Neuroprotective effect of 3,3'-diindolylmethane and ɑ-naphthoflavone, aryl hydrocarbon receptor modulators in an experimental model of ischemic stroke

Neha Dhir; Ashish Jain; Amit Raj Sharma; Ajay Prakash; Alka Bhatia; Bikash Medhi

doi:10.2174/1871527321666220418120224

Neuroprotective effect of 3,3'-diindolylmethane and ɑ-naphthoflavone, aryl hydrocarbon receptor modulators in an experimental model of ischemic stroke

CNS Neurol Disord Drug Targets. 2022 Apr 18. doi: 10.2174/1871527321666220418120224. Online ahead of print.

Authors

Neha Dhir¹, Ashish Jain¹, Amit Raj Sharma², Ajay Prakash¹, Alka Bhatia³, Bikash Medhi¹

Affiliations

¹ Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
² Department of Neurology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
³ Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

PMID: 35440324
DOI: 10.2174/1871527321666220418120224

Abstract

Background: The aryl hydrocarbon receptor (AhR) mediated signaling pathway is being emerged as a current target for neuromodulation. The present study was conducted to characterize the neuroprotective action of AhR modulators, i.e., 3,3'-diindolylmethane (DIM) and ɑ-naphthoflavone (ANF) in an experimental model of stroke using transient middle cerebral artery occlusion (MCAO) in Wistar rats.

Methods: The animals were treated with respective AhR modulators via intraperitoneal (i.p) injection 3 hrs after MCAO for 4 days (at 24 h interval). Following transient MCAO, the brain infarct volume, ND scoring, and various neuro behavioural tests were conducted to confirm the ischemic stroke. Further, oxidative stress parameters, inflammatory cytokines, and apoptotic mRNA expression were assessed. The histopathological changes in the brain of the rats were assessed using H&E staining and the results obtained were correlated with the molecular parameters.

Results: Treatment with AhR modulators had significantly decreased the brain infarct volume, ND scoring and improved neuro-behivoral deficits in animals following MCAO. A significant decrease was also observed in the oxidative stress, pro-inflammatory cytokines, and apoptotic mRNA expression in the AhR ligand treated groups. Moreover, a significant improvement was observed in the neuronal damage following MCAO in the treatment groups.

Conclusion: AhR pathway modulation may be taken as a valuable therapeutic target for treating acute ischemic stroke (AIS).

Keywords: 3; 3′-diindolylmethane (DIM); Acute ischemic stroke; alpha-Naphthoflavone (ANF); aryl hydrocarbon receptor; middle cerebral artery occlusion (MCAO).