Jiawei Erzhiwan Ameliorates Androgenetic Alopecia by Regulating the SIRT1/JNK/p38 MAPK Pathway

Zhiguang Huang,1,2,* Yuanyuan Li,3,* Yixin Xie,1,2,* Hangjie Fu,2,4 Zhiwei Weng,1,2 Jianchang Yuan,1,2 Lan Wu,1,2 Weizhou Lin,1,2 Yi Cao,3 Bin Ding1,2,5 1School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Academy of Chinese Medical Science, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 3The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4School of Public Health, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 5Jiaxing TCM Hospital Affiliated to Zhejiang Chinese Medical University, Jiaxing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Ding, College of Life Science, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Tel +86 18058107528, Email [email protected] Yi Cao, The First Affiliated Hospital of Zhejiang Chinese Medical University, 289 Shanggang Road, Xihu District, Hangzhou, 310060, People’s Republic of China, Email [email protected]: Androgenetic alopecia (AGA) is a type of hair loss. Our previous study showed AGA ameliorating capability of water extract of an herbal prescription, “Jiawei Erzhiwan” (WJWE), which was derived from the traditional formula “Erzhiwan”. However, the underlying mechanisms is still unknown.Patients and Methods: In this study, the phytochemical ingredients in WJWE were characterized via UPLC‒MS/MS analysis. The dihydrotestosterone (DHT)-induced murine model and dermal papilla cells (DPCs) assays were used to evaluate and elucidate the beneficial effects and mechanisms of WJWE on AGA.Results: WJWE promoted hair growth and hair follicle regeneration in AGA mice, improved DPCs growth and dose-dependently protected DHT-reduced DPCs viability in vitro by stimulating the Wnt5A/β-Catenin pathway. Additionally, WJWE reduced DHT-induced oxidative stress in AGA model murine skin and DHT-treated DPCs. To elucidate the regulative mechanism, we found that WJWE treatment significantly and dose-dependently increased the expression of SIRT1 and reduced the phosphorylation of JNK and p38 MAPK in both DHT-treated DPCs and AGA model mice. And the application of EX527 (a SIRT1 inhibitor) could the effect of WJWE.Conclusion: Our study provided some evidence of WJWE on AGA treatment, by which SIRT1/JNK/p38 MAPK signaling pathway might be the major target. Keywords: androgenetic alopecia, Erzhiwan, JNK, p38 MAPK, oxidative stress, SIRT1