Ginsenosides Rb₁ and Rd Regulate Proliferation of Mature Keratinocytes Through Induction of p63 Expression in Hair Follicles

Abstract

Ginsenosides Rb₁ and Rd are the two main types of ginsenosides in Panax ginseng and have been used as an additive to against alopecia. However, the mechanisms involved are largely unknown. To determine how ginsenosides prevent hair loss, we topically applied protopanaxadiol-type ginsenosides Rb₁ and Rd over the shaved skin of B57CL/6 mice, and monitored and assessed them for 35 days. We then investigated the effects of ginsenosides on cell genesis in different phases of adult hair follicles (HFs), using 5-bromo-2'-deoxyuridine as a marker for dividing cells. Moreover, p63, a specific marker and a major regulator of keratinocyte progenitor cells of the multi-layered epithelia, was detected in epidermis. Results indicated that treatment with ginsenosides Rb₁ and Rd increased cell proliferation in both anagen and telogen of HFs. However, it had no significant effect on the survival of cells in the bulge and upper follicle region. Investigation of p63 demonstrated that up-regulation of p63 expression in the matrix and outer root sheath might be one of the mechanisms by which ginsenosides Rb₁ and Rd promote cell proliferation in HFs. Our study reveals a novel mechanism by which ginsenoside promotes hair growth through p63 induction in follicular keratinocytes and indicates that ginsenosides Rb₁ and Rd might be developed as a therapeutic agent for the prevention of hair loss.

Ginsenosides and their metabolites: a review of their pharmacological activities in the skin

“…However, the potential applications for ginsenoside Rd in cosmeceuticals have been suggested in several previous papers [36,44,64]. Sung et al [36] demonstrated the wound healing effect of ginsenoside Rd using keratinocyte progenitor cells and human dermal fibroblasts, which was later confirmed by a laser burn wound model.…”

“…In a previous study, ginsenoside Rg3 induced the intrinsic apoptotic pathway in hepatocellular carcinoma (HCC) cells by altering apoptosis-related gene expression. In addition, it was observed Down-regulate the expression of p16, p21 and p53 [5,65] Hair loss prevention Induction of p63 expression [44] Rd Immune-suppression Reduce the CD4(?) and CD8(?)…”

“…After treatment with ginsenoside Rd on the skin, cell genesis in different phases of adult hair follicles was investigated. The results indicated that ginsenoside Rd promotes hair growth via cell growth acceleration, with the underlying mechanism of ginsenoside Rd proposed to be the induction of p63 expression in hair follicles [44].…”

“…and CD8(?) T cells [64] Hair loss prevention Induction of p63 expression [44] Wound healing Increase of intracellular cAMP levels and phosphorylated CEBP expression in nucleus [36] Rg3 Antitumor Reduce TPA-induced activation of NF-jB and ERK Down-regulation of NF-jB and AP-1 transcription factors [8,28,61] Anti-scar formation Decrease of VEGF and collage Type I [12,60] Compound K Antiwrinkle formation Up-regulate production of type I collagen [17] Photoprotection Increase the expression of NER complex, such as XPC and ERCC1 [6] Skin hydration Induce HAS1 upregulation and HA production [34] Anti-atopic dermatitis Reduce MDC level in serum, eosinophils' infiltration and mast cells in skin, and cytokine production in splenocytes [31] Arch Dermatol Res that ginsenoside Rg3 not only inhibits HCC tumor growth and pathology in an animal model, but also improves overall survival [22]. Mitochondrial-mediated apoptosis pathways have also been suggested as another mechanism of action for ginsenoside Rg3 [52], which increases cellular reactive oxygen species (ROS) production and subsequent accumulation of cytochrome C in the cytosol.…”

“…Many researchers have thus sought to unravel the underlying molecular mechanisms responsible for the purported beneficial effects of ginsenosides on human health [30,36,43,44]. Thirty-one ginsenosides have been identified to date, with some novel ginsenosides recently reported.…”