Abstract

Paeonia lactiflora Pallas (PL) and Poria cocos Wolf (PC) have been traditionally used to treat inflammatory diseases reported in Dongui Bogam and Shen Nong Ben Cao Jing, traditional medical books in Korean and China, respectively. We determined the efficacies and the molecular mechanisms of PL, PC, and PL + PC aqueous extracts on androgenetic alopecia (AGA) induced by testosterone propionate in C57BL/6 mice. The molecular mechanisms of PL and PC in AGA treatment were examined using experimental assays and network pharmacology. The AGA model was generated by topically applying 0.5% testosterone propionate in 70% ethanol solution to the backs of mice daily for 28 days while the normal-control (Normal-Con; no AGA induction) mice applied 70% ethanol. The 0.1% PL (AGA-PL), 0.1% PC (AGA-PC), 0.05% PL + 0.05% PC (AGA-MIX), and 0.1% cellulose (AGA-Con; control) were supplemented in a high-fat diet for 28 days in AGA-induced mice. Positive-control (AGA-Positive) were administered 2% finasteride daily on the backs of the AGA mice. Hair growth rates decreased in the order of AGA-PL, AGA-MIX, AGA-PC, AGA-Positive, and AGA-Con after 21 days of treatment (ED21). On ED28, skins were completely covered with hair in the AGA-PL and AGA-MIX groups. Serum testosterone concentrations were lower in the AGA-PL group than in the AGA-Con group and similar to concentrations in the Normal-Con group, whereas serum 17β-estradiol concentrations showed the opposite pattern with increasing aromatase mRNA expression (p < 0.05). In the dorsal skin, DKK1 and NR3C2 mRNA expressions were significantly lower, but TGF-β2, β-Catenin, and PPARG expressions were higher in the AGA-PL and AGA-PC groups than in the AGA-Con group (p < 0.05), whereas TNF-α and IL-6 mRNA expressions were lower in the AGA-PL, AGA-MIX, and Normal-Con groups than in the AGA-Con group (p < 0.05). The phosphorylation of Akt and GSK-3β in the dorsal skin was lower in AGA-Con than normal-Con, and PL and MIX ingestion suppressed their decrease similar to the Normal-Con. In conclusion, PL or PL + PC intake had beneficial effects on hair growth similar to Normal-Con. The promotion was related to lower serum testosterone concentrations and pro-inflammatory cytokine levels, and inhibition of the steroid hormone pathway, consistent with network pharmacology analysis findings.

Highlights

  • Androgenetic alopecia (AGA) is the most common cause of chronic progressive hair loss in young and middle-aged men [1] and has a worldwide incidence rate of about20% [2]

  • We aimed to evaluate the efficacy of PL and Poria cocos Wolf (PC) in androgenetic alopecia (AGA) treatment and their molecular mechanism in network pharmacology and an established AGA animal model

  • We undertook this study to determine whether PL and PC intake would improve hair growth in AGA-induced C57BL/6 mice and reduce androgen and pro-inflammatory cytokine contents

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Summary

Introduction

Androgenetic alopecia (AGA) is the most common cause of chronic progressive hair loss in young and middle-aged men [1] and has a worldwide incidence rate of about20% [2]. Androgenetic alopecia (AGA) is the most common cause of chronic progressive hair loss in young and middle-aged men [1] and has a worldwide incidence rate of about. The exact mechanism remains unclear, but excessive androgen receptor activation in the scalp shortens the anagen or growth phase in the hair growth cycle and miniaturizes the follicles. It contributes to thinner and shorter hair follicles, resulting in Pharmaceuticals 2021, 14, 1128. Pharmaceuticals 2021, 14, 1128 accelerating hair loss. Inadequate oxygen and nutrient supply due to the reduced blood supply to the scalp may cause hair loss [3]. Inflammation, dyslipidemia, hyperglycemia, and insulin resistance are involved in AGA etiology, and Western-style diets containing high sugar and cholesterol and a low mineral diet may increase the potential to induce AGA [5]

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