N-(4-bromophenethyl) Caffeamide Protects Skin from UVB-Induced Inflammation Through MAPK/IL-6/NF-κB-Dependent Signaling in Human Skin Fibroblasts and Hairless Mouse Skin

Abstract

Long-term exposure to ultraviolet (UV) irradiation causes skin inflammation and aging. N-(4-bromophenethyl) caffeamide (K36H) possesses antioxidant and antimelanogenic properties. The present study investigated the effects of K36H on UVB-induced skin inflammation in human skin fibroblasts and hairless mice and evaluated the underlying mechanisms. The in vitro results indicated that K36H reduced UVB-induced mitogen-activated protein kinase (MAP kinase) expression. Furthermore, K36H treatment reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in UVB-irradiated fibroblasts by regulating IκB and nuclear factor-kappa B (NF-κB) expression. In the animal study, topically applied K36H markedly reduced inflammation and skin thickness and prevented photodamage to the skin of hairless mice. In addition, K36H inhibited the levels of UV-upregulated inflammation-related proteins levels such as IL-1, iNOS, and NF-κB in the dermis of hairless mice. Our findings demonstrated the antioxidant and anti-inflammatory properties of K36H in human skin fibroblasts and hairless mice. Therefore, K36H can be developed as an antiphotodamage and antiphotoinflammation agent.

Protection against Ultraviolet A-Induced Skin Apoptosis and Carcinogenesis through the Oxidative Stress Reduction Effects of N-(4-bromophenethyl) Caffeamide, A Propolis Derivative

“…The results of this study indicated that K36H suppressed UVA-induced MMP-1 and MMP-2 overexpression and restored TIMP-1 protein expression in UVA-exposed HaCaT cells. Another study revealed that K36H restored total collagen in UVB-exposed Hs68 fibroblasts and reduced collagen degradation [34]. This study proved the protective effect of K36H against long-wavelength UV irradiation-induced skin damage through the inhibition of MAP kinases and the AP-1 pathway.…”

“…Survival rates higher than 80% indicated that K36H did not exhibit cytotoxicity (Figure 2a). In another study, K36H exhibited no cytotoxicity in Hs68 cells [34].…”

“…K36H is a derivative from the constituents of propolis. In another study we conducted, K36H exhibited DPPH scavenging and inhibited intracellular ROS generation, which may slow skin aging [34]. Catechol,…”

“…K36H is a derivative from the constituents of propolis. In another study we conducted, K36H exhibited DPPH scavenging and inhibited intracellular ROS generation, which may slow skin aging [34]. Catechol, the functional group of K36H, may provide hydrogen atoms that contribute to free radical scavenging and provide inherent antioxidant potential [35].…”

Chemical Constituents from Leaves of <i>Hydrangea serrata</i> and Their Anti-photoaging Effects on UVB-Irradiated Human Fibroblasts

“…23) Loss of HA has been associated with skin aging and UVB exposure causes loss of HA because of down-regulated HAS expression. 22,24) We evaluated the effects of isolated compounds on the UVB-induced loss of HA by ELISA. UVB exposure decreased HA production by 41.68%, while hydrangenol, hydrangenoside A, hydrangenoside C, and quercetin-xylo-galato significantly recovered UVB-induced HA loss.…”