Study on Catalpol inhibiting PI3K/AKT/NF-?B Signaling Pathway in the Treatment of OA through Anti-senescence of Chondrocytes

Abstract

The study aimed to explore the therapeutic effect of catalpol on articular chondrocyte senescence and osteoarthritis through cell experiments, and to explore the role of NF-κB and its upstream and downstream pathways in the therapeutic process. Rat primary chondrocytes were isolated. catalpol was added to evaluate cytotoxicity and cell viability, and the optimal catalpol concentration was determined accordingly. IL-1β was added to simulate OA inflammation, establish a cellular senescence model and detect senescence-associated β-galactosidase activity. The proportion of senescent cells, cell cycle distribution, and ROS levels in each group were measured and compared. Western blotting was used to detect the expression of Type II collagen, ADAMTS-5, MMP-13, IL-6, p16, p21, PI3K, p-PI3K, AKT, p-AKT, p65, and p-p65 proteins. After catalpol treatment, the proportion of positive chondrocytes decreased, the proportion of chondrocytes in G0-G1 phase decreased significantly, and the ROS levels of chondrocytes in the inflammatory rat model decreased significantly. IL-1β significantly elevated the expression of IL-6, p16, and p21. However, this effect of IL-1β was inhibited by catalpol. catalpol could significantly inhibit the expression of MMP-13, IL-6, ADAMTS-5, p16, and p21, significantly increased the expression of type II collagen, and significantly inhibited the activation of PI3K/AKT and NF-κB signaling pathways. Catalpol attenuated chondrocyte senescence in an IL-1β-induced in vitro OA model, suppressed PI3K/AKT/NF-κB signaling, and decreased SASP expression. These in vitro findings suggest a potential mechanistic basis for the anti-senescence effects of catalpol on chondrocytes, which requires further validation in animal models and clinical studies before any therapeutic conclusions can be drawn.