Alpinetin promotes hair regeneration via activating hair follicle stem cells

Abstract

Background Alopecia affects millions of individuals globally, with hair loss becoming more common among young people. Various traditional Chinese medicines (TCM) have been used clinically for treating alopecia, however, the effective compounds and underlying mechanism are less known. We sought to investigate the effect of Alpinetin (AP), a compound extracted from Fabaceae and Zingiberaceae herbs, in hair regeneration. Methods Animal model for hair regeneration was mimicked by depilation in C57BL/6J mice. The mice were then topically treated with 3 mg/ml AP, minoxidil as positive control (PC), or solvent ethanol as vehicle control (VC) on the dorsal skin. Skin color changes which reflected the hair growth stages were monitored and pictured, along with H&E staining and hair shaft length measurement. RNA-seq analysis combined with immunofluorescence staining and qPCR analysis were used for mechanism study. Meanwhile, Gli1CreERT2; R26RtdTomato and Lgr5EGFP−CreERT2; R26RtdTomato transgenic mice were used to monitor the activation and proliferation of Gli1+ and Lgr5+ HFSCs after treatment. Furthermore, the toxicity of AP was tested in keratinocytes and fibroblasts from both human and mouse skin to assess the safety. Results When compared to minoxidil-treated and vehicle-treated control mice, topical application of AP promoted anagen initiation and delayed catagen entry, resulting in a longer anagen phase and hair shaft length. Mechanistically, RNA-seq analysis combined with immunofluorescence staining of Lef1 suggested that Lgr5+ HFSCs in lower bulge were activated by AP via Wnt signaling. Other HFSCs, including K15+, Lef1+, and Gli1+ cells, were also promoted into proliferating upon AP treatment. In addition, AP inhibited cleaved caspase 3-dependent apoptosis at the late anagen stage to postpone regression of hair follicles. More importantly, AP showed no cytotoxicity in keratinocytes and fibroblasts from both human and mouse skin. Conclusion This study clarified the effect of AP in promoting hair regeneration by activating HFSCs via Wnt signaling. Our findings may contribute to the development of a new generation of pilatory that is more efficient and less cytotoxic for treating alopecia.

Traditional Chinese Medicine Shi-Bi-Man regulates lactic acid metabolism and drives hair follicle stem cell activation to promote hair regeneration

“…Kang et al reveal Yangxue Shengfa capsule regulates AGA associated genes, including IGF-1, DKK-1, and TGF-β, and promotes cell proliferation of dermal papilla cells [ 9 ]. Xiao et al verify that alpinetin activates HFSCs to promote hair regeneration through Wnt pathway, and has no toxicity to keratinocytes and fibroblasts [ 10 ].…”

Th22 is the effector cell of thymosin β15-induced hair regeneration in mice

“…At present, the number of patients with alopecia is increasing rapidly, regardless of gender and age [ 35 , 36 ]. Hair loss is mainly due to the decrease of hair follicle stem cell activity and hair follicle regeneration ability [ 37 ].…”

Caizhixuan hair tonic regulates both apoptosis and the PI3K/Akt pathway to treat androgenetic alopecia

“…Receiving invasive treatments, such as platelet-rich plasma (PRP) injections and hair transplantation, is often difficult, usually need to be repeated and may lead to a costly investment [22][23][24]. Recently, topical herbal preparations have become more widely available because of their higher rates of compliance, fewer side effects, wider active spectrum and less expensive price [25,26]. As a topical TCM preparation, CZX is expected to be widely used in the complementary and alternative treatment of AGA in the future.…”

“…Astragaloside IV, the active ingredient of A. membranaceus, inhibits apoptosis-regression catagen in hair follicles, leading to hair regrowth [14]. Clinical studies have shown that prescriptions containing herbs from Zingiberaceae have significant therapeutic effects on alopecia [15]. Nevertheless, the bioactive components and pharmacological mechanism of CZX are still unclear.…”