Research progress of resveratrol against intervertebral disc degeneration

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain,yet effective pharmacotherapeutic options remain limited. Resveratrol (RSV),a natural polyphenol,has demonstrated considerable potential in mitigating IVDD progression. This review systematically summarizes the multi-dimensional molecular mechanisms by which RSV exerts protective effects on nucleus pulposus (NP) cells,the central functional cells within discs,through the regulation of multiple signaling pathways. Specifically,RSV alleviates mechanical and oxidative stress-induced NP cell senescence by inhibiting pathways such as NF-κB;suppresses inflammation and high glucose-triggered apoptosis via modulating ERK1/2 and PI3K/Akt pathways;enhances cytoprotective autophagy through activating pathways like Nrf2/ARE to clear damaged cellular components; and maintains the synthesis-degradation balance of the extracellular matrix(ECM) by regulating inflammatory cytokine expression,thereby improving the disc microenvironment. Although current research is primarily based on in vitro and animal models,with insufficient focus on structures like the annulus fibrosus and cartilaginous endplate,evidence strongly suggests that RSV acts synergistically on multiple targets and pathways to intervene in key pathological processes of IVDD. Future studies should better mimic the in vivo hypoxic niche,investigate RSV's effects on other disc components,and facilitate its clinical translation,offering novel theoretical foundations and strategies for developing targeted pharmacotherapies against IVDD.