Kojyl Cinnamate Ester Derivatives Increase Adiponectin Expression and Stimulate Adiponectin-Induced Hair Growth Factors in Human Dermal Papilla Cells.

Adiponectin (APN), released mainly from adipose tissue, is a well-known homeostatic factor for regulating glucose levels, lipid metabolism, and insulin sensitivity. A recent study showed that human hair follicles express APN receptors and the presence of APN-mediated hair growth signaling, thereby suggesting that APN is a potent hair growth-promoting adipokine. Previously, kojyl cinnamate ester derivatives (KCEDs) were synthesized in our institute as new anti-aging or adiponectin-/adipogenesis-inducing compounds. Here, we tested the activity of these derivatives to induce endogenous APN secretion. Among the derivatives, KCED-1 and KCED-2 showed improved activity in inducing APN mRNA expression, secretion of APN protein, and adipogenesis in human subcutaneous fat cells (hSCFs) when compared with the effects of Seletinoid G, a verified APN inducer. When human follicular dermal papilla cells were treated with the culture supernatant of KCED-1- or KCED-2-treated hSCFs, the mRNA expression of APN-induced hair growth factors such as insulin-like growth factor, hepatocyte growth factor, and vascular endothelial growth factor was upregulated compared with that in the control. Taken together, our study shows that among kojyl cinnamate ester derivatives, KCED-1, KCED-2, as well as Seletinoid G are effective inducers of endogenous APN production in subcutaneous fat tissues, which may in turn contribute to the promotion of hair growth in the human scalp.