Beneficial effect of lupeol and metformin in mouse model of intracerebroventricular streptozotocin induced dementia

Khagesh Ram ¹, Kuldeep Kumar ^1,2, Dhandeep Singh ¹

⁰Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, 147002, Punjab, India.

Metabolic Brain Disease +

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June 6, 2024

View abstract on PubMed

Summary

Lupeol and metformin show promise in treating dementia by improving cognitive function and reducing brain damage in a mouse model. A combination of low-dose lupeol and metformin was more effective than higher doses of either drug alone.

Area Of Science

Neuroscience
Pharmacology
Biochemistry

Background

Dementia, particularly Alzheimer's disease (AD) type, poses a significant global health challenge.
Current treatments offer limited efficacy, necessitating the exploration of novel therapeutic agents.
Intracerebroventricular streptozotocin (i.c.v., STZ) administration in mice serves as a relevant model for studying dementia.

Purpose Of The Study

To investigate the therapeutic potential of lupeol and metformin in an i.c.v., STZ-induced mouse model of dementia.
To evaluate the effects of lupeol and metformin, individually and in combination, on cognitive deficits, biochemical markers, and neuroinflammation.

Main Methods

Dementia was induced in Swiss mice using i.c.v. STZ (3 mg/kg).
Animals were treated with varying doses of lupeol (50 & 100 mg/kg) and metformin (150 & 300 mg/kg) orally.
Cognitive function was assessed using the Morris Water Maze (MWM).
Biochemical assays measured acetylcholinesterase (AChE), TBARS, nitrite/nitrate, Nrf-2, GSH, and MPO activity.
Histological examination assessed neutrophil infiltration.

Main Results

STZ induction significantly impaired MWM performance and altered biochemical markers, including increased AChE, TBARS, nitrite/nitrate, MPO activity, and neutrophil infiltration, alongside decreased Nrf-2 and GSH levels.
Both lupeol and metformin treatments dose-dependently ameliorated STZ-induced behavioral, biochemical, and histological deficits.
A low-dose combination of lupeol (50 mg/kg) and metformin (150 mg/kg) exhibited a synergistic effect, outperforming higher doses of either agent alone.

Conclusions

Lupeol and metformin demonstrate significant efficacy in mitigating dementia symptoms in an STZ-induced mouse model.
The combination therapy suggests a potential synergistic interaction between lupeol and metformin.
These findings support the exploration of lupeol and metformin as potential therapeutic agents for managing Alzheimer's disease-type dementia.

Keywords:

Alzheimer Dementia Lupeol Metformin Streptozotocin