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

Lu Zhu,1, Yixuan Liang,1,2, Ling Jiang,1 Chuhan Fu,1 Xixia Dai,1 Haoran Guo,1 Qinghai Zeng,1 Shuanghai Hu,3 Jing Chen1 1Department of Dermatology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 2Institute of Dermatology, Chengdu Second People’s Hospital, Chengdu, Sichuan, 610021, People’s Republic of China; 3Department of Dermatology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, People’s Republic of ChinaThese authors contributed equally to this workCorrespondence: Shuanghai Hu, Department of dermatology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, People’s Republic of China, Email hushuanghai@whu.edu.cn Jing Chen, Department of Dermatology, The Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Changsha, Hunan, 410013, People’s Republic of China, Email 43700351@qq.comObjective: 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.Keywords: network Pharmacology, radix polygalae, tenuifolin, vitiligo, melanogenesis