as decreasing MDA and PGE2 levels, renewing activity of SOD, as well as increasing 5-HT and β-EP in the brain and suppressing the expression of NF-κB and IL-1β in the serum in a concentration-dependent manner. Overall, the current study highlights that RPS has widespread potential antinociceptive effects on a mouse model of chronic cancer pain, which may be associated with the peripheral nervous system and the central nervous system.
- Published
- 2018
27. Cerebralcare Granule® combined with nimodipine improves cognitive impairment in bilateral carotid artery occlusion rats by reducing lipocalin-2
- Author
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Yi Zhang, Xia Li, Wenyuan Gao, Song-song Jing, Juan Wang, Ou Qiao, Wenzhe Wang, Changxiao Liu, Xinyu Zhang, Xiaoying Han, Haixia Ji, and Shuli Man
- Subjects
Male ,China ,Water maze ,Lipocalin ,Pharmacology ,General Biochemistry, Genetics and Molecular Biology ,Proinflammatory cytokine ,Rats, Sprague-Dawley ,Lipocalin-2 ,Occlusion ,medicine ,Animals ,Cognitive Dysfunction ,General Pharmacology, Toxicology and Pharmaceutics ,Maze Learning ,Vascular dementia ,Nimodipine ,business.industry ,Dementia, Vascular ,General Medicine ,Neurovascular bundle ,medicine.disease ,Rats ,Disease Models, Animal ,Carotid Arteries ,Neuroprotective Agents ,business ,Perfusion ,Drugs, Chinese Herbal ,medicine.drug - Abstract
Aims Clinically, Cerebralcare Granule® (CG) has been widely utilized to treat various types of headache, chronic cerebral insufficiency and other diseases, and the effect is significant. Clinical studies have shown that CG can significantly relieve vascular dementia (VaD), however, the molecular mechanisms haven't been established. To clear the therapeutic mechanisms of CG against VaD, a hypothesis was proposed that CG could treat neurovascular injury by inhibiting the production of lipocalin-2 (LCN 2). Main methods 90 dementia rats were selected by water maze test and randomly divided into 6 groups, including nimodipine (NM), CG L (low dose) (0.314 g kg−1), CG H (high dose) (0.628 g kg−1), and combined group (CG + NM). And in vitro neuronal cell OGD modeling to evaluate the effect of CG on JAK2/STAT3. Key findings CG could significantly shorten the escape latency of two-vessel occlusion (2-VO) rats, increase their exploratory behavior, alleviate the symptoms of VaD and improve the ultrastructural pathological damage of neurovascular unit and accelerate the recovery of cerebral blood perfusion. CG combined with NM is better than NM alone. It was further showed that CG could inhibit the pathogenicity of LCN 2 through JAK2/STAT3 pathway and suppress the production of inflammatory cytokines. It plays a role in the protection of cerebral microvasculature and BBB in 2-VO rats. Significance Taken together, there data has supported notion that CG can protect the integrity of cerebral blood vessels and BBB and improve cognitive impairment through mainly inhibiting LCN 2, which provides scientific evidence for clinical application.
- Published
- 2021
28. Autophagy in vascular dementia and natural products with autophagy regulating activity
- Author
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Yi Zhang, Juan Wang, Xiaoying Han, Xinyu Zhang, Wenyuan Gao, Xia Li, Haixia Ji, Wenzhe Wang, and Ou Qiao
- Subjects
Central nervous system ,Autophagy-Related Proteins ,Apoptosis ,Disease ,Autophagy ,Animals ,Humans ,Medicine ,Effective treatment ,Vascular dementia ,Pharmacology ,Biological Products ,business.industry ,Mechanism (biology) ,Dementia, Vascular ,Brain ,food and beverages ,medicine.disease ,medicine.anatomical_structure ,Drug development ,Cerebrovascular Circulation ,Apoptosis Regulatory Proteins ,business ,Neuroscience ,Signal Transduction - Abstract
Chronic Cerebral Hypoperfusion(CCH)-induced vascular dementia(VD) is a common neurodegenerative disease which seriously affects the patient's quality of life. Therefore, it is critical to find an effective treatment of VD. Autophagy is a natural regulated mechanism that can remove dysfunctional proteins and organelles, however, over-activation or under-activation can of autophagy can induce the apoptosis of cells. Although autophagy plays a role in the central nervous system is unquestionable, the effects of autophagy in the ischemic brain are still controversial. Some autophagy regulators have been tested, suggesting that both activation and inhibition of autophagy can improve the cognitive function. This article reviews the role of autophagy in CCH-induced VD to discuss whether autophagy has the potential to become a target for drug development and provides several potential compounds for treating vascular dementia.
- Published
- 2021
29. Nanoparticle conjugation of ginsenoside Rb3 inhibits myocardial fibrosis by regulating PPARα pathway
- Author
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Wenzhe Wang, Ou Qiao, Changxiao Liu, Luqi Huang, Wenyuan Gao, Lorenzo Pecoraro, Xinyu Zhang, Yi Zhang, Zhi Li, Xiaoying Han, Juan Wang, Xia Li, Haixia Ji, Xueqian Zhang, and Shuli Man
- Subjects
Male ,0301 basic medicine ,Ginsenosides ,Cardiac fibrosis ,Drug Compounding ,Cardiomyopathy ,Transforming growth factor beta 1 (TGF-β1) ,Biological Availability ,Panax ,Alpha (ethology) ,RM1-950 ,Pharmacology ,Rats, Sprague-Dawley ,03 medical and health sciences ,Ginseng ,chemistry.chemical_compound ,0302 clinical medicine ,Polyphosphates ,Myocardial fibrosis ,medicine ,Animals ,PPAR alpha ,Receptor ,Chitosan ,Drug Carriers ,Myocardium ,Oral bioavailability enhancement ,General Medicine ,medicine.disease ,Fibrosis ,Perixisome proliferation-activated receptor alpha (PPARα) ,Rats ,Molecular Docking Simulation ,030104 developmental biology ,chemistry ,Nanoparticles conjugation with ginsenoside Rb3 (NpRb3) ,Ginsenoside ,030220 oncology & carcinogenesis ,Heart failure ,Nanoparticles ,Therapeutics. Pharmacology ,Cardiomyopathies ,Energy Metabolism ,Signal Transduction - Abstract
Background Cardiac fibrosis occurs in ischemic and non-ischemic heart failure, hereditary cardiomyopathy, diabetes and aging. Energy metabolism, which serves a crucial function in the course and treatment of cardiovascular diseases, might have therapeutic benefits for myocardial fibrosis. Ginsenoside Rb3 (G-Rb3) is one of the main components of Ginseng and exhibits poor oral bioavailability but still exerts regulate energy metabolism effects in some diseases. Therefore, the study investigated the effect of chitosan (CS) @ sodium tripolyphosphate (TPP) nanoparticles conjugation with ginsenoside Rb3 (NpRb3) on myocardial fibrosis and studied its possible mechanisms. The results showed that NpRb3 directly participates in the remodeling of myocardial energy metabolism and the regulation of perixisome proliferation-activated receptor alpha (PPARα), thereby improving the degree of myocardial fibrosis. The study also verifies the protective effect of NpRb3 on energy metabolism and mitochondrial function by targeting the PPARα pathway. Therefore, the prepared nanodrug carrier may be a potential solution for the delivery of G-Rb3, which is a promising platform for oral treatment of myocardial fibrosis.
