β-Ionone Attenuates Dexamethasone-Induced Suppression of Collagen and Hyaluronic Acid Synthesis in Human Dermal Fibroblasts

Abstract

Stress is a major contributing factor of skin aging, which is clinically characterized by wrinkles, loss of elasticity, and dryness. In particular, glucocorticoids are generally considered key hormones for promoting stress-induced skin aging through binding to glucocorticoid receptors (GRs). In this work, we aimed to investigate whether β-ionone (a compound occurring in various foods such as carrots and almonds) attenuates dexamethasone-induced suppression of collagen and hyaluronic acid synthesis in human dermal fibroblasts, and to explore the mechanisms involved. We found that β-ionone promoted collagen production dose-dependently and increased mRNA expression levels, including collagen type I α 1 chain (COL1A1) and COL1A2 in dexamethasone-treated human dermal fibroblasts. It also raised hyaluronic acid synthase mRNA expression and hyaluronic acid levels. Notably, β-ionone inhibited cortisol binding to GR, subsequent dexamethasone-induced GR signaling, and the expression of several GR target genes. Our results reveal the strong potential of β-ionone for preventing stress-induced skin aging and suggest that its effects are related to the inhibition of GR signaling in human dermal fibroblasts.

Pyracantha fortuneana (Maxim.) Li: A comprehensive review of its phytochemistry, pharmacological properties, and product development

“…Co-administration of geraniol with methotrexate may attenuate methotrexate-induced acute kidney injury (Younis et al, 2021). The β-ionone could prevent stressinduced skin aging via inhibition of GR signaling in human dermal fibroblasts (Choi et al, 2021). The α-pinene activates natural killer (NK) cells and increases NK cells cytotoxicity, suggesting it is a potential compound for cancer immunotherapy (Jo et al, 2021).…”

The long winding road to the safer glucocorticoid receptor (GR) targeting therapies

“…Luciferase and NF-kB.Luciferase reporter-based assays) [85,86]. In some cases, more thorough investigations included analysis of effects on GR expression, major steps in GR activation: its phosphorylation (mostly at activating Ser211) and nuclear translocation; and GR ligand properties assessed by molecular docking or ligand-binding assays [87][88][89][90][91][92][93][94]. Recently, focused screens for natural mimetics of cortisol were performed utilizing genetically engineered sensor cells detecting GR nuclear translocation, which demonstrated that decursin from Dong quai (Angelica sinensis, commonly known as female ginseng), and L-limonene from peppermint oil induce GR translocation similar to cortisol [95,96].…”

Dermal Olfactory Receptor OR51B5 Is Essential for Survival and Collagen Synthesis in Human Dermal Fibroblast (Hs68 Cells)

“…number and collagen synthesis in dermal fibroblasts [11][12][13][14][15], but the mechanisms involved in the regulation of cell growth and collagen synthesis are not fully established.…”

“…The human dermal fibroblast cell line (Hs68) was purchased from American Type Culture Collection (ATCC; Rockville, MD, USA). To the best of knowledge, Hs68 cell is currently the most widely used dermal fibroblast cell line for studying physiological processes in dermis, displaying typical characteristics of primary dermal fibroblasts; it is able to regulate various ECM components, including procollagen, in response to a variety of environmental stimuli (e.g., UV and stress hormone) [13,[55][56][57]. The cells were grown in Dulbecco's modified Eagle's medium (DMEM; HyClone; Waltham, MA, USA) supplemented with 10% (v/v) fetal bovine serum (FBS, HyClone) and 1% penicillinstreptomycin (Gibco; Grand Island, NE, USA) at 37 • C in a 5% carbon dioxide atmosphere.…”

“…Numerous studies have indicated that at least two factors are primarily involved in extrinsic aging, namely (1) ultraviolet (UV) radiation and (2) stress. It has been clearly demonstrated that these stimuli cause a reduction in cell number and collagen synthesis in dermal fibroblasts [11][12][13][14][15], but the mechanisms involved in the regulation of cell growth and collagen synthesis are not fully established.…”