Study on the Pharmacodynamic Substances of Simiao Wan for Treatment of Hyperuricemia and Gout Based on Disease and Syndrome Model
10.19378/j.issn.1003-9783.2024.08.006
- VernacularTitle:基于病症模型的经方四妙丸防治高尿酸血症痛风的药效物质探讨
- Author:
Yongchang ZENG
1
,
2
;
Shaoyu LIANG
;
Junhong WU
;
Dandan XU
;
Changqing LIU
;
Kang HE
;
Yu JIN
;
Zhengzhi WU
Author Information
1. 深圳大学第一附属医院中西结合科,广东 深圳 518035
2. 广州医科大学附属中医医院,广东 广州 510180
- Keywords:
Hyperuricemia and gout;
Simiao Wan;
taxifolin;
serum pharmacochemistry;
pharmacodynamic sbustances basis;
quality control;
human proximal tubular epithelial cells(HK2);
rats
- From:
Traditional Chinese Drug Research & Clinical Pharmacology
2024;35(8):1152-1162
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Methods The pharmacological model of hyperuricemia was established.The chemical components in vivo and in vitro of Simiao Wan were analyzed by UPLC-Q-Exactive-MS.Based on the components absorbed in blood,the"active ingredient-target-pathway"network of Simiao Wan for regulating hyperuricemia and gout was constructed by network pharmacology method.The key ingredients were used for molecular docking with key targets[uricogenase(XDH),uric acid transporter(ABCG2,GLUT9,OAT1,URAT1)and inflammatory targets(PTGS2,TLR2,TLR4)]of hyperuricemia and gout.Finally,experimental verification was conducted according to the results of molecular docking.Our aim is to identify the key pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Results Eighty-nine components of Simiao Wan were identified by UPLC-Q-Exactive-MS analysis,including 74 components absorbed in blood,which were confirmed as candidate ingredients.Network pharmacology was used to constructed"components absorbed in blood-target-pathway"network,and components absorbed in blood were matched with 116 targets of hyperuricemia and 173 targets of gout.It is involved in the regulation of biological processes,such as glucose and lipid metabolism,oxidative stress,inflammatory response,ERK1 and ERK2 cascade,MAPK cascade,PI3K signal transduction.Moreover,Simiao Wan plays a role in regulating the network of hyperuricemia and gout through regulating blood lipids and atherosclerosis,apoptosis,AGE-RAGE,TNF,PI3K-Akt,MAPK,TLRs,JAK-STAT,NF-κB and other signaling pathways.Molecular docking studies showed that berberine,phellodendrine,magnoflorine,jatrorrhizine,palmatine,obacunone,limonin,atractylodin,taxifolin,atractylenolide Ⅲ and β-ecdysterone had good affinity with uric acid synthase,uric acid transporter and inflammatory targets.Western Blot test showed that taxifolin negatively regulates the expression of URAT1.The above-mentioned compounds were the main pharmacodynamic substances of Simiao Wan for the treatment of hyperuricemia and gout.Conclusion This article describes the main pharmacodynamic substances of Simiao Wan in the regulation of hyperuricemia and gout,which can provides a scientific basis for the clinical application,improvement in quality evaluation and standard of Simiao Wan.
