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

• Published in: Growth hormone & IGF research Vol. 18; no. 4; pp. 335 - 344
• Main Authors: Harada, Naoaki, Okajima, Kenji, Narimatsu, Noriko, Kurihara, Hiroki, Nakagata, Naomi
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.08.2008
• Subjects: Administration, Topical; Adolescent; Adult; Advanced Basic Science; Alopecia - drug therapy; Alopecia - metabolism; Animals; Butanones - administration & dosage; Calcitonin gene-related peptide; Calcitonin Gene-Related Peptide - genetics; Cells, Cultured; Dermis - drug effects; Dermis - metabolism; Drug Evaluation, Preclinical; Elasticity - drug effects; Endocrinology & Metabolism; Female; Hair - drug effects; Hair - growth & development; Hair growth; Humans; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factor-I; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Models, Biological; Raspberry ketone; Rats; Sensory neurons; Skin elasticity; Skin Physiological Phenomena - drug effects; Calcitonin gene-related peptide; Insulin-like growth factor-I; Sensory neurons; Skin elasticity; Raspberry ketone; Hair growth
• ISSN: 1096-6374; 1532-2238
• DOI: 10.1016/j.ghir.2008.01.005

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 μM, 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.