TBG096 stimulates hair regeneration through IGF-1R-mediated angiogenesis.

Current pharmacological treatments for alopecia mainly aim to prevent further hair loss. However, efforts to identify therapeutic agents capable of reactivating the hair cycle have limited success. Herein, we identify that TBG096, a novel natural product-derived molecule with anti-aging properties promotes hair growth. In particular, we investigated hair regeneration effects of topical and oral TBG096 treatments across various models, including female and male rats, naturally aged and dihydrotestosterone (DHT)-induced alopecia model mice. TBG096 facilitated the transition of hair follicles from the telogen to the anagen phase, enhancing hair growth rate in a dose-dependent manner. Mechanistically, TBG096 directly binds and activates insulin-like growth factor 1 receptor (IGF-1R) that in turn activates downstream phosphatidylinositol 3-kinase /protein Kinase B (PI3K/AKT) signaling pathway. IGF-1R/PI3K/AKT activation increased angiogenesis in the dermal papilla to promote hair follicle proliferation and differentiation. Conversely, inhibition of IGF-1R impaired TBG096 mediated angiogenesis and hair regrowth. In addition, TBG096 also reduced DHT levels, increased keratin 15 (k15) expression and regulated growth factors like IGF-1 and epidermal growth factor (EGF), suggesting a restoration of normal follicular function. This is the first study to comprehensively demonstrate that TBG096 effectively promotes hair regeneration independent of age, gender, or application method, making it a promising candidate for treating androgenic alopecia and age-related hair loss.