Inhibiting TLR4 signaling by linarin for preventing inflammatory response in osteoarthritis

Autor: Zijian Yan, Shuaibo Sun, Haixiao Liu, Xinxian Xu, Weihui Qi, Yanlin Chen, Ping Shang, Xiaoyun Pan, Jingdi Zhan
Rok vydání: 2021
Předmět:
Zdroj: Aging (Albany NY)
ISSN: 1945-4589
DOI: 10.18632/aging.202469
Popis: Osteoarthritis (OA) is one of the most common degenerative diseases, ultimately leading to long-term joint pain and severe articular malformation. Controlling local chronic inflammation is a crucial strategy for delaying OA development. Linarin is a natural flavonoid glycoside that is widely available in Compositae, Chrysanthemum indicum and Dendrocalamus and processes protective effects in several animal models. The purpose of our work was to study the protective effect of Linarin for OA. Cellular experiments data showed that Linarin suppressed lipopolysaccharide (LPS)-caused the overproduction of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in chondrocyte. In addition, LPS-stimulated expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide nitrate (iNOS) was decreased by Linarin pre-treatment. Together, Linarin prevented the catabiosis of extracellular matrix caused by LPS. For mechanism, Linarin inhibited the formation of Toll-like receptor 4 (TLR4) / myeloid differentiation protein-2 (MD-2) dipolymer complex and subsequently intervened NF-κB activation. Our mouse DMM model further clarified the protection of Linarin in vivo. In summary, our results suggested that Linarin may be a potential effective agent for OA.
Databáze: OpenAIRE