Investigating the neuroprotective role of Synta-66 in type-2 diabetes mellitus-induced dementia in rats

Jun 12, 2025The Journal of pharmacy and pharmacology

Synta-66's potential protective effects on brain function in rats with diabetes-related dementia

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Abstract

Synta-66 at doses of 5 and 10 mg/kg reduces food and water intake and improves memory impairment.

Synta-66 may normalize glucose and insulin levels in a model of type-2 diabetes and Alzheimer's disease.
Antioxidant elements such as superoxide dismutase, glutathione, and catalase levels could be elevated by Synta-66 treatment.
Synta-66 is associated with decreased levels of thiobarbituric acid reactive substances, indicating reduced oxidative stress.
Neuroinflammation markers (IL-1β, IL-6, TNF-α, NF-κβ) may be downregulated by Synta-66, suggesting reduced inflammation.
Aβ accumulation and calcium levels are also potentially decreased with Synta-66 treatment.

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OBJECTIVES: This study explores the potential inhibitory effects of Synta-66 at doses of 1 and 5 mg/kg, with a particular emphasis on the role of ORAI-I in amyloidogenesis, a common mechanism that underlies type-2 diabetes mellitus (T2DM) and Alzheimer's disease (AD).

METHODS: Induction of T2DM-induced AD by the high-fat diet (HFD)-Streptozotocin (STZ)-Aβ25-35 model. Assessment of behavioral parameters like polydipsia, polyphagia, Morris water maze, and passive avoidance test; biochemical estimation of glucose, insulin, oxidative stress (superoxide dismutase (SOD), glutathione (GSH), catalase (Cat), and thiobarbituric acid reactive substances (TBARS)), neuroinflammation (interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κβ)), Aβ level, through ELISA technique, and calcium levels via atomic absorption spectrometer.

KEY FINDINGS: Synta-66 (5 and 10 mg/kg) results in a reduction in food and water intake, as well as a reduction in memory impairment in the Morris water maze and passive avoidance test. Furthermore, it normalizes glucose, insulin, and antioxidant elements (SOD, GSH, and Cat) level, while decreasing TBARS levels. In addition, ELISA data demonstrated a reduction in neuroinflammation (downregulation of IL-1β, IL-6, TNF-α, and NF-κβ), Aβ accumulation, and calcium levels by Synta-66 (5 and 10 mg/kg).

CONCLUSION: Consequently, ORAI can play a crucial role in the mediation of amyloidogenesis induced by T2DM, thereby establishing a connection between T2DM and AD. Therefore, Synta-66 has the potential to treat and prevent the progression of T2DM to AD.

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Investigating the neuroprotective role of Synta-66 in type-2 diabetes mellitus-induced dementia in rats

Abstract

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