- Published
- 2021
30. Effect of Natural β-Glucosidase Inhibitors in Reducing Toxicity of Amygdalin in Persicae Semen
- Author
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Chao Liu, Juan Wang, Wenyuan Gao, Xinhui Mao, Honggai Yang, and Xia Li
- Subjects
0301 basic medicine ,Pharmacology ,chemistry.chemical_classification ,food.ingredient ,Ethanol ,Amygdalin ,Glycoside ,Semen ,Biology ,In vitro ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,food ,chemistry ,In vivo ,030220 oncology & carcinogenesis ,Herb ,Toxicity - Abstract
Amygdalin can be decomposed into hydrocyanic acid, which is the primary source of Persicae Semen toxicity, by gut flora. Here, the inhibitory activity of β-glucosidase for test herb extracts was first determined and compared. In turn, optimization of the ratio of substrate and inhibitor in vitro and LD50 values of extracts, serum and liver contents of amygdalin in vivo was measured. Lycii Cortex was found to be the best inhibitory activity for β-glucosidase. The ratio of amygdalin-to-Lycii Cortex extract of 7.19:8.18 (mmol L-1 /mg mL-1 ) can be relatively suitable for inhibiting β-glucosidase activity in test in vitro reaction system. After mixed with Lycii Cortex extract, the toxicity of Persicae Semen ethanol extract in mice is significantly reduced and more amygdalin can be absorbed into the bloodstream. The study provides useful information for reducing toxicity of Persicae Semen and suggests how to better use these natural β-glucosidase inhibitors in the utilization of glycosides and aglycones. Copyright © 2017 John Wiley & Sons, Ltd.
- Published
- 2017
31. Production of Active Compounds in Medicinal Plants: From Plant Tissue Culture to Biosynthesis
- Author
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Jianli Li, Juan Wang, Jing Li, Luqi Huang, Jinxin Li, Shujie Liu, and Wenyuan Gao
- Subjects
0106 biological sciences ,Pharmacology ,Active ingredient ,Plant tissue culture ,fungi ,food and beverages ,Mutagenesis (molecular biology technique) ,Biology ,01 natural sciences ,Yeast ,Ginseng ,Synthetic biology ,chemistry.chemical_compound ,Complementary and alternative medicine ,Biochemistry ,Biosynthesis ,chemistry ,010608 biotechnology ,Botany ,Pharmacology (medical) ,Medicinal plants ,010606 plant biology & botany - Abstract
Over past decades plant tissue culture has emerged as an alternative of whole plant cultivation in the production of valuable secondary metabolites. Adventitious roots culture of Panax ginseng and Echinacea purpure has reached the scale of 1-10 kL. Some molecular biological techniques, such as transgenic technology and genetic stability are increasingly used in the studies on plant tissue cultures. The studies on elicitors have deepened into the induction mechanism, including signal molecules, functional genes, and so on. More and more biological elicitors, such as A. niger and yeast are used to increase the active compounds in plant tissue cultures. We also discussed the application of synthetic biology in the studies on biosynthesis of artemisinin, paclitaxel, and tanshinon. The studies on active ingredients biosynthesis of medicinal plants provide unprecedented possibilities to achieve mass production of active ingredients. Plant tissue cultures can not only produce active ingredients but also as experimental materials for biosynthesis. In order to improve the contents of active compounds in medicinal plants, following aspects could be carried out gene interference or gene silencing, gene overexpression, combination with chemical synthesis, application of elicitors, and site-directed mutagenesis of the key enzymes.
- Published
- 2017
32. Effects of Rhizoma Parisdis total saponins and its main compounds on gastric emptying via regulating muscarinic receptors in vitro and in vivo
- Author
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Shuli Man, Zhen Liu, Y.C. Liu, Yu Wang, Liying Han, Genbei Wang, Changxiao Liu, Wenyuan Gao, and Ting Xia
- Subjects
0301 basic medicine ,Gastric emptying ,Chemistry ,General Chemical Engineering ,Gastric motility ,General Chemistry ,Smooth muscle contraction ,Pharmacology ,Mosapride ,03 medical and health sciences ,Atropine ,030104 developmental biology ,0302 clinical medicine ,In vivo ,030220 oncology & carcinogenesis ,Muscarinic acetylcholine receptor ,medicine ,Acetylcholine ,medicine.drug - Abstract
The aim of this study was to explore the inhibitory effect of Rhizoma Parisdis total Saponins (RPS) and the main monomer compounds (polyphyllin I, II, VI and H) on gastric emptying and gastrointestinal motility in vitro and in vivo. The in vivo experiments demonstrated that mosapride (2.25 mg kg−1) and neostigmine (0.1 mg kg−1) could promote gastric emptying, while RPS (250 and 500 mg kg−1), adrenalin (0.3 mg kg−1), atropine (2 mg kg−1) and dopamine (1 mg kg−1) inhibited gastric emptying. Neostigmine markedly enhanced the delayed gastric motility induced by RPS in mice. The delaying effect of RPS was abolished by atropine and dopamine treatments but not adrenalin. RPS reduced gastric emptying by several pathways, which involved regulating muscarinic receptors. From the in vitro experiments we found that RPS and the main monomer compounds (polyphyllin I, II, VI and H) (20–160 μg ml−1) concentration-dependently inhibited the contractions in the antral circular strip compared to untreated controls. Besides, RPS and polyphyllin I, II, VI and H partly prohibited the stimulatory effect of acetylcholine (10 μM) but RPS-induced relaxation was significantly reduced by pretreatment with atropine (10 μM) on gastric antral smooth muscle contractility (GASMC). In addition, we also found that polyphyllin I and II had a stronger inhibitory effect on GASMC than that of polyphyllin VI and H. The experiment indicated that RPS could inhibit the gastric emptying, with polyphyllin I, II, VI and H being the major active ingredients. Meanwhile, the inhibition of gastric emptying and contractions of the antral circular strip by RPS predominantly involves muscarinic receptors.
