Article

Promotion of hair growth by newly synthesized ceramide mimetic compound

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Abstract

Based on the crucial roles of ceramides in skin barrier function, use of ceramides or their structural mimetic compounds, pseudoceramides, as cosmetic ingredients are getting more popular. While currently used pseudoceramides are intended to substitute the structural roles of ceramides in stratum corneum, development of bioactive pseudoceramides has been repeatedly reported. In this study, based on the potential involvement of sphingolipids in hair cycle regulation, we investigated the effects of newly synthesized pseudoceramide, bis-oleamido isopropyl alcohol (BOI), on hair growth using cultured human hair follicles and animal models. BOI treatment promoted hair growth in cultured human hair follicles ex vivo and induced earlier conversion of telogen into anagen. Although we did not find a significant enhancement of growth factor expression and follicular cell proliferation, BOI treatment resulted in an increased sphinganine and sphingosine contents as well as increased ceramides contents in cultured dermal papilla (DP) cells. Taken together, our data strongly suggest that biologically active pseudoceramide promotes hair growth by stimulating do novo synthesis of sphingolipids in DP cells.

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... Several peptide complexes, proteins and mimetics have also displayed significant hair growth potential in DPCs [139][140][141][142][143][144][145][146]. Squarticles are the nanoparticles formed from sebum-derived lipids such as squalene and fatty esters to achieve targeted drug delivery to the follicles. ...
... Hair-fiber length of vibrissae follicles (↑) [47] Crataegus pinnatifida extract Human DPC Proliferation (↑) ERK, p-38, JNK, Akt (↑) Orally administered, Anagen induction in C57BL/6 mice, Bcl-2/ Bax in skin (↑) [48] Origanum vulgare extract Human DPC No cytotoxicity or increase in proliferation by sulforhodamine (SRB) assay (↑) Topically applied, hair growth in C57BL/6 mice, IGF-1 in skin (↑) [49] *Wheat Bran (n-hexane fraction) Ceramide mimetic Human DPC Sphinganine, sphingosine, ceramides (↑) Promotion of hair growth in ex vivo cultured human hair follicles, earlier conversion of telogen into anagen [146] Table II (continued) ...
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Hair disorders such as hair loss (alopecia) and androgen dependent, excessive hair growth (hirsutism, hypertrichosis) may impact the social and psychological well‐being of an individual. Recent advances in understanding the biology of hair have accelerated the research and development of novel therapeutic and cosmetic hair growth agents. Preclinical models aid in dermocosmetic efficacy testing and claim substantiation of hair growth modulators. The in vitro models to investigate hair growth utilize the hair follicle Dermal Papilla cells (DPCs), specialized mesenchymal cells located at the base of hair follicle that play essential roles in hair follicular morphogenesis and postnatal hair growth cycles. In this review, we have compiled and discussed the extensively reported literature citing DPCs as in vitro model to study hair growth promoting and inhibitory effects. A variety of agents such as herbal and natural extracts, growth factors and cytokines, platelet‐rich plasma, placental extract, stem cells and conditioned medium, peptides, hormones, lipid‐nanocarrier, light, electrical and electromagnetic field stimulation, androgens and their analogs, stress‐serum and chemotherapeutic agents etc. have been examined for their hair growth modulating effects in DPCs. Effects on DPCs’ activity were determined from untreated (basal) or stress induced levels. Cell proliferation, apoptosis and secretion of growth factors were included as primary end‐point markers. Effects on a wide range of biomolecules and mechanistic pathways that play key role in the biology of hair growth were also investigated. This consolidated and comprehensive review summarizes the up‐to‐date information and understanding regarding DPCs based screening models for hair growth and may be helpful for researchers to select the appropriate assay system and biomarkers. This review highlights the pivotal role of DPCs in the forefront of hair research as screening platforms by providing insights into mechanistic action at cellular level, which may further direct the development of novel hair growth modulators. This article is protected by copyright. All rights reserved.
... Various plant extracts and chemicals with hair-growthstimulating effects have been reported. Although precise underlying mechanisms remain unknown, these extracts and chemicals are considered to elicit these effects by accelerating blood flow, inducing a shift from telogen to anagen, mediating activation of the dermal papilla, inhibiting dihydrotestosterone, and exerting anti-inflammatory effects (Junlatat and Sripanidkulchai, 2014;Kim et al., 2014;Park et al., 2017;Shen et al., 2018;Zhang et al., 2019;Zhou et al., 2020). The hair follicle contains several different types of cells; among these, the dermal papilla cells are major components of hair that play a critical role in inducing anagen phase and maintaining hair growth. ...
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Although thinning hair and alopecia are not recognized as severe diseases, hair loss has implications for mental health and quality of life; therefore, a large number of studies have been carried out to develop novel hair growth agents. In the present study, we aimed to examine the potential of telomerase reverse transcriptase (TERT), because TERT overexpression in skin activates resting hair follicle bulge stem cells, which triggers initiation of a new hair follicle growth phase and promotes hair synthesis. To this end, we screened polyphenols that activate TERT expression in keratinocytes, and identified resveratrol and fisetin as strong hTERT-augmenting compounds. These polyphenols also regulated the gene expression of cytokines such as IGF-1 and KGF, which activate the β-catenin pathway, and TGF-β1, which plays an important role in maintaining the niche of hair follicle stem cells, thus are thought to play roles in promoting hair growth. We additionally showed that these polyphenols, especially fisetin, promoted hair growth from the shaved dorsal skin of mice, which suggests that these polyphenols activate the transition from telogen to anagen phase. Histological studies indicated that the dorsal skin of mice treated with these polyphenols contained numerous hair follicles and was thickened compared with that in control mice. Furthermore, on the dorsal skin of mice treated with resveratrol and fisetin, a number of proliferating cells (Ki67+ cells) were observed around the hair papilla. These results suggest that resveratrol and fisetin induce a shift from telogen to anagen in the hair follicle by inducing proliferation of hair follicle bulge stem cells, thus promoting hair growth.
... loss prevention and hair growth enhancement 7 . In particular, ceramide synthase 4 (CerS4) plays an important role in the maintenance of epidermal stem cell homeostasis and regulation of the hair cycle by regulating Wnt signal and BMP signal 8 . ...
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