title: Apoptosis inhibition effect of Dihydromyricetin against UVA-exposed human keratinocyte cell line.
abstract: 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.
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou, China; Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Cuiqin
authors.initials: C
authors.lastname: Zhuo
authors.affiliation: 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.
authors.forename: Fujun
authors.initials: F
authors.lastname: Jin
authors.affiliation: Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632, China. Electronic address: twang-yf@163.com.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D044948:Flavonols / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D008856:Microscopy, Fluorescence; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D010088:Oxidoreductases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D044948:Flavonols; D006657:Histones; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D051028:bcl-2-Associated X Protein; D010088:Oxidoreductases; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases; C472036:dihydromyricetin
keywords: Apoptosis; Dihydromyricetin; HaCaT; Inflammation; UVA