Santamarine Shows Anti-Photoaging Properties via Inhibition of MAPK/AP-1 and Stimulation of TGF-β/Smad Signaling in UVA-Irradiated HDFs

Abstract

Chronic UVA exposure results in elevated reactive oxygen species in skin which leads to photoaging characterized as upregulated matrix metalloproteinase (MMP)-1 and loss of collagen. Therefore, natural antioxidants are hailed as promising agents to be utilized against photoaging. In the current study, reynosin and santamarine, two known sesquiterpene lactones isolated from Artemisia scoparia, were analyzed for their anti-photoaging properties in UVA-irradiated human dermal fibroblasts (HDFs). Results showed that UVA irradiation (8 J/cm2) upregulated the MMP-1 secretion and expression, and suppressed collagen production, which were significantly reverted by santamarine treatment (10 µM). Although both reynosin and santamarine exhibited ROS scavenging abilities, reynosin failed to significantly diminish UVA-stimulated MMP-1 release. UVA-irradiated HDFs showed increased collagen production when treated with santamarine. As a mechanism to suppress MMP-1, santamarine significantly suppressed the UVA-induced phosphorylation of p38 and JNK and nuclear translocation of p-c-Fos and p-c-Jun. Santamarine promoted collagen I production via relieving the UVA-induced suppression on TGF-β and its downstream activator Smad2/3 complex. Antioxidant properties of santamarine were also shown to arise from stimulating Nrf2-dependent expression of antioxidant enzymes SOD-1 and HO-1 in UVA-irradiated HDFs. In conclusion, santamarine was found to be a promising natural antioxidant with anti-photoaging properties against UVA-induced damages in HDFs.

Role of Phytochemicals in Skin Photoprotection via Regulation of Nrf2

“…Santamarine, a sesquiterpene lactone, isolated from sunflower family provided anti-photoaging effects via suppression of UVA (8 J/cm 2 )-induced MAPK/AP-1 pathways involved in upregulation of MMPs and via promotion of TGF-β/Smad-mediated collagen production in HDFs. Furthermore, santamarine treatment led to a significant restoration of UVA-mediated downregulation of Nrf2-dependent antioxidant defenses including SOD-1 and HO-1 at the mRNA and protein levels ( Oh et al, 2021 ). Zerumbone (ZER), a natural sesquiterpene, from Zingiber zerumbet (L.) Roscoe ex Sm.…”

Patriniaterpenes A–D: unveiling the unique structure and antioxidant properties of monoterpene–sesquiterpene conjugates from Patrinia scabra

“…Several studies have shown that monoterpenes and sesquiterpenes such as myrcene, (–)-loliolide, camphor, and santamarine exhibit anti-skin damage, antioxidant, and anti-inflammatory effects by modulating signaling pathways including MAPKs, NF-κB, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), extracellular signal-kinase (ERK), transforming growth factor-β/suppressor of mothers against decapentaplegic (TGF-β/Smad), AP-1, and Nrf2/ARE in HDFs. 34–38 Moreover, several monoterpenes and sesquiterpenes increase collagen expression and decrease MMP-1 expression. 31–38…”

Protective effects of quercetin-3-glucosyl-(1-2)-rhamnoside fromSchizophragma hydrangeoidesleaves on ultraviolet A-induced photoaging in human dermal fibroblasts

“…UV irradiation induces collagen degradation by causing overexpression of MMP-1. Therefore, reducing MMP-1 levels is a key factor in preventing UVA-induced photoaging [22]. We investigated the effects of Q-3-GR on MMP-1 production and protein expression using ELISA and western blotting.…”