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Dmso-33718-pilot-study-on-the-additive-effects-of-berberine-to-oral-typ

Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
open access to scientific and medical research Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients This article was published in the following Dove Press journal: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy16 July 2012Number of times this article has been viewed 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®) 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.
Keywords: berberine, silymarin, glycosylated hemoglobin, diabetes
Introduction
Diabetes mellitus is recognized as a group of heterogeneous disorders, with common
elements of hyperglycemia and glucose intolerance due to insulin deficiency, impaired
effectiveness of insulin action, or both. The prevalence of type 2 diabetes increases
with age, is increasing worldwide, and its economic impact currently accounts for a
significant portion of health care expenditure.1 Injection of long-acting insulin is a
common therapeutic approach for patients with type 2 diabetes that is poorly controlled
with multiple oral regimens.2 Unfortunately, although insulin use as the mainstay of
treatment for diabetes has resulted in favorable treatment outcomes, poor adherence/
compliance continues to be a problem because of fear of insulin or fear of injection, and
this can be associated with poor glycemic control, clinical complications, psychological comorbidity, poor general well being and health status, and increased mortality risk in patients with diabetes.3 Last but not least, use of insulin is very often considered to be the “point of no return” in medical intervention for diabetes. These observations submit your manuscript
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2012:5 213–217 2012 Di Pierro et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
suggest a need for implementation of new therapeutic strate- effect similar to that of metformin,14 even if it likely acts via gies to delay the need for insulin as far as possible.
a mechanism different from that of metformin.15 Berberine, an isoquinoline alkaloid of the protoberberine Berberine regulates glucose metabolism via mul- type and found in an array of plants, has been used in Indian tiple mechanisms of action. It enhances glucose uptake and Chinese medicine for many decades. It is present in by upmodulation of glucose transporter type 4, activates Hydrastis canadensis (goldenseal), Coptis chinensis (Coptis 5′-AMP-activated protein kinase as a consequence of inhi- or goldenthread), Berberis aquifolium (the Oregon grape), bition of mitochondrial function, suppresses adipogenesis Berberis vulgaris (barberry), and Berberis aristata (tree by inhibition of peroxisome proliferator-activated receptor turmeric). Berberine and extracts of berberine have demon- gamma and C-enhancer-binding protein alpha function, and strated significant antimicrobial activity against a variety of decreases intestinal glucose absorption by inhibition of alpha- organisms, including bacteria, viruses, fungi, protozoans, glucosidase.16 However, despite these functions, berberine helminths, and chlamydia. The predominant clinical uses of has poor oral bioavailability.17 In humans, this appears to berberine, at least in the recent past, have included bacterial be due to a P-glycoprotein-mediated gut extrusion process18 diarrhea and intestinal parasite infections.4 and substantial excretion in bile.19 P-glycoprotein seems to More recently, clinical research on berberine has revealed decrease the amount of berberine able to cross enterocytes novel pharmacological properties and multiple therapeutic by about 90%,20 suggesting that inhibition of P-glycoprotein applications, mainly concerning hypercholesterolemia could potentially improve its oral poor bioavailability. and diabetes.5 With regard to the lipid profile, berberine Among the potential P-glycoprotein inhibitors, silymarin upregulates low-density lipoprotein receptor expression from Silybum marianum could be a good candidate due to its independent of sterol regulatory element-binding proteins, very poor oral bioavailability and its good safety profile.21 but dependent on extracellular signal-regulated kinases and Therefore, we investigated the activity of a combination c-Jun N-terminal kinase activation, leading to reductions in of berberine and silymarin when added to oral hypoglycemic total cholesterol and low-density lipoprotein cholesterol of regimens for patients with suboptimal glycemic control. Our about 30% and 25%, respectively. This upmodulation occurs aim was to evaluate the impact of this approach on body mass via a post-transcriptional mechanism that stabilizes mRNA index, hyperglycemia, hypercholesterolemia, triglyceride and enables berberine to act as a cholesterol-lowering drug levels, and liver enzymes in patients with type 2 diabetes.
