Background:Global efforts to discover effective therapeutic agents for combating coronavirus disease 19(COVID-19)have intensified the exploration of natural compounds with potential antiviral properties.In this study,...Background:Global efforts to discover effective therapeutic agents for combating coronavirus disease 19(COVID-19)have intensified the exploration of natural compounds with potential antiviral properties.In this study,we utilized network pharmacology and computational analysis to investigate the antiviral effects of Berberine and Kuwanon Z against severe acute respiratory syndrome coronavirus 2,the viruses responsible for COVID-19.Method:Utilizing comprehensive network pharmacology approaches,we elucidated the complex interactions between these compounds and the host biological system,highlighting their multitarget mechanisms.Network pharmacology identifies COVID-19 targets and compounds through integrated protein‒protein interaction and KEGG pathway analyses.Molecular docking simulation studies were performed to assess the binding affinities and structural interactions of Berberine and Kuwanon Z with key viral proteins,shedding light on their potential inhibitory effects on viral replication and entry.Results:Network-based analyses revealed the modulation of crucial pathways involved in the host antiviral response.Compound-target network analysis revealed complex interactions(122 nodes,121 edges),with significant interactions and an average node degree of 1.37.KEGG analysis revealed pathways such as the COVID-19 pathway,chemokines and Jak-sat in COVID-19.Docking studies revealed that Kuwanon Z had binding energies of-10.5 kcal/mol for JAK2 and-8.1 kcal/mol for the main protease.Conclusion:The findings of this study contribute to the understanding of the pharmacological actions of Berberine and Kuwanon Z in the context of COVID-19,providing a basis for further experimental validation.These natural compounds exhibit promise as potential antiviral agents,offering a foundation for the development of novel therapeutic strategies in the ongoing battle against the global pandemic.展开更多
Objective Berberine(BBR)has emerged as a promising therapeutic agent for nonalcoholic fatty liver disease(NAFLD).This study aims to elucidate the underlying molecular mechanisms.Methods In this study,db/db mice were c...Objective Berberine(BBR)has emerged as a promising therapeutic agent for nonalcoholic fatty liver disease(NAFLD).This study aims to elucidate the underlying molecular mechanisms.Methods In this study,db/db mice were chosen as an animal model for NAFLD.A total of 10 healthy C57BL/6J mice and 30 db/db mice were randomly allocated to one of 4 groups:the normal control(NC)group,the diabetic control(DC)group,the Metformin(MET)therapy group,and the BBR therapy group.The total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-c),high-density lipoprotein cholesterol(HDL-c),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels in the serum were measured.The glutathione peroxidase(GSH-Px),glutathione(GSH),malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),interleukin(IL)-1β,tumor necrosis factor(TNF)-αand monocyte chemotactic protein 1(MCP-1)levels in liver tissue were measured.Hematoxylin and eosin(H&E),acid-Schiff(PAS)and TUNEL stanning was performed for histopathological analysis.Western blotting and immunohistochemistry were conducted to detect the expression levels of key proteins in the AMPK/SIRT1 pathway.Results BBR could improve lipid metabolism,attenuate hepatic steatosis and alleviate liver injury significantly.The excessive oxidative stress,high levels of inflammation and abnormal apoptosis in db/db mice were reversed after BBR intervention.BBR clearly changed the expression of AMP-activated protein kinase(AMPK)/Sirtuin 1(SIRT1),and their downstream proteins.Conclusion BBR could reverse NAFLD-related liver injury,likely by activating the AMPK/SIRT1 signaling pathway to inhibit oxidative stress,inflammation and apoptosis in hepatic tissue.展开更多
Aim To establish a reversed phase liquid chromatographic method forsimultaneous determination of three main medicinal constituents, baicalin, berberine and rhein, inSanhuang tablets. Methods The separation was perform...Aim To establish a reversed phase liquid chromatographic method forsimultaneous determination of three main medicinal constituents, baicalin, berberine and rhein, inSanhuang tablets. Methods The separation was performed on a Kromasil C_(18) column with TEA-adjusted0.02 mol·L^(-1) H_3PO_4 (pH 6.78)-acetonitrile-methanol (40 : 9 : 7) as mobile phase at aflow-rate of 1.0 mL·min^(-1), with detection at 254 ran. Considering interaction between acidic andalkaline compounds, three standard markers were added respectively and the volume of samplesolution was doubled in recovery experiments. Results Three regression equations revealed excellentlinear relationship between the peak areas and concentrations and the correlation coefficients allsurpassed 0.999 8. The average recovery was 96.1% (RSD = 2.1%) baicalin, 98.5% (RSD = 2.4%) forberberine, and 101.5% (RSD =1.3%) for rhein. Conclusion The method developed can be used to controlthe quality of Sanhuang tablets comprehensively.展开更多
