Inhibition of HYBID (KIAA1199)-mediated hyaluronan degradation and anti-wrinkle effect of Geranium thunbergii extract.

Abstract

Hyaluronan (HA) is an essential constituent of extracellular matrix in the skin. HA reduction in the dermis and overexpression of HYBID (KIAA1199), a key molecule for HA degradation in skin fibroblasts, are implicated in facial skin wrinkling. We aimed to obtain anti-wrinkle agent(s) by screening for inhibition of HYBID-mediated HA degradation. Various plant extracts were screened for inhibition of HA degradation in HYBID-stable transfectants in HEK293 (HYBID/HEK293). Inhibition of HA-degrading activity and HYBID mRNA and protein expression by Geranium thunbergii extract was studied in skin fibroblasts and HYBID/HEK293 cells. Size distribution of newly produced HA was evaluated by preparing metabolically radiolabeled HA in skin fibroblasts. A double-blind, randomized, and placebo-controlled study was performed in healthy Japanese women (n=21) by topically treating each side of the face with a lotion formulated with G.thunbergii extract or placebo for 8weeks. Among the plant extracts tested, only G.thunbergii extract abolished HA depolymerization in skin fibroblasts and HYBID/HEK293 cells by down-regulating HYBID mRNA and protein expression and by inhibiting HYBID-mediated HA-degrading activity. Although untreated skin fibroblasts produced polydispersed HA, G.thunbergii extract-treated cells produced high-molecular-weight HA. Treatment with G.thunbergii extract-formulated lotion significantly improved skin elasticity and reduced skin wrinkling scores at the outer eye corner compared with the placebo formulation. Geranium thunbergii extract inhibited HYBID-mediated HA degradation in vitro and showed anti-wrinkle activity in vivo accompanying the improvement in skin elasticity. Our study provides a possible strategy for anti-wrinkle care through inhibition of HYBID-mediated HA degradation.