Dr. Ron’s Research Review – October 24, 2012

This week’s research review focuses on Berberine.

A combination of Berberis aristata extract and Silybum marianum extract (Berberol) was studied for type 2 diabetes in terms of its additive effect when combined with a conventional oral regimen for patients with suboptimal glycemic control. After 90 days of treatment, the nutraceutical association had a positive effect on glycemic and lipid parameters, significantly reducing glycosylated hemoglobin, basal insulin, homeostatic model assessment of insulin resistance, total and low-density lipoprotein cholesterol, and triglycerides. A relevant effect was also observed in terms of liver function by measuring aspartate transaminase and alanine transaminase. The product had a good safety profile, with distinctive gastrointestinal side effects likely due to its acarbose-like action. (Di Pierro, Villanova et al. 2012)

Obese human subjects (Caucasian) were given 500 mg berberine orally three times a day for twelve weeks. Berberine treatment produced a mild weight loss (average 5 lb/subject) in obese human subjects. But more interestingly, the treatment significantly reduced blood lipid levels (23% decrease of triglyceride and 12.2% decrease of cholesterol levels) in human subjects. (Hu, Ehli et al. 2012)

Our findings suggest that the prevention of obesity and insulin resistance by berberine in high-fat diet-fed rats is at least partially mediated by structural modulation of the gut microbiota, which may help to alleviate inflammation by reducing the exogenous antigen load in the host and elevating SCFA levels in the intestine. Redundancy analysis identified 268 berberine-responding operational taxonomic units (OTUs), most of which were essentially eliminated, whereas a few putative short-chain fatty acid (SCFA)-producing bacteria, including Blautia and Allobaculum, were selectively enriched, along with elevations of fecal SCFA concentrations.  (Zhang, Zhao et al. 2012)

Dr. Ron


Articles

Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control

            (Di Pierro, Villanova et al. 2012) Download

BACKGROUND: Suboptimal glycemic control is a common situation in diabetes, regardless of the wide range of drugs available to reach glycemic targets. Basic research in diabetes is endeavoring to identify new actives working as insulin savers, use of which could delay the introduction of injectable insulin or reduce the insulin dose needed. Commonly available as a nutraceutical, berberine is a potential candidate. METHODS AND RESULTS: Because its low oral bioavailability can be overcome by P-glycoprotein inhibitors like herbal polyphenols, we have tested the nutraceutical combination of Berberis aristata extract and Silybum marianum extract (Berberol((R))) in type 2 diabetes in terms of its additive effect when combined with a conventional oral regimen for patients with suboptimal glycemic control. After 90 days of treatment, the nutraceutical association had a positive effect on glycemic and lipid parameters, significantly reducing glycosylated hemoglobin, basal insulin, homeostatic model assessment of insulin resistance, total and low-density lipoprotein cholesterol, and triglycerides. A relevant effect was also observed in terms of liver function by measuring aspartate transaminase and alanine transaminase. The product had a good safety profile, with distinctive gastrointestinal side effects likely due to its acarbose-like action. CONCLUSION: Although further studies should be carried out to confirm our data, Berberol could be considered a good candidate as an adjunctive treatment option in diabetes, especially in patients with suboptimal glycemic control.

Lipid-lowering effect of berberine in human subjects and rats

         (Hu, Ehli et al. 2012) Download

Due to serious adverse effects and the limited effectiveness of currently available pharmacological therapies for obesity, many research efforts have focused on the development of drugs from natural products. Our previous studies demonstrated that berberine, an alkaloid originally isolated from traditional Chinese herbs, prevented fat accumulation in vitro and in vivo. In this pilot study, obese human subjects (Caucasian) were given 500 mg berberine orally three times a day for twelve weeks. The efficacy and safety of berberine treatment was determined by measurements of body weight, comprehensive metabolic panel, blood lipid and hormone levels, expression levels of inflammatory factors, complete blood count, and electrocardiograph. A Sprague-Dawley rat experiment was also performed to identify the anti-obesity effects of berberine treatment. The results demonstrate that berberine treatment produced a mild weight loss (average 5 lb/subject) in obese human subjects. But more interestingly, the treatment significantly reduced blood lipid levels (23% decrease of triglyceride and 12.2% decrease of cholesterol levels) in human subjects. The lipid-lowering effect of berberine treatment has also been replicated in the rat experiment (34.7% decrease of triglyceride and 9% decrease of cholesterol level). Cortisol, calcitriol, ACTH, TSH, FT4, and SHBG levels were not significantly changed following 12 weeks of berberine treatment. However, there was interestingly, an increase in calcitriol levels seen in all human subjects following berberine treatment (mean 59.5% increase, p=0.11). Blood inflammatory factors (CRP, IL-6, TNFalpha, COX-2) and erythrocyte sedimentation rate (ESR) were not significantly affected by treatment with berberine. Tests of hematological, cardiovascular, liver, and kidney function following berberine treatment showed no detrimental side effects to this natural compound. Collectively, this study demonstrates that berberine is a potent lipid-lowering compound with a moderate weight loss effect, and may have a possible potential role in osteoporosis treatment/prevention.

