7,8-Dihydroxyflavone attenuates TNF-α-induced skin aging in Hs68 human dermal fibroblast cells via down-regulation of the MAPKs/Akt signaling pathways.

7,8-Dihydroxyflavone (7,8-DHF, 7,8-dihydroxy-2-phenyl-4H-chromen-4-one) is a natural flavone found in plants and has been frequently reported to show anti-inflammatory and anti-oxidant properties. Skin aging is induced mainly by oxidative stress. In the present study, we evaluated 7,8-DHF for its potential anti-aging effects for skin using Hs68 human dermal fibroblast cells. To establish aged skin cell model, Hs68 cells were treated with tumor necrosis factor-α (TNF-α) for 18h 7,8-DHF (0-10μM) induced collagen synthesis and suppressed the expression of matrix metalloproteinase 1 (MMP 1) in a dose-dependent manner. 7,8-DHF also significantly reduced the generation of intracellular reactive oxygen species (ROS), induced the expression of anti-oxidant enzymes, such as catalase, manganese superoxide dismutase (Mn-SOD), and heme oxygenase-1 (HO-1), and scavenged DPPH free radicals. 7,8-DHF also disturbed the mitogen-activated protein kinases (MAPKs) and Akt signaling pathways that participate in the aging process. 7,8-DHF exerted potent anti-aging effects by inhibiting MMP 1 expression and inducing Type I collagen synthesis in Hs68 cells. 7,8-DHF effectively attenuated oxidative stress by up-regulating the anti-oxidant enzymes catalase, Mn-SOD, and HO-1, and reducing activation of the Akt and MAPKs signaling pathways in aged skin cells. These results suggest that 7,8-DHF can be used as a potent facultative ingredient in health-beneficial agents to prevent or treat the skin aging or inflammatory skin disorders.