He Zhe, Zhang Li, Zhuo Cuiqin, Jin Fujun, Wang Yifei
College of Pharmacy, Jinan University, Guangzhou, China; Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632, China.
Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
J Photochem Photobiol B. 2016 Aug;161:40-9. doi: 10.1016/j.jphotobiol.2016.05.002. Epub 2016 May 5.
UVA irradiation stimulates the production of reactive oxygen species (ROS), which results in oxidative stress, cellular damage, and ultimately, cell death by interacting with other intracellular molecules. In the present study, we explored the protective role of Dihydromyricetin (DHM,1.25-10μM) against UVA-induced inflammation response and apoptosis in the human keratinocyte cell line (HaCaT cells) and the underlying mechanisms. DHM pre-treatment significantly increased HaCaT cell viability and suppressed UVA-induced production of inflammatory cytokines, as well as apoptosis of HaCaT cells. Moreover, DHM pre-treatment prohibited UVA-induced ROS generation, mitochondrial membrane potential decrease, and the phosphorylation of histone H2AX(γ-H2AX), a sensitive biomarker for DNA damage. Meanwhile, DHM could enhance GSH-Px activity and decrease the content of MDA in UVA ray treated HaCaT cells. Notably, the anti-apoptotic potential of DHM was correlated with an increased expression of anti-apoptotic proteins (Bcl-2 and Bcl-xl) and decreased expression of pro-apoptotic proteins (Bax), as well as the inhibition of caspase proteins activation. Additionally, DHM treatment also prevented the nuclear translocation of NF-κB/p65 and the phosphorylation of c-Jun. N-terminal kinase (JNK), which is an upstream modulator of NF-κB/p65. Therefore, DHM may be potentially useful in the prevention of UVA-induced skin damage.
紫外线A（UVA）照射会刺激活性氧（ROS）的产生，这会导致氧化应激、细胞损伤，并最终通过与其他细胞内分子相互作用导致细胞死亡。在本研究中，我们探讨了二氢杨梅素（DHM，1.25 - 10μM）对人角质形成细胞系（HaCaT细胞）中UVA诱导的炎症反应和细胞凋亡的保护作用及其潜在机制。DHM预处理显著提高了HaCaT细胞的活力，抑制了UVA诱导的炎性细胞因子的产生以及HaCaT细胞的凋亡。此外，DHM预处理还抑制了UVA诱导的ROS生成、线粒体膜电位降低以及组蛋白H2AX（γ-H2AX）的磷酸化，γ-H2AX是DNA损伤的敏感生物标志物。同时，DHM可以增强经UVA照射的HaCaT细胞中谷胱甘肽过氧化物酶（GSH-Px）的活性并降低丙二醛（MDA）的含量。值得注意的是，DHM的抗凋亡潜力与抗凋亡蛋白（Bcl-2和Bcl-xl）表达增加、促凋亡蛋白（Bax）表达降低以及半胱天冬酶蛋白激活受到抑制有关。此外，DHM处理还阻止了NF-κB/p65的核转位以及c-Jun氨基末端激酶（JNK）的磷酸化，JNK是NF-κB/p65的上游调节因子。因此，DHM在预防UVA诱导的皮肤损伤方面可能具有潜在用途。
