Exploring the Mechanism of Resveratrol in Reducing the Soft Tissue Damage of Osteoarthritis Based on Network Pharmacology and Experimental Pharmacology

Abstract

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-κB), 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-α, and MCP-1 in the resveratrol low-dose and high-dose groups were significantly reduced ( P < 0.05); protein levels of TLR-4, MyD88, and NF-κB p65 were significantly reduced ( P < 0.05); caspase-9 and Bax protein levels were significantly reduced ( P < 0.05), and Bcl-2 was significantly increased ( P < 0.05). Conclusion. Resveratrol may inhibit the activation of the TLR4-mediated NF-κB signaling pathway and has a repairing effect on soft tissue damage in OA.

Effect of Dietary Polyphenols on Osteoarthritis—Molecular Mechanisms

“…This nutraceutical has many health-benefiting properties, including its anti-inflammatory, antioxidant, and anticancer properties. By modulating major oxidative stress signaling pathways, resveratrol has become one of the most studied nutraceuticals in managing degenerative diseases such as OA [ 51 , 52 , 54 , 55 , 56 , 57 , 67 ] ( Table 1 ).…”

“…Two recent clinical studies confirmed the involvement of resveratrol in managing knee OA pain and its associated symptoms [ 51 , 67 ]. Supplementation of 500 mg/day resveratrol led to increased aggrecan serum levels and significantly improved pain, although no significant decrease in serum levels of IL-6, IL-1β, and TNF- α was observed [ 56 ]. Furthermore, in an in vitro study conducted on monocytic cell line (THP-1) resveratrol and its natural precursor polydatin inhibited ROS and NO production and IL-1 and IL-1β mRNA expression induced by monosodium urate and calcium pyrophosphate crystals.…”

“…The mechanism of resveratrol in reducing soft tissue damage in a rat OA model was deciphered using network pharmacological analysis; results revealed that resveratrol can inhibit the TLR4-mediated NF-κB signaling pathway and can reverse the damage of soft tissue in OA. This is evident through a significant reduction in the IL-1β, IL-6, IL-17, TNF-α, and MCP-1 serum levels, the decrease in the protein levels of TLR-4 and NF-κB p65, and the reduction in the caspase-9 and Bax protein levels [ 56 ].…”

“…↓ serum levels of IL-1 β, IL-6, IL-17, TNF-α, and MCP-1; ↓ protein levels of TLR-4, and NF-κB p65; ↓ caspase-9 Bax protein levels [ 56 ]…”

Network Pharmacology and Molecular Docking-Based Strategy to Investigate the Multitarget Mechanisms of Shenqi Yizhi Granule on Alzheimer’s Disease

“…GO enrichment analysis was used to explore the distribution of the overall proteins and grasp the correlation between proteins and biological function in a whole [ 28 – 30 ]. In this study, GO enrichment analysis was applied to classify cellular components, biological process, molecular function, and KEGG pathway of the common protein targets between SQYG and AD.…”