Aim To investigate the effect in berberine chloride （BER） on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium （DSS） solution or distil...Aim To investigate the effect in berberine chloride （BER） on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium （DSS） solution or distilled water freely with different doses of BER （15 mg·kg^-1, 45 mg·kg^-1, 150 mg·kg^-1） or sallcylazosulfapyridine （SASP, 520 mg·kg^-1）, and solvent （0. 2 mL/10 mg Wt） once a day for 7 d, respectively. The symptom of ulcerative colitis was evaluated by disease activity index （DAI）. Myeloperoxidase （MPO） and superoxide dismutase （SOD） activities and malondialdehyde （MDA） content were determined by HE staining and immunohistochemistry of expressions of NF-κB p65 and intercellular adhesion molecule 1 （ ICAM-1 ） proteins to observe the damage to colon tissues and possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-κB p65 were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of mice with different doses of BER or SASP significantly decreased DAI, MPO activity and MDA content, improved histological changes of colon tissues, blunted the expressions of NF-κB p65 and ICAM-1 proteins, and enhanced SOD activity. Conclusion Berberine chloride has excellent therapeutic effect on ulcerative colitis caused by DSS in mice. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-κB activation and ICAM-1 expression.展开更多
Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ...Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ/δ protein expression. Methods Type 2 diabetes mellitus rats were induced by an injection of 35 mg.kg^-1 streptozotocin （STZ） and a high-carbohydrate/ high-fat diet for 16 weeks. From week 17 to 32, diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg.kg^-1）, fenofibrate （100 mg.kg^-1） and rosiglitazone （4 mg.kg^-1） by oral administration, respectively. The skeletal muscle structure was observed with hematoxylin-eosin （HE） staining, glycogen and triglyceride contents were measured by spectrophotometry and PPAR α/γ/δ protein expressions were detected by immunohistochemistry. Results Fiber distribution remained normal in skeletal muscles of all the groups, middle-, high-dose berberine partly improved diabetic fibre atrophy, increased glycogen and decreased triglyceride levels in diabetic muscle （P〈 0.01）. Middle-, high-dose berberine and rosiglitazone all significantly reduced PPARy protein level in diabetic skeletal muscle （P 〈 0.01）; middle-, high-dose berberine and fenofibrate strikingly increased both PPARu and PPAR8 expression （P〈 0.01）. Conclusion Berberine modulates PPAR α/γ/δ protein expression in diabetic skeletal muscle which may contribute to ameliorate fibre damage and glucolipid metabolization.展开更多
Effects of berberine (Ber) on platelet aggregation and TXB2 and 6 keto PGF1a plasma levels were studied in rabbits with uncomplete cerebral ischemia. Ber inhibited uncomplete cerebral ischemic rabbit platelet aggreg...Effects of berberine (Ber) on platelet aggregation and TXB2 and 6 keto PGF1a plasma levels were studied in rabbits with uncomplete cerebral ischemia. Ber inhibited uncomplete cerebral ischemic rabbit platelet aggregation triggered by collagen, ADP, and arachidonic acid (AA) with the IC 50 of 0.15, 0.46, and 0.51 mg·ml 1 , respectively. In rabbits, Ber 25, or 50 mg·kg 1 iv 30 min after uncomplete cerebral ischemia, restrained the collagen ADP and AA induced platelet aggregation determined 90 min later. With radioimmunoassay, we measured the thromboxane B2 (TXB 2) and 6 ketoprostaglandin F 1α (6 keto PGF 1α ) contents in rabbit plasma. The results indicated that the TXB 2 level in rabbit 120 min after uncomplete cerebral ischemia (921±539 pg·ml 1 ) was higher than that (230±71 pg·ml 1 ) in normal rabbits ( P < 0.01), but 6 keto PGF 1α level after ischemia (73±23pg·ml 1 ) was lower than that (262±988pg·ml 1 ) in normal rabbit. Ber (5, 25 or 50 mg·kg 1 ) reduced obviously the plasma TXB 2 level in rabbit with uncomplete cerebral ischemia (504±196, 386±174, or 272±183 vs 921±539 pg·ml 1 , respectively, P < 0.01). We conclude that the decrease of TXB 2 content is one of the possible mechanisms of Ber anti cerebral ischemic effect.展开更多
