加味二止丸通过调控SIRT1/JNK/p38 MAPK通路改善雄激素性脱发

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-04-01 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S501823

Zhiguang Huang, Yuanyuan Li, Yixin Xie, Hangjie Fu, Zhiwei Weng, Jianchang Yuan, Lan Wu, Weizhou Lin, Yi Cao, Bin Ding

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引用次数: 0

摘要

目的：雄激素性脱发（AGA）是脱发的一种类型。我们之前的研究表明，从传统配方 "二至丸 "中提取的中药方剂 "加味二至丸"（WJWE）的水提取物具有改善 AGA 的能力。然而，其潜在机制尚不清楚：本研究通过UPLC-MS/MS分析对 "加味二子丸 "中的植物化学成分进行了表征。采用二氢睾酮（DHT）诱导的小鼠模型和真皮乳头细胞（DPCs）试验来评估和阐明水井坊对 AGA 的有益作用和机制：结果：WJWE通过刺激Wnt5A/β-Catenin通路，促进了AGA小鼠的毛发生长和毛囊再生，改善了DPCs的生长，并对体外DHT降低的DPCs活力起到了剂量依赖性保护作用。此外，WJWE 还能降低 AGA 模型鼠皮肤和 DHT 处理的 DPC 中 DHT 诱导的氧化应激。为了阐明其调控机制，我们发现 WJWE 可显著增加 DHT 处理的 DPCs 和 AGA 模型小鼠体内 SIRT1 的表达，并降低 JNK 和 p38 MAPK 的磷酸化水平，且与剂量相关。应用 EX527（一种 SIRT1 抑制剂）可以抑制 WJWE 的作用：我们的研究提供了 WJWE 治疗 AGA 的一些证据，其中 SIRT1/JNK/p38 MAPK 信号通路可能是主要靶点。

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

Purpose: 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.

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.