Exploring the Role of Radix Polygalae in Melanogenesis Related to Vitiligo: A Network Pharmacology Analysis with in vitro Validation

Objective: Radix Polygalae is a traditional Chinese herbal medicine with various pharmacological effects, including improvement of cognitive ability, anti-neurodegenerative property, and antiviral property, among others. Radix Polygalae was also utilized in the treatment of vitiligo in traditional folk clinics, although its mechanism of action remains unclear. This study investigates the potential active ingredients of Radix Polygalae in the treatment of vitiligo. Methods: This study screened the potential active ingredients and core target genes of Radix Polygalae in the treatment of vitiligo through network pharmacology, and validated the mechanism of Tenuifolin, the key active ingredient, through the in vitro experiments. Results: We finally identified 10 core target genes: TNF, CASP3, IL-1β, IL-6, ESR1, STAT3, VEGFA, PPARG, ALB, and IL-2. Additionally, we found 7 core active ingredients: Tenuifolin (TEN), N-Acetyl-D-Glucosamine, 1,6-Dihydroxy-3,7-dimethoxyxanthone, 1-Hydroxy-3,7-dimethoxyxanthone, aristolactam a, carvacrol, and cordarine. TEN, which contains the highest number of core target genes, was selected for further investigation of its mechanism. According to our findings, TEN could promote melanin production in pigment cells and skin, as well as induce browning of apple slices. Further investigation showed that TEN reduced the expression of CXCL10 and increased the activity of tyrosinase (TYR), without affecting the pH value or the expression of melanogenesis-related genes (MITF, TYR, TYRP1, and DCT), as well as paracrine factors of ET-1 and VEGF. Conclusion: TEN is one of the active ingredients of Radix Polygalae that shows potential in the treatment of vitiligo. It may regulate TYR to promote skin pigmentation.