基于网络药理学和实验药理学探究白藜芦醇减轻骨关节炎软组织损伤的机制
Exploring the Mechanism of Resveratrol in Reducing the Soft Tissue Damage of Osteoarthritis Based on Network Pharmacology and Experimental Pharmacology.
作者信息
Long Zhiyong, Xiang Wang, Li Jun, Yang Tiejun, Yu Ganpeng
机构信息
Shantou University Medical College, Shantou University, Shantou, Guangdong, China.
The Affiliated Hospital of Guilin Medical University, Guilin, Guangxi Province, China.
出版信息
Evid Based Complement Alternat Med. 2021 Oct 4;2021:9931957. doi: 10.1155/2021/9931957. eCollection 2021.
AIM
To explore the mechanism of resveratrol in reducing the soft tissue damage of osteoarthritis (OA) based on network pharmacology.
METHODS
Pharmmapper was used to predict the target of resveratrol, OMIM and Genecards were used to collect OA-related disease genes, and David ver 6.8 was used for enrichment analysis. Then, animal experiments were carried out for verification. The rat OA model was established and the rats were randomly divided into 4 groups: model group, resveratrol low-dose group, resveratrol high-dose group, and blank control group for follow-up experiments. Hematoxylin-eosin (HE) staining was used to detect the degree of pathological damage of rat bones and joints. Enzyme-linked immunosorbent assay (ELISA) was used for the content of inflammatory factors. Western blot was used to detect the expression of Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (MyD88), nuclear factor kappa B protein (NF-B), cysteine protease-9 (CASP-9), Bcl-2 protein, and Bax protein.
RESULTS
Through network pharmacological analysis, this study found that resveratrol may regulate the TLR4 signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, Osteoclast differentiation, Rheumatoid arthritis, etc. Animal experiments showed that compared with the model group, the pathological damage of bone and joint in the resveratrol low-dose and high-dose groups was significantly improved. Compared with the model group, the serum levels of IL-1beta, IL-6, IL-17, TNF-, and MCP-1 in the resveratrol low-dose and high-dose groups were significantly reduced ( < 0.05); protein levels of TLR-4, MyD88, and NF-B p65 were significantly reduced ( < 0.05); caspase-9 and Bax protein levels were significantly reduced ( < 0.05), and Bcl-2 was significantly increased ( < 0.05).
CONCLUSION
Resveratrol may inhibit the activation of the TLR4-mediated NF-B signaling pathway and has a repairing effect on soft tissue damage in OA.
目的
基于网络药理学探讨白藜芦醇减轻骨关节炎（OA）软组织损伤的机制。
方法
利用Pharmmapper预测白藜芦醇的靶点，通过OMIM和Genecards收集OA相关疾病基因，并使用David ver 6.8进行富集分析。随后，进行动物实验验证。建立大鼠OA模型，将大鼠随机分为4组：模型组、白藜芦醇低剂量组、白藜芦醇高剂量组和空白对照组，进行后续实验。采用苏木精-伊红（HE）染色检测大鼠骨关节的病理损伤程度。使用酶联免疫吸附测定（ELISA）检测炎症因子含量。采用蛋白质免疫印迹法检测Toll样受体4（TLR4）、髓样分化因子88（MyD88）、核因子κB蛋白（NF-κB）、半胱天冬酶-9（CASP-9）、Bcl-2蛋白和Bax蛋白的表达。
结果
通过网络药理学分析，本研究发现白藜芦醇可能调控TLR4信号通路、PI3K-Akt信号通路、FoxO信号通路、破骨细胞分化、类风湿关节炎等。动物实验表明，与模型组相比，白藜芦醇低剂量组和高剂量组的骨关节病理损伤明显改善。与模型组相比，白藜芦醇低剂量组和高剂量组血清中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-17（IL-17）、肿瘤坏死因子-α（TNF-α）和单核细胞趋化蛋白-1（MCP-1）水平显著降低（P<0.05）；TLR-4、MyD88和NF-κB p65蛋白水平显著降低（P<0.05）；半胱天冬酶-9和Bax蛋白水平显著降低（P<0.05），而Bcl-2显著升高（P<0.05）。
结论
白藜芦醇可能抑制TLR4介导的NF-κB信号通路的激活，对OA软组织损伤具有修复作用。
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