Berberine Ameliorates Spatial Learning Memory Impairment and Modulates Cholinergic Anti-Inflammatory Pathway in Diabetic Rats

Abstract

Background: Cognitive impairment caused by diabetes has been recognized. Berberine is well known for its resistance to peripheral lesions, but it is rarely used for the treatment of spatial learning and memory caused by diabetes. This study explored the mechanism of berberine to alleviate cognitive impairment via the cholinergic anti-inflammatory and insulin signaling pathways. Methods: Morris water maze was used to appraise spatial learning and memory. Positron-emission tomography (PET) imaging was adopted to detect the transport of glucose, and blood/cerebrospinal fluid (CSF) glucose was checked using commercial blood glucose meter. Insulin level was measured by ELISA kit and β-Amyloid (Aβ) formation was observed by Congo red staining. Western-blot was performed to appraise protein expression. Results: We found that berberine rectified some aberrant changes in signal molecules concerning inflammation, and cholinergic and insulin signaling pathways in the hippocampus. Furthermore, CSF/blood glucose, inflammatory response or acetyl cholinesterase enzyme (AChE) activity were reduced by berberine. Additionally, acetylcholine levels were enhanced after berberine treatment in diabetic rats. Finally, Aβ formation in diabetic hippocampus was inhibited and spatial learning memory was ameliorated by berberine. Discussion: In conclusion, berberine clears Aβ deposit and consequently ameliorates spatial learning memory impairment via the activation of the cholinergic anti-inflammatory and insulin signaling pathways in diabetic rats.

Brain Insulin Signaling, Alzheimer Disease Pathology, and Cognitive Function

“…Of particular interest is to explore the link between peripheral and central insulin signaling and inflammation, and the role of altered cholinergic signaling by age, sex, and disease state (eg, AD and diabetes), including how altered cholinergic signaling may affect inflammation. 35 Another avenue of future research is to examine the link of altered nutritional status in AD, and how nutrition may influence insulin signaling. Finally, there are widespread changes in gene expression in AD postmortem brain in relation to both disease pathology and its clinical expression.…”

The Quest to Enhance the Efficacy of Berberine for Type-2 Diabetes and Associated Diseases: Physicochemical Modification Approaches

“…Their most active compound was compound 11 (Figure 4) which displayed an increased potency of 3.23-fold over berberine; 1.39-fold over metformin and 1.20-fold over rosiglitazone. Han et al [106] synthesised some carbohydrate-modified berberine derivatives (12) (Figure 4) by assessing cytotoxicity and antidiabetic effect in HepG2 cells. In cytotoxicity assay, the mannose modified berberine derivative showed a potency (IC 50 value) improvement of 1.5 times better than berberine.…”

“…Berberine (1, Figure 1) is one of the best characterized natural compounds with diverse pharmacological effects, including anticancer [5][6][7], anti-inflammatory [8,9], cardioprotective [10,11] and enhancement of memory function [12][13][14] effects. Its antidiabetic [15][16][17], antiobesity and anti-hyperlipidaemic [16,18] effects have also been well established.…”

“…Their most active compound was compound 11 (Figure 4) which displayed an increased potency of 3.23-fold over berberine; 1.39-fold over metformin and 1.20-fold over rosiglitazone. Han et al[106] synthesised some carbohydrate-modified berberine derivatives(12)…”

Co-administration of berberine/gypenosides/bifendate ameliorates metabolic disturbance but not memory impairment in type 2 diabetic mice

“…Berberine, gypenosides and bifendate are traditional Chinese OTC herbal medicines that possess multiple pharmacological activities like anti-inflammation, anti-oxidant, and anti-tumor [ 8 , 9 , 10 ]. Studies have demonstrated the potential of berberine, gypenosides and bifendate in treatment of interconnected diseases such as diabetes, obesity and cognitive deficits.…”