title: Topical hesperidin prevents glucocorticoid-induced abnormalities in epidermal barrier function in murine skin.
abstract: Systemic and topical glucocorticoids (GC) can cause significant adverse effects not only on the dermis, but also on epidermal structure and function. In epidermis, a striking GC-induced alteration in permeability barrier function occurs that can be attributed to an inhibition of epidermal mitogenesis, differentiation and lipid production. As prior studies in normal hairless mice demonstrated that topical applications of a flavonoid ingredient found in citrus, hesperidin, improve epidermal barrier function by stimulating epidermal proliferation and differentiation, we assessed here whether its topical applications could prevent GC-induced changes in epidermal function in murine skin and the basis for such effects. When hairless mice were co-treated topically with GC and 2% hesperidin twice-daily for 9 days, hesperidin co-applications prevented the expected GC-induced impairments of epidermal permeability barrier homoeostasis and stratum corneum (SC) acidification. These preventive effects could be attributed to a significant increase in filaggrin expression, enhanced epidermal β-glucocerebrosidase activity and accelerated lamellar bilayer maturation, the last two likely attributable to a hesperidin-induced reduction in stratum corneum pH. Furthermore, co-applications of hesperidin with GC largely prevented the expected GC-induced inhibition of epidermal proliferation. Finally, topical hesperidin increased epidermal glutathione reductase mRNA expression, which could counteract multiple functional negative effects of GC on epidermis. Together, these results show that topical hesperidin prevents GC-induced epidermal side effects by divergent mechanisms.
authors: Dermatology Service, Veterans Affairs Medical Center, and Department of Dermatology, University of California San Francisco, San Francisco, CA, USA.
authors: George
authors: G
authors: Man
authors: Theodora M
authors: TM
authors: Mauro
authors: Peggy L
authors: PL
authors: Kim
authors: Melanie
authors: M
authors: Hupe
authors: Yongjiao
authors: Y
authors: Zhai
authors: Richard
authors: R
authors: Sun
authors: Debbie
authors: D
authors: Crumrine
authors: Carolyn
authors: C
authors: Cheung
authors: Almudena
authors: A
authors: Nuno-Gonzalez
authors: Peter M
authors: PM
authors: Elias
authors: Mao-Qiang
authors: MQ
authors: Man
mesh_terms: D000287:Administration, Topical; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002990:Clobetasol / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D004817:Epidermis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D000091344:Filaggrin Proteins; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects* / Q000037:antagonists & inhibitors*; D005980:Glutathione Reductase / Q000235:genetics; D006569:Hesperidin / Q000008:administration & dosage*; D007381:Intermediate Filament Proteins / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000091344:Filaggrin Proteins; D005938:Glucocorticoids; D007381:Intermediate Filament Proteins; D012333:RNA, Messenger; D002990:Clobetasol; D006569:Hesperidin; D005980:Glutathione Reductase
keywords: epidermal permeability barrier; glucocorticoid; hesperidin; skin pH