title: Protective efficacy of carnosic acid against hydrogen peroxide induced oxidative injury in HepG2 cells through the SIRT1 pathway.
abstract: Carnosic acid (CA), found in rosemary, has been reported to have antioxidant and antiadipogenic properties. Here, we investigate the molecular mechanism by which CA inhibits hydrogen peroxide (H2O2)-induced injury in HepG2 cells. Cells were pretreated with 2.5-10 μmol/L CA for 2 h and then exposed to 3 mmol/L H2O2 for an additional 4 h. CA dose-dependently increased cell viability and decreased lactate dehydrogenase activities. Pretreatment with CA completely attenuated the inhibited expression of manganese superoxide dismutase (MnSOD) and the B-cell lymphoma-extra large (Bcl-xL), and reduced glutathione activity caused by H2O2, whereas it reversed reactive oxygen species accumulation and the increase in cleaved caspase-3. Importantly, sirtuin 1 (SIRT1), a NAD(+)-dependent deacetylase, was significantly increased by CA. Considering the above results, we hypothesized that SIRT1 may play important roles in the protective effects of CA in injury induced by H2O2. As expected, SIRT1 suppression by Ex527 (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) and siRNA-mediated SIRT1 silencing (si-SIRT1) significantly aggravated the H2O2-induced increased level of cleaved caspase-3 but greatly reduced the decreased expression of MnSOD and Bcl-xL. Furthermore, the positive regulatory effect of CA was inhibited by si-SIRT1. Collectively, the present study indicated that CA can alleviate H2O2-induced hepatocyte damage through the SIRT1 pathway.
authors.affiliation: a Department of Pharmacy, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: a Department of Pharmacy, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: a Department of Pharmacy, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Fan
authors.affiliation: a Department of Pharmacy, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People's Republic of China.
authors.forename: Musen
authors.initials: M
authors.lastname: Lin
authors.affiliation: a Department of Pharmacy, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People's Republic of China.
authors.forename: Ce
authors.initials: C
authors.lastname: Zhang
authors.affiliation: a Department of Pharmacy, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People's Republic of China.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Fan
authors.affiliation: b Department of Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian 116011, People's Republic of China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Zhai
authors.affiliation: c Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: c Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People's Republic of China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: d Department of Pharmacology, Dalian Medical University, Dalian 116044, People's Republic of China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Yao
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D045784:Abietanes; D000975:Antioxidants; D016877:Oxidants; D006861:Hydrogen Peroxide; C447939:SIRT1 protein, human; D056564:Sirtuin 1; C018381:salvin
keywords: HepG2 cells; SIRT1; acide carnosique; carnosic acid; cellules HepG2; espèces réactives d’oxygène; hydrogen peroxide; peroxyde d’hydrogène; reactive oxygen species