Objective:To systematically study the key active ingredients of Jiuwei Huaban pill in the treatment of psoriasis and explore its mechanism of action.Methods:The chemical components of Jiuwei Huaban pill were systemati...Objective:To systematically study the key active ingredients of Jiuwei Huaban pill in the treatment of psoriasis and explore its mechanism of action.Methods:The chemical components of Jiuwei Huaban pill were systematically identified by UPLC-QTOF/MSE,and network pharmacology method was used to study the main pharmacodynamic substances of Jiuwei Huaban pill and discuss the mechanism of action.Molecular docking technology was used to verify the binding activity of key components and target proteins.Results:A total of 75 components of Jiuwei Huaban pill were identified,35 of which were key components for psoriasis treatment,including luteolin,baicalin,baicalin,paeoniflorin and geniposide.Enrichment analysis of 30 core target pathways showed that Jiuwei Huaban pill played its role in the treatment of psoriasis from the IL-17 signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,Th17 signaling pathway,and MAPK signaling pathway.The key active components in Jiuwei Huaban pill and targets with the highest DGREE value in the"component target disease"network have strong binding activity.Conclusion:The active ingredients and mechanism of action of Jiuwei Huaban pill in the treatment of psoriasis were preliminarily clarified,which provids reference for quality control.展开更多
One-sixth of the currently known natural products containα,β-unsaturated carbonyl groups.Our previous studies reported a rare C-sulfonate metabolic pathway.Sulfonate groups were linked to theβ-carbon ofα,β-unsatu...One-sixth of the currently known natural products containα,β-unsaturated carbonyl groups.Our previous studies reported a rare C-sulfonate metabolic pathway.Sulfonate groups were linked to theβ-carbon ofα,β-unsaturated carbonyl-based natural compounds through this pathway.However,the mechanism of this type of metabolism is still not fully understood,especially whether it is formed through enzyme-mediated biotransformation or direct sulfite addition.In this work,the enzyme-mediated and non-enzymatic pathways were studied.First,the sulfite content in rat intestine was determined by LC-MS/MS.The results showed that the amount of sulfite in rat intestinal contents was from 41.5 to 383μg·g^(-1),whereas the amount of sulfite in rat feed was lower than the lower limit of quantitation(20μg·g^(-1)).Second,the reaction kinetics of sulfite-andrographolide reactions in phosphate buffer solutions(pH 6-8)was studied.The half-lives of andrographolide ranged from minutes to hours.This was suggested that the C-sulfonate reaction of andrographolide was very fast.Third,the C-sulfonate metabolites of andrographolide were both detected when andrographolide and L-cysteine-S-conjugate andrographolide were incubated with the rat small intestine contents or sulfite,indicating that the sulfite amount in rat intestine contents was high enough to react with andrographolide,which assisted a significant portion of andrographolide metabolism.Finally,the comparison of andrographolide metabolite profiles among liver homogenate(with NADPH),liver S9(with NADPH),small intestine contents homogenate(with no NADPH),and sulfite solution incubations showed that the C-sulfonate metabolites were predominantly generated in the intestinal tract by non-enzymatic pathway.In summary,sulfite can serve as a substrate for C-sulfonate metabolism,and these results identified non-enzymatically nucleophilic addition as the potential mechanism for C-sulfonate metabolism of compounds containingα,β-unsaturated carbonyl moiety.展开更多
基金National Major Science and Technology Project for"Major New Drug Development"(No.2017ZX09301005)。
文摘Objective:To systematically study the key active ingredients of Jiuwei Huaban pill in the treatment of psoriasis and explore its mechanism of action.Methods:The chemical components of Jiuwei Huaban pill were systematically identified by UPLC-QTOF/MSE,and network pharmacology method was used to study the main pharmacodynamic substances of Jiuwei Huaban pill and discuss the mechanism of action.Molecular docking technology was used to verify the binding activity of key components and target proteins.Results:A total of 75 components of Jiuwei Huaban pill were identified,35 of which were key components for psoriasis treatment,including luteolin,baicalin,baicalin,paeoniflorin and geniposide.Enrichment analysis of 30 core target pathways showed that Jiuwei Huaban pill played its role in the treatment of psoriasis from the IL-17 signaling pathway,TNF signaling pathway,PI3K-Akt signaling pathway,Th17 signaling pathway,and MAPK signaling pathway.The key active components in Jiuwei Huaban pill and targets with the highest DGREE value in the"component target disease"network have strong binding activity.Conclusion:The active ingredients and mechanism of action of Jiuwei Huaban pill in the treatment of psoriasis were preliminarily clarified,which provids reference for quality control.
基金supported by the National Natural Science Foundation of China(No.81873079)。
文摘One-sixth of the currently known natural products containα,β-unsaturated carbonyl groups.Our previous studies reported a rare C-sulfonate metabolic pathway.Sulfonate groups were linked to theβ-carbon ofα,β-unsaturated carbonyl-based natural compounds through this pathway.However,the mechanism of this type of metabolism is still not fully understood,especially whether it is formed through enzyme-mediated biotransformation or direct sulfite addition.In this work,the enzyme-mediated and non-enzymatic pathways were studied.First,the sulfite content in rat intestine was determined by LC-MS/MS.The results showed that the amount of sulfite in rat intestinal contents was from 41.5 to 383μg·g^(-1),whereas the amount of sulfite in rat feed was lower than the lower limit of quantitation(20μg·g^(-1)).Second,the reaction kinetics of sulfite-andrographolide reactions in phosphate buffer solutions(pH 6-8)was studied.The half-lives of andrographolide ranged from minutes to hours.This was suggested that the C-sulfonate reaction of andrographolide was very fast.Third,the C-sulfonate metabolites of andrographolide were both detected when andrographolide and L-cysteine-S-conjugate andrographolide were incubated with the rat small intestine contents or sulfite,indicating that the sulfite amount in rat intestine contents was high enough to react with andrographolide,which assisted a significant portion of andrographolide metabolism.Finally,the comparison of andrographolide metabolite profiles among liver homogenate(with NADPH),liver S9(with NADPH),small intestine contents homogenate(with no NADPH),and sulfite solution incubations showed that the C-sulfonate metabolites were predominantly generated in the intestinal tract by non-enzymatic pathway.In summary,sulfite can serve as a substrate for C-sulfonate metabolism,and these results identified non-enzymatically nucleophilic addition as the potential mechanism for C-sulfonate metabolism of compounds containingα,β-unsaturated carbonyl moiety.
