title: Effect of topical application of raspberry ketone on dermal production of insulin-like growth factor-I in mice and on hair growth and skin elasticity in humans.
abstract: Sensory neurons release calcitonin gene-related peptide (CGRP) on activation. We recently reported that topical application of capsaicin increases facial skin elasticity and promotes hair growth by increasing dermal insulin-like growth factor-I (IGF-I) production through activation of sensory neurons in mice and humans. Raspberry ketone (RK), a major aromatic compound contained in red raspberries (Rubus idaeus), has a structure similar to that of capsaicin. Thus, it is possible that RK activates sensory neurons, thereby increasing skin elasticity and promoting hair growth by increasing dermal IGF-I production. In the present study, we examined this possibility in mice and humans. RK, at concentrations higher than 1 microM, significantly increased CGRP release from dorsal root ganglion neurons (DRG) isolated from wild-type (WT) mice and this increase was completely reversed by capsazepine, an inhibitor of vanilloid receptor-1 activation. Topical application of 0.01% RK increased dermal IGF-I levels at 30 min after application in WT mice, but not in CGRP-knockout mice. Topical application of 0.01% RK increased immunohistochemical expression of IGF-I at dermal papillae in hair follicles and promoted hair re-growth in WT mice at 4 weeks after the application. When applied topically to the scalp and facial skin, 0.01% RK promoted hair growth in 50.0% of humans with alopecia (n=10) at 5 months after application and increased cheek skin elasticity at 2 weeks after application in 5 females (p<0.04). These observations strongly suggest that RK might increase dermal IGF-I production through sensory neuron activation, thereby promoting hair growth and increasing skin elasticity.
authors.affiliation: Department of Translational Medical Science Research, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Harada
authors.forename: Kenji
authors.initials: K
authors.lastname: Okajima
authors.forename: Noriko
authors.initials: N
authors.lastname: Narimatsu
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurihara
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000505:Alopecia / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D002074:Butanones / Q000008:administration & dosage*; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics; D002478:Cells, Cultured; D020405:Dermis / Q000187:drug effects* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004548:Elasticity / Q000187:drug effects; D005260:Female; D006197:Hair / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D008954:Models, Biological; D051381:Rats; D012879:Skin Physiological Phenomena / Q000187:drug effects*
chemical_list: D002074:Butanones; D007334:Insulin-Like Growth Factor I; C035522:raspberry ketone; D015740:Calcitonin Gene-Related Peptide