Effects of Hura crepitans and Its Active Ingredient, Daphne Factor F3, on Dihydrotestosterone-Induced Neurotrophin-4 Activation and Hair Retardation

Abstract

Neurotrophin (NT)-4 is known to be an inducer of catagen in the hair cycle, but little is known of its role in the pathogenesis of androgenetic alopecia (AGA). We previously studied the gene expression of dermal papilla cells from AGA patients and controls and found that NT-4 was up-regulated in the AGA patients. In the present study, the etiological relationship between NT-4 and androgen, which is one of the causes of AGA, and the effect of an NT-4 inhibitor on hair growth were investigated. We established a NT-4 luciferase reporter assay system using a roughly 2-kb region upstream of the NT-4 transcriptional start site and investigated an accelerating effect of androgen on NT-4 transcription. We also screened for a NT-4 inhibitor by using the NT-4 reporter assay and evaluated the effects of NT-4 inhibitors on hair growth by using dihydrotestosterone (DHT)-implanted mice. The results show that transcriptional activity of NT-4 was accelerated by androgen, and extract of Hura crepitans L. inhibited the DHT-induced NT-4 transcriptional activation and ameliorated the retardation of hair regrowth by DHT-implanted mice. We also isolated the active ingredient in H. crepitans and found its structure to be that of 6,7-epoxy-5-hydroxyresiniferonol-14-(2,4-tetradecadienoate), i.e., daphne factor F3. These findings demonstrated that NT-4 activity accelerated by androgen might contribute to the pathogenesis of AGA and indicated that NT-4 inhibitors such as H. crepitans and daphne factor F3 might have a salutary effect on AGA.

Hepatoprotective Potential of Hura crepitans L.: A Review of Ethnomedical, Phytochemical and Pharmacological Studies

“…Uchiyama and colleagues [45] obtained the bioactive compound in Hura crepitans stem-bark; 6,7-epoxy-5-hydroxyresiniferonol-14-(2,4-tetradecadienoate) also called daphne factor F3 (Fig. 2).…”

“…They showed that Hura crepitans extract and the constituent active compound, daphne factor F3, inhibits neurotrophin-4 (NT-4) activity, thus improving hair regrowth in mice implanted with dihydrotestosterone (DHT). Their study showed unequivocally that Hura crepitans or its active compound has ameliorative effect on androgenetic alopecia (AGA) [45]. The mechanism by which Hura crepitans exerts the effect of hair growth has not been fully elucidated especially as it concerns NT-4 expression in the hair follicles of mice in which there have been implantation of DHT [45].…”

“…Their study showed unequivocally that Hura crepitans or its active compound has ameliorative effect on androgenetic alopecia (AGA) [45]. The mechanism by which Hura crepitans exerts the effect of hair growth has not been fully elucidated especially as it concerns NT-4 expression in the hair follicles of mice in which there have been implantation of DHT [45]. It The mechanisms and activity of androgen receptor (AR) and NT-4 that is inhibited by Hura crepitans has also not been sufficiently demonstrated.…”

“…Source: Uchiyama et al [45] It is the opinion however that much more profound biochemical research still need to be done to establish the hepatoprotective potentials Hura crepitans. This tree planted traditionally in the tropical rain ally for the shade which its canopy offers may yet turn out to be a great discovery in the quest for alternative healing remedies.…”

Alternative Medicine for Hair Loss

“…While H. crepitans from Peru possesses hair regrowth activity, H. crepitans from Brazil is not affect hair growth. Because, the daphne factor F3 content of H. crepitans from Peru is about 30 times more than H. crepitans from Brazil [109,110]. It has been suggested that H. crepitans inhibits the retardation of hair regrowth by DHT through inhibition the neurotrophin (NT)-4 activation induced by DHT [109].…”