Zhang Yanyan, Zhang Shiqian, Long Yunluan, Wang Wuji, Du Fanpan, Li Jingjie, Jin Feng, Li Zheng
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China.
Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou, China.
Front Pharmacol. 2022 Dec 16;13:1073392. doi: 10.3389/fphar.2022.1073392. eCollection 2022.
Hair serves important physiological functions, including temperature regulation and scalp protection. However, excessive shedding not only impacts these functions but can also significantly affect mental health and quality of life. Tianma Gouteng decoction (TGD) is a traditional Chinese medicine used for the treatment of various conditions, including hair loss. However, the associated mechanism underlying its anti-alopecia effect remains unknown. Therefore, this study aims to elucidate these mechanisms by employing systematic biology approaches, as well as and experimental validation. The chemical constituents of Tianma Gouteng decoction were identified using UHPLC-MS/MS, from which 39 potential bioactive components were screened, while an additional 131 putative Tianma Gouteng decoction beneficial components were extracted from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) database. We then applied a dual-dimensional network pharmacology approach to analyze the data, followed by validation studies combining molecular docking techniques with and experiments. From the 39 bioactive components, including quercetin, luteolin, fisetin, wogonin, oroxylin A, boldine, tetrahydroalstonine, and galangin A, 782 corresponding targets were identified. In particular, GSK3β and β-catenin exhibited strong binding activity with the bioactive compounds. Hence, construction of a bioactive component-target network revealed that the mechanism underlying the anti-alopecia mechanism of Tianma Gouteng decoction primarily involved the Wnt/β-catenin signaling pathway. Moreover, C57BL/6J mice exhibited measurable improvements in hair follicle regeneration following treatment with Tianma Gouteng decoction. Additionally, β-catenin and p-GSK3β levels were upregulated, while GSK3β was downregulated in Tianma Gouteng decoction-treated animals and dermal papilla cells compared to control group. These and outcomes validated the targets and pathways predicted in the network pharmacology analysis of Tianma Gouteng decoction. This study provides a systematic analysis approach to identify the underlying anti-alopecia mechanisms of Tianma Gouteng decoction, further providing theoretical support for clinical assessment of Tianma Gouteng decoction.
头发具有重要的生理功能,包括调节体温和保护头皮。然而,过度脱发不仅会影响这些功能,还会显著影响心理健康和生活质量。天麻钩藤饮(TGD)是一种用于治疗包括脱发在内的各种病症的传统中药。然而,其抗脱发作用的相关机制尚不清楚。因此,本研究旨在通过采用系统生物学方法以及实验验证来阐明这些机制。使用超高效液相色谱-串联质谱法(UHPLC-MS/MS)鉴定了天麻钩藤饮的化学成分,从中筛选出39种潜在的生物活性成分,同时从中药数据库和分析平台(TCMSP)数据库中提取了另外131种推定的天麻钩藤饮有益成分。然后,我们应用二维网络药理学方法分析数据,随后结合分子对接技术和实验进行验证研究。从包括槲皮素、木犀草素、非瑟酮、汉黄芩素、氧化苦参碱、波丹宁、四氢鸭脚木碱和高良姜素A在内的39种生物活性成分中,鉴定出782个相应的靶点。特别是,糖原合成酶激酶3β(GSK3β)和β-连环蛋白与生物活性化合物表现出很强的结合活性。因此,构建生物活性成分-靶点网络表明,天麻钩藤饮抗脱发机制的基础主要涉及Wnt/β-连环蛋白信号通路。此外,C57BL/6J小鼠在接受天麻钩藤饮治疗后,毛囊再生有明显改善。此外,与对照组相比,天麻钩藤饮治疗的动物和真皮乳头细胞中β-连环蛋白和磷酸化GSK3β水平上调,而GSK3β水平下调。这些结果验证了天麻钩藤饮网络药理学分析中预测的靶点和通路。本研究提供了一种系统分析方法来确定天麻钩藤饮潜在的抗脱发机制,进一步为天麻钩藤饮的临床评估提供理论支持。