- Published
- 2017
33. Effect of digestion on the phenolic content and antioxidant activity of celery leaf and the antioxidant mechanism via Nrf2/HO‐1 signaling pathways against Dexamethasone
- Author
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Xia Li, Liying Han, Ting Xia, Wenyuan Gao, Xueqian Zhang, and Xiaoxiao Gao
- Subjects
Antioxidant ,NF-E2-Related Factor 2 ,030309 nutrition & dietetics ,medicine.medical_treatment ,Flavonoid ,Biophysics ,Protective Agents ,medicine.disease_cause ,Antioxidants ,Dexamethasone ,Mice ,Phosphatidylinositol 3-Kinases ,03 medical and health sciences ,chemistry.chemical_compound ,0404 agricultural biotechnology ,Phenols ,Vegetables ,medicine ,Animals ,Food science ,Apium ,Pharmacology ,chemistry.chemical_classification ,0303 health sciences ,Reactive oxygen species ,Plant Extracts ,Chemistry ,food and beverages ,04 agricultural and veterinary sciences ,Cell Biology ,Glutathione ,Phenolic acid ,040401 food science ,Plant Leaves ,Oxidative Stress ,Apigenin ,Lipid Peroxidation ,Reactive Oxygen Species ,Luteolin ,Heme Oxygenase-1 ,Oxidative stress ,Signal Transduction ,Food Science - Abstract
The effect of digestion on the phenolic compounds and antioxidant activity of celery leaf were performed. In this work, 13 phenolic chemicals were discriminated by HPLC-MS, and content of phenolic and the antioxidant capacity were evaluated after digestion in vitro. After digestion, the content of phenols and flavonoids were increased by about 3-6-folds correlated with the average antioxidant activity (p < 0.05). It was found that the extraction of celery leaf (ET) decreased lipid peroxidation (MDA) and reactive oxygen species (ROS) level, and elevated the antioxidant activities of the liver, spleen, and thymus in Dexamethasone (Dex)-treated KM mice. Furthermore, ET increased the protein transcription of NF-E2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1) and glutathione s-transferase (GST) to against oxidation. These results suggested that ET can protect animals through the Nrf2/HO-1 signaling pathway from oxidative damage included by Dex. PRACTICAL APPLICATIONS: Celery is a daily edible vegetable with more pharmacological research focused on dietary fiber, yet fewer studies on the biological activity of small molecules, especially that in leaves. This study shows that the phenolic compounds from celery leaf have a distinct enhancement of oxidation after digestion in vitro, and the celery leaf reduces oxidative stress induced by Dex via Nrf2/HO-1 signaling pathway, indicating celery leaf or other food rich in phenolic compounds can be good source of functional food to fully use to promote the economic value. Moreover, it also provides theoretical information of celery leaf on digestion, which insinuates that food or Chinese medicine containing flavonoids, such as glycoside of apigenin or luteolin, have the similar digestion pattern, providing theoretical basis for later metabolism. Therefore, the absorption and metabolism of ET or flavonoids after digestion in body and the upstream signaling pathway activating Nrf2/HO-1, like PI3K or JNK phosphorylation, or downstream signaling pathway need further research.
- Published
- 2019
34. Quality evaluation of Panax ginseng adventitious roots based on ginsenoside constituents, functional genes, and ferric-reducing antioxidant power
- Author
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Wenyuan Gao, Juan Wang, Wenxia Liang, Lu Yao, and Shihui Wang
- Subjects
Antioxidant ,Ginsenosides ,030309 nutrition & dietetics ,medicine.medical_treatment ,Biophysics ,Panax ,Functional genes ,Plant Roots ,Antioxidants ,03 medical and health sciences ,chemistry.chemical_compound ,Ginseng ,0404 agricultural biotechnology ,Gene Expression Regulation, Plant ,Gene expression ,medicine ,Food science ,Pharmacology ,0303 health sciences ,Dammarenediol ,04 agricultural and veterinary sciences ,Cell Biology ,040401 food science ,chemistry ,Ginsenoside ,Ferric ,Composition (visual arts) ,Food Science ,medicine.drug - Abstract
In the study, six adventitious root lines of Panax ginseng have been successfully established. HPLC-ESI-MS analysis showed that 20 ginsenosides were identified in root lines, notoginsenoside Fa and notoginsenoside R2 were not found in AR lines. In AR lines, the highest accumulation of total ginsenosides was obtained in five-year main AR (24.87 mg/g). Principal component analysis classified root lines into three groups. Five-year ginseng was mostly similar with five-year main AR, five-year rootlet AR, and four-year rootlet AR in ginsenosides composition of group 1. Besides, gene expressions were consistent with the production of total ginsenosides, and correlation analysis revealed that total ginsenosides biosynthesis was significantly positively correlated with the gene expression of dammarenediol synthase. Five-year rootlet AR showed the highest activity on ferric-reducing antioxidant power test among samples. It provides a scientific evidence for the further exploitation and large-scale production of P. ginseng. PRACTICAL APPLICATIONS: This study provides valuable information for the commercial scale culture of ginseng adventitious roots. This report combines morphology, ginsenoside composition and content, gene expression, and ferric-reducing antioxidant power test to evaluate the quality of P. ginseng adventitious root, and combined with principal component analysis to screen out the high yield and stable ginseng adventitious roots. It would be profitable to use adventitious root culture of P. ginseng instead of field cultivation.
- Published
- 2019
35. Induction of signal molecules and expression of functional genes after Pichia pastoris stimulation in Glycyrrhiza uralensis Fisch adventitious roots
- Author
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Jing Li, Juan Wang, Wenxia Liang, Jianli Li, Wenyuan Gao, Kunhua Wei, and Jun Lu
- Subjects
030309 nutrition & dietetics ,Linoleic acid ,Biophysics ,Secondary metabolite ,Plant Roots ,Pichia ,Pichia pastoris ,03 medical and health sciences ,chemistry.chemical_compound ,0404 agricultural biotechnology ,Gene Expression Regulation, Plant ,medicine ,Glycyrrhiza uralensis ,Ononin ,Plant Proteins ,Pharmacology ,Flavonoids ,0303 health sciences ,biology ,Jasmonic acid ,04 agricultural and veterinary sciences ,Cell Biology ,biology.organism_classification ,Glycyrrhizic Acid ,040401 food science ,Elicitor ,Biochemistry ,chemistry ,Salicylic acid ,Food Science ,medicine.drug - Abstract
Glycyrrhiza uralensis Fisch is threatened by over-development and consumption, and therefore, in urgent need of protection. Elicitation is considered to be an effective strategy to enhance the secondary metabolites in plant cell and organ cultures. Secondary metabolite, signal molecules, and gene expression in adventitious roots were studied by HPLC-ESI-MSn , commercially available kits and qRT-PCR method, respectively. In the present study, with the addition of linolenic acid, linoleic acid, and Pichia pastoris, the highest concentration of metabolites was achieved by P. pastoris treatment. The contents of total flavonoids (7.16 mg/g) and polysaccharide (149.76 mg/g) peaked at 100 mg/L of P. pastoris, which increased by 3.09-fold and 3.28-fold compared with the control, respectively. However, the highest concentration of glycyrrhizic acid (0.62 mg/g) and glycyrrhetinic acid (0.29 mg/g) were obtained in 200 mg/L of P. pastoris and which were 3.89-fold and 2.42-fold more than the control group, respectively. ESI-MSn analysis indicated that licoricesaponine B2, licoricesapoine G2, licoricesaponine J2, ononin, uralenin, gancaonin C were only identified in the P. pastoris treatment group. Furthermore, P. pastoris also enhanced accumulation of salicylic acid, jasmonic acid, nitric oxide and activities of antioxidant enzymes involved in the plant defense response. In addition, the transcriptional activity of genes involved in glycyrrhizic acid biosynthesis was significantly increased under the treatment of P. pastoris. The results provided a scientific evidence for the further exploitation of G. uralensis adventitious roots and clinical medication. PRACTICAL APPLICATIONS: This study provided an effective strategy to enhance metabolites by Pichia pastoris treatment in adventitious roots of G. uralensis. The data provide a scientific evidence for the further exploitation of G. uralensis adventitious roots and clinical medication.
