Article

Sanguisorba Officinalis Root Extract Has FGF5 Inhibitory Activity and Reduces Hair Loss by Causing Prolongation of the Anagen Period

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Abstract

Tokushima 770-8503, Japan (Director: Prof. S. Arase) FGF-5 inhibitors with FGF-5-antagonizing activity may be effective against hair loss, as these inhibitors suppress the transition of hair follicles from the anagen to catagen phase caused by FGF-5. We screened 24 substances for their FGF-5-antagonizing activity using both an FGF receptor-1c-transfected Ba/F3 cell line and the C3H mouse, and finally detected Sanguisorba Officinalis Root Extract (SO extract) as a reliable FGF-5 inhibitor. Topical application of SO extract elongated the anagen period in C3H mice. In addition, in a clinical study using 39 volunteers with hair loss, the SO extract significantly decreased the telogen /anagen hair ratio and the number of shed hairs. This extract showed a high degree of usefulness clinically. These findings suggest that FGF-5-antagonizing activity of SO extract observed in vitro and in vivo is closely related to its clinical effects.

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... FGF5 inhibition and improving hair loss there is potential for exogenous inhibitors of FGF5 to promote hair growth, as demonstrated by Ito et al. 26 The evidence that FGF5 inhibits hair growth and is involved in the transition from anagen to catagen led us, in our previous work, 27 to screen botanical extracts for FGF5 inhibitory activity. We identified Sanguisorba officinalis root extract (SO extract) as an effective FGF5 inhibitor and demonstrated that SO extract enhanced the multiplication of outer root sheath cells in vitro. ...
... We screened a series of botanical extracts for FGF5 inhibitory activity, including the FGF5 inhibitory SO extract (Maruzen Pharmaceuticals, Onomichi, Japan) described in our previous work, 27 Camellia japonica seed extract (NOF Corporation, Tokyo, Japan) and crude eucalyptus essential oil (EPT extract) (Essentially Australia, Byron Bay, Australia). We also screened a number of isolates from the monoterpene family ( Figure 1) including 3-carene, l-carveol, 1,8-cineole, β-citronellol, dl-rose oxide, geraniol, geranyl acetate, linalool, linalyl acetate, l-menthol, nerol, piperitone, α-terpineol, (−)terpinen-4-ol, (+)terpinen-4-ol and (±)terpinen-4-ol. ...
... We first assessed the ability of test compounds to inhibit FGF5induced proliferation of the engineered FGF receptor 1-expressing BaF3 cell line. 27 The BaF3 cell line used in the study is a cell line engineered to express FGFR1c, originally used to study the splice variant of FGF5 known as FGF5s. 26 The BaF3 cell lineage is IL-3 dependent and responds to the presence of IL-3 by proliferating. ...
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Earlier studies demonstrated that knock-out of fibroblast growth factor-5 gene (Fgf-5) prolonged anagen VI phase of hair cycle, resulting long hairs in the mice. We showed the activities on hair growth of the two Fgf-5 gene products, one of which, FGF-5 suppressed hair growth by inhibiting anagen proceeding and inducing the transition from anagen to catagen, and FGF-5S, a shorter polypeptide with FGF-5-antagonizing activity translated from alternatively spliced mRNA, suppressed this activity of FGF-5. As the results suggested that FGF-5 antagonist would increase hair growth, we synthesized various peptides having partial sequences of human FGF-5 and FGF-5S and determined their FGF-5 antagonist activity. Among them, a decapeptide designated P3 (95-VGIGFHLQIY-104) that aligns with receptor binding sites of FGF-1 and FGF-2 suppressed FGF-5-induced proliferation of BALB/3T3 A31 and NIH/3T3 murine fibroblasts, and FGF receptor-1c (FGFR-1c)-transfected Ba/F3 cell line (FR-Ba/F3 cells). IC50s of this peptide on these cell proliferations were 64, 28, 146 microM, respectively. On the other hand, IC50 of this peptide on binding of FGF-5 to the FGFR-1(IIIc)/Fc chimera was 483 microM. Examination in dorsal depilated mice revealed that the P3 peptide reduced the activity of FGF-5 to recover hair pigmentation and hair follicle lengths. The classification of histologically observed skin sections showed FGF-5-induced delations of anagen procedure had reduced by the P3 peptide. The anti-Ki67 antibody staining of hair follicles was inhibited by administration of FGF-5, and this inhibition by FGF-5 was recovered by administration of the P3 peptide. The P3 peptide alone did not affect hair follicle length and hair cell proliferation. These results indicate that the decapeptide antagonized FGF-5 activity in vivo, and reduced the inhibition of FGF-5 in hair growth, confirming that FGF-5 inhibitors are promising substances against hair loss and/or for promoting hair growth.