Vitiligo is one of the most common and clinically challenging chronic depigmentary disorders. Current treatments, including corticosteroids, phototherapy, and JAK inhibitors, remain limited by incomplete or non-durable repigmentation, necessitating novel mechanism-based therapeutic strategies. Autophagy, classically defined as a lysosomal degradation pathway, is recognized as a key regulator of melanocyte homeostasis, oxidative-stress responses, and immune modulation. Although autophagy has been repeatedly implicated in vitiligo pathogenesis, whether its dysregulation is causal, consequential, or compensatory remains unresolved, and no autophagy-targeted therapy has yet been clinically validated. Here, we stratify current vitiligo therapies by whether their efficacy is directly mediated by melanocyte autophagy, is only indirectly linked to autophagy, or is supported mainly by cross-disease or preclinical evidence. Integrating advances in autophagy biology with emerging therapeutic evidence, this review identifies why the therapeutic potential of autophagy in vitiligo remains unvalidated, and outlines the evidence required to test whether autophagy modulation is causally linked to repigmentation.

Cancer remains a major global health concern, driving the search for safe and effective bioactive compounds from natural sources. Jujube peel red pigment (JP), an anthocyanin-rich extract, has shown preliminary bioactivity, yet its antitumor potential and delivery challenges remain underexplored. This study systematically evaluated the in vitro antitumor activity of JP and developed a thermosensitive hydrogel-based local delivery system (JP-H) to overcome its rapid diffusion and poor retention. JP exhibited selective cytotoxicity against HeLa cervical cancer and B16 melanoma cells, with no obvious toxicity to normal L929 and RAW264.7 cells. Mechanistically, JP induced mitochondrial-dependent apoptosis via upregulating Bax and cleaved Caspase-9/-3, while downregulating Bcl-2, and concurrently triggered G1/S phase arrest through modulation of CCND1, CDK2, CDK4, PCNA, MYC, and TP53. To enable localized delivery, JP was incorporated into an injectable chitosan/gelatin/F127 thermosensitive hydrogel (JP-H), which exhibited rapid sol-gel transition at physiological temperature, shear-thinning behavior, and a porous microstructure. JP-H not only sustained JP release but also significantly enhanced antibacterial activity against E. coli and S. aureus compared to free JP. Furthermore, JP-H markedly inhibited HeLa cell migration and induced superior apoptotic/necrotic cell death in co-culture assays, outperforming free JP. Collectively, this work establishes JP as a multi-target antitumor agent and demonstrates JP-H as a promising local therapeutic platform combining sustained delivery, antibacterial protection, and enhanced anticancer efficacy for cervical cancer treatment.

Cancer remains a major global health concern, driving the search for safe and effective bioactive compounds from natural sources. Jujube peel red pigment (JP), an anthocyanin-rich extract, has shown preliminary bioactivity, yet its antitumor potential and delivery challenges remain underexplored. This study systematically evaluated the in vitro antitumor activity of JP and developed a thermosensitive hydrogel-based local delivery system (JP-H) to overcome its rapid diffusion and poor retention. JP exhibited selective cytotoxicity against HeLa cervical cancer and B16 melanoma cells, with no obvious toxicity to normal L929 and RAW264.7 cells. In HeLa cells, JP exerted antitumor effects by initiating mitochondrial-dependent apoptosis accompanied by elevated expression of Bax and cleaved Caspase-9/-3 as well as decreased Bcl-2 level, and arrested cell cycle at the G1/S phase by regulating CCND1, CDK2, CDK4, PCNA, MYC and TP53. To enable localized delivery, JP was incorporated into an injectable chitosan/gelatin/F127 thermosensitive hydrogel (JP-H), which exhibited rapid sol-gel transition at physiological temperature, shear-thinning behavior, and a porous microstructure. JP-H not only sustained JP release but also significantly enhanced antibacterial activity against E. coli and S. aureus compared to free JP. Furthermore, JP-H markedly inhibited HeLa cell migration and induced superior apoptotic/necrotic cell death in co-culture assays, outperforming free JP. Collectively, this work establishes JP as a multi-target antitumor agent and demonstrates JP-H as a promising local therapeutic platform combining sustained delivery, antibacterial protection, and enhanced anticancer efficacy for cervical cancer treatment.