title: Liqustri lucidi Fructus inhibits hepatic injury and functions as an antioxidant by activation of AMP-activated protein kinase in vivo and in vitro.
abstract: Medicinal herbs are used to treat or prevent various diseases, and function to regulate protective mechanisms as nutraceuticals. Fructus Ligustri lucidi is the fruit of Ligustrum lucidum and has been used for its tonic effects on the liver. This study was designed to examine the effects of Fructus Ligustri lucidi water extract (FLL) against severe oxidative stress and mitochondrial impairment in vivo and in vitro and to elucidate its cellular mechanisms of action. Treatment of HepG2 cells with arachidonic acid (AA) + iron successfully induced oxidative stress and apoptosis, as indicated by depletion of glutathione, formation of ROS, decreses in mitochondrial membrane potential (Δψm), and altered expression of apoptosis-related proteins, such as procaspase-3 and Bcl-xL. FLL treatment significantly blocked these pathological changes and the mitochondrial dysfunction caused by AA + iron, which were similar with the effect of aminoimidazole-carboxamide-β-d-ribofuranoside (AICAR). Moreover, FLL induced the activation of AMP-activated protein kinase (AMPK), which was mediated by its upstream kinase LKB1. Inhibition or activation of AMPK revealed the role of AMPK in cellular protection conferred by FLL in LKB1-deficient cells. In mice, oral administration of 100 mg/kg FLL activated AMPK in the liver, and protected against oxidative stress and liver injury induced by CCl4injection. Among the components of FLL, chlorogenic acid was found to be responsible for the protection of hepatocytes against AA + iron-induced cellular damage. Overall, our results confirmed that FLL has the ability to protect hepatocytes against oxidative injury through regulation of the AMPK signaling pathway.
authors.affiliation: Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, South Korea.
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Seo
authors.affiliation: Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, South Korea.
authors.forename: Su Youn
authors.initials: SY
authors.lastname: Baek
authors.affiliation: Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, South Korea; Department of Medical Science, Daegu Haany University, Gyeongsan, South Korea.
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Lee
authors.affiliation: Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, South Korea; College of Oriental Medicine, Dongguk University, Gyeongju, South Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, South Korea.
authors.forename: Seul-Gi
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, South Korea; Department of Microbiology and Immunology, Pusan National University School of Medicine, Yagnsan, South Korea.
authors.forename: Kwang-Youn
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, South Korea.
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Jang
authors.affiliation: Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, South Korea; Department of Medical Science, Daegu Haany University, Gyeongsan, South Korea; Department of Biomedical Laboratory Science, Daekyeung College, Gyeongsan, South Korea.
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Park
authors.affiliation: Department of Biomedical Laboratory Science, Daekyeung College, Gyeongsan, South Korea; Department of Bio Health Science, College of Natural Science, Changwon National University, Changwon, South Korea.
authors.forename: Joung-Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, Daekyeung College, Gyeongsan, South Korea.
authors.forename: Keuk-Jun
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Medical Science, Daegu Haany University, Gyeongsan, South Korea.
authors.forename: Hyeong Sik
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Pusan National University School of Medicine, Yagnsan, South Korea.
authors.forename: Soon-Cheol
authors.initials: SC
authors.lastname: Ahn
authors.affiliation: Department of Pharmaceutical Engineering, Daegu Haany University, Gyeongsan, South Korea.
authors.forename: Jong Rok
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, South Korea.
authors.forename: Sook Jahr
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, South Korea. Electronic address: sckim@dhu.ac.kr.
authors.forename: Sang Chan
authors.initials: SC
authors.lastname: Kim
authors.affiliation: Medical Research Center (MRC-GHF), College of Oriental Medicine, Daegu Haany University, Gyeongsan, South Korea. Electronic address: ywkim@dhu.ac.kr.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Kim
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005638:Fruit / Q000737:chemistry / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D031659:Ligustrum / Q000737:chemistry* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D051020:bcl-X Protein; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D053148:Caspase 3
keywords: AMPK; CCl(4); LKB1; Ligustri lucidi Fructus; Liver injury