Cryptotanshinone ameliorates cladribine-induced cognitive impairment in rats

Abstract

Objective: To evaluate the neuroprotective effect of cryptotanshinone against cladribine-induced cognitive impairment in rats. Methods: Rats were administered with cladribine (1 mg/kg, p.o.) and cryptotanshinone (10 and 20 mg/kg, i.p.) for four weeks. Behavioral tests such as Morris water maze and elevated plus maze were conducted to check memory impairment caused by cladribine. On day 29, all rats were sacrificed, and the brains were separated for estimation of neuroinflammatory factors, biochemical parameters, neurotransmitters, Aβ_(1-42), blood-brain barrier permeability, nuclear factor erythroid 2-related factor 2 (Nrf2), and brain-derived neurotrophic factor (BDNF). Results: Treatment with cryptotanshinone dose-dependently enhanced spatial memory, improved the levels of neurotransmitter and antioxidant enzymes, and suppressed proinflammatory cytokine release. Cryptotanshinone also decreased Aβ_(1-42) accumulation and increased the levels of Nrf2 and BDNF in the hippocampus. Additionally, the histopathological results showed that cryptotanshinone reduced cladribine-induced neuronal death in the hippocampus. Conclusions: Cryptotanshinone exhibits a promising neuroprotective effect against cladribine-induced cognitive impairment in preclinical studies, and may be a potential phytochemical for the treatment and management of cognitive impairment.

Keywords

Alzheimer's disease / Cladribine / Cryptotanshinone / Neurotransmitters / Neuroprotective / Proinflammatory cytokines / Cognitive deficit

Acknowledgments

The authors extend their sincere thanks to IK Gujral Punjab Technical University, Kapurthala, Punjab and Sh. Parveen Garg, chairman, ISF College of Pharmacy for providing the necessary support. We would like to thanks to Indian Council of Medical Research for providing SRF to Mr. Khadga Raj Aran (Grant Number 2020-8817).

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

This research work is funded by the Indian Council of Medical Research with Grant Number 2020-8817, New Delhi, India.

Authors’ contributions

KRA conducted the experiment, collected data, and wrote the manuscript. GDG and SS designed, reviewed, analyzed and edited manuscript.

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