Shenjinhuoxue Mixture Attenuates Inflammation, Pain, and Cartilage Degeneration by Inhibiting TLR-4 and NF-κB Activation in Rats with Osteoarthritis: A Synergistic Combination of Multitarget Active Phytochemicals. (21st October 2021)

• Record Type: Journal Article
• Authors: Ma, Xiaoqin; Hao, Chenxia; Zhang, Zhaokang; Jiang, Huiting; Zhang, Weixia; Huang, Jingjing; Chen, Xiaofei; Yang, Wanhua
• Other Names: Dominguez Perles Raul Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2021(2021)
• Publication Date: 2021-10-21
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2021/4190098
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : Osteoarthritis (OA), a highly prevalent chronic joint disease, involves a complex network of inflammatory mediators that not only triggers pain and cartilage degeneration but also accelerates disease progression. Traditional Chinese medicinal shenjinhuoxue mixture (SHM) shows anti-inflammatory and analgesic effects against OA with remarkable clinical efficacy. This study explored the mechanism underlying anti-OA properties of SHM and evaluated its efficacy and safety via in vivo experiments. Through network pharmacology and published literature, we identified the key active phytochemicals in SHM, including β -sitosterol, oleanolic acid, licochalcone A, quercetin, isorhamnetin, kaempferol, morusin, lupeol, and pinocembrin; the pivotal targets of which are TLR-4 and NF- κ B, eliciting anti-OA activity. These phytochemicals can enter the active pockets of TLR-4 and NF- κ B with docking score ≤ − 3.86 kcal / mol, as shown in molecular docking models. By using surface plasmon resonance assay, licochalcone A and oleanolic acid were found to have good TLR-4-binding affinity. In OA rats, oral SHM at mid and high doses (8.72 g/kg and 26.2 g/kg) over 6 weeks significantly alleviated mechanical and thermal hyperalgesia (P < 0.0001 ). Accordingly, the expression of inflammatory mediators (TLR-4, interleukin (IL-) 1 receptor-associated kinase 1 (IRAK1), NF- κ B-p65, tumor necrosis factor (TNF-) α, IL-6, and IL-1 β ), receptor activator of the NF- κ B ligand (RANKL), and transient receptor potential vanilloid 1 (TRPV1) in the synovial and cartilage tissue of OA rats was significantly decreased (P < 0.05 ). Moreover, pathological observation illustrated amelioration of cartilage degeneration and joint injury. In chronic toxicity experiment of rats, SHM at 60 mg/kg demonstrated the safety. SHM had an anti-inflammatory effect through a synergistic combination of active phytochemicals to attenuate pain and cartilage degeneration by inhibiting TLR-4 and NF- κ B activation. This study provided the experimental foundation for the development of SHM into a more effective dosage form or new drugs for OA treatment.