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Neuroprotective effect of Reinwardtia indica against scopolamine induced memory-impairment in rat by attenuating oxidative stress

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Abstract

Reinwardtia indica belongs to Linaceae family and used as a folk medicine in Asian countries. Traditionally, it has been used in the treatment of paralysis and anti-microbial in wound healing, etc. The current study was undertaken in order to investigate the antioxidant and memory protective effect of the alcoholic (99.90%) (AERI) and hydro-alcoholic (70:30) leaves extract (HAERI) of Reinwardtia indica, against scopolamine-induced memory impairment in animals and also tried to determine the possible mechanism of action. In addition, phytochemical profiling of alcoholic leaves extract was also conducted through gas chromatography-mass spectrometry (GC-MS/MS). Rats were pretreated with AERI, HAERI (dose 250 and 500 mg/kg) and Donepezil (standard drug) along with scopolamine (1 mg/kg) for a period of 14 days followed by different test like elevated plus maze, passive avoidance, and Morris water maze to assess learning and memory ability. Acetylcholine levels, acetylcholinesterase (AChE), antioxidant enzymes (SOD, CAT & GSH), histopathology of the brain and biochemical test were also performed at the end of the treatment period. The scopolamine treatment resulted in learning and memory deficits which were partially and significantly ameliorated by the AERI at higher dose among other doses of extracts. The AERI at higher dose also counteracted the scopolamine-induced decrease in acetylcholine levels, increase in AChE activity, and decrease in antioxidant enzymes activities. No significant changes observed in the biochemical estimation of all dose of extracts. Histology of brain tissue showed the marked cellular changes in only scopolamine treated group while the standard, AERI and HAERI treated group were showing less damage at hippocampus region of the brain. The phytochemicals found after chemical profiling through GC-MS also supported the activity because of the presence of chemicals already reported for the neuroprotective, memory-enhancing and antioxidant activity, etc. The results demonstrated that the ability of the AERI at higher dose among all doses of extracts has more potential to revert the scopolamine-induced learning and memory deficits in rats by attenuating the decreased level of acetylcholine and antioxidant enzymes.

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Abbreviations

AERI:

alcoholic leaves extract of Reinwardtia indica

HAERI:

hydroalcoholic leaves extract of Reinwardtia indica

RI:

Reinwardtia indica

AD:

Alzheimer’s disease

ACh:

acetylcholine

AChE:

acetylcholinesterase

ANOVA:

analysis of variance

DPPH TLC:

2,2-diphenyl-1-picrylhydrazyl thin-layer chromatography

DNPH:

2,4-dinitrophenylhydrazine

DTNB:

5,5′-dithiobis-2-nitrobenzoic acid

GPX:

glutathione peroxidase

GSH:

glutathione

HPLC:

high-performance liquid chromatography

MAChR:

muscarinic acetylcholine receptor

MDA:

malondialdehyde

NBT:

nitroblue tetrazolium

SOD:

superoxide dismutase

GC-MS/MS:

Gas chromatography-mass spectroscopy

Cornu Amonis:

(CA1, CA2, CA3) and dentate gyrus (DG)

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Acknowledgments

All the authors express the appreciation to the late Dr. Suresh Purohit, professor, department of pharmacology for sharing their pearls of wisdom with us during the course of this research.

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All data sets analyzed and attached with a manuscript in the form of table and figure.

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Authors and Affiliations

  1. Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

    Prabhat Upadhyay

  2. Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

    Rashmi Shukla

  3. Department of Botany, MMV, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India

    Kavindra Nath Tiwari

  4. Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

    G. P. Dubey

  5. Department of Pharmaceutical, Engineering and Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India

    Sunil Kumar Mishra

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  1. Prabhat Upadhyay
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  4. G. P. Dubey
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Contributions

PU and RS performed the experimental studies and drafted the manuscript. SKM, KNT, and PU participated in the design and coordination of the study, GPD supervised the study and revised the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sunil Kumar Mishra.

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The authors declare that they have no competing interests.

Ethics approval and consent to participate

This study was approved by the Committee on the Ethics of Animal Experiments of the Institute of Medical Sciences, Banaras Hindu University Varanasi (Permit No: Dean/2016/CAEC/50) and also, efforts were made to minimize animal suffering and to reduce the number of animals used.

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Upadhyay, P., Shukla, R., Tiwari, K.N. et al. Neuroprotective effect of Reinwardtia indica against scopolamine induced memory-impairment in rat by attenuating oxidative stress. Metab Brain Dis 35, 709–725 (2020). https://doi.org/10.1007/s11011-019-00479-0

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