via a mechanism of action different from that of the statins.6 In addition to its cholesterol-lowering properties, berberine Materials and methods
reduces triglycerides by about 35%. These effects on the lipid The study was performed in routine clinical practice in profile have been observed in both animals and humans.6,7 accordance with international guidelines and in line with Berberine also has an important additive effect in the pres- the principles outlined in the Declaration of Helsinki, ence of statins.8 This is likely due to the ability of berberine to so approval from the local ethics board was not required. downmodulate proprotein convertase subtilisin/kexin type 9, This study was carried out in a single center in Italy a protein which reduces the cholesterol-lowering properties where it is not mandatory to obtain ethical approval when of statins.9 This effect of berberine could be relevant when p erforming experiments involving nutraceutical products. treating patients with suboptimal control of hypercholes- Twenty-six patients diagnosed with type 2 diabetes were terolemia despite receiving high doses of statins. Due to enrolled. The patient demographics are shown in Table 1. this additive effect, it is quite common to find nutritional Twenty-two of the 26 patients completed the study, with supplements containing berberine10 along with a natural four dropouts as a result of gastrointestinal discomfort and/ source of lovastatin (ie, Monascus purpureus).11 However, these products do not take into consideration the poor stan-dardization of the raw materials12 and the risk to consumers Table 1 Demographic characteristics of the 22 patients who
due to the possible presence of mycotoxic contaminants Berberine has also been shown to be effective in the Males n = 17
Females n = 5
treatment of diabetes, in which it significantly decreases glycosylated hemoglobin (HbA ), fasting blood glucose, and postprandial blood glucose. In this respect, berberine has an Note: All values for ages and weight are expressed as the median ± standard deviation.
submit your manuscript |
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2012:5 The main inclusion criteria were stable (for at least demonstrated to be a valid addon treatment option for 6 months) but suboptimal glycemic control (HbA 7.5%–9.5%), patients with type 2 diabetes and suboptimal glycemic body mass index . 22 kg/m2, age 25–75 years, and a negative control. As shown in Table 2, a significant reduction was pregnancy test for female patients. All patients had suboptimal observed in HbA , basal insulin, total cholesterol, low- glycemic control despite use of the following drugs, unchanged density lipoprotein cholesterol, triglycerides, HOMA-R at least in the last 3 months: metformin (n = 20), incretins (n = 4), (homeostatic model assessment for insulin resistance, cal-sulfonylureas (n = 14), glitazones (n = 3), and insulin (n = 5). culated as glucose × insulin/405, where glucose is expressed Twenty patients were also receiving antihypertensive drugs, and as mg/dL and insulin as µU/mL), and alanine transaminase. 13 were receiving anticoagulant therapy. As regards the lipid pro- Aspartate transaminase also showed a downwards trend. file, 12 patients were receiving statins, 1 was receiving a fibrate There were no significant changes in high-density lipopro- whereas 5, previously under treatment with statins, had inter- tein cholesterol, fasting glucose, body mass index, weight, rupted the therapy due to unwanted effects, mainly myalgia.
Exclusion criteria were moderate to severe liver dysfunction (serum alanine aminotransferase . 120 IU/L and Discussion
aspartate aminotransferase . 80 IU/L), abnormal renal func- Four of the 26 patients diagnosed with type 2 diabetes and tion (serum creatinine . 115 µmol/L), severe heart failure suboptimal glycemic control who enrolled in this study (New York Heart Association Class III or greater), history of dropped out, leaving data for the 22 patients who com- acute diabetic complications, including diabetic ketoacidosis pleted the study. We investigated the clinical effects of oral or hyperosmolar hyperglycemic nonketotic coma, psychiatric treatment using a nutraceutical combination of B. aristata disease, severe infection, pregnancy or planning for preg- extract (containing 85% berberine) and S. marianum extract. nancy, and fasting plasma glucose $ 200 mg/dL.
