Abstract
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 (GA), a flavonoid
found in galangal and propolis, our previous study highlighted the
therapeutic potential of GA. However, the contributions of GA 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 H2O2-induced vitiligo
mice and imiquimod-induced erythema mice to test the anti-vitiligo
effects and anti-inflammatory effects of GA. We also revealed the
potential mechanism by immunoprecipitation-mass spectrometry, pull-down
assays, Autodock and surface plasmon resonance analysis in cells. Key
Results: We found that GA exerts anti-inflammatory and antioxidant
effects through a dual mechanism: it promotes melanocyte proliferation
while inhibiting macrophage proliferation. Using
immunoprecipitation-mass spectrometry, pull-down assays, Autodock and
surface plasmon resonance analyses, we revealed that GA binds to Annexin
A2 (ANXA2) and promotes its degradation in macrophages. This interaction
led to the inhibition of macrophage proliferation and activation. In
vivo, GA administration significantly improved skin conditions in
H2O2-induced vitiligo mice and imiquimod-induced erythema mice.
Furthermore, ANXA2 knockout abolished the protective effects of GA in
these models. Conclusion and Implications: Our findings provide novel
evidence of GA’s dual mechanism in vitiligo treatment, which involves
selective binding and degradation of ANXA2 in macrophages. These results
support the potential clinical application of GA for vitiligo therapy.