文摘Background:Global efforts to discover effective therapeutic agents for combating coronavirus disease 19(COVID-19)have intensified the exploration of natural compounds with potential antiviral properties.In this study,we utilized network pharmacology and computational analysis to investigate the antiviral effects of Berberine and Kuwanon Z against severe acute respiratory syndrome coronavirus 2,the viruses responsible for COVID-19.Method:Utilizing comprehensive network pharmacology approaches,we elucidated the complex interactions between these compounds and the host biological system,highlighting their multitarget mechanisms.Network pharmacology identifies COVID-19 targets and compounds through integrated protein‒protein interaction and KEGG pathway analyses.Molecular docking simulation studies were performed to assess the binding affinities and structural interactions of Berberine and Kuwanon Z with key viral proteins,shedding light on their potential inhibitory effects on viral replication and entry.Results:Network-based analyses revealed the modulation of crucial pathways involved in the host antiviral response.Compound-target network analysis revealed complex interactions(122 nodes,121 edges),with significant interactions and an average node degree of 1.37.KEGG analysis revealed pathways such as the COVID-19 pathway,chemokines and Jak-sat in COVID-19.Docking studies revealed that Kuwanon Z had binding energies of-10.5 kcal/mol for JAK2 and-8.1 kcal/mol for the main protease.Conclusion:The findings of this study contribute to the understanding of the pharmacological actions of Berberine and Kuwanon Z in the context of COVID-19,providing a basis for further experimental validation.These natural compounds exhibit promise as potential antiviral agents,offering a foundation for the development of novel therapeutic strategies in the ongoing battle against the global pandemic.
基金supported by grants from the National Natural Science Foundation of China(No.81803799)Hubei Province Natural Science Foundation of China(No.2022CFB092).
文摘Objective Berberine(BBR)has emerged as a promising therapeutic agent for nonalcoholic fatty liver disease(NAFLD).This study aims to elucidate the underlying molecular mechanisms.Methods In this study,db/db mice were chosen as an animal model for NAFLD.A total of 10 healthy C57BL/6J mice and 30 db/db mice were randomly allocated to one of 4 groups:the normal control(NC)group,the diabetic control(DC)group,the Metformin(MET)therapy group,and the BBR therapy group.The total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-c),high-density lipoprotein cholesterol(HDL-c),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels in the serum were measured.The glutathione peroxidase(GSH-Px),glutathione(GSH),malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),interleukin(IL)-1β,tumor necrosis factor(TNF)-αand monocyte chemotactic protein 1(MCP-1)levels in liver tissue were measured.Hematoxylin and eosin(H&E),acid-Schiff(PAS)and TUNEL stanning was performed for histopathological analysis.Western blotting and immunohistochemistry were conducted to detect the expression levels of key proteins in the AMPK/SIRT1 pathway.Results BBR could improve lipid metabolism,attenuate hepatic steatosis and alleviate liver injury significantly.The excessive oxidative stress,high levels of inflammation and abnormal apoptosis in db/db mice were reversed after BBR intervention.BBR clearly changed the expression of AMP-activated protein kinase(AMPK)/Sirtuin 1(SIRT1),and their downstream proteins.Conclusion BBR could reverse NAFLD-related liver injury,likely by activating the AMPK/SIRT1 signaling pathway to inhibit oxidative stress,inflammation and apoptosis in hepatic tissue.
基金Innovation Fund of Chinese Academy of Sciences(KGCX2 SW 213 05)
文摘Aim To establish a reversed phase liquid chromatographic method forsimultaneous determination of three main medicinal constituents, baicalin, berberine and rhein, inSanhuang tablets. Methods The separation was performed on a Kromasil C_(18) column with TEA-adjusted0.02 mol·L^(-1) H_3PO_4 (pH 6.78)-acetonitrile-methanol (40 : 9 : 7) as mobile phase at aflow-rate of 1.0 mL·min^(-1), with detection at 254 ran. Considering interaction between acidic andalkaline compounds, three standard markers were added respectively and the volume of samplesolution was doubled in recovery experiments. Results Three regression equations revealed excellentlinear relationship between the peak areas and concentrations and the correlation coefficients allsurpassed 0.999 8. The average recovery was 96.1% (RSD = 2.1%) baicalin, 98.5% (RSD = 2.4%) forberberine, and 101.5% (RSD =1.3%) for rhein. Conclusion The method developed can be used to controlthe quality of Sanhuang tablets comprehensively.
