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Improvement of cognitive function in mice by Citrus reticulata var. kinnow via modulation of central cholinergic system and oxidative stress

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Abstract

Memory disorders are a result of a number of factors, of which elevated brain oxidative stress and acetylcholinesterase (AChE) activity are significant hallmarks. A number of Citrus species have cognition-enhancing capacity mediated by their antioxidant and anti-cholinesterase activities. This study was designed to assess the cognitive-enhancing, antioxidant and anticholinesterase potentials of Citrus reticulata var. kinnow (CR) leaf extracts. CR extracts were examined by bioactivity guided fractionation using in-vitro DPPH and Ellman assays to determine antioxidant and AChE inhibitory capacity. The most active component was further evaluated for memory improvement effects using mouse model of scopolamine induced amnesia. Passive shock avoidance test and elevated plus maze test were employed to determine cognitive functions while brain biochemical parameters were measured to establish the neuroprotective mechanism. The methanol extract (ME) showed marked AChE inhibitory and antioxidant activities, therefore, it was fractionated. Comparative analysis of all obtained fractions revealed that ethylacetate fraction (EAF) was most active. Both ME and EAF improved cognitive dysfunction caused by scopolamine in mice by reducing TBARS levels and brain AChE activity. TLC densitometric studies showed appreciable levels of naringenin in ME (0.32 % w/w) and EAF (1.14 % w/w). The observed memory enhancement effects of ME and EAF could be attributed to their ability to inhibit AChE activity and antioxidant effects due to presence of flavonoids.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors are highly thankful to the Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India for providing all the necessary facilities to carry out this research.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India

    Simran Pruthi, Karanpreet Kaur & Richa Shri

  2. M M College of Pharmacy, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala, Haryana, India

    Simran Pruthi

  3. Chitkara College of Pharmacy, Chitkara University, Punjab, India

    Varinder Singh

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  1. Simran Pruthi
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  2. Karanpreet Kaur
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Simran Pruthi performed the experiments, collected data and provided helpful feedback. Karanpreet Kaur and Varinder Singh performed analysis of data and drafted the manuscript. Richa Shri provided the initial conception, designed the study and drafted the manuscript.

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Correspondence to Varinder Singh or Richa Shri.

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The approval of animal experiments was duly taken from Institutional Animal Ethics Committee (IAEC), Punjabi University, Patiala, Punjab, India (approval no. 107/GO/ReBi/99/CPCSEA/2019-10). 

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Pruthi, S., Kaur, K., Singh, V. et al. Improvement of cognitive function in mice by Citrus reticulata var. kinnow via modulation of central cholinergic system and oxidative stress. Metab Brain Dis 36, 901–910 (2021). https://doi.org/10.1007/s11011-021-00687-7

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