Abstract
Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK) pathway has been proposed as mechanism for berberine’s action. This study aimed to examine whether AMPK activation was necessary for berberine’s glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC) phosphorylation were stimulated by 20 µmol/L berberine. Nevertheless, berberine was still effective on stimulating glucose utilization and lactate production, when the AMPK activation was blocked by (1) inhibition of AMPK activity by Compound C, (2) suppression of AMPKα expression by siRNA, and (3) blockade of AMPK pathway by adenoviruses containing dominant-negative forms of AMPKα1/α2. To test the effect of berberine on oxygen consumption, extracellular flux analysis was performed in Seahorse XF24 analyzer. The activity of respiratory chain complex I was almost fully blocked in C2C12 myotubes by berberine. Metformin, as a positive control, showed similar effects as berberine. These results suggest that berberine and metformin promote glucose metabolism by stimulating glycolysis, which probably results from inhibition of mitochondrial respiratory chain complex I, independent of AMPK activation.
Highlights
Berberine, a plant isoquinoline alkaloid, is used as an over-thecounter drug in China to treat infectious diarrhea
We further compared berberine with other oral hypoglycemic agents and found that the effect of berberine was independent of insulin, which was quite different from that of troglitazone, the first thiazolidinedione used in clinical setting [22,30]
The study indicated that berberine was a potent oral hypoglycemic agent with beneficial effects on lipid metabolism [4]
Summary
A plant isoquinoline alkaloid, is used as an over-thecounter drug in China to treat infectious diarrhea. Rhizoma Coptidis is a popular traditional Chinese herb used for treatment of inflammation and diabetes, and contains 5.2%–7.7% of berberine. Rhizoma Coptidis was usually used to treat infection or inflammation since diabetes was not popular in ancient time [1,2]. In folk medicine of China, berberine is used to treat diabetes, obesity and non-alcoholic fatty liver disease [3,4,5,6,7]. A variety of molecular mechanisms were proposed for the anti-diabetic effect of berberine, such as AMPK activation [12,13], inhibition of PPARc and C/EBPa function [14,15], antioxidant [16], inhibition of aldose reductase and inhibitory activities on MAPK [1,17,18,19]. AMPK pathway is one of the most important drug targets for metabolism regulation
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