Maltol inhibits the progression of osteoarthritis via the nuclear factor-erythroid 2–related factor-2/heme oxygenase-1 signal pathway in vitro and in vivo

Abstract

Osteoarthritis (OA) is a common degenerative joint disease characterized by articular cartilage degeneration and inflammation. Currently, there is hardly any effective treatment for OA due to its complicated pathology and the severe side effects of the treatment drugs used. It has been reported that maltol, a Maillard reaction product derived from ginseng, inhibits inflammation and oxidative stress in several animal models. However, the potential anti-inflammatory effects of maltol in OA treatment are unknown. This study aimed to evaluate the anti-inflammatory effects of maltol on interleukin (IL)-1β-induced mouse chondrocytes and protective effects of maltol on these chondrocytes in medial meniscus destabilization (DMM) OA mouse models. Mice, randomly divided into maltol (n = 15), vehicle (n = 15) and control (n = 15) groups were treated with the same dose of maltol or saline, respectively. The cartilage tissues were extracted for histological analysis 8 weeks postoperative. For the in vitro studies, chondrocytes were treated with 10 ng mL⁻¹ IL-1β combined with maltol at different concentrations. In vitro assays showed that the maltol pre-treatment significantly inhibited the expressions of multiple inflammatory factors induced by IL-1β, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α). In addition, maltol alleviated the degradation of the extracellular matrix (ECM) by inhibiting the expressions of matrix metalloproteinase-13 (MMP13) and thrombospondin motif 5 (ADAMTS5), as well as reversing the degradation of aggrecan and collagen II. Moreover, maltol suppressed nuclear factor kappa B (NF-κB) signaling by activating the nuclear factor-erythroid 2-related factor-2 (Nrf2) in in vitro and in vivo studies. These findings indicate that maltol reduces the inflammation induced by IL-1β in chondrocytes. Therefore, the results of this study indicated that maltol may be a potential drug for the effective treatment of OA.