School of Chemistry, Biology and Environment of Yuxi Normal University, Yuxi, 653100, Yunnan, China.
Research Institute of Resource Insects of Chinese Academy of Forestry, Kunming, 650233, Yunnan, China.
Biomed Pharmacother. 2021 Apr;136:111241. doi: 10.1016/j.biopha.2021.111241. Epub 2021 Jan 20.
Previously, we have demonstrated that policosanol from Chinese wax suppressed testosterone(T)-induced alopecia in mice. However, the underlying mechanism remained to be determined. Herein, we investigated the mechanism of policosanol against androgenetic alopecia (AGA). AGA was induced in Kunming mice by subcutaneous administration of testosterone propionate for 60 d. Policosanol (0.5 %, 1% or 2%) was applied topically on the back of mice. Finasteride (2%) was applied topically as a positive control. The serum T and estradiol (E2) concentrations were determined by ELISA after 28 and 60 days of treatment. The cutaneous expression or activity of key mediators of hair growth, such as alkaline phosphatase (ALP), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF), was measured. MTS assay was performed to evaluate cell proliferation in cultured human dermal papilla cells (DPCs) treated with dihydrotestosterone (DHT). Western blotting was performed to evaluate the protein expression of Bax, Bcl2, TGF-β2, caspase-9, and caspase-3. We found lower T and T/E2 ratio in mice treated with policosanol than in the model group. Policosanol suppressed premature hair follicle entry into the regression phase, as shown by improving VEGF and EGF expression and ALP activity. The MTS assay showed that policosanol markedly inhibited the apoptosis of DHT-treated DPCs. Western blotting showed that policosanol significantly reduced the protein expression of TGF-β2, cleaved caspese-9, cleaved caspase-3, and Bax, and increased that of Bcl2. The optimal effect was obtained with 12.50 g/mL policosanol. In conclusion, policosanol prevents androgenetic alopecia by regulating hormone levels and suppressing premature hair follicle entry into the regression phase.
先前,我们已经证明,来自中国蜂蜡的植物固醇可以抑制睾丸酮(T)诱导的小鼠脱发。然而,其潜在机制仍有待确定。在此,我们研究了植物固醇对抗雄激素性脱发(AGA)的机制。通过给昆明小鼠皮下注射丙酸睾丸酮 60 天来诱导 AGA。将植物固醇(0.5%、1%或 2%)涂于小鼠背部。将非那雄胺(2%)涂于背部作为阳性对照。治疗 28 和 60 天后,通过 ELISA 测定血清 T 和雌二醇(E2)浓度。测量毛发生长关键介质的皮肤表达或活性,如碱性磷酸酶(ALP)、血管内皮生长因子(VEGF)和表皮生长因子(EGF)。通过 MTS 测定法评估经二氢睾酮(DHT)处理的培养人真皮乳头细胞(DPC)的细胞增殖。通过 Western blot 评估 Bax、Bcl2、TGF-β2、caspase-9 和 caspase-3 的蛋白表达。我们发现与模型组相比,用植物固醇治疗的小鼠的 T 和 T/E2 比值较低。植物固醇通过改善 VEGF 和 EGF 表达和 ALP 活性来抑制毛囊过早进入退行期。MTS 测定法表明,植物固醇明显抑制了 DHT 处理的 DPC 的凋亡。Western blot 表明,植物固醇显著降低了 TGF-β2、裂解的 caspase-9、裂解的 caspase-3 和 Bax 的蛋白表达,增加了 Bcl2 的蛋白表达。12.50 g/mL 植物固醇的效果最佳。总之,植物固醇通过调节激素水平和抑制毛囊过早进入退行期来预防雄激素性脱发。