Neuroprotective Effect and Possible Mechanisms of Berberine in Diabetes-Related Cognitive Impairment: A Systematic Review and Meta-Analysis of Animal Studies

Abstract

Berberine, the main bioactive component of Coptis chinensis Franch., is widely used in the treatment of diabetes. Previous studies have reported that berberine supplementation may play a multitarget therapeutic role in diabetes-related cognitive impairment (DCI). This systematic review and meta-analysis evaluated the effect and possible mechanisms of berberine in animal models of DCI. Relevant studies were searched through PubMed, Web of Science, Embase, and three Chinese databases (CNKI, Wanfang, and VIP) until March 2022. Twenty studies involving 442 animals were included, and SYRCLE’s risk of bias tool was used to assess methodological quality. The statistical analysis was performed using STATA 15.0 to calculate the weighted standard mean difference (SMD) with a 95% confidence interval (CI). The fasting blood glucose (FBG) and Morris water maze test (MWM) were the main outcomes to be analyzed. The overall results showed that berberine could significantly improve FBG, escape latency, the times of crossing the platform, the time spent in the target quadrant, serum insulin, 2hBG of oral glucose tolerance test (OGTT), amyloid β (Aβ), acetylcholinesterase (AChE), oxidative stress, and inflammation levels. The present meta-analysis demonstrated that berberine could not only lower blood glucose levels but also improve learning and memory in DCI animal models, which might involve regulating glucose and lipid metabolism, improving insulin resistance, anti-oxidation, anti-neuroinflammation, inhibiting endoplasmic reticulum (ER) stress; and improving the cholinergic system. However, additional attention should be paid to these outcomes due to the significant heterogeneity.

The efficacy and mechanism of berberine in improving aging-related cognitive dysfunction: A study based on network pharmacology

“…There are reasonable grounds to believe that reversing MCI to reduce the burden of dementia is a viable area of interest. There is compelling evidence to suggest that BBR was effective in improving cognitive function in Diabetes-related cognitive impairment and AD (Akbar et al, 2021;Hao et al, 2022). A spectrum of studies has demonstrated the ameliorative role of BBR in AD pathologies and cognitive dysfunction (He et al, 2017;Cai et al, 2018;Lin L. et al, 2020;Wu et al, 2021;Ye et al, 2021).…”

Effect of Chinese herbal medicine therapy on risks of all-cause mortality, infections, parasites, and circulatory-related mortality in HIV/AIDS patients with neurological diseases

“…and Huang Qin (root of S. baicalensis Georgi), previously reported in LDXGT, were also present in BXXXT. Berberine, one of the main bioactive components of Huang Lian (root of C. chinensis Franch., a Chinese herb of BXXXT), has anti-diabetes-related cognitive impairment and anti-cognitive deficiency effects (Durairajan et al, 2012;Hao et al, 2022).…”

Advances of berberine against metabolic syndrome-associated kidney disease: Regarding effect and mechanism

“…Afterward, numerous studies demonstrated its weight loss ( Park et al, 2020 ), antihypertensive ( Ma et al, 2017 ), glucose-lowering ( Di et al, 2021 ), lipid-lowering ( Pirillo and Catapano, 2015 ), uric acid-lowering ( Li X. et al, 2021 ), anti-inflammatory ( Oshima et al, 2018 ; Lu et al, 2022 ), antifibrotic ( Ahmedy et al, 2022 ), antiproliferative ( Bonon et al, 2013 ), antiapoptotic ( Hu et al, 2012 ), antiaging ( Xu Z. et al, 2017 ), antioxidant ( Shou et al, 2022 ), antibacterial ( Liao et al, 2020 ), anticancer ( Liu et al, 2022 ), immunomodulatory ( Huang et al, 2021 ), gut microbiome adjustment ( Wang H. et al, 2022 ), neuroprotective ( Domitrović et al, 2013 ), cardioprotective ( Cai et al, 2021 ), and neuroprotective ( Shou et al, 2022 ) effects ( Figure 2 ). According to these pharmacological properties, BBR is promising in treating various diseases, such as MetS ( Och et al, 2022 ), hyperuricemia ( Li X. et al, 2021 ), acute kidney injury ( Shen et al, 2020 ), rheumatoid arthritis ( Huang et al, 2021 ), cardiovascular disease ( Feng et al, 2019 ), gastric cancer ( Liu et al, 2022 ), neuropsychiatric disorder ( Hao et al, 2022 ), and polycystic ovary syndrome ( Zhang et al, 2021 ).…”