Mechanism of Toddalia asiatica in treatment of osteodestruction in rheumatoid arthritis based on network pharmacology and experimental verification
- VernacularTitle:基于网络药理学及实验验证探讨三百棒治疗类风湿性关节炎骨破坏的作用机制
- Author:
Lu JIANG
1
,
2
;
Zong-Xing ZHANG
;
Wei-Yi LI
;
Dao-Zhong LIU
;
Zhuo-Ma BAO
;
Qin-Yun NIE
;
Lin YUAN
Author Information
- Keywords: rheumatoid arthritis; bone destruction; Toddalia asiatica; network pharmacology; action mecha-nism
- From: Chinese Pharmacological Bulletin 2024;40(10):1979-1990
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effect of Toddalia asiatica(TA)on bone destruction in rheumatoid ar-thritis(RA)and its possible mechanism by network pharmacology and in vitro experiments.Methods The active components and targets of TA against RA bone damage were analyzed by network pharmacology.Mo-lecular docking was performed by using AutoDock and PyMOL software pairs.MC3T3-e1 cells were cultured in vitro,and the effect of Toddalia asiatica alcohol ex-tract(TAAE)on cell viability was detected by CCK-8,and appropriate drug concentration and intervention time were screened.The osteoblast model was induced by osteogenic induction medium,and the osteogenic differentiation was detected by ALP staining,activity detection and alizarin red staining.The expression of pathway-related proteins Wnt3a and β-catenin was de-tected by Western blot,and the pathway inhibitor DKK-1 was used to further verify whether TAAE regulated osteoblast differentiation through the Wnt/β-catenin signaling pathway.Results A total of 158 anti-RA bone destruction targets and 56 core targets were se-lected.The enrichment of KEGG signaling pathway mainly included cancer pathway,phosphatidylinositol 3-kinase/protein kinase B signaling pathway and cAMP signaling pathway.The results of CCK-8 showed that 1 g·L-1 TAAE could significantly improve cell survival rate.The results of ALP staining and ALP activity de-tection showed that TAAE could significantly increase the staining positive rate and ALP activity of cells in-duced by osteogenic induction medium.Western blot showed that TAAE could increase the expression of Wnt3a and β-catenin.The expression of these proteins decreased after DKK-1 inhibitors were used.Conclu-sion TAAE can regulate osteoblast differentiation through Wnt/β-catenin signaling pathway to treat os-teodestruction in rheumatoid arthritis.
