80 results on '"Junke Song"'
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2. Exploring the potential mechanism of Dayuanyin in treating acute lung injury: A network pharmacology and experimental verification approach
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Bei Huang, Wen Zhang, Rui Li, Yifei Xie, Haiguang Yang, Junke Song, Xiaobin Pang, and Guanhua Du
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Dayuan Yin ,Acute lung injury ,Inflammation ,Molecular docking ,JAK2/STAT3/MMP-9 pathway ,Other systems of medicine ,RZ201-999 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Dayuan Yin (DYY) is a classical formula used for treating plague, known for anti-inflammatory and antioxidant effects. It has shown potential in alleviating acute lung injury (ALI), though its mechanisms remain unclear. This study aimed to investigate the effects and mechanisms of DYY in treating ALI. Methods: Network pharmacology and molecular docking techniques were used to elucidate the potential targets and mechanisms of DYY in treating ALI. Subsequently, in vivo experiment was performed to verify the findings from bioinformatics analysis. λ-Carrageenan (λ-Car) was used to establish the ALI model. At 1 h before 2% λ-Car injection, 3 g/kg or 9 g/kg DYY were administered orally. 4 h after λ-Car-induced injury, the efficacy of DYY in treating ALI was assessed using several methods, including Wright-Giemsa staining to examine inflammatory cells in mouse pleural exudates, hematoxylin and eosin staining of lung tissues, and serum cytokine levels, cytokine mRNA levels in lung tissues, key protein levels were detected. Results: Network pharmacology and molecular docking analyses suggested that signal transducer and activator of transcription 3 (STAT3), interleukin-6, and tumor necrosis factor alpha might be the key regulated proteins, while the nuclear factor kappa-B (NF-κB) pathway could be the pathway involved. In vivo, the lung injury score of mice decreased to 0.78 from 3.44 after treating 9 g/kg DYY. Compared with the λ-Car group, the number of inflammatory cells in the DYY groups were decreased by 63 - 73% in pleural effusion. Further analysis showed that DYY could reduce the release of inflammatory cytokines, inhibit the activation of NF-κB signaling pathway, and downregulate the expression of p-janus kinase 2 (JAK2), p-STAT3, and matrix metalloproteinase-9 (MMP-9), thereby protecting against ALI. Conclusion: The study revealed remarkable potential of DYY in alleviating λ-Car-induced ALI through inhibiting the JAK2/STAT3/MMP-9 and NF-κB signaling pathways.
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- 2024
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3. Salvianolic acids for injection alleviates cerebral ischemia-induced neurodegeneration by inhibiting endoplasmic reticulum stress and neuroinflammation
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Wen Zhang, Sen Zhang, Haiguang Yang, Yangyang He, Xue Zhang, Rong Yan, Junke Song, Xiaobin Pang, and Guanhua Du
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Salvianolic acids for injection ,Cerebral ischemia ,Neurodegeneration ,Endoplasmic reticulum stress ,Neuroinflammation ,Other systems of medicine ,RZ201-999 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Cerebral ischemia is one of the leading causes of neurological deficit, dementia, and disability globally. Salvianolic acids for injection (SAFI), a multi-component drug derived from Salvia miltiorrhiza L., has been clinically used in China to treat ischemic stroke. Purpose: This study was designed to investigate the mechanisms of SAFI in alleviating cerebral ischemia-induced neurodegeneration, especially its regulatory effects on excessive ER stress. Basic procedures: The rat acute cerebral ischemic injury model was established by a 1.5 h occlusion of the middle cerebral artery followed by 24 h of reperfusion. The neurological deficits, neurobehavior, cerebral infarct volume and edema of rats were examined. Hematoxylin and eosin staining, transmission electron microscopy analysis and TUNEL staining were performed to study the brain injury and cell apoptosis. Western blot and immunofluorescence assay were carried out to study the effects and mechanism of SAFI on ischemic injury. Main findings: Results showed that SAFI significantly inhibited the acute neurodegeneration, reduced brain infarct volumes and decreased brain water content of rats. SAFI also downregulated the relative protein levels of Bax/Bcl-2, Bim, Caspase-12, and reduced the number of TUNEL-positive cells in brain tissue, indicating the anti-apoptotic effects of SAFI. Both of immunofluorescence assay and western blot results showed that SAFI downregulated the expression of endoplasmic reticulum (ER) stress maker GRP78. SAFI dramatically inhibited the ER stress-related PERK/eIF2α/ATF4/CHOP and IRE1α/TRAF2/ASK1/JNK signaling pathways. SAFI also alleviated NF-κB triggered inflammatory response, and inhibited the production of IL-6 and IL-β. Conclusions: Our studies indicated that inhibition of excessive ER stress contributes to the protective effects of SAFI against cerebral ischemia-induced neurodegeneration and neuroinflammation.
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- 2023
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4. Molecular Characterization of Cryptosporidium spp., Giardia duodenalis, Enterocytozoon bieneusi and Escherichia coli in Dairy Goat Kids with Diarrhea in Partial Regions of Shaanxi Province, China
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Xin Yang, Junwei Wang, Shuang Huang, Junke Song, Yingying Fan, and Guanghui Zhao
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Cryptosporidium spp. ,Giardia duodenalis ,Enterocytozoon bieneusi ,Escherichia coli ,goat ,Shaanxi ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Cryptosporidium spp., Giardia duodenalis, Enterocytozoon bieneusi and Escherichia coli are important diarrheal pathogens threatening the health of humans and various animals. Goats, especially pre-weaned goat kids, that carry these pathogens are important reservoirs related to human infection. In the present study, PCR-based sequencing techniques were applied to characterize Cryptosporidium spp., G. duodenalis, E. bieneusi and E. coli in 202 fecal samples of diarrheal kids for Guanzhong dairy goats from five locations in Shaanxi Province. The positive rates of Cryptosporidium spp., G. duodenalis, E. bieneusi and E. coli were 37.6% (76/202), 16.3% (33/202), 55.4% (112/202) and 78.7% (159/202) in these goat kids, respectively. Co-infection of two to four pathogens was found in 114 of 202 fecal samples. Significant differences (p < 0.001) in the positive rates of Cryptosporidium spp. and G. duodenalis were found among locations and age groups. Furthermore, two Cryptosporidium species (C. parvum and C. xiaoi), two G. duodenalis assemblages (E and A), nine E. bieneusi genotypes (CHG3, CHG1, BEB6, CHG5, CHG2, SX1, CHG28, COS-II and CD6) and two E. coli pathotypes (EPEC and EHEC) were identified. As for Cryptosporidium, two (IIdA19G1 and IIdA19G2) and two (XXIIIa and XXIIIg) subtypes were recognized in samples positive for C. parvum and C. xiaoi, respectively. A phylogenetic analysis based on the ITS locus of E. bieneusi indicated that all nine genotypes of E. bieneusi identified in this study belonged to the group 2. Four virulence factors (ehxA, eae, stx2 and stx1) of EPEC and EHEC were found in E. coli strains. Collectively, this study explored the colonization frequency of Cryptosporidium spp., G. duodenalis, E. bieneusi and E. coli in diarrheal kids of Guanzhong dairy goats in Shaanxi Province and expanded our understanding of the genetic composition and zoonotic potential of these pathogens in goats.
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- 2023
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5. C3a/C3aR Affects the Propagation of Cryptosporidium parvum in the Ileum Tissues of Mice by Regulating the Gut Barrier, Cell Proliferation, and CD4+ T Cell Main Effectors
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Xin Yang, Xuemei Wu, Shuang Huang, Qian Yao, Xi Chen, Junke Song, Yingying Fan, and Guanghui Zhao
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Cryptosporidium parvum ,C3a/C3aR signaling ,propagation ,intestinal barrier function ,cell proliferation ,CD4+ T cell-related cytokines ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Cryptosporidium parvum is an important zoonotic protozoon that threatens the health of humans and animals, but the interaction mechanisms between C. parvum and hosts are poorly understood. Our previous study indicated that the expression levels of C3a and C3aR were up-regulated in mice during C. parvum infection, but the mechanisms of C3a/C3aR signaling during C. parvum infection have not been elucidated. In the present study, an optimized BALB/c suckling mouse model infected with C. parvum was used to explore the function of C3a/C3aR signaling during C. parvum infection. The expression levels of C3aR in the ileum tissues of mice infected with C. parvum were analyzed using real-time PCR, Western blot and immunohistochemistry. The mRNA levels of the Cryptosporidium 18S rRNA gene, tight junction proteins (zo-1, claudin 3, and occludin), intestinal stem cell marker lgr5, cell proliferation marker ki67, Th1 cell-related cytokine ifn-γ, and Treg cell-related cytokine tgf-β in mouse ileum tissues were analyzed by real-time PCR. The pathological injury of ileal mucosa was examined by histopathology analysis. The mRNA expression levels of Cryptosporidium 18S rRNA gene were significantly up-regulated in the ileum tissues of C3aR-inhibited mice during C. parvum infection. Meanwhile, histopathology analysis of ileal mucosa in mice showed that inhibition of C3aR significantly aggravated the changes in villus length, villus diameter, mucosal thickness and the ratio of villus length to crypt depth during C. parvum infection. Further studies found inhibition of C3aR aggravated the down-regulation of occludin at most time points during C. parvum infection. The mRNA levels of ki67 and lgr5 in the ileum tissues of mice infected with C. parvum were significantly down-regulated. Inhibition of C3aR significantly down-regulated the mRNA expression levels of lgr5 at most time points, but significantly up-regulated the mRNA expression levels of ki67 at most time points. The mRNA expression levels of ifn-γ and tgf-β were significantly up-regulated and down-regulated in the ileum tissues of mice infected with C. parvum, respectively. However, inhibition of C3aR significantly increased the mRNA expression levels of ifn-γ and tgf-β in the ileum tissues of mice infected with C. parvum. Taken together, C3a/C3aR signaling could possibly affect the propagation of C. parvum in mouse ileum tissues by regulating the gut barrier, cell proliferation and CD4+ T cell main effectors, which would contribute to our understanding of the interaction between Cryptosporidium and hosts.
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- 2023
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6. Research Progress of the Antiviral Bioactivities of Natural Flavonoids
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Lin Wang, Junke Song, Ailin Liu, Bin Xiao, Sha Li, Zhang Wen, Yang Lu, and Guanhua Du
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Antiviral bioactivities ,Natural flavonoids ,Cellular and molecular mechanisms ,Therapeutic applications ,Botany ,QK1-989 - Abstract
Abstract Flavonoids are now considered as an indispensable component in a variety of nutraceutical and pharmaceutical applications. Most recent researches have focused on the health aspects of flavonoids for humans. Especially, different flavonoids have been investigated for their potential antiviral activities, and several natural flavonoids exhibited significant antiviral properties both in vitro and in vivo. This review provides a survey of the literature regarding the evidence for antiviral bioactivities of natural flavonoids, highlights the cellular and molecular mechanisms of natural flavonoids on viruses, and presents the details of most reported flavonoids. Meanwhile, future perspectives on therapeutic applications of flavonoids against viral infections were discussed.
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- 2020
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7. Preparation and Certification of a New Salvianolic Acid A Reference Material for Food and Drug Research
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Dezhi Yang, Bin Su, Yancai Bi, Li Zhang, Baoxi Zhang, Junke Song, Yang Lu, and Guanhua Du
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Certified reference material ,Salvianolic acid A ,Mass balance method ,qNMR ,High resolution mass spectrum ,Botany ,QK1-989 - Abstract
Abstract Salvianolic acid A (Sal A), a water-soluble ingredient in Danshen, has various biological activities. Sal A and its impurities have similar physical and chemical properties, as well as strong reducibility; therefore, they are difficult to prepare and purify. In this study, high-purity Sal A was obtained by purification of sephadex chromatography and preparative chromatography. Furthermore, HPLC–DAD tandem ECD and HPLC–DAD tandem MS methods were used for non-volatile organic impurity analysis, ICP-MS method was used for non-volatile inorganic impurities and mass balance method and quantitative nuclear magnetic resonance were employed to certify the product. The structures of Sal A and its relative impurities were validated by nuclear magnetic resonance spectroscopy and mass spectrometry, and their contents were quantified as well. Following the principles of ISO Guides 34:2009 and 35:2005, a Sal A reference material was certified, covering homogeneity studies, stability studies, characterization, and uncertainty estimations. Graphic Abstract
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- 2020
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8. Baicalein alleviates depression-like behavior in rotenone- induced Parkinson's disease model in mice through activating the BDNF/TrkB/CREB pathway
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Xiaoyue Zhao, Dewen Kong, Qimeng Zhou, Guangyi Wei, Junke Song, Yu Liang, and Guanhua Du
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Parkinson’s disease ,Depression ,Rotenone ,Baicalein ,BDNF ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in the world. In addition to motor symptoms, a variety of non-motor symptoms seriously affect the life quality of PD patients. Baicalein, a flavonoid extracted from the herb Scutellaria baicalensis Georgi, exhibits anti-PD activity through alleviation of its motor symptoms. However, its effects on non-motor symptoms were barely reported. This study aimed to investigate the therapeutic effects of baicalein on PD-related depression. Methods: After a 2-week injection of rotenone, mice with PD-related depression behavior were selected, divided into three groups, and administrated saline, baicalein, or madopar orally for four weeks. Behavior, neuroinflammation, neurotransmitters, and synaptic plasticity were evaluated. Results: Our results showed that 4-week baicalein treatment significantly alleviated the depression-like behavior in the rotenone-induced mice model. Repeated baicalein treatment reduced α-synuclein aggregation, inhibited neuroinflammation, and maintained neurotransmitters homeostasis. Moreover, we found that baicalein treatment could remarkably protect the synaptic plasticity and activate the BDNF/TrkB/CREB pathway in the PD-related depression mice model. As traditional dopamine replacement therapy unleashed few effects on depression-like symptom amelioration and synaptic function protection, baicalein might be a more appropriate choice for PD-related depression. Conclusions: The current results suggested that baicalein could act as a treatment for PD-related depression.
