# Skin-Whitening Effects of Cannabinol (CBN) Through Melanin Inhibition in B16F10 Melanoma Cells

## TL;DR

Cannabinol (CBN) reduces melanin production in melanoma cells by inhibiting key signaling pathways, suggesting it could be a safe skin-whitening agent.

## Contribution

This study is the first to demonstrate CBN's depigmenting effects and its selective modulation of melanogenesis signaling.

## Key findings

- CBN significantly inhibits melanin synthesis and tyrosinase activity without cytotoxicity.
- CBN downregulates melanogenic genes MITF, TYR, TYRP1, and TYRP2 at both mRNA and protein levels.
- CBN selectively suppresses phosphorylation of p38, JNK, and NF-κB, but not ERK, in melanogenesis pathways.

## Abstract

Melanogenesis, the key biological process underlying skin hyperpigmentation, is tightly regulated by complex molecular signaling pathways. Consequently, targeting molecular regulators of this pathway is a crucial strategy for developing effective skin-whitening agents. Cannabinol (CBN), a minor cannabinoid, has been largely unexplored owing to its role in modulating skin pigmentation. This study aimed to elucidate the molecular mechanisms of CBN’s depigmenting effects using an α-MSH-induced B16F10 melanoma cell model. High-purity CBN was obtained via conversion of cannabidiol (CBD) and confirmed by HPLC. CBN significantly inhibited melanin synthesis and tyrosinase activity in a concentration-dependent manner, without any cytotoxicity. Furthermore, we investigated CBN’s impact on the melanogenesis signaling cascade. Our analysis revealed that CBN significantly downregulated the mRNA and protein levels of key melanogenic master regulators, including MITF, TYR, TYRP1, and TYRP2. Importantly, we also observed that CBN treatment selectively suppressed the protein phosphorylation of upstream signaling molecules such as p38 and JNK MAP kinases and NF-κB, while ERK phosphorylation remained unaffected. This finding indicates that its mechanism of action involves the selective modulation of pro-melanogenic signaling components. Collectively, these findings demonstrate that CBN effectively modulates the melanogenesis signaling pathway by targeting both upstream kinases and downstream melanogenic genes. These findings suggest that CBN holds great promise as a bioactive agent for skin-whitening applications and warrants further research to confirm its clinical efficacy and safety.