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In vitro antiglycating effect and in vivo neuroprotective activity of Trigonelline in d-galactose induced cognitive impairment

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Abstract

Background

Alzheimer’s disease (AD) is characterized by amyloid beta (Aβ) plaques, neurofibrillary tangles (NFTs) and cognitive impairment. Literature cites the role of advanced glycation end products (AGEs) in AD due to increased cytotoxicity via oxidative stress. d-galactose (d-gal) induced amnesia stimulates Aβ overproduction via increased oxidative stress and AGEs. Trigonelline (TRG), a naturally occurring alkaloid has been reported to have neuroprotective and antidiabetic properties.

Methods

Present study assessed the protective effect of TRG against in vitro AGEs formation. Since chronic administration of d-gal increases AGEs, we subsequently investigated the neuroprotective role of TRG (50 and 100 mg/kg as per body weight) against d-gal induced amnesia. Mice were subcutaneously (sc) injected with d-gal (150 mg/kg) for 6 weeks. Behavioral assessments in Morris water maze (MWM) and Y-maze were performed, followed by biochemical estimations to deduce the probable mechanism of action.

Results

In vitro experiments demonstrated that TRG stalled early and late AGEs formation. Chronic d-gal administration significantly impaired cognitive performance in MWM and Y maze, caused marked oxidative damage, elevated the AGEs levels and significantly increased the acetylcholinesterase levels as compared to sham group. TRG (50 and 100 mg/kg) treatment significantly ameliorated cognitive performance, reversed the oxidative damage, decreased AGE levels and caused significant decline in acetylcholine esterase levels as compared to d-gal group.

Conclusion

Present study highlights the neuroprotective role of TRG against d-gal induced amnesia due to the antioxidant, antiglycative and anticholinesterase properties.

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Abbreviations

Aβ:

amyloid beta

AChE:

acetyl cholinesterase

AD:

Alzheimer’s disease

AG:

aminoguanidine

AGEs:

advanced glycation end products

ANOVA:

analysis of variance

AU:

arbitrary units

BSA:

bovine serum albumin

d-gal:

d-galactose

DNP:

Donepezil

GSH:

reduced glutathione

MDA:

malonaldehyde

MWM:

Morris water maze

NADPH:

nicotinamide adenine dinucleotide phosphate oxidase

NFTs:

neurofibrillary tangles

PBS:

phosphate buffer saline

ROS:

reactive oxygen species

RFU:

relative fluorescence units

SAB:

spontaneous alteration behaviour

SD:

standard deviation

SOD:

superoxide dismutase

SEM:

standard error of the mean

TRG:

trigonelline

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Technology (DPST), Institute of Chemical Technology (ICT), N. P. Marg, Matunga (E), Mumbai, India

    Amrita A. Chowdhury, Nitin B. Gawali, Vipin D. Bulani, Pankaj S. Kothavade, Snehal N. Mestry, Padmini S. Deshpande & Archana R. Juvekar

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  1. Amrita A. Chowdhury
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  2. Nitin B. Gawali
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Correspondence to Archana R. Juvekar.

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Chowdhury, A.A., Gawali, N.B., Bulani, V.D. et al. In vitro antiglycating effect and in vivo neuroprotective activity of Trigonelline in d-galactose induced cognitive impairment. Pharmacol. Rep 70, 372–377 (2018). https://doi.org/10.1016/j.pharep.2017.09.006

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