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Ameliorative effect of fisetin against lipopolysaccharide and restraint stress-induced behavioral deficits via modulation of NF-κB and IDO-1

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Abstract

Background

Fisetin, a plant active polyphenol, is well known for its antioxidant and free radical scavenging activities. The present study was designed to explore the detailed molecular mechanism underlying its neuroprotective effects.

Methods

The young male mice were either administered a single dose of lipopolysaccharide (0.83 mg/kg) or subjected to restraint stress (6 h per day for 28 days) to induce behavioral deficits in different groups. Fisetin (15 mg/kg) was orally administered for the last 14 days of the study.

Results

Lipopolysaccharide (LPS) as well as restraint stress (RS) exposure caused behavioral alterations (anxiety and depressive-like behavior). Gene expression analysis showed upregulation of nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and indoleamine 2,3-dioxygenase (IDO)-1 gene expression along with downregulation of Nrf-2 (nuclear factor erythroid 2-related factor 2), HO-1 (heme oxygenase-1), and ChAT (choline acetyltransferase) gene expression level in RS and RS+LPS groups. Fisetin administration significantly ameliorated behavioral and neurochemical deficits in LPS, RS, and RS+LPS groups.

Conclusion

These findings clearly indicated that fisetin administration improved behavioral functions and suppressed the NF-κB and IDO-1 (indoleamine 2,3-dioxygenase) activation along with their antioxidant effect, suggesting fisetin as an intriguing nutraceutical for the management of inflammation-associated neurological disorders.

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Acknowledgements

The authors are also grateful to SBT Hub, College of Veterinary Sciences, Guwahati for providing technical support.

Funding

Authors would like to thank the National Institute of Pharmaceutical Education and Research (NIPER), Guwahati for financial assistance.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, India

    Priyansha Choubey, Mohit Kwatra, Surya Narayan Pandey, Dinesh Kumar, Durgesh Kumar Dwivedi, Prabha Rajput & Ashok Jangra

  2. Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

    Abhishek Mishra

  3. Department of Pharmacology, Gauhati Medical College, Guwahati, Assam, India

    Mangala Lahkar

  4. Department of Pharmacology, KIET School of Pharmacy, KIET Group of Institutions, Ghaziabad, Uttar Pradesh, India

    Ashok Jangra

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  1. Priyansha Choubey
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Correspondence to Ashok Jangra.

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All the experiments were carried out in accordance with the regulation of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India guidelines.

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Choubey, P., Kwatra, M., Pandey, S.N. et al. Ameliorative effect of fisetin against lipopolysaccharide and restraint stress-induced behavioral deficits via modulation of NF-κB and IDO-1. Psychopharmacology 236, 741–752 (2019). https://doi.org/10.1007/s00213-018-5105-3

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