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- 2021
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9. Development and Preliminary Evaluation of a Nanoparticle-Assisted PCR Assay for the Detection of Cryptosporidium parvum in Calves
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Qian Yao, Xin Yang, Yi Wang, Junwei Wang, Shuang Huang, Junke Song, and Guanghui Zhao
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Cryptosporidium parvum ,nanoparticle-assisted PCR ,cgd3_330 ,calves ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
C. parvum is an important diarrheal pathogen in humans and animals, especially in young hosts. To accurately and rapidly detect C. parvum infection in calves, we established a nano-PCR assay targeting the cgd3_330 gene for the specific detection of C. parvum. This nano-PCR assay was ten times more sensitive than that of the normal PCR assay by applying the same primers and did not cross-react with C. andersoni, C. bovis, C. ryanae, Balantidium coli, Enterocytozoon bieneusi, Giardia lamblia, and Blastocystis sp. To further test the nano-PCR in clinical settings, a total of 20 faecal samples from calves were examined by using the nano-PCR, the normal PCR, and the nested PCR assays. The positive rates were 30% (6/20), 30% (6/20), and 25% (5/20) for the nano-PCR, the normal PCR, and the nested PCR assays, respectively, indicating that the nano-PCR and the normal PCR assays had the same positive rate (30%). Taken together, the present study could provide a candidate method for the specific detection of C. parvum infection in calves in clinical settings.
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- 2022
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10. Inhibition of FOXO3a/BIM signaling pathway contributes to the protective effect of salvianolic acid A against cerebral ischemia/reperfusion injury
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Junke Song, Wen Zhang, Jinhua Wang, Haiguang Yang, Qimeng Zhou, Haigang Wang, Li Li, and Guanhua Du
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Therapeutics. Pharmacology ,RM1-950 - Abstract
Salvianolic acid A (SalA) is an effective compound extracted from traditional Chinese medicine Salvia miltiorrhiza Bunge. The Forkhead box O3a (FOXO3a) signaling pathway plays crucial roles in the modulation of ischemia-induced cell apoptosis. However, no information about the regulatory effect of SalA on FoxO3a is available. To explore the anti-cerebral ischemia effect and clarify the therapeutic mechanism of SalA, SH-SY5Y cells and Sprague–Dawley rats were applied, which were exposed to oxygen glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion/reperfusion (MCAO/R) injuries, respectively. The involved pathway was identified using the specific inhibitor LY294002. Results showed that SalA concentration-dependently inhibited OGD/R injury triggered cell viability loss. SalA reduced cerebral infarction, lowered brain edema, improved neurological function, and inhibited neuron apoptosis in MCAO/R rats, which were attenuated by the treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) specific inhibitor LY294002. SalA time- and concentration-dependently upregulated the phosphorylation levels of protein kinase B (AKT) and its downstream protein FOXO3a. Moreover, the nuclear translocation of FOXO3a was inhibited by SalA both in vivo and in vitro, which was also reversed by LY294002. The above results indicated that SalA fought against ischemia/reperfusion damage at least partially via the AKT/FOXO3a/BIM pathway. KEY WORDS: Salvianolic acid A, Ischemia reperfusion, FOXO3a, BIM, Neuroprotection
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- 2019
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11. Molecular Characterization of Anaplasma spp. among Dairy, Cashmere, and Meat Goats in Shaanxi Province, Northwestern China
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Xin Yang, Mingzhe Fu, Zhengqing Yu, Junwei Wang, Junke Song, and Guanghui Zhao
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anaplasmosis ,16S rRNA gene ,msp4 gene ,prevalence ,blood DNA ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Anaplasma spp. are important tick-borne pathogens endangering the health of humans and various animals. Although several studies have reported Anaplasma infection in livestock in China, little is known about the impact of production categories on the occurrence of Anaplasma species. In the present study, PCR tools targeting the 16S rRNA and msp4 genes were applied to investigate the prevalence of Anaplasma spp. in 509 blood samples of dairy (n = 249), cashmere (n = 139), and meat (n = 121) goats from Shaanxi province. The prevalence of Anaplasma spp. was 58.5% (298/509) in goats, and significant differences (p < 0.001) were identified in the prevalence among production categories, with the highest in meat goats (84.3%, 102/121), followed by cashmere goats (58.3%, 81/139) and dairy goats (46.2%, 115/249). Significant differences (p < 0.001) in prevalence were also found among sampling sites and age groups. Meanwhile, the prevalence was 36.9% (188/509) for A. phagocytophilum, 36.1% (184/509) for A. bovis, and 11.0% (56/509) for A. ovis, and significant differences (p < 0.001) in prevalence of A. phagocytophilum, A. bovis and A. ovis were recognized among production categories and sampling sites. A. phagocytophilum, A. bovis and A. ovis were dominant species in meat, dairy, and cashmere goats, respectively, and A. ovis was absent in meat goats. Co-infections were found in 124 (24.4%) investigated samples. Goats aged < 2, 3–6, and 7–12 months, and goats from Qingjian and Zhenba were risk factors associated with the occurrence of Anaplasma. Phylogenetic analysis indicated separate clades for the distribution of A. phagocytophilum from different ruminant, reflecting potential host adaption within this species. This study reported the colonization occurrence of Anaplasma spp. among production categories in goats in Shaanxi province and enriched our knowledge on the transmission of Anaplasma spp. in goats in China. Considering the existence of zoonotic A. phagocytophilum in goats in this study and previous reports, interventions based on One Health are needed to be developed to control the transmission of Anaplasma spp. between humans and animals.
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- 2022
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12. Molecular Characterization of 18S rDNA, ITS-1, ITS-2, and COI from Eimeria christenseni and E. arloingi in Goats from Shaanxi Province, Northwestern China
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Gaoxing Liang, Xin Yang, Ding Liu, Yuan Li, Junwei Wang, Xi Chen, Guanghui Zhao, and Junke Song
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goats ,Eimeria arloingi ,Eimeria christenseni ,18S rDNA ,ITS ,COI ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Coccidiosis caused by Eimeria is one of the most common and significant diseases in goats, leading to serious economic losses in the development of the goat industry. Although several genetic loci, such as 18S rDNA, ITS-1, ITS-2, and COI, have been applied in the molecular characterization of Eimeria in chicken, rabbits, turkey, and wildlife, little is known about these molecular markers of Eimeria in goats. In the present study, we isolated purified oocysts of highly pathogenic Eimeriaarloingi and Eimeria christenseni from fecal samples of goats in Shaanxi province, China, and then subjected these purified oocysts to genomic DNA isolation, PCR amplification, and sequencing of 18S rDNA, ITS-1, ITS-2, and COI loci of Eimeria arloingi and Eimeria christenseni. Finally, the obtained sequences were used for phylogenetic analysis of Eimeria species in goats and other livestock. The lengths of the 18S rDNA, ITS-1, ITS-2, and COI were 1790 bp, 403 bp, 584 bp, and 1268 bp for E. arloingi and 1796 bp, 386 bp, 565 bp, and 1268 bp for E. christenseni, respectively. The phylogenetical analysis based on 18S rDNA indicated that E. christenseni and E. arloingi were the most closely related to ovine Eimeria, followed by E. bovis, E. ellipsoidalis, and E. zuernii from cattle. The phylogenetical analysis based on ITS-1 and ITS-2 could not effectively distinguish ovine Eimeria from caprine Eimeria. The phylogenetical analysis based on the COI locus could effectively distinguish between Eimeria species from goats and cattle, but it was ineffective in distinguishing between Eimeria species from sheep and goats. To the best of our knowledge, this is the first characterization of 18S rDNA, ITS-1, ITS-2, and COI in E. arloingi and E. christenseni; it can provide useful genetic markers for molecular epidemiological and population genetic studies on E. arloingi and E. christenseni in goats and contribute to the prevention and control of goat coccidiosis.
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- 2022
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13. Cocrystals of Praziquantel with Phenolic Acids: Discovery, Characterization, and Evaluation
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Shiying Yang, Qiwen Liu, Weiwen Ji, Qi An, Junke Song, Cheng Xing, Dezhi Yang, Li Zhang, Yang Lu, and Guanhua Du
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cocrystal ,praziquantel ,phenolic acid ,solubility ,evaluation ,Organic chemistry ,QD241-441 - Abstract
Solvent-assisted grinding (SAG) and solution slow evaporation (SSE) methods are generally used for the preparation of cocrystals. However, even by using the same solvent, active pharmaceutical ingredient (API), and cocrystal coformer (CCF), the cocrystals prepared using the two methods above are sometimes inconsistent. In the present study, in the cocrystal synthesis of praziquantel (PRA) with polyhydroxy phenolic acid, including protocatechuic acid (PA), gallic acid (GA), and ferulic acid (FA), five different cocrystals were prepared using SAG and SSE. Three of the cocrystals prepared using the SAG method have the structural characteristics of carboxylic acid dimer, and two cocrystals prepared using the SSE method formed cocrystal solvates with the structural characteristics of carboxylic acid monomer. For phenolic acids containing only one phenolic hydroxyl group (ferulic acid), when preparing cocrystals with PRA by using SAG and SSE, the same product was obtained. In addition, the weak molecular interactions that were observed in the cocrystal are explained at the molecular level by using theoretical calculation methods. Finally, the in vitro solubility of cocrystals without crystal solvents and in vivo bioavailability of PRA-FA were evaluated to further understand the influence on the physicochemical properties of API for the introduction of CCF.
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- 2022
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14. Salvianolic Acid D Alleviates Cerebral Ischemia-Reperfusion Injury by Suppressing the Cytoplasmic Translocation and Release of HMGB1-Triggered NF-κB Activation to Inhibit Inflammatory Response
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Wen Zhang, Junke Song, Wan Li, Dewen Kong, Yu Liang, Xiaoyue Zhao, and Guanhua Du
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Pathology ,RB1-214 - Abstract
Inflammatory response participates in the overall pathophysiological process of stroke. It is a promising strategy to develop antistroke drugs targeting inflammation. This study is aimed at investigating the therapeutic effect and anti-inflammatory mechanism of salvianolic acid D (SalD) against cerebral ischemia/reperfusion (I/R) injury. A rat middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established, and an oxygen-glucose deprivation/reoxygenation (OGD/R) injury model was established in PC12 cells. Neurological deficit score, cerebral infarction, and edema were studied in vivo. Cell viability was achieved using the MTT method in vitro. The Bax, Bcl-2, cytochrome c, HMGB1, TLR4, TRAF6, NF-κB p65, p-NF-κB p65, and cleaved caspase-3 and -9 were tested via the Western blot method. Cytokines and cytokine mRNA, including TNF-α, IL-1β, and IL-6, were studied via ELISA and PCR methods. The translocation of HMGB1 and NF-κB were studied by immunofluorescence assay. The HMGB1/NeuN, HMGB1/GFAP, and HMGB1/Iba1 double staining was carried out to observe the localization of HMGB1 in different cells. Results showed that SalD alleviated neurological impairment, decreased cerebral infarction, and reduced edema in I/R rats. SalD improved OGD/R-downregulated PC12 cell viability. SalD also promoted Bcl-2 expression and suppressed Bax, cytochrome c, and cleaved caspase-3 and -9 expression. SalD decreased the intensity of TLR4, MyD88, and TRAF6 proteins both in vivo and in vitro, and significantly inhibited the NF-κB nuclear translocation induced by I/R and OGD/R. What’s more, SalD inhibited HMGB1 cytoplasmic translocation in neurons, astrocytes, and microglia in both the cortex and hippocampus regions of I/R rats. In conclusion, SalD can alleviate I/R-induced cerebral injury in rats and increase the PC12 cell viability affected by OGD/R. The anti-inflammatory mechanism of SalD might result from the decreased nuclear-to-cytoplasmic translocation of HMGB1 and the inhibition on its downstream TLR4/MyD88/NF-κB signaling.
