Objective:To assess acute toxicity,the in vitro and in vivo effects of methanol and ethyl acetate extracts(JME and JEE)of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the acti...Objective:To assess acute toxicity,the in vitro and in vivo effects of methanol and ethyl acetate extracts(JME and JEE)of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes.Methods:Acute toxicity of JME and JEE was determined using Lorke’s method.In vitro and in vivo opening of the mitochondrial membrane permeability transition pore(MMPT pore)was spectrophotometrically assayed.Production of malondialdehyde(MDA)as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase(ALP),aspartate and alanine aminotransferase(AST and ALT)and gamma-glutamyl transferase(GGT)was also investigated.Results:JME had an LD_(50) of 3808 mg/kg b.w whereas JEE had an LD_(50) greater than 5000 mg/kg b.w.of rats.After the rats have been fed with both extracts,a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity.From the in vitro and in vivo studies,both extracts prompted intact mitochondria to open their MMPT pores.When compared to the control,lipid peroxide product release and ATPase activity were significantly increased(P<0.05)in vitro and in vivo.The activities of AST,ALT,and GGT were all reduced at 50 mg/kg when treated with JME,but the activity of AST was considerably enhanced when treated with JEE(P<0.05).The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity,profound MMPTpore induction,and enhanced ATPase activity,but an increased MDA production.Conclusion:Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis,however,further studies are needed to better clarify the molecular mechanism involved in these phenomena.展开更多
Objective:To identify the safe and effective natural inhibitors of spike glycoprotein and main protease 3CLpro using potential natural antiviral compounds which are studied under various animal models and viral cell l...Objective:To identify the safe and effective natural inhibitors of spike glycoprotein and main protease 3CLpro using potential natural antiviral compounds which are studied under various animal models and viral cell lines.Methods:First,compounds were retrieved from the Pub Chem database and predicted for their druggability using the Mol Soft web server,and compounds having drug-like property were predicted for major adverse drug reactions like cardiotoxicity,hepatotoxicity,arrhythmia,myocardial infarction,and nephrotoxicity using ADVERpred.Docking of nontoxic antiviral compounds with spike glycoprotein and main protease 3CLpro was performed using Auto Dock vina by PyRx 0.8 version.The stability of compoundprotein interactions was checked by molecular dynamic(MD)simulation using Schrodinger Desmond software.Results:Based on the druggable and nontoxic profile,nine compounds were selected.Among them,Withanone from Withania somnifera showed the highest binding affinity and best fit at active sites 1 of spike glycoprotein(glycosylation site)and main protease 3CLpro via interacting with active site amino acid residues before and after MD simulation at 50 ns.Withanone,which may reduce the glycosylation of SARS-CoV-2 via interacting with Asn343 and inhibit viral replication.Conclusion:The current study reports Withanone as a non-toxic antiviral against SARS-CoV-2 and serve as a potential lead hit for further experimental validation.展开更多
文摘Objective:To assess acute toxicity,the in vitro and in vivo effects of methanol and ethyl acetate extracts(JME and JEE)of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes.Methods:Acute toxicity of JME and JEE was determined using Lorke’s method.In vitro and in vivo opening of the mitochondrial membrane permeability transition pore(MMPT pore)was spectrophotometrically assayed.Production of malondialdehyde(MDA)as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase(ALP),aspartate and alanine aminotransferase(AST and ALT)and gamma-glutamyl transferase(GGT)was also investigated.Results:JME had an LD_(50) of 3808 mg/kg b.w whereas JEE had an LD_(50) greater than 5000 mg/kg b.w.of rats.After the rats have been fed with both extracts,a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity.From the in vitro and in vivo studies,both extracts prompted intact mitochondria to open their MMPT pores.When compared to the control,lipid peroxide product release and ATPase activity were significantly increased(P<0.05)in vitro and in vivo.The activities of AST,ALT,and GGT were all reduced at 50 mg/kg when treated with JME,but the activity of AST was considerably enhanced when treated with JEE(P<0.05).The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity,profound MMPTpore induction,and enhanced ATPase activity,but an increased MDA production.Conclusion:Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis,however,further studies are needed to better clarify the molecular mechanism involved in these phenomena.
文摘Objective:To identify the safe and effective natural inhibitors of spike glycoprotein and main protease 3CLpro using potential natural antiviral compounds which are studied under various animal models and viral cell lines.Methods:First,compounds were retrieved from the Pub Chem database and predicted for their druggability using the Mol Soft web server,and compounds having drug-like property were predicted for major adverse drug reactions like cardiotoxicity,hepatotoxicity,arrhythmia,myocardial infarction,and nephrotoxicity using ADVERpred.Docking of nontoxic antiviral compounds with spike glycoprotein and main protease 3CLpro was performed using Auto Dock vina by PyRx 0.8 version.The stability of compoundprotein interactions was checked by molecular dynamic(MD)simulation using Schrodinger Desmond software.Results:Based on the druggable and nontoxic profile,nine compounds were selected.Among them,Withanone from Withania somnifera showed the highest binding affinity and best fit at active sites 1 of spike glycoprotein(glycosylation site)and main protease 3CLpro via interacting with active site amino acid residues before and after MD simulation at 50 ns.Withanone,which may reduce the glycosylation of SARS-CoV-2 via interacting with Asn343 and inhibit viral replication.Conclusion:The current study reports Withanone as a non-toxic antiviral against SARS-CoV-2 and serve as a potential lead hit for further experimental validation.