- Published
- 2018
36. Protective effect of magnolol on oxaliplatin-induced intestinal injury in mice
- Author
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Zhaoxiang Jin, Shuli Man, Wenyuan Gao, Jingze Zhang, Changxiao Liu, Ting Xia, Xia Li, Liying Han, and Juan Wang
- Subjects
Male ,Ileum ,Antineoplastic Agents ,Flowers ,Pharmacology ,Occludin ,medicine.disease_cause ,Lignans ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,medicine ,Animals ,Intestinal Mucosa ,chemistry.chemical_classification ,0303 health sciences ,Glutathione peroxidase ,030302 biochemistry & molecular biology ,Biphenyl Compounds ,Glutathione ,Magnolol ,Oxaliplatin ,medicine.anatomical_structure ,chemistry ,030220 oncology & carcinogenesis ,Toxicity ,Oxidative stress ,medicine.drug - Abstract
Oxaliplatin (OXL) is the first line treatment therapy for gastrointestinal (GI) cancers and often combines with other chemotherapy. However, few reports have studied on its GI toxicity. Magnolol (MG), one of the mainly active constituents in Magnolia, has been reported to treat digestive diseases. Therefore, the purpose of this study is to evaluate the intestinal protective effect of MG in OXL treatment group. OXL administration mice showed body weight loss, diarrhea, and intestinal damage characterized by the shortening of villi and destruction of intestinal crypts, as well as the colon length change. MG significantly reduced body weight loss, alleviated diarrhea, reversed histopathological changes, and prevented colon length reduction. Oxidative stress and inflammation were activated after OXL, and these responses were repressed by MG through increasing the activities of superoxide dismutase, glutathione peroxidase, and glutathione, decreasing level of nuclear factor of kappa b and downregulating the following pro-inflammatory cytokines. Although the expression of tight junction protein occludin and numbers of proliferative crypt cells were reduced on ileum and colon after OXL, MG administration promoted these expressions. The fecal gut microbiota composition disturbed by OXL was significantly reversed by MG. Thus, MG could prevent the development and progression of mucositis induced by oxaliplatin through multipathway.
- Published
- 2018
37. Paris saponin II-induced paraptosis-associated cell death increased the sensitivity of cisplatin
- Author
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Changxiao Liu, Wenyuan Gao, Furui Liu, Shuli Man, Jingxia Cui, Lei Peng, Long Ma, and Panpan Lv
- Subjects
0301 basic medicine ,Programmed cell death ,MAP Kinase Signaling System ,Antineoplastic Agents ,macromolecular substances ,Diosgenin ,Toxicology ,Paraptosis ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Autophagy ,medicine ,Humans ,Cytotoxicity ,Pharmacology ,Cisplatin ,Cell Death ,Chemistry ,food and beverages ,Cancer ,Saponins ,Endoplasmic Reticulum Stress ,medicine.disease ,030104 developmental biology ,Apoptosis ,030220 oncology & carcinogenesis ,Cancer research ,Unfolded protein response ,medicine.drug - Abstract
Paris Saponin II (PSII) has been regarded as an effective and imperative component isolated from Rhizoma Paridis saponins (RPS) and exhibited strong anti-tumor effects on a variety of cancer. Our results revealed that human non-small lung cancer cell lines NCI-H460 and NCI-H520 were exposed to 1 μM of PSII, which inhibited the proliferation of lung cancer cells and activated apoptosis, autophagy and paraptosis. PSII induced paraptosis-associated cell death prior to apoptosis and autophagy. It induced paraptosis based on ER stress through activation of the JNK pathway. Meanwhile, PSII increased the cytotoxicity of cisplatin through paraptosis-associated pathway. All in all, PSII induced paraptosis based on induction of non-apoptotic cell death, which would be a possible approach to suppress the multi-drug resistant to apoptosis.
- Published
- 2020
38. Protective effect and potential mechanisms of Wei-Chang-An pill on high-dose 5-fluorouracil-induced intestinal mucositis in mice
- Author
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Zhaoxiang Jin, Jingze Zhang, Hong Zheng, Yuling Chen, Wenyuan Gao, and Lei Wang
- Subjects
Male ,0301 basic medicine ,Time Factors ,medicine.medical_treatment ,Anti-Inflammatory Agents ,H&E stain ,Administration, Oral ,Pharmacology ,Mass Spectrometry ,Mice ,0302 clinical medicine ,Intestinal mucosa ,Drug Discovery ,Intestinal Mucosa ,Chromatography, High Pressure Liquid ,Cytokine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cytokines ,Fluorouracil ,Inflammation Mediators ,Tablets ,Diarrhea ,Mucositis ,Enterocyte ,Ileum ,Proinflammatory cytokine ,03 medical and health sciences ,medicine ,Animals ,Rats, Wistar ,Gastrointestinal Transit ,Cell Proliferation ,Dose-Response Relationship, Drug ,Gastric emptying ,business.industry ,Methanol ,medicine.disease ,Disease Models, Animal ,Enterocytes ,030104 developmental biology ,Gastric Emptying ,Cytoprotection ,Immunology ,Solvents ,business ,Biomarkers ,Drugs, Chinese Herbal - Abstract
Ethnopharmacological relevance Wei-Chang-An pill (WCA pill), a traditional Chinese pharmaceutical preparation, possessed potential anti-inflammatory advantages and noteworthy gastrointestinal regulations in digestive diseases, which might represent a promising candidate for the treatment of intestinal mucositis (IM) induced by 5-fluorouracil (5-FU). Aim of the study To analyze the bioactive constituents and investigate the effect of methanol extraction from WCA pill (WCA ext) on 5-FU induced IM with underlying mechanisms. Materials and methods The analysis of serum bioactive constituents after WCA ext administration in rats was carried out by UHPLC-Quadrupole-Time of Flight-Mass Spectrometry. In mice, IM was induced by 5-FU and physical manifestations were measured during the period of drug delivery. Half of mice were assessed with histology, expression of inflammatory cytokines in ileum and plasma via hematoxylin and eosin staining, immunohistochemical staining as well as cytokine enzyme-linked immunosorbent assay test, respectively. Besides, gastric emptying (GE) and gastrointestinal transit (GIT) were further tested in the other half of 5-FU induced mice. Results Twenty-two compounds were identified or tentatively characterized. IM induced by 5-FU was improved significantly after treatment with WCA ext through reducing the body weight loss, relieving the severe diarrhea, and inhibiting the GE as well as GIT. Further assessments validated that WCA ext promoted the recovery of intestinal mucosa, evaluated the activity of enterocyte proliferation, maintained the integrity of tight junction, and ameliorated the inflammatory disturbances. Conclusions These results suggested that WCA ext promoted the restoration of intestinal function in 5-FU-induced IM via regulating multiple sites of actions in intestinal homeostasis. Accordingly, WCA pill might be a promising therapeutic candidate for the prevention of IM during cancer chemotherapy.
