Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Punicalagin alleviates brain injury and inflammatory responses, and regulates HO-1/Nrf-2/ARE signaling in rats after experimental intracerebral haemorrhage

Fuchi Zhang¹, Kang Wu¹, Xiaolin Wu², Can Xin², Minghui Zhou¹, Jin Lei¹, Jincao Chen²

¹Department of Neurosurgery, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Tongji 430030; ²Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.

For correspondence:- Jincao Chen Email: CoryGlassszj@yahoo.com Tel:+862783665261

Accepted: 27 January 2020 Published: 29 April 2020

Citation: Zhang F, Wu K, Wu X, Xin C, Zhou M, Lei J, et al. Punicalagin alleviates brain injury and inflammatory responses, and regulates HO-1/Nrf-2/ARE signaling in rats after experimental intracerebral haemorrhage. Trop J Pharm Res 2020; 19(4):727-737 doi: 10.4314/tjpr.v19i4.8

© 2020 The authors.
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Abstract

Purpose: To investigate the effect of punicalagin, an ellagitannin present in pomegranates, on intracerebral haemorrhage (ICH)-induced inflammatory responses and oxidative stress, and also unravel the underlying mechanism(s) of action.

Methods: Collagenase type IV (0.2 U) was used to induce ICH in adult male Sprague-Dawley rats. Punicalagin was given to the rats at doses of 25, 50, and 75 mg/kg body weight via oral gavage for 15 days before ICH induction. The animals were sacrificed 24h following induction of ICH, and their brains were excised immediately and used for analysis. Histological changes were determined with Haematoxylin and Eosin (H&E) staining. Permeability to blood-brain barrier (BBB) was determined by quantifying the extent of extravasation of Evan Blue (EB). Protein expressions of HO-1/Nrf-2/ARE and NF-κB signaling were assayed using immunoblotting and RT-PCR. Levels of reactive oxygen species (ROS) and serum levels of cytokines were also determined.

Results: Punicalagin treatment reduced inflammatory cell infiltration and cell damage, improved brain tissue architecture and BBB integrity. The punicalagin treatment increased the activities of antioxidant enzymes, and enhanced antioxidant status via activation of Nrf-2/ARE/HO-1 signaling pathway (p < 0.05). The treatment upregulated the expressions of HO-1 to 174 %, relative to 127 % in ICH control rats. Furthermore, it enhanced NF-κB levels and reversed the ICH injury-induced upregulations of IL-6, IL-18 and IL-1β.

Conclusion: These findings indicate that punicalagin exerts neuroprotective effect in rats after experimental ICH through regulation of theHO-1/Nrf-2/ARE signaling pathway. Thus, punicalagin has therapeutic potential for ICH

Keywords: Brain injury, Haemoxygenase-1, Intracerebral haemorrhage, Inflammatory responses, Nrf2/ARE signalling, Punicalagin