Tectoridin Stimulates the Activity of Human Dermal Papilla Cells and Promotes Hair Shaft Elongation in Mouse Vibrissae Hair Follicle Culture.

To search hair growth-promoting herbal extract, a screening platform of having HEK293T fibroblast being transfected with pTOPFLASH DNA construct was developed over a thousand of herbal extracts and phytochemicals were screened. One of the hits was ethanolic extract of Rhizoma Belamcandae, the rhizome of Belamcanda chinensis (L.) DC. Tectoridin, an isoflavone from Rhizoma Belamcandae, was shown to be responsible for this activation of promoter construct, inducing the transcription of pTOPFLASH in the transfected fibroblasts in a dose-dependent manner. The blockage by DKK-1 suggested the action of tectoridin could be mediated by the Wnt receptor. The hair growth-promoting effects of tectoridin were illustrated in human follicular dermal papilla cells and mouse vibrissae organ cultures. In tectoridin-treated dermal papilla cultures, an activation of Wnt signaling was demonstrated by various indicative markers, including TCF/LEF1 transcriptional activity, nuclear translocation of ß-catenin, expressions level of mRNAs encoding axin-related protein, (AXIN2), ß-catenin, lymphoid enhancer-binding factor-1 (LEF-1), insulin-like growth factor 1 (IGF-1) and alkaline phosphatase (ALP). In addition, an increase of hair shaft elongation was observed in cultured mouse vibrissae upon the treatment of tectoridin. Tectoridin, as well as the herbal extract of Rhizoma Belamcandae, possesses hair promoting activity, which deserves further development.

Amauroderma rugosum Protects PC12 Cells against 6-OHDA-Induced Neurotoxicity through Antioxidant and Antiapoptotic Effects.

Amauroderma rugosum (AR) is a dietary mushroom in the Ganodermataceae family whose pharmacological activity and medicinal value have rarely been reported. In this study, the antioxidant capacity and neuroprotective effects of AR were investigated. The aqueous extract of AR was confirmed to contain phenolic compounds, polysaccharides, and triterpenes. The results of 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and total antioxidant capacity assays revealed that AR extract scavenged reactive oxygen species. Moreover, AR extract decreased the cytotoxicity, oxidative stress, mitochondrial dysfunction, and apoptosis of PC12 cells induced by 6-hydroxydopamine (6-OHDA). In addition, 6-OHDA upregulated the expressions of proapoptotic proteins and downregulated the Akt (protein kinase B)/mTOR- (mammalian target of rapamycin-) and MEK (mitogen-activated protein kinase kinase)/ERK- (extracellular signal-regulated kinases-) dependent signaling pathways. These effects of 6-OHDA were abolished or partially reversed by AR extract. Furthermore, the neuroprotective effects of AR in 6-OHDA-treated PC12 cells were significantly abolished by Akt and MEK inhibitor. Thus, AR extract possesses neuroprotective effects, probably through its antioxidant and antiapoptotic effects. These findings suggest the potential application of AR in the prevention or treatment of oxidative stress-related neurodegenerative diseases such as Parkinson's disease.

Progressive expression of PPARGC1α is associated with hair miniaturization in androgenetic alopecia.

Current opinion views androgens as the pathogenic driver in the miniaturization of hair follicles of androgenetic alopecia by interfering with the dermal papilla. This cannot be the sole cause and therefore it is important for therapeutic and diagnostic purposes to identify additional pathways. Comparative full transcriptome profile analysis of the hair bulb region of normal and miniaturized hair follicles from vertex and occipital region in males with and without androgenetic alopecia revealed that next to the androgen receptor as well the retinoid receptor and particularly the PPAR pathway is involved in progressive hair miniaturization. We demonstrate the concurrent up-regulation of PPARGC1a in the epithelial compartment and androgen receptor in the dermal papilla of miniaturized hair. Dynamic Ppargc1a expression in the mouse hair cycle suggests a possible role in regulating hair growth and differentiation. This is supported by reduced proliferation of human dermal papilla and predominantly epithelial keratinocytes after incubation with AICAR, the agonist for AMPK signaling which activates PPARGC1a and serves as co-activator of PPARγ. In addition, miRNA profiling shows enrichment of miRNA-targeted genes in retinoid receptors and PPARGC1α/PPARγ signaling, and antigen presentation pathways.

Microbiome in the hair follicle of androgenetic alopecia patients.

Androgenetic alopecia is the most common form of hair loss in males. It is a multifactorial condition involving genetic predisposition and hormonal changes. The role of microflora during hair loss remains to be understood. We therefore analyzed the microbiome of hair follicles from hair loss patients and the healthy. Hair follicles were extracted from occipital and vertex region of hair loss patients and healthy volunteers and further dissected into middle and lower compartments. The microbiome was then characterized by 16S rRNA sequencing. Distinct microbial population were found in the middle and lower compartment of hair follicles. Middle hair compartment was predominated by Burkholderia spp. and less diverse; while higher bacterial diversity was observed in the lower hair portion. Occipital and vertex hair follicles did not show significant differences. In hair loss patients, miniaturized vertex hair houses elevated Propionibacterium acnes in the middle and lower compartments while non-miniaturized hair of other regions were comparable to the healthy. Increased abundance of P. acnes in miniaturized hair follicles could be associated to elevated immune response gene expression in the hair follicle.

Aging in hair follicle stem cells and niche microenvironment.

Hair graying and hair loss are prominent and common characteristics of the elderly population. In some individuals these processes can significantly impact their quality of life, leading to depression, anxiety and other serious mental health problems. Accordingly, there has been much interest in understanding the complex physiological changes within the hair follicle in the aging individual. It is now known that hair follicles represent a prototypical stem cell niche, where both micro- and macroenvironmental influences are integrated alongside stem cell-stem cell and stem cell-stem niche interactions to determine hair growth or hair follicle senescence. Recent studies have identified imbalanced stem cell differentiation and altered stem cell activity as important factors during hair loss, indicating new avenues for the development of therapeutic agents to stimulate hair growth. Here, we pull together the latest findings on the hair follicle stem cell niche and the multifactorial interactions underlying the various forms of hair loss.