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- 2020
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15. Antihyperuricemic effect of mangiferin aglycon derivative J99745 by inhibiting xanthine oxidase activity and urate transporter 1 expression in mice
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Zhizhen Qin, Shoubao Wang, Yihuang Lin, Ying Zhao, Shengqian Yang, Junke Song, Tao Xie, Jinlong Tian, Song Wu, and Guanhua Du
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Therapeutics. Pharmacology ,RM1-950 - Abstract
A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase (XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7th day to induce hyperuricemia. Meanwhile, J99745 (3, 10, and 30 mg/kg), allopurinol (20 mg/kg) or benzbromarone (20 mg/kg) were orally administered to mice for 7 days. On the 7th day, uric acid and creatinine in serum and urine, blood urea nitrogen (BUN), malondialdehyde (MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin (H&E) staining. Hepatic XOD, renal urate transporter 1 (URAT1), glucose transporter type 9 (GLUT9), organic anion transporter 1 (OAT1) and ATP-binding cassette transporter G2 (ABCG2) were detected by Western blot and real time polymerase chain reaction (PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid (FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our results suggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent. KEY WORDS: Antihyperuricemic effect, Mangiferin aglycon, Derivative, Xanthine oxidase, Urate transporter 1
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- 2018
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16. Some pharmacokinetic parameters of salvianolic acid A following single-dose oral administration to rats
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Jialin Sun, Junke Song, Wen Zhang, Fanbo Jing, Wen Xu, Ping Leng, Xianghua Quan, Guanhua Du, and Zhongguo Sui
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absorption ,bioavailability ,transportation ,first-pass metabolism ,elimination ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Context: Salvianolic acid A (Sal A) is a hydrophilic bioactive compound isolated from Salvia miltiorrhiza Bunge (Lamiaceae). It exerts beneficial effects after oral administration on diabetic complications. Objective: To systematically study the absorption, distribution and excretion of Sal A after single-dose oral administration. Materials and methods: Animal experiments were conducted in Sprague-Dawley rats. Plasma was sampled at designated times after oral doses of 5, 10 and 20 mg/kg, and an intravenous dose of 50 μg/kg. Tissues were harvested at 10, 60 and 120 min postdosing. Bile, urine and feces were collected at specified intervals before and after dosing. Absorption and distribution characteristics were analyzed by LC–MS, and excretion characteristics were analyzed by UPLC–MS/MS. The Caco-2 cell model was applied to investigate potential mechanisms. Results: The Cmax (5 mg/kg: 31.53 μg/L; 10 mg/kg: 57.39 μg/L; 20 mg/kg: 111.91 μg/L) of Sal A increased linearly with doses (r> 0.99). The calculated absolute bioavailability was 0.39–0.52%. Transport experiment showed poor permeability and the ratio of PB–A to PA–B was 3.13–3.97. The highest concentration of Sal A was achieved in stomach followed by small intestine and liver, and it could also be detected in brain homogenate. Approximately 0.775% of its administered dose was excreted via feces, followed by bile (0.00373%) and urine (0.00252%). Discussion and conclusions: These results support the future development of Sal A as an oral drug for the treatment of diabetic complications. Future research should be conducted to investigate the reason for its poor bioavailability and improve this situation.
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- 2018
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17. Molecular Characterization of Blastocystis sp. in Camelus bactrianus in Northwestern China
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Xin Yang, Yunhui Li, Yuxin Wang, Junwei Wang, Peng Lai, Yuan Li, Junke Song, Meng Qi, and Guanghui Zhao
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Blastocystis sp. ,Camelus bactrianus ,prevalence ,subtyping ,northwestern China ,Veterinary medicine ,SF600-1100 ,Zoology ,QL1-991 - Abstract
Blastocystis sp. is an important zoonotic protist in humans and various animals with worldwide distribution. However, there have been no data on the occurrence of Blastocystis sp. in C. bactrianus, an important economic animal in northwestern China. In the present study, a PCR-sequencing tool based on the SSU rRNA gene was applied to investigate the prevalence and genetic diversity of Blastocystis sp. in 638 faecal samples from C. bactrianus in 21 sampling sites within three main breeding areas (Gansu, Inner Mongolia and Xinjiang) in northwestern China. The total prevalence of Blastocystis sp. was 21.8% (139/638) in C. bactrianus, with the infection rates of 29.5% (18/61), 50.0% (14/28) and 19.5% (107/549) for animals aged 6 years, respectively. Significant differences in prevalence were detected among C. bactrianus from three geographic areas (χ2 = 19.972, df = 2, p < 0.001) and all sampling sites (χ2 = 104.154, df = 20, p < 0.001). A total of 16 of 21 sampling sites were positive for Blastocystis sp., with the prevalence ranging from 7.7% to 70.6%. Sequence analysis of the SSU rRNA gene identified eight subtypes in C. bactrianus in the present study, including seven animal adapted subtypes (ST10, ST14, ST21, ST24, ST25, ST26 and ST30) and one potentially novel subtype, with ST10 being the dominant one. To the best of our knowledge, this study provides the first insight for the occurrence and genetic make-up of Blastocystis sp. in C. bactrianus and contributes to the understanding of the transmission of Blastocystis infection in C. bactrianus in China.
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- 2021
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18. Cocrystal of Apixaban–Quercetin: Improving Solubility and Bioavailability of Drug Combination of Two Poorly Soluble Drugs
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Li Zhang, Dewen Kong, Hongjuan Wang, Lingtai Jiao, Xiaoyue Zhao, Junke Song, Dezhi Yang, Haiguang Yang, Shiying Yang, Guanhua Du, and Yang Lu
- Subjects
drug–drug cocrystal ,apixaban ,quercetin ,solubility ,bioavailability ,Organic chemistry ,QD241-441 - Abstract
Drug combinations have been the hotspot of the pharmaceutical industry, but the promising applications are limited by the unmet solubility and low bioavailability. In this work, novel cocrystals, consisting of two antithrombotic drugs with poor solubility and low bioavailability in vivo, namely, apixaban (Apx) and quercetin (Que), were developed to discover a potential method to improve the poor solubility and internal absorption of the drug combination. Compared with Apx, the dissolution behavior of Apx–Que (1:1) and Apx–Que–2ACN (1:1:2) was enhanced significantly, while the physical mixture of the chemicals failed to exhibit the advantages. The dissolution improvements of Apx–Que–2ACN could be explained by the fact that the solid dispersion-like structure and column-shaped cage of Que accelerated the access of the solvent to the inner layer of Apx. The fracture of the hydrogen bonds of Apx, which was the joint of the adjacent Que chains, facilitated the break-up of the structures. Besides, the bioavailability of Apx–Que was increased compared with the physical mixture and Apx, and Apx–Que remained stable in high temperature and illumination conditions. Therefore, a drug–drug cocrystal of two antithrombotic agents with poor solubility was developed, which exhibited greatly improved solubility, bioavailability and superior stability, indicating a novel method to overcome the shortages of drug combination.
- Published
- 2021
- Full Text
- View/download PDF
19. Pharmacokinetic study of gallocatechin-7-gallate from Pithecellobium clypearia Benth. in rats
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Chao Li, Xiaowei Song, Junke Song, Xiaocong Pang, Zhe Wang, Ying Zhao, Wenwen Lian, Ailin Liu, and Guanhua Du
- Subjects
Gallocatechin-7-gallate ,LC–MS ,Pharmacokinetics ,Dose proportionality ,Non-compartment model ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The pharmacokinetic profile of gallocatechin-7-gallate (J10688) was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD) rats received 1, 3, and 10 mg/kg (i.v.) of J10688 and plasma drug concentrations were determined by a high performance liquid chromatography-mass spectrometry (LC–MS) method. The pharmacokinetic software Data Analysis System (Version 3.0) was used to calculate the pharmacokinetic parameters. For different i.v. doses of J10688, the mean peak plasma concentration (C0) values ranged from 11.26 to 50.82 mg/L, and mean area under the concentration-time curve (AUC0–t) values ranged from 1.75 to 11.80 (mg·h/L). J10688 lacked dose-dependent pharmacokinetic properties within doses between 1 and 10 mg/kg, based on the power model. The method developed in this study was sensitive, precise, and stable. The pharmacokinetic properties of J10688 in SD rats were shown to have rapid distribution and clearance values. These pharmacokinetic results may contribute to an improved understanding of the pharmacological actions of J10688.
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- 2016
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20. A Novel Co-Crystal of Bexarotene and Ligustrazine Improves Pharmacokinetics and Tissue Distribution of Bexarotene in SD Rats
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Shuyue Ren, Lingtai Jiao, Shiying Yang, Li Zhang, Junke Song, Haoying Yu, Jingrong Wang, Tingting Lv, Lan Sun, Yang Lu, and Guanhua Du
- Subjects
pharmaceutical co-crystals ,active pharmaceutical ingredients ,bexarotene ,solubility ,bioavailability ,cerebral distribution ,Pharmacy and materia medica ,RS1-441 - Abstract
Bexarotene (BEX), a specific retinoic acid X receptor (RXR) agonist granted by Food and Drug Administration (FDA) approval for the clinical treatment of T cell lymphoma, has now been found to exert pharmacological effects in the nervous system, with low bioavailability and poor cerebral distribution limiting its application in treatment on neurological disorders. Pharmaceutical co-crystal was a helpful method to improve the bioavailability and tissue distribution of active pharmaceutical ingredients (APIs). Here, 2bexarotene-ligustrazine (2BEX-LIG), a novel co-crystal system of BEX and ligustrazine (LIG) of which with BEX is an API, was constructed with satisfactory stability and enhanced solubility. The pharmacokinetics characteristics of BEX were detected, and the results showed that the absolute bioavailability and the cerebral concentration of BEX in rats administrated with 2BEX-LIG were enhanced from 22.89% to 42.86% and increased by 3.4-fold, respectively, compared with those in rats administrated an equivalent of BEX. Hence, our present study indicated that the novel co-crystal of 2BEX-LIG contributed to improving BEX oral bioavailability and cerebral distribution, thereby providing significant advantages for clinical application of brain tumors and other neurological diseases.
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- 2020
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21. Pharmacokinetic study of salvianolic acid D after oral and intravenous administration in rats
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Junke Song, Wen Zhang, Jialin Sun, Xiaona Xu, Xue Zhang, Li Zhang, Zhangying Feng, and Guan-hua Du
- Subjects
Salvianolic acid D ,LC-MS ,Pharmacokinetics ,Bioavailability ,Dose proportionality ,Salvia miltiorrhiza ,Danshen ,Analysis method ,Therapeutics. Pharmacology ,RM1-950 - Abstract
A sensitive, specific and rapid LC-MS method was developed and validated for the determination of salvianolic acid D (SalD) in rat plasma. This method used a single quadrupole mass spectrometer with an electrospray ionization (ESI) source. A single ion monitoring scanning (SIM) mode was employed. It showed good linearity over the concentration range from 3.3 to 666.7 ng/mL for the determination of SalD. The R.S.D.% of intra-day and inter-day precision values were no more than 7.69%, and the accuracy was within 91%−104% at all quality control levels. This LC-MS method was applied to the pharmacokinetic study of SalD in rats. A two-compartmental model analysis was employed. The plasma concentrations at 2 min (C2min) were 5756.06±719.61, 11,073.01±1783.46 and 21,077.58±5581.97 μg/L for 0.25, 0.5 and 1 mg/kg intravenous injection, respectively. The peak plasma concentration (Cmax) was 333.08±61.21 μg/L for 4 mg/kg oral administration. The area under curve (AUC0−t) was 14,384.379±8443.184, 22,813.369±11,860.823, 46,406.122±27,592.645 and 8201.740±4711.961 μg/L·h for intravenous injection (0.25, 0.5 and 1 mg/kg) and oral administration (4 mg/kg), respectively. The bioavailability of SalD was calculated to be 4.159%±0.517%.
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- 2015
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22. Lipid Profiling Reveals Browning Heterogeneity of White Adipose Tissue by Β3-Adrenergic Stimulation
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Ping He, Biyu Hou, Yanliang Li, Chunyang Xu, Peng Ma, Sin Man Lam, Victoria Gil, Xinyu Yang, Xiuying Yang, Li Zhang, Guanghou Shui, Junke Song, Guifen Qiang, Chong Wee Liew, and Guanhua Du
- Subjects
lipid profiling ,white adipose tissue ,browning heterogeneity ,visceral adipose tissue ,subcutaneous adipose tissue ,Microbiology ,QR1-502 - Abstract
Background: White adipose tissue (WAT) browning confers beneficial effects on metabolic diseases. However, visceral adipose tissue (VAT) is not as susceptible to browning as subcutaneous adipose tissue (SAT). Aim: Interpreting the heterogeneity of VAT and SAT in brown remodeling and provide promising lipid targets to promote WAT browning. Methods: We first investigated the effects of β3-adrenergic stimulation by CL316,243 on systemic metabolism. Then, high-coverage targeted lipidomics approach with multiple reaction monitoring (MRM) was utilized to provide extensive detection of lipid metabolites in VAT and SAT. Results: CL316,243 notably ameliorated the systemic metabolism and induced brown remodeling of SAT but browning resistance of VAT. Comprehensive lipidomics analysis revealed browning heterogeneity of VAT and SAT with more dramatic alteration of lipid classes and species in VAT rather than SAT, though VAT is resistant to browning. Adrenergic stimulation differentially affected glycerides content in VAT and SAT and boosted the abundance of more glycerophospholipids species in VAT than in SAT. Besides, CL316,243 increased sphingolipids in VAT without changes in SAT, meanwhile, elevated cardiolipin species more prominently in VAT than in SAT. Conclusions: We demonstrated the browning heterogeneity of WAT and identified potential lipid biomarkers which may provide lipid targets for overcoming VAT browning resistance.
