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Protective effects of berberine against diabetes-associated cognitive decline in mice
Mrinal Gupta1, Mohammad Rumman2, Babita Singh1
1Department of Biochemistry , King George's Medical University , Lucknow, Uttar Pradesh, India.
Aims:
Diabetes associated cognitive decline (DACD) is a common CNS-related consequence of diabetes. The primary clinical manifestation of DACD includes learning and memory impairment. Unfortunately, there is no cure to delay the cognitive symptoms of diabetes. Although berberine (BBR) has shown promising effect in the treating diabetes and cognitive dysfunction, more research is needed to understand the mechanism of its therapeutic effect. For better understanding, we investigated the functions of BBR involved in anti-inflammation, anti-oxidant and neuroprotection in the hippocampus of diabetic mice.
Methods:
Diabetes was induced in mice using STZ. BBR was administered for 4 weeks before (pre-treatment), and after (post-treatment) STZ administration. The effect of BBR on cognitive functions in diabetic mice was determined using neurobehavioural test. Moreover, how BBR affected neuroinflammation, oxidative stress, and acetylcholine levels in the hippocampus and BBB permeability were analyzed using standard biochemical assays. Lastly, we evaluated the mRNA expression of neuroprotective genes in the hippocampus to uncover the mechanism of BBR.
Results:
Treatment with BBR improved cognition in diabetic mice. It significantly reduced the levels of IL-6, iNOS, TNF-α, IL-1β, ROS and MDA and increased the levels of TAC, GSH, SOD and Catalase. Moreover, levels of acetylcholine and BBB permeability were reduced in the diabetic mice which was reversed by BBR treatment and increased the expression of IGF and BDNF in the hippocampus of diabetic mice.
Conclusion:
Our results suggest that BBR might be a potential therapeutic candidate for the treatment of DACD. Our study might serve as a basis for developing novel drugs for treating DACD.
Insights
Berberine (BBR) treatment improved cognitive function in diabetic mice by reducing inflammation and oxidative stress. This suggests BBR is a potential therapeutic for diabetes-associated cognitive decline.
Area of Science:
- Neuroscience
- Pharmacology
- Endocrinology
Background:
- Diabetes-associated cognitive decline (DACD) is a growing concern, marked by learning and memory impairments.
- Current treatments for DACD are limited, necessitating research into novel therapeutic strategies.
- Berberine (BBR) shows potential in managing diabetes and cognitive dysfunction, but its precise mechanisms require further elucidation.
Purpose of the Study:
- To investigate the therapeutic mechanisms of Berberine (BBR) in mitigating diabetes-associated cognitive decline (DACD).
- To evaluate BBR's effects on neuroinflammation, oxidative stress, and neuroprotection in the hippocampus of diabetic mice.
Main Methods:
- Diabetes was induced in mice using streptozotocin (STZ).
- Mice received BBR treatment pre- and post-STZ administration.
- Cognitive function, neuroinflammation, oxidative stress markers, acetylcholine levels, blood-brain barrier (BBB) permeability, and neuroprotective gene expression in the hippocampus were assessed.
Main Results:
- BBR treatment significantly improved cognitive function in diabetic mice.
- BBR reduced key markers of inflammation (IL-6, iNOS, TNF-α, IL-1β) and oxidative stress (ROS, MDA).
- BBR increased antioxidant capacity (TAC, GSH, SOD, Catalase), normalized acetylcholine levels and BBB permeability, and upregulated neuroprotective genes (IGF, BDNF).
Conclusions:
- Berberine (BBR) demonstrates significant therapeutic potential for treating diabetes-associated cognitive decline (DACD).
- BBR's mechanisms involve anti-inflammatory, antioxidant, and neuroprotective effects in the hippocampus.
- This study provides a foundation for developing new drugs targeting DACD.
