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Can J Physiol Pharmacol. 2015 Aug;93(8):625-31. doi: 10.1139/cjpp-2014-0513. Epub 2015 Mar 18.

Protective efficacy of carnosic acid against hydrogen peroxide induced oxidative injury in HepG2 cells through the SIRT1 pathway.

Author information

1
a Department of Pharmacy, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People's Republic of China.
2
b Department of Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian 116011, People's Republic of China.
3
c Department of General Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, People's Republic of China.
4
d Department of Pharmacology, Dalian Medical University, Dalian 116044, People's Republic of China.

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.

KEYWORDS:

HepG2 cells; SIRT1; acide carnosique; carnosic acid; cellules HepG2; espèces réactives d’oxygène; hydrogen peroxide; peroxyde d’hydrogène; reactive oxygen species

PMID:
26059423
DOI:
10.1139/cjpp-2014-0513
[Indexed for MEDLINE]

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