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- 2019
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23. Edaravone Dexborneol Alleviates Cerebral Ischemic Injury via MKP-1-Mediated Inhibition of MAPKs and Activation of Nrf2
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Wen Zhang, Haiguang Yang, Mei Gao, Hengai Zhang, Lili Shi, Xiaoyan Yu, Rui Zhao, Junke Song, and Guanhua Du
- Subjects
Article Subject ,General Immunology and Microbiology ,NF-E2-Related Factor 2 ,JNK Mitogen-Activated Protein Kinases ,NF-kappa B ,Dual Specificity Phosphatase 1 ,General Medicine ,Nitric Oxide ,p38 Mitogen-Activated Protein Kinases ,General Biochemistry, Genetics and Molecular Biology ,Rats ,Brain Injuries ,Malondialdehyde ,Edaravone ,Animals ,Extracellular Signal-Regulated MAP Kinases ,Peroxidase - Abstract
The edaravone and dexborneol concentrated solution for injection (edaravone-dexborneol) is a medication used clinically to treat neurological impairment induced by ischemic stroke. This study was aimed at investigating the preventive effects and the underlying mechanisms of edaravone-dexborneol on cerebral ischemic injury. A rat four-vessel occlusion (4-VO) model was established, and the neuronal injury and consequent neurological impairment of rats was investigated. Brain tissue malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) levels were determined. The levels of proteins in mitogen-activated protein kinases (MAPKs), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-κB (NF-κB) signaling pathways were determined by western immunoblotting. The function of mitogen-activated protein kinase phosphatase 1 (MKP-1) was investigated using both western blot and immunofluorescence methods, and the effect of the MKP-1 inhibitor, (2E)-2-benzylidene-3-(cyclohexylamino)-3H-inden-1-one (BCI), was investigated. The results indicated that edaravone-dexborneol alleviated neurological deficiency symptoms and decreased apoptosis and neuron damage in the hippocampal CA1 area of the ischemic rats. Edaravone-dexborneol increased the MKP-1 level; decreased the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK); inhibited NF-κB p65 activation; and boosted Nrf2 activation, all of which were partially reversed by the MKP-1 inhibitor, BCI. The above results indicated that the upregulation of MKP-1 contributed to the protective effects of edaravone-dexborneol against ischemic brain injury. Our findings support the hypothesis that edaravone-dexborneol can alleviate cerebral ischemic injury via the upregulation of MKP-1, which inhibits MAPKs and activates Nrf2.
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- 2022
24. Quercetin attenuates ischemia reperfusion injury by protecting the blood-brain barrier through Sirt1 in MCAO rats
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Shu-Han Chen, Miao Chen, Jiaying Zhao, Yanjia Shen, Guanhua Du, Junke Song, Li Li, Ran Yang, and Wen Zhang
- Subjects
Ischemia ,Pharmaceutical Science ,Pharmacology ,medicine.disease_cause ,Blood–brain barrier ,Neuroprotection ,Brain Ischemia ,Analytical Chemistry ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Sirtuin 1 ,Drug Discovery ,medicine ,Animals ,heterocyclic compounds ,Molecular Structure ,business.industry ,Organic Chemistry ,Infarction, Middle Cerebral Artery ,General Medicine ,medicine.disease ,Rats ,Neuroprotective Agents ,medicine.anatomical_structure ,Complementary and alternative medicine ,chemistry ,Blood-Brain Barrier ,Reperfusion Injury ,cardiovascular system ,Molecular Medicine ,Quercetin ,Signal transduction ,business ,Reperfusion injury ,Bbb permeability ,Oxidative stress - Abstract
The purpose of the present study was to examine the protective action and mechanisms of quercetin on the blood-brain barrier (BBB) in rats subjected to transient middle cerebral artery occlusion (tMCAO) and reperfusion. Quercetin (10, 30, 50 mg/kg) was intraperitoneally administered at the onset of reperfusion. The results showed that quercetin significantly reduced cerebral infarct volume, neurological deficit, BBB permeability and ROS generation via Sirt1/Nrf2/HO-1 signaling pathway. Moreover, EX527, a selective inhibitor of Sirt1, reversed these neuroprotective effects. Our findings indicate that quercetin has neuroprotective effects against cerebral ischemia-reperfusion injury by protecting BBB through Sirt1 signaling pathway in MCAO rats.
- Published
- 2021
25. Luteolin alleviates cognitive impairment in Alzheimer’s disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation
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Jiejian Kou, Yi Yan, Yang-Yang He, Jiao-Jiao Hao, Xinmei Xie, Dong-Mei Luo, Guanhua Du, Hai-Yu Zhang, Xiaobin Pang, Jun-Zhuo Shi, and Junke Song
- Subjects
Mice, Transgenic ,Protein Serine-Threonine Kinases ,Pharmacology ,Neuroprotection ,Article ,Proinflammatory cytokine ,Mice ,chemistry.chemical_compound ,Alzheimer Disease ,Endoribonucleases ,medicine ,Animals ,Cognitive Dysfunction ,Pharmacology (medical) ,Luteolin ,Neuroinflammation ,business.industry ,Cell growth ,Endoplasmic reticulum ,General Medicine ,Endoplasmic Reticulum Stress ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,chemistry ,Neuroinflammatory Diseases ,Unfolded protein response ,business ,Astrocyte - Abstract
Luteolin is a flavonoid in a variety of fruits, vegetables, and herbs, which has shown anti-inflammatory, antioxidant, and anti-cancer neuroprotective activities. In this study, we investigated the potential beneficial effects of luteolin on memory deficits and neuroinflammation in a triple-transgenic mouse model of Alzheimer’s disease (AD) (3 × Tg-AD). The mice were treated with luteolin (20, 40 mg · kg(−1) · d(−1), ip) for 3 weeks. We showed that luteolin treatment dose-dependently improved spatial learning, ameliorated memory deficits in 3 × Tg-AD mice, accompanied by inhibiting astrocyte overactivation (GFAP) and neuroinflammation (TNF-α, IL-1β, IL-6, NO, COX-2, and iNOS protein), and decreasing the expression of endoplasmic reticulum (ER) stress markers GRP78 and IRE1α in brain tissues. In rat C6 glioma cells, treatment with luteolin (1, 10 µM) dose-dependently inhibited LPS-induced cell proliferation, excessive release of inflammatory cytokines, and increase of ER stress marker GRP78. In conclusion, luteolin is an effective agent in the treatment of learning and memory deficits in 3 × Tg-AD mice, which may be attributable to the inhibition of ER stress in astrocytes and subsequent neuroinflammation. These results provide the experimental basis for further research and development of luteolin as a therapeutic agent for AD.
- Published
- 2021
26. An innovative rhein-matrine cocrystal: Synthesis, characterization, formation mechanism and pharmacokinetic study
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Hongjuan Wang, Dezhi Yang, Wen Zhang, Junke Song, Ningbo Gong, Mingchao Yu, Shiying Yang, Baoxi Zhang, Qiwen Liu, Guanhua Du, and Yang Lu
- Subjects
General Chemistry - Published
- 2023
27. Molecular Characterization of
- Author
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Xin, Yang, Mingzhe, Fu, Zhengqing, Yu, Junwei, Wang, Junke, Song, and Guanghui, Zhao
- Published
- 2022
28. Research Progress of the Antiviral Bioactivities of Natural Flavonoids
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Bin Xiao, Lin Wang, Ai-Lin Liu, Guanhua Du, Sha Li, Yang Lu, Zhang Wen, and Junke Song
- Subjects
Pharmacology toxicology ,Plant Science ,Review ,Biology ,Toxicology ,Biochemistry ,Cellular and molecular mechanisms ,Analytical Chemistry ,03 medical and health sciences ,0302 clinical medicine ,Nutraceutical ,Natural flavonoids ,heterocyclic compounds ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Traditional medicine ,Organic Chemistry ,fungi ,Botany ,food and beverages ,Therapeutic applications ,carbohydrates (lipids) ,Antiviral bioactivities ,030220 oncology & carcinogenesis ,QK1-989 ,Plant biochemistry ,Food Science - Abstract
Flavonoids are now considered as an indispensable component in a variety of nutraceutical and pharmaceutical applications. Most recent researches have focused on the health aspects of flavonoids for humans. Especially, different flavonoids have been investigated for their potential antiviral activities, and several natural flavonoids exhibited significant antiviral properties both in vitro and in vivo. This review provides a survey of the literature regarding the evidence for antiviral bioactivities of natural flavonoids, highlights the cellular and molecular mechanisms of natural flavonoids on viruses, and presents the details of most reported flavonoids. Meanwhile, future perspectives on therapeutic applications of flavonoids against viral infections were discussed.
- Published
- 2020
29. Preparation and Certification of a New Salvianolic Acid A Reference Material for Food and Drug Research
- Author
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Yan-Cai Bi, Baoxi Zhang, Junke Song, Dezhi Yang, Yang Lu, Li Zhang, Bin Su, and Guanhua Du
- Subjects
Plant Science ,Toxicology ,Mass spectrometry ,01 natural sciences ,Biochemistry ,Analytical Chemistry ,03 medical and health sciences ,Ingredient ,Impurity ,parasitic diseases ,High resolution mass spectrum ,030304 developmental biology ,Pharmacology ,0303 health sciences ,Chromatography ,Salvianolic acid A ,Tandem ,Chemistry ,010401 analytical chemistry ,Organic Chemistry ,Botany ,Nuclear magnetic resonance spectroscopy ,qNMR ,0104 chemical sciences ,Mass balance method ,Certified reference materials ,QK1-989 ,Plant biochemistry ,Original Article ,Certified reference material ,Food Science - Abstract
Salvianolic acid A (Sal A), a water-soluble ingredient in Danshen, has various biological activities. Sal A and its impurities have similar physical and chemical properties, as well as strong reducibility; therefore, they are difficult to prepare and purify. In this study, high-purity Sal A was obtained by purification of sephadex chromatography and preparative chromatography. Furthermore, HPLC–DAD tandem ECD and HPLC–DAD tandem MS methods were used for non-volatile organic impurity analysis, ICP-MS method was used for non-volatile inorganic impurities and mass balance method and quantitative nuclear magnetic resonance were employed to certify the product. The structures of Sal A and its relative impurities were validated by nuclear magnetic resonance spectroscopy and mass spectrometry, and their contents were quantified as well. Following the principles of ISO Guides 34:2009 and 35:2005, a Sal A reference material was certified, covering homogeneity studies, stability studies, characterization, and uncertainty estimations. Graphic Abstract Electronic supplementary material The online version of this article (10.1007/s13659-020-00236-2) contains supplementary material, which is available to authorized users.
- Published
- 2020
30. Salvianolic Acid D Alleviates Cerebral Ischemia-Reperfusion Injury by Suppressing the Cytoplasmic Translocation and Release of HMGB1-Triggered NF-κB Activation to Inhibit Inflammatory Response
- Author
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Dewen Kong, Guanhua Du, Wan Li, Yu Liang, Junke Song, Xiaoyue Zhao, and Wen Zhang
- Subjects
Article Subject ,Microglia ,biology ,Chemistry ,Immunology ,Inflammation ,Cell Biology ,Pharmacology ,HMGB1 ,medicine.disease ,medicine.anatomical_structure ,nervous system ,In vivo ,Pathology ,medicine ,TLR4 ,biology.protein ,RB1-214 ,Viability assay ,medicine.symptom ,NeuN ,Reperfusion injury - Abstract
Inflammatory response participates in the overall pathophysiological process of stroke. It is a promising strategy to develop antistroke drugs targeting inflammation. This study is aimed at investigating the therapeutic effect and anti-inflammatory mechanism of salvianolic acid D (SalD) against cerebral ischemia/reperfusion (I/R) injury. A rat middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established, and an oxygen-glucose deprivation/reoxygenation (OGD/R) injury model was established in PC12 cells. Neurological deficit score, cerebral infarction, and edema were studied in vivo. Cell viability was achieved using the MTT method in vitro. The Bax, Bcl-2, cytochrome c, HMGB1, TLR4, TRAF6, NF-κB p65, p-NF-κB p65, and cleaved caspase-3 and -9 were tested via the Western blot method. Cytokines and cytokine mRNA, including TNF-α, IL-1β, and IL-6, were studied via ELISA and PCR methods. The translocation of HMGB1 and NF-κB were studied by immunofluorescence assay. The HMGB1/NeuN, HMGB1/GFAP, and HMGB1/Iba1 double staining was carried out to observe the localization of HMGB1 in different cells. Results showed that SalD alleviated neurological impairment, decreased cerebral infarction, and reduced edema in I/R rats. SalD improved OGD/R-downregulated PC12 cell viability. SalD also promoted Bcl-2 expression and suppressed Bax, cytochrome c, and cleaved caspase-3 and -9 expression. SalD decreased the intensity of TLR4, MyD88, and TRAF6 proteins both in vivo and in vitro, and significantly inhibited the NF-κB nuclear translocation induced by I/R and OGD/R. What’s more, SalD inhibited HMGB1 cytoplasmic translocation in neurons, astrocytes, and microglia in both the cortex and hippocampus regions of I/R rats. In conclusion, SalD can alleviate I/R-induced cerebral injury in rats and increase the PC12 cell viability affected by OGD/R. The anti-inflammatory mechanism of SalD might result from the decreased nuclear-to-cytoplasmic translocation of HMGB1 and the inhibition on its downstream TLR4/MyD88/NF-κB signaling.
