The in vitro and in vivo depigmentation activity of coenzyme Q₀, a major quinone derivative from Antrodia camphorata, through autophagy induction in human melanocytes and keratinocytes

Background Coenzyme Q(0) (CoQ(0)), a novel quinone derivative of Antrodia camphorata, has been utilized as a therapeutic agent (including antioxidant, anti-inflammatory, antiangiogenic, antiatherosclerotic, and anticancer agents); however, its depigmenting efficiency has yet to be studied. Methods We resolved the depigmenting efficiency of CoQ(0) through autophagy induction in melanoma (B16F10) and melanin-feeding keratinocyte (HaCaT) cells and in vivo Zebrafish model. Then, MPLC/HPLC analysis, MTT assay, Western blotting, immunofluorescence staining, LC3 transfection, melanin formation, GFP-LC3 puncta, AVO formation, tyrosinase activity, and TEM were used. Results CoQ(0)-induced autophagy in B16F10 cells was shown by enhanced LC3-II accumulation, ATG7 expression, autophagosome GFP-LC3 puncta, and AVOs formation, and ATG4B downregulation, and Beclin-1/Bcl-2 dysregulation. In alpha-MSH-stimulated B16F10 cells, CoQ(0) induced antimelanogenesis by suppressing CREB-MITF pathway, tyrosinase expression/activity, and melanin formation via autophagy. TEM data disclosed that CoQ(0) increased melanosome-engulfing autophagosomes and autolysosomes in alpha-MSH-stimulated B16F10 cells. CoQ(0)-inhibited melanogenesis in alpha-MSH-stimulated B16F10 cells was reversed by pretreatment with the autophagy inhibitor 3-MA or silencing of LC3. Additionally, CoQ(0)-induced autophagy in HaCaT cells was revealed by enhanced LC3-II accumulation, autophagosome GFP-LC3 puncta and AVO formation, ATG4B downregulation, ATG5/ATG7 expression, and Beclin-1/Bcl-2 dysregulation. In melanin-feeding HaCaT cells, CoQ(0) induced melanin degradation by suppressing melanosome gp100 and melanin formation via autophagy. TEM confirmed that CoQ(0) increased melanosome-engulfing autophagosomes and autolysosomes in melanin-feeding HaCaT cells. Treatment with 3-MA reversed CoQ(0)-mediated melanin degradation in melanin-feeding HaCaT cells. In vivo study showed that CoQ(0) suppressed endogenous body pigmentation by antimelanogenesis and melanin degradation through autophagy induction in a zebrafish model. Conclusions Our results showed that CoQ(0) exerted antimelanogenesis and melanin degradation by inducing autophagy. CoQ(0) could be used in skin-whitening formulations as a topical cosmetic application.