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Biomed Pharmacother. 2018 Jul;103:499-508. doi: 10.1016/j.biopha.2018.04.073. Epub 2018 Apr 24.

Betulinic acid attenuates dexamethasone-induced oxidative damage through the JNK-P38 MAPK signaling pathway in mice.

Author information

1
Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China; Changsha Lvye Bio-Technology Co., Ltd, Changsha City, 410199, China.
2
Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China.
3
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Norwida 31, 50-375, Wroclaw, Poland.
4
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX, 77843, USA.
5
Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China. Electronic address: 12145090@qq.com.
6
Colleges of Veterinary Medicine, Hunan Agricultural University, Changsha City, 410128, China. Electronic address: yijine@gmail.com.

Abstract

Dexamethasone (Dex), a potent anti-inflammatory/immunosuppressive agent, has been shown to induce oxidative stress. Betulinic acid (BA) is a pentacyclic lupane triterpene with a potent antioxidant activity. The aim of this study was to investigate the ameliorative effect and underlying mechanisms of BA on Dex-induced oxidative damage. Mice were pretreated with BA orally (0, 0.25, 0.5, and 1.0 mg/kg) daily for 14 days, and then a single dose of Dex (25 mg/kg body weight) was administered intraperitoneally 8 h after the last administration of BA to induce oxidative stress. BA pretreatment significantly alleviated Dex-induced changes of blood biochemical indices, increased the total antioxidant capacity (T-AOC), the activity of superoxide dismutase (SOD), and the ability of inhibiting hydroxyl radical (AIHR), reduced the level of malondialdehyde (MDA) in serum. Moreover, BA pretreatment enhanced the T-AOC, AIHR and the activity of peroxidase (POD) in liver, spleen and thymus. Concomitant with these biochemical parameters, BA pretreatment significantly reduced gene and protein expressions of apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK) and P38 mitogen-activated protein kinase (P38 MAPK) in the lymphatic organs of Dex-treated mice. BA was found to effectively attenuate Dex-induced oxidative damage. These protective effects may be mediated in part through the JNK-P38 MAPK signaling transduction pathway and BA may be a potential therapeutic agent due to its anti-oxidative properties.

KEYWORDS:

Apoptosis; Betulinic acid; Dexamethasone; JNK; Oxidative damage; P38

PMID:
29677535
DOI:
10.1016/j.biopha.2018.04.073
[Indexed for MEDLINE]

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