- Published
- 2020
31. Neutrophil extracellular traps: A novel target for the treatment of stroke
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Ziyuan, Zhao, Zirong, Pan, Sen, Zhang, Guodong, Ma, Wen, Zhang, Junke, Song, Yuehua, Wang, Linglei, Kong, and Guanhua, Du
- Subjects
Pharmacology ,Pharmacology (medical) - Abstract
Stroke is a threatening cerebrovascular disease caused by thrombus with high morbidity and mortality rates. Neutrophils are the first to be recruited in the brain after stroke, which aggravate brain injury through multiple mechanisms. Neutrophil extracellular traps (NETs), as a novel regulatory mechanism of neutrophils, can trap bacteria and secret antimicrobial molecules, thereby degrading pathogenic factors and killing bacteria. However, NETs also exacerbate certain non-infectious diseases by activating autoimmune or inflammatory responses. NETs have been found to play important roles in the pathological process of stroke in recent years. In this review, the mechanisms of NETs formation, the physiological roles of NETs, and the dynamic changes of NETs after stroke are summarized. NETs participate in stroke through various mechanisms. NETs promote the coagulation cascade and interact with platelets to induce thrombosis. tPA induces the degranulation of neutrophils to form NETs, leading to hemorrhagic transformation and thrombolytic resistance. NETs aggravate stroke by mediating inflammation, atherosclerosis and vascular injury. In addition, the regulation of NETs in stroke, the potential of NETs as biomarker and the treatment of stroke targeting NETs are discussed. The increasing evidences suggest that NETs may be a potential target for stroke treatment. Inhibition of NETs formation or promotion of NETs degradation plays protective effects in stroke. However, how to avoid the adverse effects of NETs-targeted therapy deserves further study. In summary, this review provides a reference for the pathogenesis, drug targets, biomarkers and drug development of NETs in stroke.
- Published
- 2023
32. Cocrystal of Apixaban–Quercetin: Improving Solubility and Bioavailability of Drug Combination of Two Poorly Soluble Drugs
- Author
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Haiguang Yang, Shiying Yang, Dezhi Yang, Junke Song, Li Zhang, Yang Lu, Jiao Lingtai, Hongjuan Wang, Guanhua Du, Dewen Kong, and Xiaoyue Zhao
- Subjects
Male ,Pharmaceutical Science ,Organic chemistry ,02 engineering and technology ,01 natural sciences ,Cocrystal ,Analytical Chemistry ,quercetin ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,QD241-441 ,X-Ray Diffraction ,Drug Discovery ,Solubility ,Dissolution ,Chromatography, High Pressure Liquid ,media_common ,Calorimetry, Differential Scanning ,Chemistry ,drug–drug cocrystal ,Temperature ,food and beverages ,021001 nanoscience & nanotechnology ,Solvent ,Drug Combinations ,Pharmaceutical Preparations ,Chemistry (miscellaneous) ,Thermogravimetry ,Molecular Medicine ,Powders ,Crystallization ,0210 nano-technology ,Quercetin ,Drug ,Pyridones ,media_common.quotation_subject ,apixaban ,Biological Availability ,010402 general chemistry ,Article ,Fibrinolytic Agents ,Animals ,Physical and Theoretical Chemistry ,solubility ,Hydrogen Bonding ,APX ,Combinatorial chemistry ,Rats ,0104 chemical sciences ,Bioavailability ,Solvents ,Pyrazoles ,bioavailability - Abstract
Drug combinations have been the hotspot of the pharmaceutical industry, but the promising applications are limited by the unmet solubility and low bioavailability. In this work, novel cocrystals, consisting of two antithrombotic drugs with poor solubility and low bioavailability in vivo, namely, apixaban (Apx) and quercetin (Que), were developed to discover a potential method to improve the poor solubility and internal absorption of the drug combination. Compared with Apx, the dissolution behavior of Apx–Que (1:1) and Apx–Que–2ACN (1:1:2) was enhanced significantly, while the physical mixture of the chemicals failed to exhibit the advantages. The dissolution improvements of Apx–Que–2ACN could be explained by the fact that the solid dispersion-like structure and column-shaped cage of Que accelerated the access of the solvent to the inner layer of Apx. The fracture of the hydrogen bonds of Apx, which was the joint of the adjacent Que chains, facilitated the break-up of the structures. Besides, the bioavailability of Apx–Que was increased compared with the physical mixture and Apx, and Apx–Que remained stable in high temperature and illumination conditions. Therefore, a drug–drug cocrystal of two antithrombotic agents with poor solubility was developed, which exhibited greatly improved solubility, bioavailability and superior stability, indicating a novel method to overcome the shortages of drug combination.
- Published
- 2021
33. A Novel UPLC-MS/MS Method for the Determination of Salvianolic Acid A in Rat Urine, Feces, and Bile and its Application to Excretion Study
- Author
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Qie Guo, Guanhua Du, Bing Han, Wen Xu, Jialin Sun, Xiao Li, Fanbo Jing, Junke Song, and Wei Sun
- Subjects
Chromatography ,Salvianolic acid A ,Chemistry ,010401 analytical chemistry ,Biophysics ,Pharmaceutical Science ,Urine ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Excretion ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Molecular Medicine ,Uplc ms ms ,Feces - Abstract
Background: Salvianolic acid A (SAA) is a polyphenolic acid extracted from Salvia miltiorrhiza Bunge. It showed protective effect against diabetic complications after oral administration with a low bioavailability of 1.42%. Attempts have been made to develop it into a new medication. Intracorporal process of SAA is indistinct and no report regarding the excretion is available. Our preliminary experiment revealed that previous reported methods were unsuitable for the excretion study due to the serious matrix effect. Methods: To better clarify its pharmacokinetics and avoid the interference of complex endogenous substances, a sensitive UPLC-MS/MS method with a better resolution was developed for the excretion study of SAA for the first time. The analytes were separated by reversed-phase chromatography with acetonitrile-water (containing 0.1% formic acid) gradient elution. The mass spectrometer was operated in the negative ESI mode and multiple reaction monitoring mode. Results: This method was linear over the concentration range of 2.5-100, 5-100 and 5-100 ng/mL in urine, feces and bile, respectively. The accuracy, precision, stability, recovery and matrix effect were satisfactory in all matrices examined. The validated method was successfully applied to an excretion study in rats. After oral administration of 20 mg/kg, the average accumulated excretion amount of SAA in urine, feces and bile were 99.80, 32046.30 and 161.03 ng, respectively. Conclusion: A quick but low elimination was observed. The date is useful for the clinical trial design of SAA.
- Published
- 2019
34. Investigation of common chemical components and inhibitory effect on GES-type β-lactamase (GES22) in methanolic extracts of Algerian seaweeds
- Author
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Abdelhalim Khenchouche, Li Zhang, Selma Houchi, Xiaocong Pang, Cemal Sandalli, Wen Zhang, Junke Song, Guanhua Du, and Rachid Mahdadi
- Subjects
0301 basic medicine ,Codium tomentosum ,Linoleic acid ,030106 microbiology ,Phaeophyta ,Microbiology ,beta-Lactamases ,03 medical and health sciences ,chemistry.chemical_compound ,Phenols ,Chlorophyta ,Mediterranean Sea ,Nitrocefin ,Food science ,IC50 ,Enzyme Assays ,Arachidonic Acid ,biology ,Plant Extracts ,Chemistry ,Methanol ,alpha-Linolenic Acid ,Seaweed ,biology.organism_classification ,Baicalein ,Oleic acid ,030104 developmental biology ,Infectious Diseases ,Ulva intestinalis ,Algeria ,Flavanones ,Scoparia ,Oleic Acid - Abstract
This study aimed to investigate the total phenolic content (TPC), the identification of the common compounds by HPLC-ESI-MS and HPLC-ESI-MS-TOF and the inhibitory effects against class A-type β-lactamase (GES-22 variant, produced recombinantly) in methanolic extracts (MEs) of four Algerian seaweeds [Ulva intestinalis, Codium tomentosum, Dictyota dichotoma and Halopteris scoparia]. The TPC varied among the four species, ranging between 0.93 ± 0.65 and 2.66 ± 1.33 mg GAEs/g DW. C.tomentosum had higher total phenol content than other seaweeds while, all of them inhibited uncompetitively GES-22 activity in a dose-dependent manner. Nitrocefin was used as chromogenic substrate to evaluate the inhibitory effect on GES-22. The methanolic extract of D.dichotoma exhibited significant inhibitory effect on GES-22 (IC50 = 13.01 ± 0.046 μg/mL) more than clavulanate, sulbactam and tazobactam (classical β-lactam inhibitors) (IC50 = 68.38 ± 0.17 μg/mL, 52.68 ± 0.64 μg/mL, and 29.94 ± 0.01 μg/mL, respectively). IC50 of the other ME of U.intestinalis, C.tomentosum, and H.scoparia were 16.87 ± 0.10 μg/mL, 16.54 ± 0.048 μg/mL, and 25.72 ± 0.15 μg/mL, respectively. Except H. scoparia, other three seaweed extracts showed almost two times or more inhibition on GES-22. Furthermore, four common compounds in these MEs were identified, α-linolenic acid (C18:3ω3), linoleic acid (C18:2ω6), oleic acid (C18:1ω9), the eicosanoid precursors ‘‘arachidonic acid’’ (C20:4ω6). Baicalein (C15H10O5) was identified in U.intestinalis and D.dichotoma seaweeds. The fact that all seaweed extracts inhibited the GES-22 better than commercial samples makes these seaweeds candidate for discovering new inhibitors against β-lactamases. Besides that, they contain important components with potential health benefits.
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- 2019
35. A Novel Co-Crystal of Bexarotene and Ligustrazine Improves Pharmacokinetics and Tissue Distribution of Bexarotene in SD Rats
- Author
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Tingting Lv, Shuyue Ren, Jingrong Wang, Haoying Yu, Guanhua Du, Li Zhang, Shiying Yang, Junke Song, Lan Sun, Jiao Lingtai, and Yang Lu
- Subjects
Agonist ,active pharmaceutical ingredients ,medicine.drug_class ,cerebral distribution ,Retinoic acid ,Pharmaceutical Science ,lcsh:RS1-441 ,02 engineering and technology ,pharmaceutical co-crystals ,Pharmacology ,Retinoid X receptor ,010402 general chemistry ,01 natural sciences ,Article ,lcsh:Pharmacy and materia medica ,chemistry.chemical_compound ,Pharmacokinetics ,medicine ,Distribution (pharmacology) ,Receptor ,Bexarotene ,business.industry ,solubility ,bexarotene ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Bioavailability ,chemistry ,0210 nano-technology ,business ,bioavailability ,medicine.drug - Abstract
Bexarotene (BEX), a specific retinoic acid X receptor (RXR) agonist granted by Food and Drug Administration (FDA) approval for the clinical treatment of T cell lymphoma, has now been found to exert pharmacological effects in the nervous system, with low bioavailability and poor cerebral distribution limiting its application in treatment on neurological disorders. Pharmaceutical co-crystal was a helpful method to improve the bioavailability and tissue distribution of active pharmaceutical ingredients (APIs). Here, 2bexarotene-ligustrazine (2BEX-LIG), a novel co-crystal system of BEX and ligustrazine (LIG) of which with BEX is an API, was constructed with satisfactory stability and enhanced solubility. The pharmacokinetics characteristics of BEX were detected, and the results showed that the absolute bioavailability and the cerebral concentration of BEX in rats administrated with 2BEX-LIG were enhanced from 22.89% to 42.86% and increased by 3.4-fold, respectively, compared with those in rats administrated an equivalent of BEX. Hence, our present study indicated that the novel co-crystal of 2BEX-LIG contributed to improving BEX oral bioavailability and cerebral distribution, thereby providing significant advantages for clinical application of brain tumors and other neurological diseases.
