The protective impact of myricetin against PM-induced cellular apoptosis by inhibiting endoplasmic reticulum stress.
Herath Mudiyanselage Udari Lakmini Herath, Musun Park, Mei Jing Piao, Kyoung Ah Kang, Pincha Devage Sameera Madushan Fernando, Herath Mudiyanselage Maheshika Madhuwanthi Senavirathna, Hee-Sun Kim, Sungwook Chae, Young Ree Kim, Jin Won Hyun
Author Information
Herath Mudiyanselage Udari Lakmini Herath: Department of Biochemistry, College of Medicine, Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea.
Musun Park: Korean Medicine Data Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.
Mei Jing Piao: Department of Biochemistry, College of Medicine, Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea.
Kyoung Ah Kang: Department of Biochemistry, College of Medicine, Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea.
Pincha Devage Sameera Madushan Fernando: Department of Biochemistry, College of Medicine, Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea.
Herath Mudiyanselage Maheshika Madhuwanthi Senavirathna: Department of Biochemistry, College of Medicine, Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea.
Hee-Sun Kim: Department of Molecular Medicine, Inflammation-Cancer Microenvironment Research Center, School of Medicine, Ewha Womans University, Seoul 07804, Republic of Korea.
Sungwook Chae: Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea.
Young Ree Kim: Department of Laboratory Medicine, Jeju National University Hospital, College of Medicine, Jeju National University, Jeju 63241, Republic of Korea. Electronic address: namu8790@jejunu.ac.kr.
Jin Won Hyun: Department of Biochemistry, College of Medicine, Jeju Research Center for Natural Medicine, Jeju National University, Jeju 63243, Republic of Korea. Electronic address: jinwonh@jejunu.ac.kr.
Particulate matter 2.5 (PM) exposure is responsible for skin inflammation, aging, and disruption of skin homeostasis. The objective of this investigation was to assess the potential of myricetin in protecting against skin damage caused by PM. Human keratinocytes (HaCaT) were pretreated with myricetin and subsequently exposed to PM. Cell viability, reactive oxygen species (ROS) generation, oxidized cellular components, mitochondrial damage, cellular apoptosis, and endoplasmic reticulum (ER) stress were assessed. A mitogen-activated protein kinase (MAPK) signaling network was constructed, and the action site of myricetin was explored through docking analysis. PM induced oxidative stress, resulting in DNA damage, lipid peroxidation, protein carbonylation, and cellular apoptosis. Myricetin counteracted these effects by reducing the PM-induced ROS levels. Additionally, myricetin mitigated the PM-induced cytochrome c release into the cytoplasm and caspase activation, thereby ameliorating cellular apoptosis. Myricetin reduced PM-induced cytosolic Ca level and ER-related signaling molecules. Furthermore, myricetin inhibited cellular cytotoxicity by downregulating the MAPK signaling pathway. Docking and network analyses identified 12 major MAPK proteins targeted by myricetin, and these proteins primarily affected the classical MAPK pathway. These findings suggest that myricetin mitigates skin impairments caused by PM exposure by reducing ROS, mitochondrial damage, ER stress, and apoptosis via downregulating the MAPK signaling pathway.
