title: Quercitrin from Toona sinensis (Juss.) M.Roem. Attenuates Acetaminophen-Induced Acute Liver Toxicity in HepG2 Cells and Mice through Induction of Antioxidant Machinery and Inhibition of Inflammation.
abstract: Quercitrin is found in many kinds of vegetables and fruits, and possesses various bioactive properties. The aim of the present study was to elucidate hepatoprotective mechanisms of quercitrin isolated from Toona sinensis (Juss.) M.Roem. (syn. Cedrela sinensis Juss.), using acetaminophen (APAP)-treated HepG2 cell and animal models. In an in vitro study, quercitrin suppressed the production of reactive oxygen species and enhanced expression of nuclear factor E2-related factor 2 (Nrf2), activity of antioxidant response element (ARE)-reporter gene, and protein levels of NADPH: quinone oxidoreductase 1 (NQO1), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase 2 (SOD-2) in APAP-treated HepG2 cells. In an in vivo study, Balb/c mice were orally administered with 10 or 50 mg/kg of quercitrin for 7 days and followed by the injection with single dose of 300 mg/kg APAP. Quercitrin decreased APAP-caused elevation of alanine aminotransferase and aspartate aminotransferase levels, liver necrosis, the expression of pro-inflammatory factors including inducible nitric oxide synthase, cyclooxygenase 2 and inerleukin-1β, and phosphorylation of kinases including c-Jun N-terminal kinase and p38. Quercitrin restored protein levels of Nrf2, NQO1 and activities and expressions of CAT, GPx, SOD-2. The results suggested that quercitrin attenuates APAP-induced liver damage by the activation of defensive genes and the inhibition of pro-inflammatory genes via the suppressions of JNK and p38 signaling.
authors.affiliation: Department of Smart Food and Drug, College of Biomedical Science &amp; Engineering, Inje University, Gimhae 50834, Korea. truonglongpro@gmail.com.
authors.forename: Van-Long
authors.initials: VL
authors.lastname: Truong
authors.affiliation: Department of Smart Food and Drug, College of Biomedical Science &amp; Engineering, Inje University, Gimhae 50834, Korea. kose91@daum.net.
authors.forename: Se-Yeon
authors.initials: SY
authors.lastname: Ko
authors.affiliation: Department of Food and Science &amp; Nutrition, Dong-A University, Busan 49315, Korea. mjun@dau.ac.kr.
authors.forename: Mira
authors.initials: M
authors.lastname: Jun
authors.affiliation: Department of Smart Food and Drug, College of Biomedical Science &amp; Engineering, Inje University, Gimhae 50834, Korea. jeongws@inje.ac.kr.
authors.forename: Woo-Sik
authors.initials: WS
authors.lastname: Jeong
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000627:therapeutic use; D061745:Antioxidant Response Elements / Q000187:drug effects; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D019587:Dietary Supplements; D020834:Ethnopharmacology; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008518:Medicine, East Asian Traditional; D029582:Meliaceae / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D009336:Necrosis / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D018515:Plant Leaves / Q000737:chemistry; D011794:Quercetin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D011897:Random Allocation
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; C012526:quercitrin; D000082:Acetaminophen; D011794:Quercetin
keywords: Nrf2/ARE; acetaminophen; antioxidant; hepatoprotection; quercitrin