- Published
- 2020
36. Chemical and pharmacological research on the polyphenol acids isolated from Danshen: A review of salvianolic acids
- Author
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Guanhua, Du, Junke, Song, Lida, Du, Li, Zhang, Guifen, Qiang, Shoubao, Wang, Xiuying, Yang, and Lianhua, Fang
- Subjects
Animals ,Humans ,Polyphenols ,Apoptosis ,Salvia miltiorrhiza ,Alkenes ,Medicine, Chinese Traditional ,Drugs, Chinese Herbal - Abstract
Danshen, the dried root of Salvia miltiorrhiza Bge, is a common medicinal herb in Traditional Chinese Medicine, which has been used for the treatment of a number of diseases for thousands of years. More than 2000 years ago, the Chinese early pharmacy monograph "Shennong Materia Medica" recorded that Danshen could be used for the treatment of gastrointestinal diseases, cardiovascular diseases, certain gynecological diseases, etc. Since then, Danshen has been widely used clinically in many different prescriptions for many different diseases, especially for the treatment of cardiovascular diseases. Nowadays, many pharmacological studies about the water-soluble components from Danshen have been reported, especially salvianolic acids. It turned out that salvianolic acids showed strong anti-lipid peroxidation and anti-thrombic activities, and among them, SalAA and SalAB were the most potent. This review focused on the achievements in research of salvianolic acids regarding their bioactivities and pharmacological effects. These studies not only shed light on the water-soluble active components of Danshen and their mechanisms at the molecular level, but also provided theoretical information for the development of new medicines from Danshen for the treatment of cardiovascular and cerebrovascular diseases, inflammatory diseases, metabolic diseases, etc.
- Published
- 2020
37. Chemical and pharmacological research on the polyphenol acids isolated from Danshen: A review of salvianolic acids
- Author
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Guanhua Du, Guifen Qiang, Shou-Bao Wang, Li Zhang, Xiuying Yang, Lianhua Fang, Junke Song, and Lida Du
- Subjects
0303 health sciences ,Traditional medicine ,business.industry ,Pharmacological research ,030302 biochemistry & molecular biology ,Materia medica ,Pharmacy ,Traditional Chinese medicine ,Salvia miltiorrhiza ,03 medical and health sciences ,Molecular level ,Polyphenol ,Medicine ,Medicinal herbs ,business - Abstract
Danshen, the dried root of Salvia miltiorrhiza Bge, is a common medicinal herb in Traditional Chinese Medicine, which has been used for the treatment of a number of diseases for thousands of years. More than 2000 years ago, the Chinese early pharmacy monograph "Shennong Materia Medica" recorded that Danshen could be used for the treatment of gastrointestinal diseases, cardiovascular diseases, certain gynecological diseases, etc. Since then, Danshen has been widely used clinically in many different prescriptions for many different diseases, especially for the treatment of cardiovascular diseases. Nowadays, many pharmacological studies about the water-soluble components from Danshen have been reported, especially salvianolic acids. It turned out that salvianolic acids showed strong anti-lipid peroxidation and anti-thrombic activities, and among them, SalAA and SalAB were the most potent. This review focused on the achievements in research of salvianolic acids regarding their bioactivities and pharmacological effects. These studies not only shed light on the water-soluble active components of Danshen and their mechanisms at the molecular level, but also provided theoretical information for the development of new medicines from Danshen for the treatment of cardiovascular and cerebrovascular diseases, inflammatory diseases, metabolic diseases, etc.
- Published
- 2020
38. Salvianolic acid A relieves cognitive disorder after chronic cerebral ischemia: Involvement of Drd2/Cryab/NF-κB pathway
- Author
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Junke Song, Nan Jiang, Nan-nan Liu, Guanhua Du, Shan Liu, Guangyi Wei, Sen Zhang, Haiguang Yang, and Yujiao Yang
- Subjects
Male ,Hippocampus ,Morris water navigation task ,Pharmacology ,Neuroprotection ,Brain Ischemia ,chemistry.chemical_compound ,Caffeic Acids ,Cell Line, Tumor ,Animals ,Humans ,Medicine ,Cognitive Dysfunction ,Rats, Wistar ,Neuroinflammation ,TUNEL assay ,Receptors, Dopamine D2 ,business.industry ,NF-kappa B ,Brain ,NF-κB ,Crystallins ,Cell Hypoxia ,Blot ,Glucose ,Neuroprotective Agents ,chemistry ,Apoptosis ,Chronic Disease ,Neuroinflammatory Diseases ,Lactates ,business ,Microtubule-Associated Proteins - Abstract
Chronic cerebral ischemia (CCI) refers to long-term hypoperfusion of cerebral blood flow with the main clinical manifestations of progressive cognitive impairment. The pathological mechanism of CCI is complex, and there is a lack of effective treatments. Salvianolic acid A (SalA) is a neuroprotective extract of Salvia miltiorrhiza with the effects of anti-inflammation and anti-apoptosis. In this study, the effect of SalA on cognitive function and Drd2/Cryab/NF-κB signaling pathway in rats with CCI was investigated. Morris water maze and open field test were used to observe the effects of SalA on the cognitive function of CCI rats. The pathological changes in the brain were observed by HE, Nissl, and LFB staining. TUNEL staining, enzyme-linked immunosorbent assay, and western blot analysis were used to detect the inflammatory and apoptosis in the cortex and hippocampus. The expression of Drd2/Cryab/NF-κB pathway-related molecules and Drd2 localization were detected by western blotting and dual immunofluorescence, respectively. SH-SY5Y cells were exposed to chronic hypoglycemic and hypoxic injury in vitro, and Drd2 inhibitor haloperidol was used to verify the involved pathway. The results showed that SalA could improve the cognitive function of CCI rats, reduce pathological damage of cortex and hippocampus, inhibit neuroinflammation and apoptosis, and suppress the activation of NF-κB by regulating Drd2/Cryab pathway. And SalA inhibited NF-κB activation and nuclear translocation in SH-SY5Y cells by upregulating Drd2/Cryab pathway, which was reversed by haloperidol interference. In conclusion, SalA could relieve CCI-induced cognitive impairment in rats, at least partly through the Drd2/Cryab/NF-κB pathway.
- Published
- 2022
39. Activation of Nrf2 signaling by salvianolic acid C attenuates NF‑κB mediated inflammatory response both in vivo and in vitro
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Qimeng Zhou, Xiaoyue Zhao, Haiguang Yang, Haigang Wang, Jinhua Wang, Wen Zhang, Junke Song, Li Li, and Guanhua Du
- Subjects
Lipopolysaccharides ,0301 basic medicine ,NF-E2-Related Factor 2 ,Immunology ,Anti-Inflammatory Agents ,AMP-Activated Protein Kinases ,Alkenes ,Pharmacology ,Cell Line ,Proinflammatory cytokine ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,In vivo ,medicine ,Animals ,Immunology and Allergy ,MTT assay ,Viability assay ,Neuroinflammation ,Microglia ,NF-kappa B ,Brain ,Polyphenols ,AMPK ,NF-κB ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Cytokines ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Neurodegenerative diseases are closely related to neuroinflammation. Drugs targeting inflammation have been proved to be effective in many animal models. Salvianolic acid C (SalC) is a compound isolated from Salvia miltiorrhiza Bunge, a plant with reported effects of inhibiting inflammation. However, the anti-inflammation effects and biological mechanisms of SalC on LPS-stimulated neuroinflammation remain unknown. The aim of this paper was to study its protective effects and its anti-inflammation mechanisms. LPS was used both in vivo and in vitro to induce neuroinflammation in SD rats and microglia cells. MTT assay was carried out to detect cell viability. The levels of TNF‑α, IL‑1β, IL‑6, IL‑10 and PGE 2 were detected by ELISA method. The expressions of p‑AMPK, p‑NF‑κB p65, p‑IκBα, Nrf2, HO‑1 and NQO1 proteins were examined by Western blot analysis. The nuclear translocation of NF‑κB p65 was studied by immunofluorescence assay. The specific Nrf2 siRNA was used to clarify the interaction between Nrf2 and NF‑κB p65. The AMPK inhibitor Compound C was used study the upstream protein of Nrf2. Results showed that LPS induced the overexpression of inflammatory cytokines and mediated the phosphorylation and nuclear translocation of NF‑κB p65 in rat brains and microglia cells. SalC reversed the inflammatory response induced by LPS and inhibited the NF‑κB activation. SalC also upregulated the expression of p‑AMPK, Nrf2, HO‑1 and NQO1. But the anti-inflammation and NF‑κB inhibition effects of SalC were attenuated by transfection with specific Nrf2 siRNA or interference with the potent AMPK inhibitor Compound C. In conclusion, SalC inhibited LPS-induced inflammatory response and NF‑κB activation through the activation of AMPK/Nrf2 signaling both in vivo and in vitro.
- Published
- 2018
40. Total flavonoids from Anchusa italica Retz. Improve cardiac function and attenuate cardiac remodeling post myocardial infarction in mice
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Li Zhang, Rong-rong Wang, Lianhua Fang, Yan Zhao, Shou-Bao Wang, Junke Song, Li Gao, Yang Lu, and Guanhua Du
- Subjects
Cardiac function curve ,Male ,Cardiac fibrosis ,H&E stain ,Anti-Inflammatory Agents ,Myocardial Infarction ,Apoptosis ,Pharmacology ,Ventricular Function, Left ,Masson's trichrome stain ,03 medical and health sciences ,0302 clinical medicine ,Drug Discovery ,medicine ,Animals ,Myocardial infarction ,Protein kinase B ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,Cardioprotection ,Flavonoids ,0303 health sciences ,Ventricular Remodeling ,business.industry ,Plant Extracts ,Myocardium ,TOR Serine-Threonine Kinases ,Cardiovascular Agents ,medicine.disease ,Boraginaceae ,Fibrosis ,Mice, Inbred C57BL ,Disease Models, Animal ,030220 oncology & carcinogenesis ,Inflammation Mediators ,Phosphatidylinositol 3-Kinase ,business ,Apoptosis Regulatory Proteins ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Ethnopharmacological relevance The plant Anchusa italica Retz. (Anchusa azurea Mill.) has been traditionally used in Uygur medicine for the treatment of cardiovascular and cerebrovascular diseases in China. Our previous study showed that total flavonoids from Anchusa italica Retz. (TFAI) exhibited potent cardioprotection in acute ischemia/reperfusion injured rats. Aim of the study This study was undertaken to investigate the effects of TFAI on chronic myocardial infarction (MI) in mice and the underlying mechanism. Materials and methods Total flavonoids were extracted from the whole herb of Anchusa italica Retz. and were characterized using HPLC-MS analysis. The left anterior descending branch of the coronary artery was ligated to simulate MI injury in mice. After surgery, mice were orally fed with TFAI at the doses of 10, 30 and 50 mg/kg body weight/day for a total of four weeks. Cardiac function and infarct size were measured, and inflammatory mediators were detected. Hematoxylin and eosin (H&E) staining and Masson's trichrome staining were performed on heart sections. The apoptotic factors, such as Bax, Bcl-2 and cleaved caspase 3, as well as the key proteins in the PI3K/Akt/mTOR signaling pathway were examined by Western blot. Results The content of total flavonoids in TFAI was 56.2%. Four weeks following the MI surgery, TFAI enhanced the survival rate in post-MI mice. TFAI treatment at the doses of 30 and 50 mg/kg remarkably reduced infarct size and improved cardiac function as indicated by elevated EF and FS. Assay of the inflammatory factors showed that sera levels of TNF-α, IL-1β and IL-6 were markedly decreased by TFAI treatment compared to the MI group. H&E staining and Masson's trichrome staining demonstrated that TFAI suppressed myocyte hypertrophy and cardiac fibrosis as indicated by the decreased cross-section area and collagen volume. Western blot analysis showed that cleaved caspase 3 and Bax/Bcl-2 were significantly downregulated following TFAI treatment. Furthermore, TFAI treatment significantly suppressed the activation of the PI3K/Akt/mTOR signaling pathway. Conclusions Our data suggest that TFAI exerts a potent protective effect against chronic MI injury, and its beneficial effects on cardiac function and cardiac remodeling might be attributable, at least in part, to anti-inflammation and inhibition of the PI3K/Akt/mTOR signaling pathway.
