Harada Naoaki, Okajima Kenji, Arai Masatoku, Kurihara Hiroki, Nakagata Naomi
Department of Translational Medical Science Research, Nagoya City University, Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Growth Horm IGF Res. 2007 Oct;17(5):408-15. doi: 10.1016/j.ghir.2007.04.009. Epub 2007 Jun 13.
Insulin-like growth factor-I (IGF-I) plays an important role in hair growth. Capsaicin activates vanilloid receptor-1, thereby increasing the release of calcitonin gene-related peptide (CGRP) from sensory neurons, and CGRP has been shown to increase IGF-I production. We recently reported that isoflavone, a phytoestrogen, increases production of CGRP by increasing its transcription in sensory neurons. These observations raise the possibility that administration of capsaicin and isoflavone might promote hair growth by increasing IGF-I production. In the present study, we examined this possibility in mice and humans with alopecia.
Dermal IGF-I levels, immunohistochemical expression of IGF-I in the skin and hair regrowth were examined after capsaicin and isoflavone administration to wild-type (WT) mice and CGRP-knockout mice. Plasma levels of IGF-I and promotion of hair growth were evaluated in 48 volunteers with alopecia after administration of capsaicin and isoflavone for 5 months.
Subcutaneous administration of capsaicin significantly increased dermal IGF-I levels at 30 min after administration in WT mice (p < 0.01), but not in CGRP-knockout mice. Dermal levels of IGF-I were significantly higher in WT mice administered capsaicin and isoflavone for 4 wks than in those administered capsaicin alone for 4 wks (p < 0.01) and in those administered neither of them (p < 0.01). Immunohistochemical expression of IGF-I at dermal papillae in hair follicles was increased in WT mice administered capsaicin and isoflavone and in those administered capsaicin alone at 4 wks. Hair regrowth was clearly more accelerated in WT mice administered capsaicin and isoflavone for 4 wks than in those administered capsaicin alone for 4 wks and in those administered neither of them. Plasma levels of IGF-I were significantly increased from baseline levels in 31 volunteers with alopecia at 5 months after oral administration of capsaicin (6 mg/day) and isoflavone (75 mg/day) (p < 0.01), while they were not increased in 17 volunteers with alopecia administered placebo. The number of volunteers with alopecia who showed promotion of hair growth at 5 months after administration was significantly higher among volunteers administered capsaicin and isoflavone (20/31: 64.5%) than among those administered placebo (2/17: 11.8%) (p < 0.01).
These observations strongly suggested that combined administration of capsaicin and isoflavone might increase IGF-I production in hair follicles in the skin, thereby promoting hair growth. Such effects of capsaicin and isoflavone might be mediated by sensory neuron activation in the skin.
胰岛素样生长因子-I(IGF-I)在毛发生长中起重要作用。辣椒素激活香草酸受体-1,从而增加感觉神经元中降钙素基因相关肽(CGRP)的释放,并且已表明CGRP可增加IGF-I的产生。我们最近报道,植物雌激素异黄酮通过增加其在感觉神经元中的转录来增加CGRP的产生。这些观察结果提示,给予辣椒素和异黄酮可能通过增加IGF-I的产生来促进毛发生长。在本研究中,我们在患有脱发的小鼠和人类中检验了这种可能性。
对野生型(WT)小鼠和CGRP基因敲除小鼠给予辣椒素和异黄酮后,检测皮肤中IGF-I水平、IGF-I的免疫组化表达以及毛发生长情况。对48名脱发志愿者给予辣椒素和异黄酮5个月后,评估其血浆IGF-I水平和毛发生长促进情况。
皮下注射辣椒素后30分钟,WT小鼠皮肤中IGF-I水平显著升高(p<0.01),而CGRP基因敲除小鼠中未升高。给予辣椒素和异黄酮4周的WT小鼠皮肤中IGF-I水平显著高于仅给予辣椒素4周的小鼠(p<0.01)以及未给予任何一种药物的小鼠(p<0.01)。给予辣椒素和异黄酮以及仅给予辣椒素4周的WT小鼠毛囊真皮乳头处IGF-I的免疫组化表达增加。给予辣椒素和异黄酮4周的WT小鼠毛发生长明显比仅给予辣椒素4周以及未给予任何一种药物的小鼠加速更快。口服辣椒素(6毫克/天)和异黄酮(75毫克/天)5个月后,31名脱发志愿者的血浆IGF-I水平较基线水平显著升高(p<0.01),而给予安慰剂的17名脱发志愿者血浆IGF-I水平未升高。给予辣椒素和异黄酮的志愿者中,给药5个月后出现毛发生长促进的人数显著高于给予安慰剂的志愿者(20/31:64.5%比2/17:11.8%)(p<0.01)。
这些观察结果强烈提示,联合给予辣椒素和异黄酮可能增加皮肤毛囊中IGF-I的产生,从而促进毛发生长。辣椒素和异黄酮的这种作用可能是通过激活皮肤中的感觉神经元介导的。