- Published
- 2016
39. Analysis of bioactive components and pharmacokinetic study of herb–herb interactions in the traditional Chinese patent medicine Tongmai Yangxin Pill
- Author
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Yaya Fan, Zhen Liu, Hongfa Li, Shuli Man, Y.C. Liu, and Wenyuan Gao
- Subjects
Male ,food.ingredient ,Chinese patent medicine ,Clinical Biochemistry ,Herb-Drug Interactions ,Pharmaceutical Science ,Pharmacology ,01 natural sciences ,High-performance liquid chromatography ,Analytical Chemistry ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,food ,Pharmacokinetics ,Tandem Mass Spectrometry ,Oral administration ,Drug Discovery ,Animals ,Medicine, Chinese Traditional ,Chromatography, High Pressure Liquid ,Spectroscopy ,010401 analytical chemistry ,Rats ,0104 chemical sciences ,chemistry ,030220 oncology & carcinogenesis ,Herb ,Liquiritigenin ,Isoliquiritigenin ,Liquiritin ,Drugs, Chinese Herbal - Abstract
Tongmai Yangxin (TMYX) Pill is a traditional Chinese patent medicine, composed of eleven Chinese medicinal herbs. It has been used to treat coronary heart disease for several decades. In this study, six male Sprague-Dawley rats were dosed orally with TMYX methanol extract, and a serum pharmacochemistry technique was used to screen absorbed bioactive compounds by UPLC/Q-TOF-MS. By comparing MS spectra to the published literature data, 40 bioactive components were identified. The results indicated that almost 45% of the absorbed compounds were from Radix Glycyrrhizae (GC). Subsequently, a reliable HPLC method was used to determine the concentrations of liquiritin, liquiritigenin, isoliquiritigenin, glycyrrhizic acid, and glycyrrhetinic acid in rat plasma following oral administration of GC or the combination of GC and Ramulus Cinnamomi (GZ). The results showed that GZ enhanced the absorption of four bioactive components: liquiritigenin, isoliquiritigenin, glycyrrhizic acid, and glycyrrhetinic acid. The data demonstrate that herb combination in TMYX Pill exhibit a synergistic action.
- Published
- 2016
40. Antihypertensive and cardioprotective effects of Cerebralcare granule ® on spontaneously hypertensive rats from the perspective of the gaseous triumvirate NO–CO–H 2 S system
- Author
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Jingze Zhang, Liqin Huo, Hanhan Huang, Wenyuan Gao, Hong Chen, Zhuo Qu, and Hongfa Li
- Subjects
Male ,0301 basic medicine ,Vasodilator Agents ,Health, Toxicology and Mutagenesis ,Administration, Oral ,Aorta, Thoracic ,Pharmacology ,Nitric Oxide ,Toxicology ,In vitro model ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,Rats, Inbred SHR ,medicine.artery ,medicine ,Animals ,Thoracic aorta ,Hydrogen Sulfide ,Antihypertensive Agents ,Cardioprotection ,business.industry ,Granule (cell biology) ,General Medicine ,Tunica intima ,In vitro ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,Mechanism of action ,chemistry ,Anesthesia ,Heart Function Tests ,Hypertension ,cardiovascular system ,medicine.symptom ,Tunica Intima ,business ,Drugs, Chinese Herbal - Abstract
Cerebralcare granule(®) (CG) has been reported to have hypotensive effect. However, several pathways involved in the mechanism of hypotension are still unclear. This study was designed to verify the antihypertensive effect of CG and to characterize its mechanism of action, especially from the perspective of gasotrasmmiter NO/cGMP, CO/HO and H2S/CSE systems. By using the widely used in vitro model of rat isolated thoracic aortic rings, the vasorelaxant effect of CG were studied. Furthermore, we assessed the chronic hypotensive effect of CG on spontaneously hypertensive rats (SHRs) and further to explore the potential mechanisms of its antihypertensive activity. Data in the present study demonstrated that oral treatment with CG could induce a potent antihypertensive effect. CG could reduce the intima-media thickness (IMT) of thoracic aorta significantly and increase the serum NO and H2S levels. In addition, the present results indicated that CG played a critical protective role against pressure overload-induced cardiac hypertrophy. CG not only inhibited the development of cardiac hypertrophy but also improved ventricular function. In vitro, the results showed that CG induced relaxation in rat aortic rings through an endothelium-dependent pathway mediated by NO/cGMP, CO/HO and H2S/CSE systems. Taken together, the present study demonstrated that CG could induce a potent antihypertensive effect that was partly due to the improvement of endothelial function. Also CG played a critical protective role against pressure overload-induced cardiac hypertrophy. In addition, CG could induce relaxation in rat aortic rings.
- Published
- 2016
41. Reparative activity of costunolide and dehydrocostus in a mouse model of 5-fluorouracil-induced intestinal mucositis
- Author
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Lei Wang, Hong Zheng, Wenyuan Gao, Yuling Chen, Zhaoxiang Jin, and Jingze Zhang
- Subjects
0301 basic medicine ,chemistry.chemical_classification ,Reactive oxygen species ,Costunolide ,Cancer chemotherapy ,business.industry ,General Chemical Engineering ,General Chemistry ,Pharmacology ,medicine.disease ,Body weight ,03 medical and health sciences ,Diarrhea ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,Intragastric administration ,Fluorouracil ,030220 oncology & carcinogenesis ,Mucositis ,medicine ,medicine.symptom ,business ,medicine.drug - Abstract
The aim of the study was to investigate the protective effects of costunolide (Co) and dehydrocostus (De) in 5-fluorouracil (5-FU)-induced intestinal mucositis (IM) as well as the potential mechanisms involved. Male Kunming mice were given 5-FU (60 mg kg−1 per day) by intraperitoneal injections for 5 consecutive days and IM was evaluated histochemically. Co (5, 20 mg kg−1) and De (5, 20 mg kg−1) were orally administered once daily for 8 days. Repeated 5-FU treatment caused severe IM including morphological damage, which was accompanied by feeding reduction, body weight loss and diarrhea. Daily intragastric administration of Co or De significantly relieved the severity of IM through promoting intestinal mucosal recovery, inhibiting reactive oxygen species and ameliorating the inflammatory responses. Accordingly, Co and De may be promising therapeutic candidates and clinically used for the prevention of IM during cancer chemotherapy.
- Published
- 2016
42. Antidiabetic effect of ligustilide-rich total lactones derived from Shunaoxin dropping pills on mice with type 2 diabetes induced by a high-fat diet and streptozotocin
- Author
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Yuming Li, Hong Chen, Hong Zhou, Honggai Yang, Zhuo Qu, Y.C. Liu, Changxiao Liu, Wenyuan Gao, and Jingze Zhang
- Subjects
0301 basic medicine ,Angelica sinensis ,biology ,business.industry ,General Chemical Engineering ,General Chemistry ,Traditional Chinese medicine ,Type 2 diabetes ,Pharmacology ,medicine.disease ,biology.organism_classification ,Streptozotocin ,Ferulic acid ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,In vivo ,Oral administration ,Diabetes mellitus ,medicine ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Shunaoxin dropping pill, a well-known Traditional Chinese Medicine formula, has been used to treat cerebrovascular diseases in China since 2005. It is composed of two herbs named Chuanxiong (Ligusticum chuanxiong Hort, Umbelliferae) and Danggui (Angelica sinensis radix, Umbelliferae). It has been reported that these two herbs have anti-diabetic activities. Phenolic acids and lactones are the main active components in Chuanxiong and Danggui. Ferulic acid and ligustilide are the representative compounds of phenolic acids and lactones, respectively. Previous study has documented the hypoglycemic activity of ferulic acid. However, the anti-diabetic activities of total lactones from Chuanxiong and Danggui or ligustilide have not been well studied. Therefore, the present study was designed to demonstrate the antihyperglycemic and antihyperlipidemic activities of ligustilide-rich total lactones (LT) from Shunaoxin dropping pills in vivo, thereby elucidating its probable antidiabetic mechanism. The present results showed that after 3 weeks of treating with LT, the blood glucose levels were significantly reduced in diabetic mice, and the oral glucose tolerance test showed that LT could improve glucose tolerance. The serum insulin concentration was also dramatically reduced. In addition, there was a marked decline in the serum levels of TG, TC, and LDL-C in mice treated with LT. In addition, the serum level of HDL-C was enhanced to a certain degree in diabetic mice treated with LT. In the histopathological examination of the mouse pancreas, LT showed significant protection of the pancreas in diabetic mice. The results provide a sound rationale for future clinical trials of the oral administration of LT for the primary prevention of diabetes mellitus.