- Published
- 2019
41. Antihyperuricemic effect of mangiferin aglycon derivative J99745 by inhibiting xanthine oxidase activity and urate transporter 1 expression in mice
- Author
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Ying Zhao, Shengqian Yang, Shou-Bao Wang, Yi-huang Lin, Song Wu, Jinlong Tian, Guanhua Du, Zhi-Zhen Qin, Tao Xie, and Junke Song
- Subjects
0301 basic medicine ,Organic anion transporter 1 ,Short Communication ,Antihyperuricemic effect ,Allopurinol ,Pharmacology ,Excretion ,03 medical and health sciences ,chemistry.chemical_compound ,Benzbromarone ,0302 clinical medicine ,medicine ,Hyperuricemia ,Xanthine oxidase ,Urate transporter 1 ,General Pharmacology, Toxicology and Pharmaceutics ,biology ,lcsh:RM1-950 ,Mangiferin aglycon ,Derivative ,Xanthine ,medicine.disease ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,Biochemistry ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Uric acid ,medicine.drug - Abstract
A mangiferin aglycon derivative J99745 has been identified as a potent xanthine oxidase (XOD) inhibitor by previous in vitro study. This study aimed to evaluate the hypouricemic effects of J99745 in experimental hyperuricemia mice, and explore the underlying mechanisms. Mice were orally administered 600 mg/kg xanthine once daily for 7 days and intraperitoneally injected 250 mg/kg oxonic acid on the 7th day to induce hyperuricemia. Meanwhile, J99745 (3, 10, and 30 mg/kg), allopurinol (20 mg/kg) or benzbromarone (20 mg/kg) were orally administered to mice for 7 days. On the 7th day, uric acid and creatinine in serum and urine, blood urea nitrogen (BUN), malondialdehyde (MDA) content and XOD activities in serum and liver were determined. Morphological changes in kidney were observed using hematoxylin and eosin (H&E) staining. Hepatic XOD, renal urate transporter 1 (URAT1), glucose transporter type 9 (GLUT9), organic anion transporter 1 (OAT1) and ATP-binding cassette transporter G2 (ABCG2) were detected by Western blot and real time polymerase chain reaction (PCR). The results showed that J99745 at doses of 10 and 30 mg/kg significantly reduced serum urate, and enhanced fractional excretion of uric acid (FEUA). H&E staining confirmed that J99745 provided greater nephroprotective effects than allopurinol and benzbromarone. Moreover, serum and hepatic XOD activities and renal URAT1 expression declined in J99745-treated hyperuricemia mice. In consistence with the ability to inhibit XOD, J99745 lowered serum MDA content in hyperuricemia mice. Our results suggest that J99745 exerts urate-lowering effect by inhibiting XOD activity and URAT1 expression, thus representing a promising candidate as an anti-hyperuricemia agent., Graphical abstract Mangiferin aglycon derivative J99745 possessed potent xanthine oxidase (XOD) inhibition in vitro. In hyperuricemic mice, J99745 reduced serum urate and MDA content, enhanced fractional excretion of uric acid, and attenuated kidney damage. J99745 might represent a promising antihyperuricemia agent by inhibiting XOD activity and urate transporter 1 expression.fx1
- Published
- 2018
42. Baicalein alleviates depression-like behavior in rotenone- induced Parkinson's disease model in mice through activating the BDNF/TrkB/CREB pathway
- Author
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Dewen Kong, Qimeng Zhou, Yu Liang, Xiaoyue Zhao, Guang-yi Wei, Guanhua Du, and Junke Song
- Subjects
Male ,0301 basic medicine ,Parkinson's disease ,Tropomyosin receptor kinase B ,Pharmacology ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Homeostasis ,Medicine ,Cyclic AMP Response Element-Binding Protein ,Neurotransmitter Agents ,Membrane Glycoproteins ,Neuronal Plasticity ,biology ,Depression ,Parkinson Disease ,General Medicine ,Protein-Tyrosine Kinases ,Neuroprotective Agents ,030220 oncology & carcinogenesis ,Flavanones ,Scutellaria baicalensis ,Signal Transduction ,medicine.drug ,RM1-950 ,CREB ,03 medical and health sciences ,Dopamine ,Rotenone ,Animals ,Neuroinflammation ,Flavonoids ,Inflammation ,business.industry ,Brain-Derived Neurotrophic Factor ,Baicalein ,medicine.disease ,biology.organism_classification ,Mice, Inbred C57BL ,Disease Models, Animal ,BDNF ,030104 developmental biology ,chemistry ,Synaptic plasticity ,Parkinson’s disease ,biology.protein ,Therapeutics. Pharmacology ,business - Abstract
Background Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in the world. In addition to motor symptoms, a variety of non-motor symptoms seriously affect the life quality of PD patients. Baicalein, a flavonoid extracted from the herb Scutellaria baicalensis Georgi, exhibits anti-PD activity through alleviation of its motor symptoms. However, its effects on non-motor symptoms were barely reported. This study aimed to investigate the therapeutic effects of baicalein on PD-related depression. Methods After a 2-week injection of rotenone, mice with PD-related depression behavior were selected, divided into three groups, and administrated saline, baicalein, or madopar orally for four weeks. Behavior, neuroinflammation, neurotransmitters, and synaptic plasticity were evaluated. Results Our results showed that 4-week baicalein treatment significantly alleviated the depression-like behavior in the rotenone-induced mice model. Repeated baicalein treatment reduced α-synuclein aggregation, inhibited neuroinflammation, and maintained neurotransmitters homeostasis. Moreover, we found that baicalein treatment could remarkably protect the synaptic plasticity and activate the BDNF/TrkB/CREB pathway in the PD-related depression mice model. As traditional dopamine replacement therapy unleashed few effects on depression-like symptom amelioration and synaptic function protection, baicalein might be a more appropriate choice for PD-related depression. Conclusions The current results suggested that baicalein could act as a treatment for PD-related depression.
- Published
- 2021
43. Salvianolic Acid D Alleviates Cerebral Ischemia-Reperfusion Injury by Suppressing the Cytoplasmic Translocation and Release of HMGB1-Triggered NF
- Author
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Wen, Zhang, Junke, Song, Wan, Li, Dewen, Kong, Yu, Liang, Xiaoyue, Zhao, and Guanhua, Du
- Subjects
Male ,Cytoplasm ,Middle Cerebral Artery ,Cell Survival ,Anti-Inflammatory Agents ,Apoptosis ,Alkenes ,PC12 Cells ,Brain Ischemia ,Rats, Sprague-Dawley ,Animals ,HMGB1 Protein ,Cell Nucleus ,Inflammation ,Neurons ,NF-kappa B ,Brain ,Polyphenols ,Infarction, Middle Cerebral Artery ,Rats ,Protein Transport ,nervous system ,Gene Expression Regulation ,Astrocytes ,Reperfusion Injury ,Microglia ,Signal Transduction ,Research Article - Abstract
Inflammatory response participates in the overall pathophysiological process of stroke. It is a promising strategy to develop antistroke drugs targeting inflammation. This study is aimed at investigating the therapeutic effect and anti-inflammatory mechanism of salvianolic acid D (SalD) against cerebral ischemia/reperfusion (I/R) injury. A rat middle cerebral artery occlusion/reperfusion (MCAO/R) injury model was established, and an oxygen-glucose deprivation/reoxygenation (OGD/R) injury model was established in PC12 cells. Neurological deficit score, cerebral infarction, and edema were studied in vivo. Cell viability was achieved using the MTT method in vitro. The Bax, Bcl-2, cytochrome c, HMGB1, TLR4, TRAF6, NF-κB p65, p-NF-κB p65, and cleaved caspase-3 and -9 were tested via the Western blot method. Cytokines and cytokine mRNA, including TNF-α, IL-1β, and IL-6, were studied via ELISA and PCR methods. The translocation of HMGB1 and NF-κB were studied by immunofluorescence assay. The HMGB1/NeuN, HMGB1/GFAP, and HMGB1/Iba1 double staining was carried out to observe the localization of HMGB1 in different cells. Results showed that SalD alleviated neurological impairment, decreased cerebral infarction, and reduced edema in I/R rats. SalD improved OGD/R-downregulated PC12 cell viability. SalD also promoted Bcl-2 expression and suppressed Bax, cytochrome c, and cleaved caspase-3 and -9 expression. SalD decreased the intensity of TLR4, MyD88, and TRAF6 proteins both in vivo and in vitro, and significantly inhibited the NF-κB nuclear translocation induced by I/R and OGD/R. What's more, SalD inhibited HMGB1 cytoplasmic translocation in neurons, astrocytes, and microglia in both the cortex and hippocampus regions of I/R rats. In conclusion, SalD can alleviate I/R-induced cerebral injury in rats and increase the PC12 cell viability affected by OGD/R. The anti-inflammatory mechanism of SalD might result from the decreased nuclear-to-cytoplasmic translocation of HMGB1 and the inhibition on its downstream TLR4/MyD88/NF-κB signaling.
- Published
- 2019
44. Molecular characterization of Blastocystis sp. in Chinese bamboo rats (Rhizomys sinensis)
- Author
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Junke Song, Xin Yang, Xun Ma, Xuemei Wu, Yuxin Wang, Zhili Li, Guohua Liu, and Guanghui Zhao
- Subjects
China ,Rhizomys sinensis ,Veterinary (miscellaneous) ,Hunan Province ,Blastocystis sp ,Infectious and parasitic diseases ,RC109-216 ,Blastocystis Infections ,Muridae ,Subtyping ,Feces ,Infectious Diseases ,Insect Science ,Blastocystis ,Prevalence ,Animals ,Animal Science and Zoology ,Parasitology ,Phylogeny ,Research Article - Abstract
Blastocystis sp., a parasitic eukaryote, widely colonizes the intestines of humans and a large number of animals, including rodents and lagomorphs. More than 30 million bamboo rats (Rhizomys sinensis) are farmed in China as a source of meat for human consumption. However, there have been no published articles on Blastocystis infection in Chinese bamboo rats prior to the present study. Herein, 480 fresh faecal samples were collected from R. sinensis on six farms located in four cities (Wugang, Chenzhou, Huaihua and Jishou) in Hunan Province, south-central China, and were examined for Blastocystis infection using polymerase chain reaction (PCR) targeting the small subunit ribosomal RNA (SSU rRNA) gene. The total prevalence of Blastocystis in R. sinensis was 4.58% (22/480), and significant differences in prevalence were detected among four age groups (6 months, 6-12 months, 12-24 months and24 months), with the highest prevalence (7.81%) in rats aged 6-12 months but with no positive samples in rats over 24 months. All farms, except for one in Jishou, were positive for Blastocystis infection, with the prevalence ranging from 1.80% to 7.27%. Sequence and phylogenetic analyses revealed two potentially zoonotic subtypes (namely ST4 and ST5) in these rodents, with ST4 predominant in all except one farm in Huaihua. Seven and five sequence types were identified within ST4 and ST5, respectively. This is the first report of Blastocystis infection in Chinese bamboo rats and the findings suggest the potential of R. sinensis to transmit Blastocystis to humans.Caractérisation moléculaire de Blastocystis sp. chez le rat des bambous chinois (Rhizomys sinensis).Blastocystis sp., un parasite eucaryote, colonise largement les intestins de l’homme et d’un grand nombre d’animaux dont les rongeurs et les lagomorphes. Plus de 30 millions de rats des bambou (Rhizomys sinensis) sont élevés en Chine comme source de viande pour la consommation humaine. Cependant, il n’y a eu aucun article publié sur l’infection à Blastocystis chez les rats des bambou chinois avant la présente étude. Ici, 480 échantillons de matières fécales fraîches ont été prélevés sur R. sinensis dans six fermes situées dans quatre villes (Wugang, Chenzhou, Huaihua et Jishou) de la province du Hunan, dans le centre-sud de la Chine, et ont été examinés pour une infection à Blastocystis en utilisant la réaction en chaîne par polymérase (PCR) ciblant le gène de l’ARN ribosomique de la petite sous-unité (ARNr SSU). La prévalence totale de Blastocystis chez R. sinensis était de 4,58 % (22/480), et des différences significatives de prévalence ont été détectées parmi quatre groupes d’âge (6 mois, 6–12 mois, 12–24 mois et24 mois), avec la prévalence la plus élevée (7,81 %) chez les rats âgés de 6 à 12 mois mais sans échantillon positif chez les rats de plus de 24 mois. Toutes les fermes, à l’exception d’une à Jishou, étaient positives pour l’infection à Blastocystis, avec une prévalence allant de 1,80 % à 7,27 %. Les analyses de séquences et phylogénétiques ont révélé deux sous-types potentiellement zoonotiques (à savoir ST4 et ST5) chez ces rongeurs, ST4 prédominant dans toutes les exploitations sauf une à Huaihua. Sept et cinq types de séquences ont été identifiés parmi ST4 et ST5, respectivement. Il s’agit du premier rapport d’infection à Blastocystis chez des rats des bambou chinois et les résultats suggèrent le potentiel de R. sinensis à transmettre Blastocystis à l’homme.
