Exploring the chondroprotective effect of Chaenomeles speciosa on Glucose-6-Phosphate Isomerase model mice using an integrated approach of network pharmacology and experimental validation

采用网络药理学和实验验证相结合的方法探索木瓜对葡萄糖-6-磷酸异构酶模型小鼠的软骨保护作用

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作者:Zhihao Duan, Can Jin, Ying Deng, Jinlang Liu, Chengyi Gu, Jie Wang, Xiangquan Cai, Shigang Li, You Zhou

Aim of the study

Exploring anti-inflammatory and chondroprotective effects of CSP on rheumatoid arthritis (RA) and its possible targets of action. Materials and

Conclusion

This study showed that CSP has multi-component, multi-target and multi-pathway characteristics in treating cartilage damage in RA, which can achieve the effect of treating RA by inhibiting the expression of inflammatory factors, reducing neovascularization and alleviating the damage to cartilage caused by the diffusion of synovial vascular opacities, and reducing the degradation of cartilage by MMPs to play a protective role in RA cartilage damage. In conclusion, this study indicates that CSP is a candidate Chinese medicine for further research in treating cartilage damage in RA.

Methods

In this study, we performed an integrated approach of network pharmacology, molecular docking and experimental studies to explore the potential mechanism of action of CSP in the treatment of cartilage damage in RA.

Results

Studies have shown that Quercetin, ent-Epicatechin and Mairin may be the main active compounds of CSP in the treatment of RA, while AKT1, VEGFA, IL-1β, IL-6, MMP9 etc. are considered as core target proteins to which the main active compounds in CSP bind, as further confirmed by molecular docking. In addition, the potential molecular mechanism of CSP for the treatment of cartilage damage in RA predicted by network pharmacology analysis was validated by in vivo experiments. CSP was found to downregulate the expression of AKT1, VEGFA, IL-1β, IL-6, MMP9, ICAM1, VCAM1, MMP3, MMP13 and TNF-α and increase the expression of COL-2 in the joint tissue of Glucose-6-Phosphate Isomerase (G6PI) model mice. Thus CSP contributes to the treatment of rheumatoid arthritis cartilage destruction.

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