Galangin alleviates vitiligo by targeting ANXA2 degradation in macrophages

Background and Purpose Vitiligo, a common depigmenting skin disorder, is characterised by the selective loss of melanocytes, which leads to distinctive non-scaly, chalky-white macules. Galangin is a flavonoid found in galangal and propolis; our previous study highlighted the therapeutic potential of galangin. However, the contributions of galangin to restoring skin pigmentation and maintaining immune homeostasis, as well as its detailed molecular roles in vitiligo management, have not been fully elucidated. Experimental Approach We used C57BL/6J mice with H 2 O 2 -induced vitiligo or imiquimod-induced erythema, to test the anti-vitiligo effects and anti-inflammatory effects of galangin. Other techniques used included immunoprecipitation-mass spectrometry, pull-down assays, Autodock and surface plasmon resonance (SPR) analysis in cultured cells. Key Results Galangin exerted anti-inflammatory and antioxidant effects through two mechanisms, promoting melanocyte proliferation while inhibiting macrophage proliferation. Using immunoprecipitation-mass spectrometry, pull-down assays, Autodock and SPR analyses, we found that galangin bound to annexin A2 and promoted its degradation in macrophages. This interaction led to inhibition of macrophage proliferation, activation and polarisation. In vivo, galangin significantly improved skin conditions in mice with H 2 O 2 -induced vitiligo or imiquimod-induced erythema. Furthermore, annexin A2 knockout abolished the protective effects of galangin in these models. Conclusions and Implications Galangin bound to annexin A2 and promoted its degradation in macrophages, decreasing release of inflammatory factors and chemokines. These findings provide experimental evidence supporting the potential application of galangin in clinical treatments for vitiligo and highlight ANXA2 as a promising therapeutic target for managing this condition.