| The hair follicle, a unique characteristic organ of mammals, represents a stem cell-rich, prototypic neuroectodermal-mesodermal interaction sysytem. A unique feature of hair follicles is their cyclical behavior. Starting with anagen, the hair follicle and its shaft pass through catagen, telogen, and finally exogen. The dermal papilla is necessary to both induce and maintain the hair follicle. The volume of the dermal papilla, which is determined by the number of matrix cells in the hair bulb, determines the diameter of the induced hair shaft and may also determine the duration of anagen. In the other hand, the dermal papilla cells also play an important role in determining and maintaining the proliferation and differentiation of the matrix cells in the hair bulb, which is the key point controlling the hair growth. Epithelial-mesenchymal interactions play pivotal roles during the hair cycle. As it is known, dermal papilla cells produce many kinds of growth factors and cytokines, including insulin-like growth factor (IGF)-1, fibroblast growth factor (FGF)-7, hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), tumour necrosis factor (TNF)-αand interleukin (IL)-1, IL-6. These cytokines, growth factors and other transcription factors, neuropeptides and enzymes form molecular signaling pathways which are involved in regulating hair follicle cycling. Recently, the studies showed that VEGF played an essential role in hair cycle and hair growth, which could be blocked by VEGF neutralizing antibodies. These results confirmed that VEGF was an autocrine growth factor of hair dermal papilla cells. It was assumed that VEGF regulated hair cycle and hair growth by two following possible mechanisms:The first, VEGF stimulated dermal papilla cell proliferation and migration. VEGF could obviously promote cell proliferation and migration when different concentrations of VEGF were incubated with mouse bristle dermal papilla cells. VEGF maybe regulated hair cycle and hair growth through inducing dermal papilla cells proliferation and migration.The second, VEGF induced perifollicular vascularization in anagen. The periodical cycling of hair follicle is accompanied by the changes of perifollicular vascularization. There is a significant increase of perifollicular vascularization during the growth phase of the hair cycle, followed by regression of angiogenic blood vessels during the involution and the resting phase. Perifollicular angiogenesis was temporally and spatially correlated with upregulation of VEGF mRNA expressed by follicular keratinocytes of the outer root sheath. Transgenic overexpression of VEGF in outer root sheath keratinocytes of hair follicles strongly induced perifollicular vascularization, resulting in accelerated hair regrowth after depilation and increased size of hair follicles and hair shaft elongation. Conversely, systemic treatment with a neutralizing anti-VEGF antibody led to hair growth retardation and the diminution of hair follicle size.The use of plants is as old as mankind. Traditional Chinese medicinal herb is very popular in clinical therapy of hair loss. In this research, we try to screen effective ingredients such as baicalin, oleanolic acid and licorice, to study their effects on DPCs proliferation, VEGF secretion of DPCs and hair growth in vitro.The thesis consists of two parts:Part one: The effects of baicalin, oleanolic acid and licorice on the cell proliferation and VEGF synthesis in human dermal papillce cellsNormal human dermal papilla cells (DPCs) were isolated from human hair follicle, which were incubated with baicalin, oleanolic acid and licorice in different concentrations for 72h respectively. The rate of cell proliferation was measured by methyl thiazolyl tetrazolium (MTT) method and VEGF protein synthesis was investigated using a VEGF ELISA kit. Baicalin (below 60.0μg/mL), oleanolic acid (below 50.0μg/mL) and licorice (below 30.0μg/mL) had no effect on cell proliferation of DPCs. VEGF protein synthesis was significantly elevated in the treated DPCs with baicalin and licorice compared with controls, but oleanolic acid in different concentration had no effect on VEGF protein synthesis. We conclude that baicalin and licorice stimulates VEGF protein synthesis in human DPCs, which may play a role in increasing hair growth.Part two: The effects of baicalin, oleanolic acid and licorice on human hair follicles in vitroBy observing the hair growth, morphological change in the bulb of hair follicle we studied the biology of human hair follicles in the anagen stage of hair cyele cultured with baicalin, oleanolic acid and licorice in different concentrations in vitro. The follicles cultured with baicalin (7.5μg/mL, 15.0μg/mL, 30.0μg/mL and 45.0μg/mL) and oleanolic acid (20.0μg/mL, 30.0μg/mL and 40.0μg/mL) kept growing over 8 days and produced fine growing fibers significantly faster than that in the control group (P＜0.05). The morphology study showed that the follicles treated with 30.0ng/mL baicalin and 30.0μg/mL oleanolic acid still kept anagen-like pattern at the day 8 of culture, but those in the control group showed catagen/tolegen-like pattern. Licorice with different concentrations had on effect on the hair growth in vitro. The study showed that baicalin and oleanolic acid remarkably stimulated the hair growth of human hair follicles cultured in vitro and we considered it may be due to prolonging of the anagen phase of the hair growth cycle. Our results suggest baicalin promote the growth of cultured human hair follicles and stimulate VEGF protein synthesis in human dermal papilla cells, which might contribute to the observed hair growth-promoting effects. Oleanolic acid promotes hair growth not by upregulating VEGF synthesis. |
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