Hirsutanone Isolated from the Bark of Alnus japonica Attenuates Melanogenesis via Dual Inhibition of Tyrosinase Activity and Expression of Melanogenic Proteins

Summary

Researchers found that hirsutanone, a natural compound from East Asian alder bark, can reduce skin pigmentation by blocking melanin production through two mechanisms: directly inhibiting the tyrosinase enzyme and suppressing the cellular signals that trigger melanin-producing genes. In laboratory tests with both mouse and human skin cells, hirsutanone proved more effective than a related compound called oregonin at reducing melanin without harming the cells. This discovery suggests hirsutanone could potentially be developed into a treatment for pigmentation problems like age spots and melasma.

Background

Excessive melanin production causes hyperpigmentation disorders such as freckles, solar lentigo, melasma, and cancer. Alnus japonica bark has been used in traditional Asian medicine and contains diarylheptanoids with various bioactivities. However, the effects of hirsutanone and oregonin on melanin biosynthesis have not been previously studied.

Objective

This study investigated the anti-melanogenic activity of hirsutanone (Hir) and oregonin (Ore) isolated from Alnus japonica bark in murine melanoma B16-F1 cells and normal human epidermal melanocytes (HEMn-DP). The mechanisms of action were elucidated through assessment of tyrosinase activity, melanogenic enzyme expression, and transcription factor signaling.

Results

Hir and Ore suppressed α-MSH-induced melanin synthesis in B16-F1 cells without cytotoxicity, with Hir showing stronger inhibitory effects (IC50 3.87 µM vs 16.71 µM for Ore). Hir reduced melanin content in HEMn-DP cells and partially inhibited tyrosinase activity. Hir suppressed protein expression of tyrosinase, TRP-1, and TRP-2, and inhibited CREB phosphorylation and MITF expression.

Conclusion

Hirsutanone attenuates melanogenesis through dual inhibition of tyrosinase activity and the CREB/MITF signaling pathway that regulates melanogenic enzyme expression. These findings suggest that hirsutanone could be developed as a potent cosmetic and therapeutic agent for hyperpigmentation disorders. Further animal studies and clinical trials are needed to confirm efficacy.
Scroll to Top