Inhibitory effects of Sanguisorba officinalis root extract on HYBID (KIAA1199)‐mediated hyaluronan degradation and skin wrinkling

Abstract

OBJECTIVES: Hyaluronan (HA), an important constituent of extracellular matrix in the skin, has many biological activities such as hydration that contributes to firmness and bounciness of the skin. We have reported that reduction in HA in the papillary dermis and over-expression of HYBID (HYaluronan Binding protein Involved in hyaluronan Depolymerization, alias KIAA1199 or CEMIP), a key molecule for HA degradation in skin fibroblasts, are implicated in facial skin wrinkling in Japanese and Caucasian women. However, little or no information is available for substances which inhibit the HYBID-mediated HA degradation. METHODS: Inhibition of Sanguisorba officinalis root extract and ziyuglycoside I, one of the components of Sanguisorba officinalis root extract, to the HYBID-mediated HA degradation was assessed by size-exclusion chromatography of HA depolymerized by stable transfectants of HYBID in HEK293 cells (HYBID/HEK293 cells) or normal human skin fibroblasts (Detroit 551 cells and NHDF-Ad cells). The HYBID mRNA and protein expression was examined by quantitative real-time PCR and immunoblotting in the skin fibroblasts treated with Sanguisorba officinalis root extract, and size distribution of newly produced HA was evaluated by preparing metabolically radiolabelled HA. A double-blind, randomized and placebo-controlled study was carried out in the 21 healthy Japanese women, who were topically treated with the formulation containing Sanguisorba officinalis root extract or the placebo on each side of the face including crow's foot area. RESULTS: Sanguisorba officinalis root extract, but not ziyuglycoside I, abolished HYBID-mediated HA degradation by HYBID/HEK293 cells. Sanguisorba officinalis root extract also inhibited HYBIDmediated HA degradation in skin fibroblasts by down-regulating HYBID mRNA and protein expression. Although control untreated skin fibroblasts produced polydispersed HA, the cells treated with Sanguisorba officinalis root extract produced only high-molecularweight HA. Treatment with Sanguisorba officinalis root extract-formulated lotion significantly improved skin elasticity, and reduced

Role of HYBID (Hyaluronan Binding Protein Involved in Hyaluronan Depolymerization), Alias KIAA1199/CEMIP, in Hyaluronan Degradation in Normal and Photoaged Skin

“…However, no information was available for cosmetic agents that can modulate HYBID expression or activity. Therefore, we screened extracts from plants that are traditionally used as herbal or folk medicines in Asia and/or Europe, and discovered that Geranium thunbergii ( G. thunbergii ) extract and Sanguisorba officinalis ( S. officinalis ) root extract completely inhibit HA degradation in HYBID/HEK293 cells and normal human skin fibroblasts [59,60]. These extracts not only inhibited HA-degrading activity of HYBID but also downregulated the HYBID gene expression, leading to production of high-molecular-weight HA [59,60].…”

“…Therefore, we screened extracts from plants that are traditionally used as herbal or folk medicines in Asia and/or Europe, and discovered that Geranium thunbergii ( G. thunbergii ) extract and Sanguisorba officinalis ( S. officinalis ) root extract completely inhibit HA degradation in HYBID/HEK293 cells and normal human skin fibroblasts [59,60]. These extracts not only inhibited HA-degrading activity of HYBID but also downregulated the HYBID gene expression, leading to production of high-molecular-weight HA [59,60]. Small-scale clinical trials of G. thunbergii extract and S. officinalis root extract as an anti-wrinkle agent were performed with Japanese females, who topically applied the test formulation containing each extract on one side of the outer eye-corner and the placebo formulation on the other side twice daily for eight weeks.…”

“…Small-scale clinical trials of G. thunbergii extract and S. officinalis root extract as an anti-wrinkle agent were performed with Japanese females, who topically applied the test formulation containing each extract on one side of the outer eye-corner and the placebo formulation on the other side twice daily for eight weeks. As a result, G. thunbergii extract- and S. officinalis root extract-formulated lotions significantly enhanced the Ur/Uf (Immediate retraction/Final deformation) value (the ratio of elastic recovery to the total deformation), which is reported to negatively correlate with skin roughness [61,62,63], compared with the placebo formulation [59,60]. When a dermatologist evaluated the skin, the wrinkle scores of the side treated with the extract-formulated lotion were significantly lower than those of the other side treated with the placebo formulation [59,60].…”

“…As a result, G. thunbergii extract- and S. officinalis root extract-formulated lotions significantly enhanced the Ur/Uf (Immediate retraction/Final deformation) value (the ratio of elastic recovery to the total deformation), which is reported to negatively correlate with skin roughness [61,62,63], compared with the placebo formulation [59,60]. When a dermatologist evaluated the skin, the wrinkle scores of the side treated with the extract-formulated lotion were significantly lower than those of the other side treated with the placebo formulation [59,60]. Thus, these results suggest that inhibition of HYBID-mediated HA degradation by G. thunbergii extract and S. officinalis root extract would be a promising strategy for anti-wrinkle care.…”

A Comprehensive Review of Genus Sanguisorba: Traditional Uses, Chemical Constituents and Medical Applications

“…Several in vivo and in vitro studies have demonstrated that ZY-I increases the contents of collagen and elastic fibers in a dose-dependent manner and also inhibits the production of the collagen-degrading enzyme MMP-3 in the skin, thereby demonstrating an anti-wrinkle effect (Kim et al, 2008;Yun et al, 2019). In a randomized double-blind placebo experiment conducted with 21 Japanese women, it was observed that at the cellular level, it was the S. officinalis root extract, rather than ziyuglycoside-I, that inhibited the hyaluronic acid degradation and consequently exerted the anti-wrinkle effect (Yoshida et al, 2018). Interestingly, when the chemical constituents of the root, stem, and leaf extracts of S. minor were analyzed, it was revealed that the content of polyphenols was significantly higher in the stem and leaf extracts compared to that in the root extracts.…”