- Published
- 2021
45. The strategies and techniques of drug discovery from natural products
- Author
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Biyu Hou, Junke Song, Li Zhang, Yang Lu, Tianyi Yuan, Linglei Kong, Wan Li, Guanhua Du, and Wen Zhang
- Subjects
0301 basic medicine ,Pharmacology ,Biological Products ,Natural product ,Bacteria ,Plant Extracts ,Tissue Extracts ,Drug discovery ,Natural (archaeology) ,High-Throughput Screening Assays ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,chemistry ,Artificial Intelligence ,030220 oncology & carcinogenesis ,Drug Discovery ,Animals ,Humans ,Pharmacology (medical) ,Business ,Biochemical engineering - Abstract
Natural products have been the main sources of new drugs. The different strategies have been developed to find the new drugs based on natural products. The traditional and ethic medicines have provided information on the therapeutic effects and resulted in some notable drug discovery of natural products. The special activities of the medicine plants such as the side effects have inspired scientists to develop the novel small molecular. The microorganisms and the endogenous active substances from human or animal also become the important approaches to the drug discovery. The tremendous progress in technology led to the new strategies in drug discovery from natural products. The bioinformation and artificial intelligence have facilitated the research and development of natural products. We will provide a scene of strategies and technologies for drug discovery from natural products in this review.
- Published
- 2020
46. Effect of recombinant plasminogen activator timing on thrombolysis in a novel rat embolic stroke model
- Author
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Yi-huang Lin, Ma Yinzhong, Guanhua Du, Junke Song, Huifang Zhang, Li Li, and Zi-Ran Niu
- Subjects
Male ,medicine.medical_treatment ,Reteplase ,030204 cardiovascular system & hematology ,Tissue plasminogen activator ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Fibrinolytic Agents ,Thromboembolism ,medicine ,Animals ,Myocardial infarction ,Cerebral Hemorrhage ,Pharmacology ,Cerebral infarction ,business.industry ,Thrombolysis ,medicine.disease ,Thrombosis ,Recombinant Proteins ,Stroke ,Disease Models, Animal ,Carotid Arteries ,Cerebral blood flow ,Tissue Plasminogen Activator ,Anesthesia ,business ,030217 neurology & neurosurgery ,Fibrinolytic agent ,medicine.drug - Abstract
The treatment of acute ischemic stroke (AIS) using thrombolysis with recombinant tissue-plasminogen activator (rtPA, alteplase) is limited by its narrow time window and the risk of hemorrhage. Recombinant plasminogen activator (rPA, reteplase) has been used clinically on coronary artery thrombosis and acute myocardial infarction. It is necessary to induce strokes experimentally as a means of validating the rPA timing on patients with AIS. However, current embolic models cannot mimic clinical situations well due to the embolus's composition of dried blood clots or artificial materials. In this paper, we used two novel rat thromboembolic models to determine the dosage-effect relationship and therapeutic time window of r-PA. Male rats were administered rPA or rtPA intravenously at 2-12h postischemia. Cerebral blood flow, behavioral outcomes and infarct volume within the same animal group were determined. Our results demonstrated that rPA (0.2 and 0.4mg/kg) or rtPA (0.2mg/kg) restored focal perfusion, reduced cerebral infarction, and improved behavioral outcomes at 2-4h postischemia. rPA but not rtPA significantly restored focal perfusion at 6h postischemia. However, delayed rPA-treatment neither decreased infarct volume nor improved the neurological disorder. Cerebral hemorrhage occurred at 6h postischemia detected by Evan's blue leakage and tissue hemoglobin content. Collectively, Thrombolysis with rPA may be beneficial in revascularization at an acceptable dosage of 0.2-0.4mg/kg within 6h after the cerebral infarct onset.
- Published
- 2016
47. Pharmacokinetic study of gallocatechin-7-gallate from Pithecellobium clypearia Benth. in rats
- Author
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Xiaocong Pang, Chao Li, Ai-Lin Liu, Junke Song, Wenwen Lian, Zhe Wang, Guanhua Du, Xiaowei Song, and Ying Zhao
- Subjects
Pharmacology ,LC–MS ,030226 pharmacology & pharmacy ,01 natural sciences ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Data analysis system ,Liquid chromatography–mass spectrometry ,Gallocatechin ,Distribution (pharmacology) ,Medicine ,Pithecellobium clypearia ,General Pharmacology, Toxicology and Pharmaceutics ,Non-compartment model ,010405 organic chemistry ,business.industry ,lcsh:RM1-950 ,Gallate ,Gallocatechin-7-gallate ,0104 chemical sciences ,lcsh:Therapeutics. Pharmacology ,Peak plasma ,Dose proportionality ,Original Article ,business - Abstract
The pharmacokinetic profile of gallocatechin-7-gallate (J10688) was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD) rats received 1, 3, and 10 mg/kg (i.v.) of J10688 and plasma drug concentrations were determined by a high performance liquid chromatography-mass spectrometry (LC–MS) method. The pharmacokinetic software Data Analysis System (Version 3.0) was used to calculate the pharmacokinetic parameters. For different i.v. doses of J10688, the mean peak plasma concentration (C0) values ranged from 11.26 to 50.82 mg/L, and mean area under the concentration-time curve (AUC0–t) values ranged from 1.75 to 11.80 (mg·h/L). J10688 lacked dose-dependent pharmacokinetic properties within doses between 1 and 10 mg/kg, based on the power model. The method developed in this study was sensitive, precise, and stable. The pharmacokinetic properties of J10688 in SD rats were shown to have rapid distribution and clearance values. These pharmacokinetic results may contribute to an improved understanding of the pharmacological actions of J10688., Graphical abstract A simple, selective, and sensitive LC–MS method was developed and validated. Pharmacokinetic study of gallocatechin-7-gallate (J10688) in rats was carried out. The pharmacokinetic properties of J10688 in SD rats were characterized as quick distribution and clearance. fx1
- Published
- 2016
48. A novel embolic middle cerebral artery occlusion model induced by thrombus formed in common carotid artery in rat
- Author
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Xiangshan Zhou, Li Li, Xie Fusheng, Guanhua Du, Haifeng Liu, Zi-Ran Niu, Ma Yinzhong, and Junke Song
- Subjects
Brain Infarction ,Carotid Artery Diseases ,Male ,medicine.medical_specialty ,Time Factors ,External carotid artery ,Rats, Sprague-Dawley ,Fibrinolytic Agents ,medicine.artery ,Internal medicine ,Forelimb ,medicine ,Animals ,cardiovascular diseases ,Common carotid artery ,Thrombus ,Postural Balance ,Stroke ,Analysis of Variance ,business.industry ,Infarction, Middle Cerebral Artery ,medicine.disease ,Rats ,Surgery ,Disease Models, Animal ,medicine.anatomical_structure ,Neurology ,Cerebral blood flow ,Rotarod Performance Test ,Tissue Plasminogen Activator ,Middle cerebral artery ,cardiovascular system ,Cardiology ,Neurology (clinical) ,Nervous System Diseases ,Internal carotid artery ,business ,Artery - Abstract
Stroke is a major cause of death and disability worldwide. However, treatment options to date are very limited. To meet the need for validating the novel therapeutic approaches and understanding the physiopathology of the ischemic brain injury, experimental stroke models were critical for preclinical research. However, commonly used embolic stroke models are reluctant to mimic the clinical situation and not suitable for thrombolytic timing studies. In this paper, we established a standard method for producing a rat embolic stroke model with autologous thrombus formed within the common carotid artery (CCA) by constant galvanic stimulation. Then the thrombus was shattered and channeled into the origin of the MCA and small (lacunar) artery. To identify the success of MCA occlusion, regional cerebral blood flow was monitored, neurological deficits and infarct volumes were measured at 2, 4 and 6h postischemia. This model developed a predictable infarct volume (38.37 ± 2.88%) and gradually reduced blood flow (20% of preischemic baselines) within the middle cerebral artery (MCA) territory. The thrombus occluded in the MCA was able to be lysed by a tissue-type plasminogen activator (t-PA) within 4h postischemia. The techniques presented in this paper would help investigators to overcome technical problems for stroke research.
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- 2015
49. The comprehensive study on the therapeutic effects of baicalein for the treatment of COVID-19 in vivo and in vitro
- Author
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Junke Song, Li Zhang, Yanfeng Xu, Dezhi Yang, Shiying Yang, Wen Zhang, Jinhua Wang, Shuo Tian, Shengqian Yang, Tianyi Yuan, Ailin Liu, Qi Lv, Fengdi Li, Hongqi Liu, Biyu Hou, Xiaozhong Peng, Yang Lu, and Guanhua Du
- Subjects
0301 basic medicine ,Male ,EEP, end-expiratory pause ,DENV, dengue virus ,SI, selection index ,Pharmacology ,ZIKV, Zika virus ,Biochemistry ,Antioxidants ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Mice ,Random Allocation ,0302 clinical medicine ,Oral administration ,BALF, bronchoalveolar lavage fluid ,Chlorocebus aethiops ,Respiratory function ,MOI, multiplicity of infection ,Mice, Inbred BALB C ,biology ,HIV, human immunodeficiency virus ,H & E, Hematoxylin and eosin ,Treatment Outcome ,CPE, cytopathic effect ,030220 oncology & carcinogenesis ,COVID-19, Coronavirus Disease 2019 ,Flavanones ,Scutellaria baicalensis ,Female ,ANOVA, Analysis of variance ,Inflammation Mediators ,LLOQ, lower limit of quantitation ,Acute Lung Injury ,JEV, Japanese encephalitis virus ,Mice, Transgenic ,Lung injury ,Cavg, average steady-state plasma concentration ,SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 ,Article ,03 medical and health sciences ,EC50, half-maximal effective concentrations ,In vivo ,medicine ,Animals ,Cell damage ,Vero Cells ,ComputingMethodologies_COMPUTERGRAPHICS ,Dose-Response Relationship, Drug ,SARS-CoV-2 ,COVID-19 ,biology.organism_classification ,medicine.disease ,Baicalein ,In vitro ,Penh, enhanced pause ,Rats ,COVID-19 Drug Treatment ,CC50, half-cytotoxic concentration ,Mpro, main protease ,030104 developmental biology ,chemistry ,PEF, peak expiratory flow ,Cmax, peak plasma concentration ,hACE2, human angiotensin-converting enzyme 2 - Abstract
Graphical abstract, Baicalein is the main active compound of Scutellaria baicalensis Georgi, a medicinal herb with multiple pharmacological activities, including the broad anti-virus effects. In this paper, the preclinical study of baicalein on the treatment of COVID-19 was performed. Results showed that baicalein inhibited cell damage induced by SARS-CoV-2 and improved the morphology of Vero E6 cells at a concentration of 0.1 μM and above. The effective concentration could be reached after oral administration of 200 mg/kg crystal form β of baicalein in rats. Furthermore, baicalein significantly inhibited the body weight loss, the replication of the virus, and relieved the lesions of lung tissue in hACE2 transgenic mice infected with SARS-CoV-2. In LPS-induced acute lung injury of mice, baicalein improved the respiratory function, inhibited inflammatory cell infiltration in the lung, and decreased the levels of IL-1β and TNF-α in serum. In conclusion, oral administration of crystal form β of baicalein could reach its effective concentration against SARS-CoV-2. Baicalein could inhibit SARS-CoV-2-induced injury both in vitro and in vivo. Therefore, baicalein might be a promising therapeutic drug for the treatment of COVID-19.
- Published
- 2020
50. Control over Polymorph Formation of Polydatin in Binary Solvent System and Structural Characterization
- Author
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Yang Lu, Ningbo Gong, Shiying Yang, Xue Wang, Ying Wang, Junke Song, and Guanhua Du
- Subjects
Diffraction ,Infrared ,Clinical Biochemistry ,Pharmaceutical Science ,Binary number ,Crystal structure ,Crystallography, X-Ray ,01 natural sciences ,Analytical Chemistry ,symbols.namesake ,Glucosides ,X-Ray Diffraction ,Spectroscopy, Fourier Transform Infrared ,Stilbenes ,Drug Discovery ,Spectroscopy ,Calorimetry, Differential Scanning ,010405 organic chemistry ,Chemistry ,010401 analytical chemistry ,0104 chemical sciences ,Amorphous solid ,Fourier transform ,Polymorphism (materials science) ,Chemical engineering ,Solvents ,symbols ,Crystallization ,Single crystal - Abstract
Polydatin is a natural product used for anti-oxidant, anti-inflammatory and anti-tumor purposes, and often added in medicine, nutraceutical, cosmetics, and dietary supplement. Polymorphism is a key feature of solid-state pharmaceutical products. Polymorphic modifications may exhibit different physical and chemical properties. Here we report two different polymorphs, and the amorphous form of Polydatin. Polymorphs were prepared in binary solvent system. The crystal structures of the two forms were revealed for the first time. The structure and 3D packing were determined with single crystal X-ray diffraction analysis. The batch consistency and stability were identified with Powder X-ray diffraction analysis. Various functional groups present in the polymorphs were analyzed with fourier transform infrared spectroscopic method. The thermal properties were investigated with DSC and TGA. HPLC-MS was used for the pharmacokinetic study. Results show that form B has the faster absorption, and can be maintained in animal bodies for a longer time than form A.
- Published
- 2020
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