The latter ingredient is included with the aim of enhancing All patients received addon nutraceutical therapy, ie, the oral bioavailability of berberine, mostly by reducing Berberol® (PharmExtracta, Pontenure, Italy), an oral tablet P-glycoprotein activity in the gut. To be eligible for entry containing 588 mg of B. aristata extract titered as 85% ber- into this study, patients had to have had suboptimal glycemic berine and 105 mg of S. marianum extract titered as .60% control (HbA 7.5%–9.5%) unchanged for at least 3 months flavonolignans. The product, in agreement with the Italian despite at least 6 months of treatment with a multidrug legislation (law number 169/2004) had been notified to the r egimen. According to the international guidelines, HbA Minister of Health in 2010 (E10 40753Y) and registered values in this range are linked with an increased risk of as a food supplement, with both its actives (standardized developing microvascular and macrovascular complications, extracts of B. aristata and S. marianum) belonging to the list of botanicals approved as nutraceuticals and its excipients all Table 2 Effect of adjunctive Berberol therapy after 90 days of
being food grade. The patients took two tablets per day on an treatment in 22 patients with type 2 diabetes and suboptimal empty stomach in the late evening for the 90-day duration of the study. Berberol was manufactured by SIIT (Trezzano S/N, Parameter
P value
Milan, Italy). The two actives, ie, B. aristata extract and S. marianum extract, were provided, respectively, by SIIT and Indena, both located in Milano, Italy.
The statistical analysis was performed using SPSS 12.0 for Windows (SPSS Inc, Chicago, IL). Statistical differ- ences between baseline and different time points were analyzed using the nonparametric paired t-test. The α level HOMA-R Notes: All values are expressed as the median ± standard deviation at baseline
(t = 0) and after 90 days (t = 90) of daily therapy. Δ% corresponds to the difference
(percent) between t = 0 and t = 90.
Abbreviations: BI, basal insulin; FG, fasting glucose; HOMA-R, homeostatic model
Berberol containing extracts of B. aristata and S. marianum assessment of insulin resistance (FG × BI/405); LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; HbA , glycosylated extract, dosed at two tablets daily for 90 days, was hemoglobin; ns, not statistically significant; TC, total cholesterol.
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2012:5 submit your manuscript
and all possible medical effort should be made to reduce Conclusion
HbA below 7%.22 Use of injectable insulin should be Berberol is a nutraceutical combination of highly standard- delayed as long as possible using oral insulin-saving drug ized herbal extracts of B. aristata and S. marianum titered, cocktails. The basis for using such cocktails, precisely estab- respectively, as 85% berberine and .60% flavanolignans. lished on the basis of the metabolic features of a patient, have Berberol seems to have positive effects in patients with type 2 to be considered carefully, not only because of the very poor diabetes and suboptimal glycemic control when given orally patient compliance with insulin injections, but also because in addition to a conventional regimen (ie, metformin, dipep- delaying insulin therapy should spare endogenous insulin tidyl peptidase-4 inhibitors, glitazones, acarbose or insulin, alone or as multidrug therapy). Berberol seems to improve In patients with suboptimal glycemic control, we the cholesterol-lowering properties of statins, and has a posi- observed an HbA reduction of about 0.85% after tive effect on liver enzymes. Treatment seems to be safe and 3 months of treatment with Berberol, which was maintained tolerated at the doses tested, with minimal unwanted effects, after 6 months of treatment (data not shown). Such a which resolve on cessation of treatment without any further percentage reduction is comparable with that normally consequences. The results of our pilot study performed in obtained in patients treated with acarbose, dipeptidyl 26 patients need confirmation by larger trials and with better peptidase-4 inhibitors (sitagliptin, vildagliptin, saxagliptin), definition of the diabetic patients enrolled. Allowing for these or glitazones, used alone or adjunctive to metformin, to limitations, Berberol can still be considered as a potential oral nutraceutical suitable for use in addition to conventional We did not modify any drug or treatment protocol estab- therapy for type 2 diabetes, with the aim of ameliorating lished before starting treatment with Berberol in any of the suboptimal glycemic control as a strategy for postponing 22 patients who completed the study. At the same time, no modifications in terms of food intake or lifestyle were suggested or adopted before or during the trial, and this is Disclosure
reflected by the minimal changes in body weight and waist FDP developed and has patented the Berberol used in A possible mechanism of action of Berberol could be its ability to increase insulin sensitivity, as shown by the References
reduction in HOMA-R. Another possible mechanism of 1. Shamseddeen H, Getty JZ, Hamdallah IN, Ali MR. Epidemiology and economic impact of obesity and type 2 diabetes. Surg Clin North Am. action could be linked to the acarbose-like action observed by some clinicians.24 This hypothesis should explain some of 2. Donner T, Muñoz M. Update on insulin therapy for type 2 diabetes. the gastrointestinal side effects observed, and could explain J Clin Endocrinol Metab. March 22, 2012.
