Dr. Ron’s Research Review – April 18, 2012

This week’s research review focuses on berberine for neural regeneration and weight loss in type 2 diabetes.

The following excerpts are from a recent article in the New England Journal of Medicine. (Zimmet and Alberti 2012)

Type 2 diabetes is one of the fastest growing epidemics in human history.

Existing algorithms, such as that from the American Diabetes Association, may actually set up clinicians for therapeutic failure. Each algorithmic step occurs because the preceding recommendation has failed, with the path finally ending with the administration of insulin, often combined with one or more oral agents.

Diabetic peripheral neuropathy is a common and troublesome complication in patients with type 2 diabetes mellitus. (Ko and Cha 2012)

Treatment-related weight gain is a side effect of many oral anti-diabetes agents and insulin. (Ross, Dzida et al. 2011)

A recent study showed that Berberine enhanced neurite outgrowth in a neuronal cell line and axonal regeneration in the rat peripheral nervous system (PNS). In an injury model of the rat sciatic nerve, four weeks of berberine (20 mg/kg i.p. once per day for 1 week), improved the thickness of remyelinated axons approximately 1.4-fold in the distal stump of the injury site. (Han, Heo et al. 2012)

An older study showed that berberine may also work to reduce body weight. Berberine reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in db/db mice. Similarly, berberine reduced body weight and plasma triglycerides and improved insulin action in high-fat-fed Wistar rats. (Lee, Kim et al. 2006)

Dr. Ron
Articles

Surgery or Medical Therapy for Obese Patients with Type 2 Diabetes?

         (Zimmet and Alberti 2012) Download

Type 2 diabetes is one of the fastest growing epidemics in human history and is closely associated with obesity.(1) Furthermore, the disease has multiple manifestations and is associated with progressive beta-cell failure.(2) Although lifestyle measures, including weight loss and physical activity, should be first-line treatment, success is difficult to achieve, and pharmaceutical intervention is almost always required. Because of the multiplicity of causal factors involved, it is unrealistic to expect that a patient will achieve excellent glycemic control with any single oral hypoglycemic agent or any combination of agents.(3) The progressive nature of type 2 diabetes requires ongoing assessment of . . .

Berberine promotes axonal regeneration in injured nerves of the peripheral nervous system

            (Han, Heo et al. 2012) Download

Abstract Berberine, an isoquinoline alkaloid component of Coptidis Rhizoma (goldenthread) extract, has been reported to have therapeutic potential for central nervous system disorders such as Alzheimer's disease, cerebral ischemia, and schizophrenia. We have previously shown that berberine promotes the survival and differentiation of hippocampal precursor cells. In a memory-impaired rat model induced by ibotenic acid injection, the survival of pyramidal and granular cells was greatly increased in the hippocampus by berberine administration. In the present study, we investigated the effects of berberine on neurite outgrowth in the SH-SY5Y neuronal cell line and axonal regeneration in the rat peripheral nervous system (PNS). Berberine enhanced neurite extension in differentiating SH-SY5Y cells at concentrations of 0.25-3 mug/mL. In an injury model of the rat sciatic nerve, we examined the neuroregenerative effects of berberine on axonal remyelination by using immunohistochemical analysis. Four weeks after berberine administration (20 mg/kg i.p. once per day for 1 week), the thickness of remyelinated axons improved approximately 1.4-fold in the distal stump of the injury site. Taken together, these results indicate that berberine promotes neurite extension and axonal regeneration in injured nerves of the PNS.


Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states

            (Lee, Kim et al. 2006) Download

Berberine has been shown to have antidiabetic properties, although its mode of action is not known. Here, we have investigated the metabolic effects of berberine in two animal models of insulin resistance and in insulin-responsive cell lines. Berberine reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in db/db mice. Similarly, berberine reduced body weight and plasma triglycerides and improved insulin action in high-fat-fed Wistar rats. Berberine 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 in 3T3-L1 adipocytes and L6 myotubes, increased GLUT4 translocation in L6 cells in a phosphatidylinositol 3' kinase-independent manner, and reduced lipid accumulation in 3T3-L1 adipocytes. These findings suggest that berberine displays beneficial effects in the treatment of diabetes and obesity at least in part via stimulation of AMPK activity.


References

Han, A. M., H. Heo, et al. (2012). "Berberine promotes axonal regeneration in injured nerves of the peripheral nervous system." J Med Food 15(4): 413-7.

Ko, S. H. and B. Y. Cha (2012). "Diabetic peripheral neuropathy in type 2 diabetes mellitus in Korea." Diabetes Metab J 36(1): 6-12.

Lee, Y. S., W. S. Kim, et al. (2006). "Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states." Diabetes 55(8): 2256-64.

Ross, S. A., G. Dzida, et al. (2011). "Impact of weight gain on outcomes in type 2 diabetes." Curr Med Res Opin 27(7): 1431-8.

Zimmet, P. and K. G. Alberti (2012). "Surgery or Medical Therapy for Obese Patients with Type 2 Diabetes?" N Engl J Med.