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Licensed Unlicensed Requires Authentication Published by De Gruyter February 8, 2021

Pharmacological investigations on efficacy of Phlorizin a sodium-glucose co-transporter (SGLT) inhibitor in mouse model of intracerebroventricular streptozotocin induced dementia of AD type

  • Reena Rani , Amit Kumar , Amteshwar Singh Jaggi and Nirmal Singh

Abstract

Objectives

The study has been commenced to discover the potential of Phlorizin (dual SGLT inhibitor) in streptozotocin induced dementia of Alzheimer’s disease (AD) type.

Material and methods

Injection of Streptozotocin (STZ) was given via i.c.v. route (3 mg/kg) to induce dementia of Alzheimer’s type. In these animals learning and memory was evaluated using Morris water maze (MWM) test. Glutathione (GSH) and thiobarbituric acid reactive species (TBARS) level was quantified to evaluate the oxidative stress; cholinergic activity of brain was estimated in term of acetylcholinesterase (AChE) activity; and the levels of myeloperoxidase (MPO) were measured as inflammation marker.

Results

The mice model had decreased performance in MWM, representing impairment of cognitive functions. Biochemical evaluation showed rise in TBARS level, MPO and AChE activity, and fall in GSH level. The histopathological study revealed severe infiltration of neutrophils. In the study, Phlorizin/Donepezil (serving as positive control) treatment mitigate streptozotocin induced cognitive decline, histopathological changes and biochemical alterations.

Conclusions

The results suggest that Phlorizin decreased cognitive function via its anticholinesterase, antioxidative, antiinflammatory effects and probably through SGLT inhibitory action. It can be conferred that SGLTs can be an encouraging target for the treatment of dementia of AD.


Corresponding authors: Dr. Nirmal Singh, Professor and Head, Department of Pharmaceutical Sciences and Drug Research, Faculty of Medicine, Punjabi University, Patiala 147002, Punjab, India, Phone: +91 9815129884, E-mail: ; Dr. Amit Kumar, Assistant Professor, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India, Phone: +91 9855647106, Email:

Acknowledgments

The authors are highly thankful to Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala and Chitkara University, Punjab for providing the necessary facilities for conducting the research work. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

  1. Research funding: None declared.

  2. Author contributions: 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: Not applicable.

  5. Ethical approval: The animal protocol was approved by IAEC (Institutional Animal Ethics Committee).

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Received: 2020-07-08
Accepted: 2020-10-09
Published Online: 2021-02-08

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