- Published
- 2016
43. Global metabolic profiling for the study of Rhizoma Paridis saponins-induced hepatotoxicity in rats
- Author
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Jing Li, Liming Zhang, Shuli Man, Wenyuan Gao, and Peiyu Qiu
- Subjects
0301 basic medicine ,Liver injury ,medicine.diagnostic_test ,Chemistry ,Health, Toxicology and Mutagenesis ,CYP1A2 ,General Medicine ,Management, Monitoring, Policy and Law ,CYP2E1 ,Pharmacology ,Toxicology ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,medicine.anatomical_structure ,Oral administration ,Hepatocyte ,Toxicity ,medicine ,Glycolysis ,Liver function tests - Abstract
Rhizoma Paridis saponins (RPS) is a traditional Chinese medicine (TCM) from the plant Paris polyphylla var. yunnanensis (Fr.) Hand.-Mazz. Despite its potentially clinical utility such as anticancer and anti-inflammation, it has slight side effects and toxicity as previous report. In this work, 90-day administration of RPS induced liver injury. 1 H-NMR- and GC/MS-based metabonomic analyses in conjunction with histopathological examinations, blood biochemistry and hepatic phase I and II enzymes assays were performed to evaluate the toxic mechanisms of RPS induced in rats. As a result, oral administration of RPS possessed certain liver toxicity in SD rats. 1 H-NMR and GC/MS data indicated that RPS inhibited the oxidation of fatty acids, glycolysis, and TCA cycle pathway, and disturbed glycine, serine, and threonine metabolism. Low expression of TG, T-CHO, and LDL-C and high levels of ALT and AST indicated that chronic exposure to RPS caused hepatocyte damage, synthesis dysfunction, and transportation failure of lipoproteins. In addition, RPS downregulated the mRNA levels of CYP1A2, CYP2E1, and UGTs. In conclusion, we used metabonomics approach to study the toxicity of RPS for the first time. This research demonstrated that metabonomics method was a promising tool to study and diagnose TCM-induced toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 99-108, 2017.
- Published
- 2015
44. Combinatorial treatment of Rhizoma Paridis saponins and sorafenib overcomes the intolerance of sorafenib
- Author
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Long Ma, Shuli Man, Li Yang, Wenyuan Gao, Honghong Dong, and Jingwen Yao
- Subjects
0301 basic medicine ,Drug ,Sorafenib ,Carcinoma, Hepatocellular ,Side effect ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,Clinical Biochemistry ,Antineoplastic Agents ,Mitochondrion ,Pharmacology ,Biochemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Endocrinology ,medicine ,Tumor Cells, Cultured ,Animals ,Humans ,Metabolomics ,Glycolysis ,neoplasms ,Molecular Biology ,media_common ,Chemistry ,Liver Neoplasms ,Lipid metabolism ,Cell Biology ,Saponins ,medicine.disease ,Xenograft Model Antitumor Assays ,digestive system diseases ,030104 developmental biology ,Anaerobic glycolysis ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Molecular Medicine ,Drug Therapy, Combination ,Female ,Rhizome ,medicine.drug ,Signal Transduction - Abstract
Sorafenib, as a multi-kinase inhibitor, was the first FDA-approved anti- hepatocellular carcinoma (HCC) drug. Rhizoma Paridis saponins (RPS) as natural products have shown antitumor activity through regulation of glycolytic and lipid metabolism which was regarded as the side effect limited the utility of sorafenib. In this research, we tried to use metabolomics to verify the probability of combinatorial treatment of RPS and Sorafenib. As a result, Sorafenib + RPS increased the antitumor effect of sorafenib and RPS in H22 mice. They mitigated the change of liver weight and the increasing levels of AST and ALT in serum, and AFP and MDA in liver tissues, which indicated their liver protective activity. They also up-regulated the activity of NOX and SDH, concentration of ATP, and down-regulated the mRNA and protein levels of HIF-1a and concentration of lactate, which suggested they protected against mitochondria damage and inhibited anaerobic glycolysis. Meanwhile, the combination group remarkably down-regulated the concentration of octadecanoic acid and hexadecanoic acid in serum, and tetradecanoic acid in liver tissues compared with model group (p 0.05). Relative regulation mechanism included their decreasing mRNA levels of FASN, CPT1, GLUT1, Myc, Akt, mTOR and LDHA, and increasing the protein expression of p53 in tumor and liver tissues (p 0.05). Furthermore, similar influence can be observed in protein levels of CPT1A, p-PI3K, p-mTOR and p53 in liver tissues and FASN in serum. All of that provided possibility to overcome the intolerance of sorafenib by drug compatibility through protection against mitochondria damage, inhibition of anaerobic glycolysis and suppression of lipid synthesis based on PI3K/Akt/mTOR pathway.
