中药成分联合米诺地尔抗雄激素性脱发的作用研究

Study on the Effect of Chinese Medicine Ingredients Combined with Minoxidil Against Androgenic Alopecia

关键词:  雄激素性脱发  米诺地尔  中药成分  雪松醇  联合用药  5α-还原酶  人毛囊乳头细胞

Key words:  androgenic alopecia  minoxidil  ingredients of Chinese medicine  cedrol  combination therapy  5α-reductase  human dermal papilla cells

摘要:

目的 研究中药成分与米诺地尔联用抗雄激素性脱发的作用。方法 将莽草酸、黄芩苷和雪松醇3种中药成分分别与米诺地尔联用，采用人毛囊乳头细胞(human dermal papilla cells，hDPC)细胞增殖试验验证中药成分协同米诺地尔提高细胞活力的作用，并确定最佳联用比例，利用睾酮干扰的C57BL/6小鼠模拟雄激素性脱发模型评价药物联用组合促进毛发再生的效果，5α-还原酶抑制试验探究雪松醇对抗雄激素性脱发的起效机制。结果 细胞增殖试验表明，莽草酸、黄芩苷和雪松醇3种中药成分在5 μmol·L^–1浓度下均能发挥促进细胞增殖的作用，且3种中药成分与米诺地尔联用都能协同提高细胞活力；雪松醇与米诺地尔1∶1摩尔比联用、黄芩苷与米诺地尔1∶1摩尔比联用的细胞存活率最高。体内药效学试验表明，雪松醇与米诺地尔联合给药组的同期毛发覆盖率、再生毛发长度药效评价指标都显著高于其他组别。5α-还原酶抑制试验显示雪松醇对5α-还原酶的抑制率>(69.60±0.89)%，雪松醇-米诺地尔联用对5α-还原酶的抑制作用显著高于米诺地尔。结论 莽草酸、黄芩苷和雪松醇3种中药成分与米诺地尔联用均能协同促进人毛囊乳头细胞增殖。雪松醇-米诺地尔1∶1联用在提高细胞活力、促进毛囊分化、诱导毛囊周期转变、促进毛发再生方面都显示出良好的协同增效作用，可以作为抗雄激素性脱发的最佳联合给药方案。抑制5α-还原酶活性是雪松醇的主要起效机制之一。

Abstract:

OBJECTIVE To study the effect of Chinese medicine ingredients combined with minoxidil against androgenic alopecia. METHODS Shikimic acid, baicalin and cedrol were combined with minoxidil, respectively. Human dermal papilla cell(hDPC) proliferation assays were utilized to verify the effect of the Chinese medicine ingredients combined with minoxidil on improving cell viability and determine the optimized combination ratio. C57BL/6 mice model of androgenic alopecia with testosterone intervention was utilized to evaluate the hair regeneration effect of the combination of drugs. The 5α-reductase inhibition experiment was used to explore the action mechanism of cedrol against androgenic alopecia. RESULTS Cell proliferation assays showed that shikimic acid, baicalin and cedrol remarkably promoted cell proliferation at the concentration of 5 μmol·L^-1, and the combination of these Chinese medicine ingredients with minoxidil could synergically improve cell viability. Combination therapies of cedrol and minoxidil, baicalin and minoxidil at 1:1 molar ratio exhibited the highest cell viability. In vivo, the pharmacodynamic indicators of cedrol and minoxidil combination group were significantly higher than those of other administration groups, such as hair cover area, the length of regenerated hair. The 5α-reductase inhibition experiment show that the inhibitory rate of cedrol on 5α-reductase was higher than(69.60±0.89)%, and the inhibition of combination therapy of cedrol-minoxidil on 5α-reductase was significantly higher than minoxidil. CONCLUSION Shikimic acid, baicalin and cedrol combined with minoxidil can synergically promote the proliferation of human dermal papilla cells. The combination therapy of cedrol-minoxidil(1:1), as the best combination of anti-androgenetic alopecia, shows synergistic effect in improving cell viability, promoting hair follicle differentiation, inducing hair follicle cycle transition and accelerating hair regeneration. Inhibition of 5α-reductase activity is one of the main mechanisms of cedrol.