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Photo-protective Activities Of Pogostone And Andrographolide Sodium Bisulfite Against UV-induced Skin Premature Aging In Mice

Posted on:2017-04-15Degree:MasterType:Thesis
Country:ChinaCandidate:X F WangFull Text:PDF
GTID:2284330488988359Subject:Pharmacy
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ObjectiveSkin photoaging is a process of premature skin aging attributed to continuous and long-term exposure to solar ultraviolet (UV) radiation. Researches confirmed that UV-induced photoaging is responsible for about 90% aging of the exposed skin. Photoaging will cause coarse, wrinkle and sagging skin, even more, cause skin cancer, which will seriously endanger our health. UV irradiation damages skin connective tissue is initiated by photochemical generation of ROS and resulting accumulation of inflammation cytokines, and thereby up-regulates the MMPs expressions which result in the structural and functional alterations of ECM. In consideration of the underlying mechanism of skin photoaging, it can be reasonably concluded that anti-oxidative and anti-inflammatory agents might represent potential therapeutic candidates for this disease.Pogostone (PO), which is a major bioactive compound of Pogostemonis Herba and its essential oil, has been reported to possess anti-oxidative and anti-inflammatory properties. Andrographolide sodium bisulfite (ASB) is a kind of solublederivative of andrographolide, which is the major bioactive compound of Andrographis paniculata. Moreover, ASB is reported to have anti-oxidative and anti-inflammatory activities. However, the anti-photoaging effect of PO or ASB has still not been revealed. In the present study, we investigated the protective effect as well as the underlying mechanism of PO and ASB on mice skin photoaging induced by UV irradiation.MethodsIn the present study, female mice were irradiated by UVA combined with UVB to build the photoaging model. The shaved dorsal skins of experimental mice were topically applied with PO or ASB and the anti-photoaging effect of these compounds were investigated by skin macroscopic evaluation, elasticity test and thickness quantification. Anti-photoaging effect of PO and ASB was further evaluated by histological analysis of the skin specimens after routine H&E staining coupled with elastic fibers staining and collagen fibers staining to detect the skin structure alterations, epidermal thickness and the situation of the elastic fibers and collagen. In order to further evaluate the underlying mechanism, the anti-oxidative enzymes (CAT, GSH-Px and SOD,) activities, the content of the MDA and collagen were measured by biochemical detection method; the expression inflammatory cytokines (TNF-a, IL-6, IL-10, IL-1β, COX-2 and PGE2) and the level of MMP-1 and MMP-3 were quantified by ELISA method.Results1. The anti-photoaging effect of POMacroscopic evaluation showed that PO could significantly ameliorate the macroscopic appearance, elasticity and thickness of the photoaged mice skin; Histological observation demonstrated that PO could evidently decrease UV-induced epidermal hyperplasia, inhibit the degradation of collagen and elastic fibres.-Furthermore, topical application of PO markedly increased the activities of the antioxidant enzymes, including CATn SOD and GSH-Px, and observably decreased MDA content. Analysis of inflammatory cytokines showed obvious down-regulation of TNF-a, IL-6, IL-1β and COX-2, PGE2 in the PO groups. In addition, PO pretreatment evidently inhibited the abnormal expression of MMP-1 and MMP-3.2. The anti-photoaging effect of ASBMacroscopic evaluation showed that ASB could significantly ameliorate the macroscopic appearance, elasticity and thickness of the photoaged mice skin; Histological observation demonstrated that ASB could evidently decrease UV-induced epidermal hyperplasia, inhibit the degradation of collagen and elastic fibres. Furthermore, topical application of ASB markedly increased the activities of the antioxidant enzymes (CAT and SOD), and observably decreased MDA content. Analysis of inflammatory cytokines showed obvious down-regulation of TNF-a, IL-1β, IL-6 and IL-10 in the ASB groups. In addition, ASB pretreatment evidently inhibited the abnormal expression of MMP-1 and MMP-3.ConclusionThe present study, for the first time, evaluated the protective effect of PO and ASB on mice skin photoaging induced by UV irradiation. The UV-induced macroscopic and histopathological lesions were efficaciously ameliorated by pretreatment of PO and ASB. The mechanisms of these protection mainly involved their anti-oxidative and anti-inflammatory properties. PO and ASB conspicuously counteracted the UV-induced increase of MMP-1 and MMP-3 secretion by enhancing the activities of various antioxidant enzymes, inhibiting the content of MDA, and suppressing the excessive inflammatory cytokines, then mitigated the degradation of the ECM, reversed the UV-mediated collagen and elastic fibres destruction, and thereby protected skin from actinic damage.
Keywords/Search Tags:Pogostone, Andrographolide sodium bisulfite, Photoaging, Antioxidant, Anti-inflammation
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