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Alpha-pinene modulates inflammatory response and protects against brain ischemia via inducible nitric oxide synthase-nuclear factor–kappa B-cyclooxygenase-2 pathway

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Abstract

Backgrounds

Cerebral ischemia-reperfusion leads to brain tissue injury. Inflammation and apoptosis play pivotal roles in the pathology.

Objective

α-Pinene is an organic compound of many aromatic plants and is known as a potent agent to possess antioxidant, and anti-inflammatory properties. Here, we sought to identify the anti-inflammatory and anti-apoptosis mechanism by which α-Pinene improves brain ischemia injury.

Results

Male Wistar rats underwent MCAO surgery for 1 h and different doses of alpha-pinene (25, 50, and 100 mg/kg) were intraperitoneally injected immediately after reperfusion to test this hypothesis. IV, NDS, gene and protein expression of inducible nitric oxide synthase (iNOS), cyclogenase-2 (COX-2), nuclear factor kappa B (NF-κB) p65, and caspase-3 were assessed 24 h after reperfusion. Results demonstrated that NF-κB p65, iNOS, and COX-2 gene and protein expression increased in the hippocampus, cortex, and striatum after 24 h of reperfusion, and alpha-pinene significantly inhibited NF-kB p65, iNOS, and COX-2 expression. Also, alpha-pinene significantly reduced the ischemia/reperfusion-induced caspase-3 activation in CA1 area of hippocampus.

Conclusion

Results showed that alpha-pinene protects the cerebral against ischemic damage caused by MCAO, and this effect may be through the regulating iNOS -NF-kappa B- COX-2 and caspase-3 inflammatory and apoptotic pathways.

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Acknowledgements

The authors would like to thank Kerman medical university for concerning this manuscript.

Funding

This study was supported by Kerman Neuroscience Research Center, Kerman University of Medical Sciences.

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Authors and Affiliations

  1. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Mohammad Shabani

  2. Department of Biology, Faculty of Science, Ilam University, Ilam, Iran

    Sohaila Erfani

  3. Department of Biophysics, Faculty of Advanced Technologies, University of Mohaghegh Ardabili, Namin, Iran

    Arash Abdolmaleki

  4. Department of Animal Science and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

    Fatemeh Ephtekhar Afzali

  5. Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

    Seyedeh Mahdieh Khoshnazar

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  1. Mohammad Shabani
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Contributions

MK conceived of the presented idea. MK and SE designed, directed and edited the project. MS, AA edited the project. MK and FE performed the experiments. All authors discussed the results and contributed to the final manuscript.

Corresponding author

Correspondence to Seyedeh Mahdieh Khoshnazar.

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Conflict of interest

All authors of this manuscript say that they have no conflicts of interest to disclose.

Ethical approval

All experimental protocols were accomplished according to the Kerman University of Medical Sciences Ethics Committee guidelines. The date of the Ethic approval Code is 2022-05-22. The Code of ethics is IR.KMU.REC.2022.078. The date of approval of the project in the scientific committee/council is 2022/04/13. The project number in the university system (research code) is 400000286.

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Shabani, M., Erfani, S., Abdolmaleki, A. et al. Alpha-pinene modulates inflammatory response and protects against brain ischemia via inducible nitric oxide synthase-nuclear factor–kappa B-cyclooxygenase-2 pathway. Mol Biol Rep 50, 6505–6516 (2023). https://doi.org/10.1007/s11033-023-08480-8

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