1. Deciphering the molecular mechanisms of Simiaowan in the treatment of hyperuricemia: in vivo and in silico approaches.
- Author
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Yong-Chang Zeng, Jun-Hong Wu, Dan-Dan Xu, Kang He, Chang-Qing Liu, Li-Fei Song, Zheng-Zhi Wu, Qian-Qian Jiang, and Shao-Yu Liang
- Subjects
TRANSCRIPTION factors ,ORGANIC acids ,BIOACTIVE compounds ,ORAL drug administration ,CHINESE medicine ,ATP-binding cassette transporters ,URIC acid - Abstract
Background: Simiaowan (SMW), a well-known traditional Chinese medicine, has beenemployed to treat hyperuricemia (HUA) and gout for centuries. However, the bio active components and underlying mechanisms have not been elucidated. The objective of thisstudy was to identify the active components and potential mechanisms of SMW by integrating pharmacological experimentation, serum pharmacochemistry, network pharmacology and molecular docking. Methods: HUA rats modelling by high-fat/high-sugar diet and potassium oxonate/adenine oral administration were usedtoevaluate the pharmacodynamic effects of SMW. UPLC-Q-Exactive-MS/MS was employed to detect the bioactive components present in SMW-containing serum. Network pharmacology and molecular docking were utilized to elucidate the potential targets and underlying mechanisms. Results: SMW effectively ameliorated HUA rats via the inhibitionof uric acid (UA) production, promotion of UA excretion, improvement of lipid and glucose metabolic abnormalities, antioxidant, anti-inflammatory and anti-insulinresistance effects. A total of 73 compounds detected in SMW-containing serum were identified as potential active components, with alkaloids, flavonoids, organic acids, and terpenoids emerging as the primary active ingredients. Totally 203 corresponding targets were obtained as SMW anti-HUA/gout targets, which mainly participated in apoptosis, insulin resistance, TNF, PI3K-Akt, HIF-1, NF-κB, MAPK, IL-17 and TLR signaling pathways. Molecular docking indicated that active compounds (e.g. berberine, phellodendrine, quercetin, formononetin, ferulic acid) had superior binding abilities to the key targets (e.g. solute carrier family 22 member 12 (URAT1), solute carrier family 22 member 6 (OAT1), ATP-binding cassette sub-family G member 2 (ABCG2), solute carrier family 2, facilitatedglucose transporter member 9 (GLUT9), xanthine dehydrogenase/oxidase (XDH), transcription factor p65 (RELA), toll-like receptor 4 (TLR4), prostaglandin G/Hsynthase2(PTGS2), caspase-3 (CASP3), insulin (INS)). Conclusion: SMWexerted regulatoryinfluence over the disease network of HUA and gout through a multiplicity of components, targets, and pathways. Alkaloids, flavonoids, organic acids, and terpenoids weretheprimary active components, exerting anti-HUA/gout effects via antioxidant, anti-inflammatory, anti-insulin resistance, anti-apoptosis, inhibition of UA production, and promotion of UA excretion. This study revealed the active components and molecular mechanisms of SMW, providing insights into the development of natural products derived from SMW. [ABSTRACT FROM AUTHOR]
- Published
- 2025
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