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In vivo protective effect of betulinic acid on dexamethasone induced thymocyte apoptosis by reducing oxidative stress

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Abstract

Background

Dexamethasone (Dex), a synthetic glucocorticoid, is strictly controlled for use due to its serious side effects, including immune suppression. Betulinic acid (BA), an antioxidant prepared from the white birch, exhibits immunomodulation properties. To assess the implications and investigate the mechanisms of BA-elicited immunomodulation, we hypothesized that Dex induced thymocyte apoptosis via oxidative stress could be lessened by BA.

Methods

Mice were given oral doses of BA (0.25, 0.5, and 1.0 mg/kg) daily for 14 days, and induced oxidative stress by giving a single dose of Dex intraperitoneal at the dosage of 25 mg/kg body weight 8 h after the last administration of BA.

Results

Dex administration alone significantly decreased antioxidant enzyme activities, while significantly increased reactive oxygen species (ROS) production, lipid peroxidation, mitochondrial dysfunctions, caspase-3 activation and cellular apoptosis. However, pretreatment with BA dose-dependently mitigated Dex-induced oxidative damage after 14 days of feeding. In addition to ROS scavenging activity in Dex-induced thymocyte, BA administration decreased lipid peroxidation, up-regulated antioxidant enzymes, restored mitochondrial function, increased Bcl-2 expression but reduced Bax expression, inhibited caspase-3 activation, and improved cell survival.

Conclusions

These findings reveal a protective capability of BA against Dex-induced cell death by reducing oxidative stress via mitochondrial mediated signal pathway which could be the potential mechanism underlying BA-elicited immunomodulation.

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Authors and Affiliations

  1. College of Veterinary Medicine, Hunan Agricultural University, Changsha City, China

    Jine Yi, Ruocen Zhu, Jing Wu, Wei Xia, Lijuan Zhu, Weiwei Jiang, Siting Xiang & Zhuliang Tan

  2. Department of Agricultural, Food and Nutritional Science, 4-10 Ag/For Center, University of Alberta, Edmonton, Canada

    Jianping Wu

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  1. Jine Yi
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  2. Ruocen Zhu
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  3. Jianping Wu
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  4. Jing Wu
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  5. Wei Xia
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  6. Lijuan Zhu
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  9. Zhuliang Tan
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Correspondence to Jine Yi or Zhuliang Tan.

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Yi, J., Zhu, R., Wu, J. et al. In vivo protective effect of betulinic acid on dexamethasone induced thymocyte apoptosis by reducing oxidative stress. Pharmacol. Rep 68, 95–100 (2016). https://doi.org/10.1016/j.pharep.2015.07.003

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  • DOI: https://doi.org/10.1016/j.pharep.2015.07.003

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