Fisetin Promotes Hair Growth by Augmenting TERT Expression

Abstract

Although thinning hair and alopecia are not recognized as severe diseases, hair loss has implications for mental health and quality of life; therefore, a large number of studies have been carried out to develop novel hair growth agents. In the present study, we aimed to examine the potential of telomerase reverse transcriptase (TERT), because TERT overexpression in skin activates resting hair follicle bulge stem cells, which triggers initiation of a new hair follicle growth phase and promotes hair synthesis. To this end, we screened polyphenols that activate TERT expression in keratinocytes, and identified resveratrol and fisetin as strong hTERT-augmenting compounds. These polyphenols also regulated the gene expression of cytokines such as IGF-1 and KGF, which activate the β-catenin pathway, and TGF-β1, which plays an important role in maintaining the niche of hair follicle stem cells, thus are thought to play roles in promoting hair growth. We additionally showed that these polyphenols, especially fisetin, promoted hair growth from the shaved dorsal skin of mice, which suggests that these polyphenols activate the transition from telogen to anagen phase. Histological studies indicated that the dorsal skin of mice treated with these polyphenols contained numerous hair follicles and was thickened compared with that in control mice. Furthermore, on the dorsal skin of mice treated with resveratrol and fisetin, a number of proliferating cells (Ki67 + cells) were observed around the hair papilla. These results suggest that resveratrol and fisetin induce a shift from telogen to anagen in the hair follicle by inducing proliferation of hair follicle bulge stem cells, thus promoting hair growth.

Exosomes Derived from Fisetin-Treated Keratinocytes Mediate Hair Growth Promotion

“…RNA was extracted from cells and skin samples using the High Pure RNA Isolation Kit (Roche Diagnostics GmbH, Mannheim, Germany) and RNeasy Fibrous Tissue Mini Kit (Qiagen, Hilden, Germany), respectively, according to the manufacturers’ instructions. cDNA synthesis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were performed, as described previously [ 3 , 10 ]. Samples were analyzed in triplicate, and gene expression levels were normalized to the corresponding β-actin gene level.…”

“…Samples were analyzed in triplicate, and gene expression levels were normalized to the corresponding β-actin gene level. The PCR primer sequences were described previously [ 3 ].…”

“…In a previous study, we constructed a system for screening food components that can activate the TERT promoter in keratinocytes and identified fisetin, a type of polyphenol. Fisetin activated keratinocytes, promoted hair growth, increased skin thickness, activated β-catenin, and increased the proliferation of HFSCs [ 3 ].…”

Integrating Ethnobotany, Phytochemistry, and Pharmacology of Cotinus coggygria and Toxicodendron vernicifluum: What Predictions can be Made for the European Smoketree?

“…A recent study showed that fisetin stimulates hair growth. When applied topically in C57BL/6 mice, fisetin acts on hair growth by stimulating the transition from telogen to anagen phase, effect related to its activity on TERT (telomerase reverse transcriptase) expression in the dorsal skin cells of treated mice (Kubo et al, 2020).…”

Potential of Naturally Derived Compounds in Telomerase and Telomere Modulation in Skin Senescence and Aging

“…Unsaturated omega-3 fatty acids, present in fish oil, and omega-6, which are found in vegetable oils, play a significant role in maintaining the proper redox balance in cells. Fermented fish oil (FFO) has been shown to reduce ROS production and inhibit MMPs [158]. Vegetable fats also have a beneficial effect on skin conditions.…”