黄芪甲苷通过调节TLR4/NF-κB通路预防紫外线诱导的角质形成细胞损伤。
Astragaloside prevents UV-induced keratinocyte injury by regulating TLR4/NF-κB pathway.
作者信息
Wang Jie, Ke Jin, Wu Xing, Yan Yuehua
机构信息
Department of Dermatology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
出版信息
J Cosmet Dermatol. 2022 Mar;21(3):1163-1170. doi: 10.1111/jocd.14174. Epub 2021 Aug 19.
BACKGROUND
Ultraviolet (UV) radiation is a key risk factor of environment to contribute photoaging and skin cancer through production of reactive oxygen species (ROS) and inflammatory responses. Astragaloside IV (AS-IV) is an active component from Astragalus membranaceus, and shows various pharmacological effects on inflammation, oxidative stress and apoptosis. However, whether AS-IV shows protective effect on UVB-induced injury in epidermal keratinocytes remain unknown.
AIMS
To explored the effects of AS-IV on UVB-induced oxidative injury and inflammatory response in human epidermal keratinocytes.
METHODS
HaCaT keratinocytes were exposed to UVB irradiation, followed by AS-IV incubation. The cell viability, intracellular ROS level, oxidative stress, and apoptosis were determined. The regulatory effects of AS-IV on toll-like receptor 4 (TLR4) pathway in UVB-exposed HaCaT cells were also investigated.
RESULTS
Astragaloside IV pretreatment (10, 25, 50, 100 and 150 μM) increased cell viability in UVB-exposed HaCaT cells. AS-IV (50 μM) significantly reduced intracellular ROS level and lipid oxidation product malondialdehyde (MDA) content, and increased a ROS-scavenging enzyme superoxide dismutase (SOD) in HaCaT cells with UVB irradiation. In addition, AS-IV pretreatment suppressed apoptosis, increased Bax protein, caspase-3 and 9, and decreased BCL-2 protein in contrast to HaCaT cells with UVB-irradiation. AS-IV suppressed proinflammatory cytokine production, inhibited TLR4 and its downstream signaling molecules NF-κB, iNOS and cyclooxygenase-2 (COX-2) protein expression. We also found that the effects of AS-IV on cell viability and TLR4 expression was reversed by NAC. The protective of AS-IV on UVB-induced damage and TLR4 expression was dependent on ROS, as the increase in viability and decrease in TLR4 protein by AS-IV was significantly attenuated by ROS scavenger NAC (1 mM).
CONCLUSION
Astragaloside IV prevent UVB-induced oxidative damage and inflammation by inhibiting TLR4 expression.
背景
紫外线（UV）辐射是环境中的一个关键风险因素，可通过产生活性氧（ROS）和炎症反应导致光老化和皮肤癌。黄芪甲苷IV（AS-IV）是黄芪中的一种活性成分，对炎症、氧化应激和细胞凋亡具有多种药理作用。然而，AS-IV是否对紫外线B（UVB）诱导的表皮角质形成细胞损伤具有保护作用尚不清楚。
目的
探讨AS-IV对UVB诱导的人表皮角质形成细胞氧化损伤和炎症反应的影响。
方法
将HaCaT角质形成细胞暴露于UVB照射下，然后进行AS-IV孵育。测定细胞活力、细胞内ROS水平、氧化应激和细胞凋亡。还研究了AS-IV对UVB照射的HaCaT细胞中Toll样受体4（TLR4）信号通路的调节作用。
结果
黄芪甲苷IV预处理（10、25、50、100和150μM）可提高UVB照射的HaCaT细胞的活力。AS-IV（50μM）显著降低UVB照射的HaCaT细胞内的ROS水平和脂质氧化产物丙二醛（MDA）含量，并增加一种ROS清除酶超氧化物歧化酶（SOD）。此外，与UVB照射的HaCaT细胞相比，AS-IV预处理可抑制细胞凋亡，增加Bax蛋白、半胱天冬酶-3和-9，并降低BCL-2蛋白。AS-IV抑制促炎细胞因子的产生，抑制TLR4及其下游信号分子NF-κB、诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2）蛋白的表达。我们还发现NAC可逆转AS-IV对细胞活力和TLR4表达的影响。AS-IV对UVB诱导的损伤和TLR4表达的保护作用依赖于ROS，因为ROS清除剂NAC（1 mM）可显著减弱AS-IV对细胞活力的提高和TLR4蛋白的降低作用。
结论
黄芪甲苷IV通过抑制TLR4表达预防UVB诱导的氧化损伤和炎症。
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