Berberine ameliorates neuronal AD‐like change via activating Pi3k/PGCε pathway

Abstract

IR (insulin resistance) in diabetic brain gave rise to the generation of toxic factor Aβ42 and axon collapse which were the marker of AD (Alzheimer's disease)‐like lesions in the circumstance of diabetes mellitus. But the underling molecular mechanism was not clear. Chronic HGHI (high glucose and high insulin) exposure accelerates IR has been reported in type II diabetes models. Berberine has been shown to promising effect for IR in vitro and in vivo. This study demonstrates the protective effect and the underlying mechanism of berberine on HGHI‐induced IR. HGHI‐induced cells were used to mimic the hyperinsulinemia resulting in IR. Berberine was used to uncover the mechanisms for the treatment of hyperinsulinemia in IR model. Morris water maze (MWM), PET imaging, CCK8 assay, ELISA assay, glucose kits, microscopy, and western blot analysis were performed to evaluate the protective effects of berberine. Berberine‐improved HGHI‐induced IR was correlated with the increase of glucose application in neurons. Meanwhile, the expressions of Pi3K, as well as GLUT3, PKCε, and APP were downregulated in the model, while p‐IRS Ser307 was upregulated compared with Normal group. Fortunately, these scenes were reversed by berberine administration. Furthermore, berberine decreased GSK3β Y216 expressions, inhibited the production of oligomer Aβ42 and extended neuronal axon. The monomeric berberine treatment improves IR that may be involved in glucose effective application, rectifying the related proteins of the aberrant insulin pathway. Additionally, it suppressed the generation of Aβ42 and ameliorated neuron axon damage. Finally, berberine improves DM (diabetes mellitus)‐induced cognitive impairment.

Berberine attenuates cognitive dysfunction and hippocampal apoptosis in rats with prediabetes

“…(2018) uncovered that berberine treatment ameliorated cognitive deficits in rats with aging‐induced diabetes. Additionally, berberine has been shown to improve neuronal Alzheimer's disease‐like changes via activating the PI3K/PGC pathway in insulin‐resistant rats (Wu et al., 2021). Our study re‐emphasized that berberine also had a preventive effect on prediabetes‐induced cognitive dysfunction.…”

Dapagliflozin improves diabetic cognitive impairment via indirectly modulating the mitochondria homeostasis of hippocampus in diabetic mice

“…In accordance with previous literature, 12 Graph Pad Prism 8 software, ImageJ and other software were used to analyze all experimental data, and all data were expressed in the form of mean ± SEM. One‐Way ANOVA analysis of variance test was used, and P < 0.05 was considered as statistically significant.…”

“…It is characterized by loss of executive function and clinical manifestations similar to that of AD 8 ; the brain pathological features of diabetic cognitive impairment are mainly AD‐like lesions, which are manifested as extracellular senile plaques caused by β‐amyloid (Aβ) deposition 9 . Previous studies have shown that the cascade effect caused by Aβ activates the hyperphosphorylation of the tau protein, 10 and impaired clearance of Aβ in the brain has demonstrated that the toxic effect of Aβ plays an important role in diabetes 11,12 . Subsequently, some scholars also denominate AD as “type III diabetes”, which indicates that there is a close relationship between diabetes and AD 8 .…”

“…9 Previous studies have shown that the cascade effect caused by Aβ activates the hyperphosphorylation of the tau protein, 10 and impaired clearance of Aβ in the brain has demonstrated that the toxic effect of Aβ plays an important role in diabetes. 11,12 Subsequently, some scholars also denominate AD as "type III diabetes", which indicates that there is a close relationship between diabetes and AD. 8 Abnormal glucose metabolism and brain blood flow in diabetic patients can also damage neurons in the brain, which in turn damages the central nervous system, affects brain energy metabolism and β-amyloid clearance, and causes cognitive impairment.…”