3. Fu AZ, Qiu Y, Radican L. Impact of fear of insulin or fear of injection why four patients dropped out of the trial.
on treatment outcomes of patients with diabetes. Curr Med Res Opin. We observed a relevant reduction in total cholesterol, 4. [No authors listed]. Berberine. Altern Med Rev. 2000;5(2):175–177.
low-density lipoprotein cholesterol, and triglycerides in our 5. Vuddanda PR, Chakraborty S, Singh S. Berberine: a potential patients, all of whom had a cholesterol value within normal phytochemical with multispectrum therapeutic activities. Expert Opin range or were on treatment with statins. This result, already Investig Drugs. 2010;19(10):1297–1307.
6. Kong W, Wei J, Abidi P, et al. Berberine is a novel cholesterol-lowering observed by many clinicians, is likely due to the hypocho- drug working through a unique mechanism distinct from statins. lesterolemic activity of berberine and to an additive effect Nat Med. 2004;10(12):1344–1351.
7. Hu Y, Davies GE. Berberine inhibits adipogenesis in high-fat of berberine when combined with statin therapy.
diet-induced obesity mice. Fitoterapia. 2010;81(5):358–366.
Another effect was the reduction in alanine and aspartate 8. Kong WJ, Wei J, Zuo ZY, et al. Combination of simvastatin with ber- transaminase levels. Similar observations have been made berine improves the lipid-lowering efficacy. Metabolism. 2008;57(8): 1029–1037.
in animals and in humans, and berberine has been shown 9. Cameron J, Ranheim T, Kulseth MA, Leren TP, Berge KE. to reduce liver necrosis both in nonalcoholic steatosis and Berberine decreases PCSK9 expression in HepG2 cells. Atherosclerosis. 2008;201(2):266–273.
in steatosis due to hepatitis C infection.25 However, these 10. Affuso F, Ruvolo A, Micillo F, Saccà L, Fazio S. Effects of a nutra- observations need to be confirmed by studies specifically ceutical combination (berberine, red yeast rice and policosanols) designed to demonstrate a protective effect of berberine on on lipid levels and endothelial function randomized, double-blind, placebo-controlled study. Nutr Metab Cardiovasc Dis. 2010;20(9): submit your manuscript |
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2012:5 11. Klimek M, Wang S, Ogunkanmi A. Safety and efficacy of red yeast rice 19. Tsai PL, Tsai TH. Hepatobiliary excretion of berberine. Drug Metab (Monascus purpureus) as an alternative therapy for hyperlipidemia. Dispos. 2004;32(4):405–412.
20. Chae HW, Kim IW, Jin HE, Kim DD, Chung SJ, Shim CK. Effect of 12. Gordon RY, Cooperman T, Obermeyer W, Becker DJ. Marked ion-pair formation with bile salts on the in vitro cellular transport of v ariability of monacolin levels in commercial red yeast rice products: berberine. Arch Pharm Res. 2008;31(1):103–110.
buyer beware! Arch Intern Med. 2010;170(19):1722–1727.
21. Zhou S, Lim LY, Chowbay B. Herbal modulation of P-glycoprotein. 13. Lin YL, Wang TH, Lee MH, