Hong Xiang,Yu Zhang,Jiaming Li,Li Li,Ziwei Li,Rui Ni,Dan Peng,Lining Jiang,Jianhong Chen,Yao Liu
Ethnopharmacological relevance Terminalia bellirica (Gaertn.) Roxb. (TBR) , a popular herbal remedy in India and Southeast Asia, has been demonstrated to possess multiple pharmacological activities. However, systematic studies on the medicinal effects and mechanism of TBR for the androgenetic alopecia (AGA) treatment are deficient. Materials and methods Human Umbilical Vein Endothelial Cells (HUVECs) and testosterone-induced AGA mice were used to evaluate the hair regrowth activity of TBR extracts. Chemical constituents and potential active components of TBR extracts were analyed by UPLC-Q-TOF-MS in vitro / vivo . The hair regrowth mechanisms of TBR were elucidated through network pharmacology and experimental validation. Results Totally 28 chemical constituents in TBR were identified, of which 15 were predicted as potential active components for AGA therapy. TBR could significantly scavenge ROS, promote VEGF level/cell migration of HUVECs, and inhibiting type II 5α-reductase activity (the inhibit rate: 82.35 ± 1.02 %). Pharmacodynamic evaluation suggested that TBR effectively led to hair regrowth in C57BL6 mice compared to minoxidil. TBR promoted the hair follicle (HF) transition from the telogen phase to anagen phase by decreasing MDA levels, increasing VEFG expression and up-regulating phosphorylated P38/ERK protein levels in the MAPK signalling pathway. Conclusions TBR reversed AGA via inhibiting SRD5A2 activity and stimulating the MAPK pathway. Meantime, TBR could remodel the follicle microenvironment by reducing oxidative stress and increasing angiogenesis.
Finasteride, a selective Type II 5α-reductase inhibitor, has been approved as an oral drug for the treatment and prevention of androgenetic alopecia (AGA). The daily administration of finasteride by oral route may lead to various undesirable systemic side effects. In the present study, finasteride niosomes (FIN-NIS) as a dermal topical delivery system were developed evaluated in vitro / in vivo in an attempt to overcome the limitations of the oral administration of finasteride, enhance the retention of finasteride into hair follicles, and cause fewer adverse effects. FIN-NIS were prepared by ethanol injection method and characterized for particle size, entrapment efficiency (EE), in vitro release and in vitro skin retention. Testosterone-induced AGA mice model was used to evaluate the therapeutic effect of FIN-NIS. The results show that the particle size of FIN-NIS was about 260 nm with a good loading capacity, and the EE was greater than 90%. FIN-NIS had the sustained-release effect to some extent. Compared with the hydroethanolic solution of finasteride (FIN-hydroethanol) and finasteride suspension (FIN-suspension), FIN-NIS showed higher drug concentration in the excised rat skin, especially in the hair follicle area. The drug accumulation of FIN-NIS in the hair follicles was 20 times higher than that of FIN-hydroalcohol. In addition, FIN-NIS was more effective to promote hair regeneration in AGA mice than FIN-suspension, and the effectiveness of FIN-NIS even exceeded that of minoxidil . In conclusion, FIN-NIS could become a promising dermal topical delivery system for enhancing the performance of finasteride for the management of AGA and avoiding the possible risk of systemic side effects associated with oral administration.
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