- Published
- 2018
45. Dioscin-6'-O-acetate inhibits lung cancer cell proliferation via inducing cell cycle arrest and caspase-dependent apoptosis
- Author
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Song-song Jing, Chengcheng Zhao, Wenyuan Gao, Ying Wang, Zhuo Qu, Shuli Man, Xia Li, and Xuejiao Li
- Subjects
MAPK/ERK pathway ,Lung Neoplasms ,Pharmaceutical Science ,Caspase 3 ,Apoptosis ,p38 Mitogen-Activated Protein Kinases ,03 medical and health sciences ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Cell Line, Tumor ,Drug Discovery ,Spirostans ,Cytotoxic T cell ,Humans ,Protein kinase B ,Caspase ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,Cell Proliferation ,Pharmacology ,Membrane Potential, Mitochondrial ,0303 health sciences ,biology ,Chemistry ,NF-kappa B ,Cell Cycle Checkpoints ,Cell cycle ,Saponins ,Antineoplastic Agents, Phytogenic ,Complementary and alternative medicine ,030220 oncology & carcinogenesis ,Caspases ,biology.protein ,Cancer research ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Apoptosis Regulatory Proteins ,Reactive Oxygen Species ,Signal Transduction - Abstract
Background Lung cancer is the leading cause of global cancer-related mortality. Dioscin-6′-O-acetate (DA), a novel natural steroidal saponin, was firstly isolated from the rhizomes of Dioscorea althaeoides R. Knuth. Until now, there were no studies on its pharmacological activities. Purpose Here, we investigated the growth inhibitory effect and explored the underlying molecular mechanisms of DA against lung cancer cells. Methods/study designs NSCLC H460, H1299, H520 cells and SCLC H446 cells were treated with DA. To display the cytotoxic effects and possible mechanism of DA on these cells, MTT assay, flow cytometry and western blot analysis were carried out. Results Our results showed that DA exerted strong anti-proliferative activity against lung cancer cells in a concentration- and time-dependent manner. Flow cytometry demonstrated DA induced the cell cycle arrest at S-phase (NCI-H460, NCI-H1299, NCI-H520) or G1-phase (NCI-H446), caused cellular apoptosis, generation of reactive oxygen species (ROS) and loss of mitochondrial membrane potential. Western blotting analysis showed DA treatment increased the levels of caspase 3, 8, 9, Bax, p21, p53, phosphorylated JNK and p38 MAPK and markedly decreased the expression of Bcl-2, p-ERK, p-PI3K, p-AKT and NF-κB. Blockade of caspases with Z-VAD-FMK converted apoptosis-related proteins. Suppression of p53 with pifithrin-α (PFT) attenuated cell cycle-related protein. Inhibition of ROS with N-acetyl-cysteine (NAC) adjusted apoptosis-related proteins and phosphorylated MAPK and PI3K, as well as NF-κB. Conclusion Overall, our study indicated that DA suppressed lung cancer cells proliferation via inducing cell-cycle arrest and enhancing caspase-dependent apoptosis, at least partly, through ROS-mediated PI3K/AKT, MAPK and NF-κB signaling pathways.
- Published
- 2018
46. Curcumin alleviated the toxic reaction of Rhizoma Paridis saponins in a 45-day subchronic toxicological assessment of rats
- Author
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Zhen Liu, Hongyan Chai, Jing Liu, Jiaming Wang, Shuli Man, Jing Li, and Wenyuan Gao
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0301 basic medicine ,Liver injury ,Antioxidant ,biology ,Health, Toxicology and Mutagenesis ,medicine.medical_treatment ,General Medicine ,Glutathione ,Management, Monitoring, Policy and Law ,Pharmacology ,Toxicology ,medicine.disease_cause ,medicine.disease ,Malondialdehyde ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,chemistry ,Biochemistry ,Alanine transaminase ,Toxicity ,medicine ,Curcumin ,biology.protein ,Oxidative stress - Abstract
Rhizoma Paridis saponins (RPS), as steroid saponins, are the main components in Paris polyphylla. Curcumin (diferuloylmethane) is the most important component in the spice turmeric. In our previous research, RPS exhibited side effects such as nausea, vomiting, diarrhea, and so forth. Combination with curcumin not only alleviated the toxicity and gastric stimulus induced by RPS, but also improved the quality life of mice bearing tumor cells and enhanced their anticancer effect. This study evaluated subchronic toxicity of 45th dietary of RPS and curcumin on histopathology, biochemistry, and antioxidant index. As a result, RPS-treatment caused a slight liver injury (the elevation of serum AST, alkaline phosphatase (AKP), alanine transaminase (ALT), and gamma glutamyl transpeptidase (γ-GT), histopathological changes in liver section), oxidative stress (the enhancement of reactive oxygen species (ROS), malondialdehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OHdG), separation of thioredoxin (Trx) and thioredoxin-interacting protein (TXNIP), but enhancement of heme oxygenase-1 (HO-1), glutathione S-transferase (GST), and nuclear factor-regulated factor 2 (Nrf2)), and inflammation (up-regulation of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and nuclear factor kappaB (NF-κB)). However, these changes were alleviated through co-treatment with curcumin. In conclusion, our work provided useful data for further research and new drug exploration of RPS and curcumin. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1935-1943, 2016.
- Published
- 2015
47. The genus Polygonatum: A review of ethnopharmacology, phytochemistry and pharmacology
- Author
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Peigen Xiao, Luqi Huang, Xia Li, Chengcheng Zhao, Ping Zhao, Wenyuan Gao, and Qingzhi Gao
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0301 basic medicine ,Phytochemistry ,Phytochemicals ,01 natural sciences ,03 medical and health sciences ,Triterpenoid ,Asparagaceae ,Functional food ,Genus ,Drug Discovery ,Animals ,Humans ,Medicinal plants ,Pharmacology ,Plants, Medicinal ,Traditional medicine ,biology ,010405 organic chemistry ,Plant Extracts ,Polygonatum ,biology.organism_classification ,0104 chemical sciences ,030104 developmental biology ,Ethnobotany ,Ethnopharmacology ,Phytotherapy - Abstract
Ethnopharmacological relevance The genus Polygonatum (Asparagaceae) comprises 71 species distributed throughout the temperate Northern Hemisphere. The medicinal plants of Polygonatum have been traditionally used as tonics in China, India, Pakistan, Iran and Japan, and have been demonstrated to be highly effective in clinical practice for treating age-related diseases, diabetes, lung diseases, fatigue, feebleness and indigestion. Aim of the review This paper aims to provide the links among traditional uses, chemical constituents, pharmacological effects and toxicity to support their therapeutic potential and uncover opportunities for future research. Materials and methods The relevant information on the genus Polygonatum was gathered from scientific databases (Google Scholar, Web of Science, SciFinder, ScienceDirect, ACS Publications, PubMed, Wiley Online Library, CNKI). Information was also obtained from online databases, books, Ph.D. dissertations and M.Sc. theses. The literature cited in this review dates from 1917 to June 2017. Results At least 37 species and 1 variety of Polygonatum plants have been used as traditional medicine and functional food. The major chemical constituents of Polygonatum plants are steroidal saponins, triterpenoid saponins, homoisoflavanones, polysaccharides and lectins. A putative biosynthetic pathway of steroidal saponins and triterpenoid saponins has been established based on the compounds isolated from Polygonatum plants. The crude extracts and certain pure compounds from Polygonatum plants have shown a wide range of pharmacological effects such as anti-aging, anti-diabetic, anti-fatigue, and anticancer effects. The rhizomes of Polygonatum plants have a low degree of toxicity after processing. Conclusions Based on this review, some traditional uses of Polygonatum species have been confirmed by pharmacological studies, such as its anti-osteoporosis, neuroprotective, immunomodulatory, anti-diabetic and anti-fatigue effects. Most of the pharmacological effects of this genus can be attributed to its polysaccharides, saponins and lectins. However, to clarify the chemical differences that lead to the different traditional uses between “Huangjing” (derived from P. sibiricum, P. kingianum, P. cyrtonema) and “Yuzhu” (derived from P. odoratum), a systematic comparison of the small molecule compositions and polysaccharides of these four species is needed. In addition to these four species, other locally used medicinal Polygonatum species should be the subject of research, and the chemical and pharmacological relationships of these species should be investigated to expand the medicinal resources and standardize the use of Polygonatum species.
