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Kolaviron ameliorates chronic unpredictable mild stress-induced anxiety and depression: involvement of the HPA axis, antioxidant defense system, cholinergic, and BDNF signaling

  • Ismail O. Ishola EMAIL logo , Taiwo G. Olubodun-Obadun , Oluwasayo A. Bakre , Emmanuel S. Ojo and Olufunmilayo O. Adeyemi
Published/Copyright: February 24, 2022
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Drug Metabolism and Personalized Therapy
From the journal Drug Metabolism and Personalized Therapy Volume 37 Issue 3

Abstract

Objectives

This study sought to investigate the beneficial effect of kolaviron (KV) (a biflavonoid) isolated from Garcinia kola seed on chronic unpredictable mild stress (CUMS)-induced anxiety- and depressive-like behavior.

Methods

Male albino mice were randomly divided into six groups (n=8) as follows; Group I: vehicle-control unstressed; Group II: CUMS-control; Group III-V: CUMS + KV 1, 5 or 50 mg/kg, respectively, Group VI: KV (50 mg/kg, p.o.) unstressed mice. Animals were subjected to CUMS for 14 days, followed by estimation of depressive- and anxiety-like behavior from days 14–16. This was followed by biochemical assays for oxidative stress, hypothalamo-pituitary axis, cholinergic, and BDNF signaling.

Results

CUMS caused significant reduction in time spent in open arms of elevated plus maze test (EPM) and increase in immobility time in tail suspension test (TST) and forced swim test (FST) ameliorated by KV treatments. KV administration also attenuated CUMS-induced malondialdehyde/nitrite generation and decrease in antioxidant enzymes activities in the prefrontal cortex and hippocampus. CUMS increased serum corticosterone, acetylcholinesterase activity, and reduced BDNF level in the PFC and hippocampus were attenuated by KV administration.

Conclusions

KV prevented CUMS induced anxiety- and depression-like behavior in mice through enhancement of antioxidant defense mechanisms, neurotrophic factors, and cholinergic systems.

Keywords: anxiety; brain derived neurotrophic factor; chronic-unpredictable stress; depression; hypothalamo-pituitary axis; kolaviron
Corresponding author: Ismail O. Ishola, PhD, Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos State, Nigeria; and African Centre of Excellence for Drug Research, Herbal Medicine Development and Regulatory Science, Lagos, Nigeria, E-mail:

Acknowledgments

Authors are grateful to Mr. Chijioke C.M. of the Department of Pharmacology, Therapeutics and Toxicology and Mr. S.A. Adenekan of the Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, for their technical assistance.

  1. Research funding: None declared.

  2. Author contributions: IOI, OOT, and OAB conceived and designed the study, IOI and OAB conducted experiments. IOI, ESO, and OOA analyzed data and wrote the manuscript. All authors read and approved the manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: Ethical approval (CMUL/HREC/11/17/267) for this study was obtained from the Health Research Ethics Committee of the College of Medicine, University of Lagos.

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Received: 2020-12-24
Revised: 2021-06-12
Accepted: 2021-08-11
Published Online: 2022-02-24

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/dmpt-2021-0125
Keywords for this article
anxiety; brain derived neurotrophic factor; chronic-unpredictable stress; depression; hypothalamo-pituitary axis; kolaviron

Articles in the same Issue

  1. Frontmatter
  2. Reviews
  3. Genotype-based chemotherapy for patients with gastrointestinal tumors: focus on oxaliplatin, irinotecan, and fluoropyrimidines
  4. Factors influencing methotrexate and methotrexate polyglutamate in patients with rheumatoid arthritis: a systematic review of population pharmacokinetics
  5. Original Articles
  6. Predicting drug–drug interactions by electrochemically driven cytochrome P450 3A4 reactions
  7. Evaluation of the stability of furosemide in tablet form during six-month storage in spaceflight and peculiarities of its pharmacokinetics and pharmacodynamics under conditions of anti-orthostatic hypokinesia
  8. CYP450 2D6 and 2C19 genotypes in ADHD: not related with treatment resistance but with over-representation of 2C19 ultra-metabolizers
  9. The markers of the organic acidemias and their ratios in healthy neonates in Serbian population
  10. Kolaviron ameliorates chronic unpredictable mild stress-induced anxiety and depression: involvement of the HPA axis, antioxidant defense system, cholinergic, and BDNF signaling
  11. The efficacy of topical Marham-e-Akbar in chronic atopic dermatitis – an open-label interventional study
  12. In vitro metabolic biomodulation of irinotecan to increase potency and reduce dose-limiting toxicity by inhibition of SN-38 glucuronide formation
  13. Datura stramonium abrogates depression- and anxiety-like disorders in mice: possible involvement of monoaminergic pathways in its antidepressant activity
  14. Synergistic anti-cancer effects of Nigella sativa seed oil and conventional cytotoxic agent against human breast cancer
  15. Short Communication
  16. MTHFR c.665C>T guided fluoropyrimidine therapy in cancer: gender-dependent effect on dose requirements
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