Effect of berberine on Escherichia coli, Bacillus subtilis, and their mixtures as determined by isothermal microcalorimetry

            (Kong, Xing et al. 2012) Download

The strong toxicity of pathogenic bacteria has resulted in high levels of morbidity and mortality in the general population. Developing effective antibacterial agents with high efficacy and long activity is in great demand. In this study, the microcalorimetric technique based on heat output of bacterial metabolism was applied to evaluate the effect of berberine on Escherichia coli, Bacillus subtilis, individually and in a mixture of both using a multi-channel microcalorimeter. The differences in shape of the power-time fingerprints and thermokinetic parameters of microorganism growth were compared. The results revealed that low concentration (20 mug/mL) of berberine began to inhibit the growth of E. coli and mixed microorganisms, while promoting the growth of B. subtilis; high concentration of berberine (over 100 mug/mL) inhibited B. subtilis. The endurance of E. coli to berberine was obviously lower than B. subtilis, and E. coli could decrease the endurance of B. subtilis to berberine. The sequence of half-inhibitory concentration (IC(50)) of berberine was: B. subtilis (952.37 mug/mL) > mixed microorganisms (682.47 mug/mL) > E. coli (581.69 mug/mL). Berberine might be a good selection of antibacterial agent used in the future. The microcalorimetric method should be strongly suggested in screening novel antibacterial agents for fighting against pathogenic bacteria.


Structural Changes of Gut Microbiota during Berberine-Mediated Prevention of Obesity and Insulin Resistance in High-Fat Diet-Fed Rats

            (Zhang, Zhao et al. 2012) Download

Berberine, a major pharmacological component of the Chinese herb Coptis chinensis, which was originally used to treat bacterial diarrhea, has recently been demonstrated to be clinically effective in alleviating type 2 diabetes. In this study, we revealed that berberine effectively prevented the development of obesity and insulin resistance in high-fat diet (HFD)-fed rats, which showed decreased food intake. Increases in the levels of serum lipopolysaccharide-binding protein, monocyte chemoattractant protein-1, and leptin and decrease in the serum level of adiponectin corrected for body fat in HFD-fed rats were also significantly retarded by the co-administration of berberine at 100 mg/kg body weight. Bar-coded pyrosequencing of the V3 region of 16S rRNA genes revealed a significant reduction in the gut microbiota diversity of berberine-treated rats. UniFrac principal coordinates analysis revealed a marked shift of the gut microbiota structure in berberine-treated rats away from that of the controls. Redundancy analysis identified 268 berberine-responding operational taxonomic units (OTUs), most of which were essentially eliminated, whereas a few putative short-chain fatty acid (SCFA)-producing bacteria, including Blautia and Allobaculum, were selectively enriched, along with elevations of fecal SCFA concentrations. Partial least square regression models based on these 268 OTUs were established (Q(2)>0.6) for predicting the adiposity index, body weight, leptin and adiponectin corrected for body fat, indicating that these discrete phylotypes might have a close association with the host metabolic phenotypes. Taken together, our findings suggest that the prevention of obesity and insulin resistance by berberine in HFD-fed rats is at least partially mediated by structural modulation of the gut microbiota, which may help to alleviate inflammation by reducing the exogenous antigen load in the host and elevating SCFA levels in the intestine.


References

Di Pierro, F., N. Villanova, et al. (2012). "Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control." Diabetes Metab Syndr Obes 5: 213-7.

Hu, Y., E. A. Ehli, et al. (2012). "Lipid-lowering effect of berberine in human subjects and rats." Phytomedicine 19(10): 861-7.

Kong, W. J., X. Y. Xing, et al. (2012). "Effect of berberine on Escherichia coli, Bacillus subtilis, and their mixtures as determined by isothermal microcalorimetry." Appl Microbiol Biotechnol 96(2): 503-10.

Zhang, X., Y. Zhao, et al. (2012). "Structural Changes of Gut Microbiota during Berberine-Mediated Prevention of Obesity and Insulin Resistance in High-Fat Diet-Fed Rats." PLoS One 7(8): e42529.