基金AProject of the Health Bureau of Chongqing (No.2004-B-31)
文摘Aim To investigate the effect in berberine chloride （BER） on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium （DSS） solution or distilled water freely with different doses of BER （15 mg·kg^-1, 45 mg·kg^-1, 150 mg·kg^-1） or sallcylazosulfapyridine （SASP, 520 mg·kg^-1）, and solvent （0. 2 mL/10 mg Wt） once a day for 7 d, respectively. The symptom of ulcerative colitis was evaluated by disease activity index （DAI）. Myeloperoxidase （MPO） and superoxide dismutase （SOD） activities and malondialdehyde （MDA） content were determined by HE staining and immunohistochemistry of expressions of NF-κB p65 and intercellular adhesion molecule 1 （ ICAM-1 ） proteins to observe the damage to colon tissues and possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-κB p65 were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of mice with different doses of BER or SASP significantly decreased DAI, MPO activity and MDA content, improved histological changes of colon tissues, blunted the expressions of NF-κB p65 and ICAM-1 proteins, and enhanced SOD activity. Conclusion Berberine chloride has excellent therapeutic effect on ulcerative colitis caused by DSS in mice. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-κB activation and ICAM-1 expression.
文摘Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ/δ protein expression. Methods Type 2 diabetes mellitus rats were induced by an injection of 35 mg.kg^-1 streptozotocin （STZ） and a high-carbohydrate/ high-fat diet for 16 weeks. From week 17 to 32, diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg.kg^-1）, fenofibrate （100 mg.kg^-1） and rosiglitazone （4 mg.kg^-1） by oral administration, respectively. The skeletal muscle structure was observed with hematoxylin-eosin （HE） staining, glycogen and triglyceride contents were measured by spectrophotometry and PPAR α/γ/δ protein expressions were detected by immunohistochemistry. Results Fiber distribution remained normal in skeletal muscles of all the groups, middle-, high-dose berberine partly improved diabetic fibre atrophy, increased glycogen and decreased triglyceride levels in diabetic muscle （P〈 0.01）. Middle-, high-dose berberine and rosiglitazone all significantly reduced PPARy protein level in diabetic skeletal muscle （P 〈 0.01）; middle-, high-dose berberine and fenofibrate strikingly increased both PPARu and PPAR8 expression （P〈 0.01）. Conclusion Berberine modulates PPAR α/γ/δ protein expression in diabetic skeletal muscle which may contribute to ameliorate fibre damage and glucolipid metabolization.
文摘Effects of berberine (Ber) on platelet aggregation and TXB2 and 6 keto PGF1a plasma levels were studied in rabbits with uncomplete cerebral ischemia. Ber inhibited uncomplete cerebral ischemic rabbit platelet aggregation triggered by collagen, ADP, and arachidonic acid (AA) with the IC 50 of 0.15, 0.46, and 0.51 mg·ml 1 , respectively. In rabbits, Ber 25, or 50 mg·kg 1 iv 30 min after uncomplete cerebral ischemia, restrained the collagen ADP and AA induced platelet aggregation determined 90 min later. With radioimmunoassay, we measured the thromboxane B2 (TXB 2) and 6 ketoprostaglandin F 1α (6 keto PGF 1α ) contents in rabbit plasma. The results indicated that the TXB 2 level in rabbit 120 min after uncomplete cerebral ischemia (921±539 pg·ml 1 ) was higher than that (230±71 pg·ml 1 ) in normal rabbits ( P < 0.01), but 6 keto PGF 1α level after ischemia (73±23pg·ml 1 ) was lower than that (262±988pg·ml 1 ) in normal rabbit. Ber (5, 25 or 50 mg·kg 1 ) reduced obviously the plasma TXB 2 level in rabbit with uncomplete cerebral ischemia (504±196, 386±174, or 272±183 vs 921±539 pg·ml 1 , respectively, P < 0.01). We conclude that the decrease of TXB 2 content is one of the possible mechanisms of Ber anti cerebral ischemic effect.
