Nuciferine attenuates the progression of osteoarthritis by targeting PI3K/Akt/NF-κB signaling pathway

Abstract

The schematical diagram of the anti-inflammatory effect of Nuciferine (Nuf) on OA. Nuf suppresses the production of inflammation cytokines and alleviates the degradation of extracellular matrix induced by IL-1β through the inhibition of PI3K/Akt/NF-κB signaling pathway. Nuf attenuates the progression of osteoarthritis in vitro and in vivo. • Nuciferine showed little toxicity to chondrocytes. • Nuciferine inhibited inflammation response induced by IL-1β in vitro. • Nuciferine alleviated the ECM degradation in vitro. • Nuciferine ameliorated the progression of OA in vivo. • Nuf had protective effect against OA through PI3K/Akt/NF-κB signaling pathway. Osteoarthritis (OA), a chronic disease featured by severe pain and persistent inflammation, significantly affects human health and lowers the quality of life. Nuciferine (Nuf) is major alkaloids abundant in lotus leaf and has various biological activities. In current study, we aimed to explored the protective effect of Nuf against OA and its underlying mechanism in vitro and in vivo. It was found that Nuf alleviated the degradation of extracellular matrix (ECM) under the stimulation of IL-1β and inhibited the production of inflammation cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in vitro. Meanwhile, it was demonstrated that Nuf suppressed the activation of PI3K/Akt/NF-κB signaling pathway induced by IL-1β. Besides, there was favorable binding ability between Nuf and PI3K. Nuf significantly alleviated the development of OA in vivo in the rat OA model established by anterior cruciate ligament transaction (ACLT). Together, our results indicated that Nuf attenuates the progression of OA by targeting PI3K/Akt/NF-κB signaling pathway, which makes Nuf as a promising candidate for the treatment of OA.