Plant essense for diabetes has scientific backing

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April 3, 2007  
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Medical News Today – Reports of a traditional Chinese medicine having beneficial effects for people suffering from type 2 diabetes now has some scientific evidence to back up the claims.

A collaboration between Chinese, Korean, and Australian scientists at Sydney’s Garvan Institute, has revealed that the natural plant product berberine could be a valuable new treatment.

Berberine (huang lian su, ?????) is found in the roots and bark of a number of plants used for medicinal purposes including wound healing and treatment of diarrhea. It has also been documented in Chinese literature as having a glucose lowering effect when administered to people with diabetes; yet, until now, its mode of action was unknown.

What is berberine? Berberine is an isoquinoline alkaloid isolated from herb plants, such as Cortex phellodendri (huang bai, ??) and Rhizoma coptidis (huang lian, ??). Huang lian and huang bai have used as “heat-removing” agents. In addition, berberine has been reported to anti-inflammatory effect both in vivo and in vitro. Inflammatory is tightly related to immunity.

Berberine (or plant material containing berberine) has also been documented as having anti-microbial, antitumour and anti-inflammatory properties as an oral medicine.

Garvan scientist Dr Jiming Ye says: “Our studies in animal models of diabetes show that berberine acts in part by activating an enzyme in the muscle and liver that is involved in improving sensitivity of the tissue to insulin – this in turn helps lower blood sugar levels. In addition, it seems berberine can help reduce body weight”.
Picture of the CD Rom

Current medicines for treating type 2 diabetes include metformin and the TZD group of drugs (TZD = Thiazolidinedione, a class of diabetes drugs, e.g. Avandia, Actos). However, a large number of patients cannot tolerate metformin and the TZDs can cause undesirable weight gain. Therefore, it is critical to develop new therapies to treat type 2 diabetes, which is a growing health problem.

“Berberine has been used for decades, if not centuries, with few reported side effects. Given the limitations of existing medicines we are excited to have evidence that berberine may be a helpful new treatment for type 2 diabetes; however, despite its widespread use in traditional medicine practices, it will still have to be evaluated properly following the defined clinical trials process”, said Professor James, head of the Garvan’s Diabetes & Obesity Research Program and co-author of the Diabetes paper.

In the present study, the researchers investigated the metabolic effects of berberine in two animal models of insulin resistance and in insulin-responsive cell lines.

Results show that berberine reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in mice. Similarly, berberine reduced body weight and plasma triglycerides and improved insulin action in high-fat–fed Wistar rats. Berberine also downregulated the expression of genes involved in lipogenesis and upregulated those involved in energy expenditure in adipose tissue and muscle.

Berberine treatment resulted in increased AMP-activated protein kinase (AMPK) activity, increased glucose uptake and reduced lipid accumulation. These findings suggest that berberine displays beneficial effects in the treatment of diabetes and obesity at least in part via stimulation of AMPK activity.

What is AMPK? AMPK consists of three proteins (subunits) that together make a functional enzyme, conserved from yeast to humans, that plays a role in cellular energy homeostasis. It is expressed in a number of tissues, including the liver, brain, and skeletal muscle.

The net effect of AMPK activation is stimulation of hepatic fatty acid oxidation and ketogenesis (the process by which ketone bodies are produced as a result of fatty acid breakdown), inhibition of cholesterol synthesis, lipogenesis (conversion of carbohydrates into fat), and triglyceride synthesis, inhibition of adipocyte lipolysis (breakdown of fat stored in fat cells which then released into bloodstream) and lipogenesis, stimulation of skeletal muscle fatty acid oxidation and muscle glucose uptake, and modulation of insulin secretion by pancreatic beta-cells.

AMPK acts as a metabolic master switch regulating several intracellular systems including the cellular uptake of glucose, the ?-oxidation of fatty acids and the biogenesis of glucose transporter and mitochondria. The energy-sensing capability of AMPK is sensitive to energy levels during rest and exercise (muscle stimulation).

Recent research on mice at Harvard University has shown that when the activity of AMPK was inhibited, the mice ate less and lost weight, but these data are controversial. When AMPK levels were artificially raised the mice ate more and gained weight.

In conclusion, the researchers said that berberine, a purified component from a traditional oriental medicine, reduces whole-body adiposity (the quality or state of being fat) and improves insulin sensitivity in two separate animal models of insulin resistance, at least in part, by activating AMPK in multiple cell types.

Collectively, these effects lead to changes in biochemical processes and gene expression that lead to a net switch in the metabolic program of the organism to catabolism of fuel stores, an adaptation that may be of some benefit in the face of disorders characterized by insulin resistance.

[Diabetes. 2006 Aug;55(8):2256-64.]