Intervertebral disc (IVD) degeneration (IDD) is a prevalent musculoskeletal disorder. Nucleus pulposus cells (NPCs) play a significant role in the normal functioning of the IVD. Myricetin is an agent that exerts anti-inflammatory and antioxidant effects in various pathological conditions. Here, we investigated the ameliorative effects of myricetin on the IVD degeneration. NPCs were obtained from the IVD of rats, and were treated with myricetin (0, 5, 10, 15, 20 μM) for 24 h before 20 ng/mL IL-1β stimulation. RT-qPCR, western blotting, and ELISA were applied to evaluate the levels of inflammatory factors (iNOS, COX-2, TNF-α, IL-6, PGE2, and Nitrite) and extracellular matrix (ECM)-associated components (MMP13, ADAMTS-5, aggrecan, and collagen II) in NPCs. Activation status of related signaling pathways (NF-κB and Nrf2) was determined using western blotting and immunofluorescence staining. Experimental rat models of IDD were established using a needle puncture method. Myricetin (20 mg/kg) was administrated intraperitoneally, and the degeneration was evaluated using histopathological analysis. Myricetin treatment attenuated the IL-1β-induced production of inflammatory factors in NPCs. Downregulation of aggrecan and collagen II as well as upregulation of MMP-13 and ADAMTS-5 in NPCs caused by IL-1β was reversed by myricetin treatment. Mechanistically, myricetin blocked NF-κB signaling by activation of Nrf2 in IL-1β-stimulated NPCs. Moreover, inhibition of Nrf2 reversed the protective effects of myricetin in NPCs. The in vivo experiments showed that myricetin ameliorated the IDD progression in rats. The present work suggests that Nrf2 is involved in the pathogenesis of IDD and shows the protective effects as well as the underlying mechanism of myricetin on Nrf2 activation in NPCs.
Keywords: Extracellular matrix; IL-1β; Inflammation; Intervertebral disc degeneration; Myricetin; NF-κB; Nrf2/HO-1; Nucleus pulposus.
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.