Antidiabetic Properties of Berberine: From Cellular Pharmacology to Clinical Effects

Abstract

Berberine is an alkaloid that is highly concentrated in the roots, rhizomes, and stem bark of various plants. It affects glucose metabolism, increasing insulin secretion, stimulating glycolysis, suppressing adipogenesis, inhibiting mitochondrial function, activating the 5' adenosine monophosphate-activated protein kinase (AMPK) pathway, and increasing glycokinase activity. Berberine also increases glucose transporter-4 (GLUT-4) and glucagon-like peptide-1 (GLP-1) levels. On GLP-1 receptor activation, adenylyl cyclase is activated, and cyclic adenosine monophosphate is generated, leading to activation of second messenger pathways and closure of adenosine triphosphate-dependent potassium channels. Increased intracellular potassium causes depolarization, and calcium influx through the voltage-dependent calcium channels occurs. This intracellular calcium increase stimulates the migration and exocytosis of the insulin granules. In glucose-consuming tissues, such as adipose, or liver or muscle cells, berberine affects both GLUT-4 and retinol-binding protein-4 in favor of glucose uptake into cells; stimulates glycolysis by AMPK activation; and has effects on the peroxisome proliferator-activated receptor γ molecular targets and on the phosphorylation of insulin receptor substrate-1, finally resulting in decreased insulin resistance. Moreover, recent studies suggest that berberine could have a direct action on carbohydrate metabolism in the intestine. The antidiabetic and insulin-sensitizing effect of berberine has also been confirmed in a few relatively small, short-term clinical trials. The tolerability is high for low dosages, with some gastrointestinal complaints appearing to be associated with use of high dosages.

O-Hexadecyl-Dextran Entrapped Berberine Nanoparticles Abrogate High Glucose Stress Induced Apoptosis in Primary Rat Hepatocytes

“…Berberine, an alkaloid, has been reported to have anti-diabetic activity [36], [37]. Moreover, a direct action of berberine on carbohydrate metabolism in the intestine has been suggested in the recent studies [38]–[41]. Short-term clinical trials have also confirmed the anti-diabetic and insulin-sensitizing effect of berberine [38].…”

Berberis Vulgaris and Berberine: An Update Review

“…Many mechanisms such as increasing insulin sensitivity, modulating gut microbiota, activating the adenosine AMPK pathway, promoting intestinal glucagon‐like protein‐1 secretion, stimulating glycolysis in peripheral tissue cells, inhibiting gluconeogenesis in liver, increasing glucose transporter, and upregulating hepatic low‐density lipoprotein receptor mRNA expression have been proposed for antidiabetic activity of berberine (Vuddanda et al ., ; Xiao et al ., ; Derosa et al , ). Regarding there are more than ten review articles about berberine and diabetes (Cicero and Tartagni, ; Dong et al ., ; Pang et al ., ), we refer the readers to those papers.…”

In VitroScreening for Antihepatic Steatosis Active Components within Coptidis Rhizoma Alkaloids Extract Using Liver Cell Extraction with HPLC Analysis and a Free Fatty Acid-Induced Hepatic Steatosis HepG2 Cell Assay

“…This antidiabetic and insulin sensitizing effect of berberine has been confirmed in a few relatively small, short-term clinical trials [29]. To date, very few reports on the lipid regulation by the other alkaloids derived from CAE have been published.…”