- Published
- 2017
48. Tripterygium wilfordii Inhibiting Angiogenesis for Rheumatoid Arthritis Treatment
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Weisan Zhang, Fengtan Li, and Wenyuan Gao
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0301 basic medicine ,Angiogenesis ,Tripterygium ,Angiogenesis Inhibitors ,Pharmacology ,Chronic inflammatory disease ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Therapeutic strategy ,biology ,Neovascularization, Pathologic ,business.industry ,General Medicine ,biology.organism_classification ,medicine.disease ,030104 developmental biology ,Treatment Outcome ,030220 oncology & carcinogenesis ,Rheumatoid arthritis ,Antirheumatic Agents ,Tripterygium wilfordii ,business ,Drugs, Chinese Herbal ,Phytotherapy - Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease with a serious pre-vascular inflammatory phase, followed by significant increase in vessel growth. Inhibition of angiogenesis is a novel therapeutic strategy against RA. The Chinese herbal remedy Tripterygium wilfordii, Hook. f. (TwHf) has been reported to be therapeutically efficacious in the treatment of RA. Recent studies have revealed that treatment with TwHf extracts inhibit angiogenesis of RA, thereby elaborately attenuation RA symptom. This review mainly addresses the anti-angiogenesis effect of TwHf in treatment of RA.
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- 2017
49. Longitudinal fasting blood glucose patterns and arterial stiffness risk in a population without diabetes
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Yuntao Wu, Jingsheng Gao, Cheng Jin, Xiaoming Zheng, Yun Li, Guoqing Wei, Wenyuan Gao, Shouling Wu, Jinmei Su, and Junxing Yu
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Blood Glucose ,Male ,Physiology ,Social Sciences ,lcsh:Medicine ,Blood Pressure ,030204 cardiovascular system & hematology ,Surveys ,Vascular Medicine ,Biochemistry ,Stiffness ,0302 clinical medicine ,Endocrinology ,Sociology ,Risk Factors ,Odds Ratio ,Medicine and Health Sciences ,030212 general & internal medicine ,Longitudinal Studies ,lcsh:Science ,Pulse wave velocity ,education.field_of_study ,Multidisciplinary ,Drugs ,Fasting ,Middle Aged ,Blood Sugar ,Body Fluids ,Blood ,Research Design ,Physical Sciences ,Cardiology ,Female ,Anatomy ,Research Article ,Adult ,medicine.medical_specialty ,Endocrine Disorders ,Lipoproteins ,Population ,Materials Science ,Material Properties ,Blood sugar ,Pulse Wave Analysis ,Research and Analysis Methods ,Education ,03 medical and health sciences ,Vascular Stiffness ,Diabetes mellitus ,Internal medicine ,medicine ,Diabetes Mellitus ,Humans ,Mechanical Properties ,Ankle Brachial Index ,education ,Pharmacology ,Survey Research ,business.industry ,lcsh:R ,Biology and Life Sciences ,Proteins ,Odds ratio ,medicine.disease ,Confidence interval ,Blood pressure ,Logistic Models ,Medical Education ,Metabolic Disorders ,Arterial stiffness ,lcsh:Q ,business ,Medical Humanities ,Antihypertensives - Abstract
Objective To identify long-term fasting blood glucose trajectories and to assess the association between the trajectories and the risk of arterial stiffness in individuals without diabetes. Methods We enrolled 16,454 non-diabetic participants from Kailuan cohort. Fasting blood glucose concentrations were measured in 2006, 2008, and 2010 survey. Brachial-ankle pulse wave velocities were measured during 2011 to 2016. Multivariate regression model was used to estimate the difference of brachial-ankle pulse wave velocity levels and logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of arterial stiffness risk, according to the fasting blood glucose trajectories. Results We identified five distinct fasting blood glucose trajectories and each of the trajectories was labeled according to its range and change over 2006–2010 survey: elevated-stable pattern (5.0% of participants), elevated-decreasing pattern (6.6%), moderate-increasing pattern (10.9%), moderate-stable pattern (59.3%), and low-stable pattern (18.2%). After adjustment for potential confounders, individuals with elevated-stable pattern had a 42.6 cm/s (95%CI: 24.7 to 60.6 cm/s) higher brachial-ankle pulse wave velocity level and a 37% (OR 1.37, 95%CI: 1.14 to 1.66) higher arterial stiffness risk, and individuals with moderate-increasing pattern had a 19.6 cm/s (95%CI: 6.9 to 32.3 cm/s) higher brachial-ankle pulse wave velocity level and a 17% (OR 1.17, 95%CI: 1.03 to 1.33) higher arterial stiffness risk, related to individuals with moderate-stable pattern. We did not find significant associations of the elevated-decreasing or low-stable patterns with arterial stiffness. Consistently, the cumulative average, variability, and increased rate of fasting blood glucose during 2006–2010 survey were significantly associated with the arterial stiffness risk. Conclusion Discrete fasting blood glucose trajectories were associated with the arterial stiffness risk in non-diabetic individuals.
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- 2017
50. Synergistic effects of Rhizoma Paridis and Rhizoma Curcuma longa on different animal tumor models
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Shanshan Wu, Yao Zhang, Changxiao Liu, Hongfa Li, Zhen Liu, Wenyuan Gao, Shuli Man, and Jingze Zhang
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Stereochemistry ,Health, Toxicology and Mutagenesis ,Pharmacology ,Toxicology ,Polysaccharide ,Median lethal dose ,Magnoliopsida ,Mice ,Polysaccharides ,Neoplasms ,Animals ,Curcuma ,chemistry.chemical_classification ,Gastric emptying ,biology ,Plant Extracts ,Drug Synergism ,General Medicine ,Saponins ,biology.organism_classification ,Antineoplastic Agents, Phytogenic ,Acute toxicity ,Tumor Burden ,Bioavailability ,Disease Models, Animal ,Animal tumor ,Gastric Emptying ,chemistry ,Toxicity ,Female ,Rhizome ,Phytotherapy - Abstract
Rhizoma Paridis saponins (RPS) with a good antitumor effect in clinical use showed low bioavailability and toxicity. Combination of Rhizoma Curcuma longa with RPS, which called LouHuang preparation (LH), not only overcame the RPS limitations but also improved its anticancer effect. The median lethal dose (LD₅₀) of LH in mice was 3410.9 mg/kg by oral acute toxicity test. LH relieved the inhibition of RPS on the gastric emptying (70.13 ± 4.80% vs. 49.12 ± 8.06%). As for the antitumor effect, the tumor weight/volume inhibition rate, tumor volume growth rate, and water/food efficiency ratio were calculated. LH had the highest inhibition ratio of 57.07 ± 2.97% for H22 model, 43.22 ± 0.72% for S180 model, and 46.8 ± 0.97% for EAC model, which were higher than RPS. Compared to ZiLongJin (ZLJ), a marked antitumor drug in China, LH also had the higher inhibition rate for tumor weight and tumor volume growth, which weaker than CTX. The water/food efficiency ratio reflected the difference of the quality life of the mice bearing tumor cells or not. CTX attenuated body weight gain and increased food efficiency ratio compared to control group. LH did not affect the body weight or water/food intake. The active part of LH was RPS and turmeric polysaccharides with the inhibition of 58% and 47% on H22 and S180 tumor models. The research provided theoretical and practical basis for LH application.
- Published
- 2014
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