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Black cohosh (Cimicifuga racemosa) has been used as therapeutics for pain and inflammation in Korean folk medicine. The potential effects of black cohosh extract (BCE) on mast cell-dependent allergy reaction, however, have not been well elucidated yet. In the present study, we investigated the effect of BCE on the allergy reaction using mast cell-dependent in vivo and in vitro models. BCE showed no potential of skin sensitization in local lymph node assay (LLNA). The oral administration of BCE significantly inhibited the anti-IgE-induced passive cutaneous anaphylaxis (PCA) reaction. BCE also showed inhibitory potential on the compound 48/80-induced histamine release from rat peritoneal mast cells. In addition, BCE inhibited the IL-4, IL-5 and TNF-alpha mRNA induction by PMA and A23187 in human leukemia mast cells, HMC-1. These results demonstrated that BCE has an anti-allergic potential and it may be due to the inhibition of histamine release and cytokine gene expression in the mast cells.

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Abstract. Hair regression and balding are distressing concerns for an increasing number of people due to changes in lifestyle and serious nutritional imbalances. Therapies for treatment of hair loss are needed. Among potential therapeutics, adenosine has been suggested as a potent regulator of hair growth. In this study, we investigated the effects of adenosine on hair follicles and dermal papilla (DP) cells, and the mechanism underlying the action of adenosine. Hair follicles are organs, including DP cells, that are responsible for the production of hair fibers by inducing and maintaining the hair growth phase (anagen). In a culture of DP cells in vitro, adenosine stimulated proliferation of DP cells by increasing thymidine uptake. Subsequently, adenosine activated and elongated the anagen phase by increasing the uptake of radiolabeled cysteine in an organ culture of mouse vibrissae hair follicles. We also confirmed that adenosine promoted the expression of several growth factors that are responsible for hair growth, including fibroblast growth factors (FGF)-7, FGF-2, insulin-like growth factor (IGF)-1, and vascular endothelial growth factor (VEGF) in a cDNA microarray with semi-quantitative RT-PCR. Transcriptional activation of β-catenin in DP cells was increased by adenosine in a luciferase assay. β-catenin is a co-activator of Wnt/β-catenin signaling that induces morphogenesis and differentiation of hair follicles and also acts to transactivate downstream signaling pathways, including the ERK pathway. Using Western blotting, we found that adenosine stimulated phosphorylation of ERK, CREB and AKT. These results suggest that adenosine stimulates growth of hair follicles by triggering the expression of growth factors and β-catenin, and by inducing their downstream target signaling pathways.

Cyclosporin A (CsA) has been used as a potent immunosuppressive agent for inhibiting the graft rejection after organ transplantation. However, CsA provokes lots of side effects including hirsutism, the phenomenon of abnormal hair growth in the body. In the present study, we investigated the hair growth stimulating effect of CsA using in vivo and in vitro test models. When topically applied on the back skin of mice, CsA induced fast telogen to anagen transition. In contrast, CsA had no effect on the growth of human hair follicle tissues cultured in vitro, indicating that it might not have the mitogenic effect on hair follicles. To identify the genes related with CsA-induced hair growth, we performed differential display RT-PCR. Among the genes obtained, the expression of synapse associated protein 102 (SAP102) was verified using competitive RT-PCR. The result showed that the expression of SAP102 was significantly induced by CsA treatment in the back skin of C57BL/6 mice. However, the increase of SAP102 mRNA was also seen in spontaneous anagen mice, suggesting that induction of SAP102 is one event of the anagen hair growth response regardless of how the growth state was induced. SAP102 was not expressed in cultured human hair outer root sheath and dermal papilla cells. Immunohistochemistry analysis showed that CsA induced the expression of SAP102 in perifollicular region of mouse anagen hair. Together, these results suggest that SAP102 is one of hair-cycle-dependent genes, whose expression is related with the anagen progression.