Sinensetin Reduces Osteoarthritis Pathology in the Tert-Butyl Hydroperoxide-Treated Chondrocytes and the Destabilization of the Medial Meniscus Model Mice via the AMPK/mTOR Signaling Pathway

Abstract

As a common degenerative disease, osteoarthritis (OA) usually causes disability in the elderly and socioeconomic burden. Previous studies have shown that proper autophagy has a protective effect on OA. Sinensetin (Sin) is a methylated flavonoid derived from citrus fruits. Studies have shown that Sin is a good autophagy inducer and has shown excellent therapeutic effects in a variety of diseases; however, its role in the treatment of OA is not fully understood. This study proved the protective effect of Sin on OA through a series of in vivo and in vitro experiments. In vitro experiments have shown that Sin may inhibit chondrocyte apoptosis induced by tert-butyl hydroperoxide (TBHP); at the same time, it might also inhibit the production of MMP13 and promote the production of aggrecan and collagen II. Mechanism studies have shown that Sin promotes chondrocyte autophagy by activating AMPK/mTOR signaling pathway. On the contrary, inhibition of autophagy can partially abolish the protective effect of Sin on TBHP-treated chondrocytes. In vivo experiments show that Sin may protect against DMM-induced OA pathogenesis. These results provide evidence that Sin serves as a potential candidate for the treatment of OA.

Sinensetin attenuates IL-1β-induced cartilage damage and ameliorates osteoarthritis by regulating SERPINA3

“…The rats were randomly divided into 3 groups: sham operation group, OA group (DMM + saline) and SIN group (DMM + SIN, a dose of 20 mg kg −1 was given by intragastric administration every day) for 6 weeks. 20,21…”

Combination of UHPLC‐Q Exactive‐Orbitrap MS and network pharmacology to reveal the mechanism of Eucommia ulmoides leaves in the treatment of osteoarthritis

“…The activation of the PI3K/Akt/mTOR signaling pathway could inhibit the autophagy of articular chondrocytes and promote inflammation response in rats with OA (Xue et al, 2017). Moreover, the AMPK/mTOR signaling pathway plays an important role in chondrocyte autophagy (Zhou et al, 2021).…”

“…Moreover, the AMPK/mTOR signaling pathway plays an important role in chondrocyte autophagy (Zhou et al, 2021).…”

Phytochemicals Mediate Autophagy Against Osteoarthritis by Maintaining Cartilage Homeostasis

“…In vitro experiments by Zhou et al showed that Sinensetin activated the AMPK/mTOR signaling pathway in a time- and dose-dependent mannersignificantly improved the autophagy function of mice chondrocytes and inhibited TBHP-induced apoptosis in mouse chondrocytes. In vivo experiments yielded similar results, and Sinensetin protected against DMM-induced mice ( Zhou et al, 2021b ). These results provide evidence that Sinensetin could be a potential candidate for the treatment of OA.…”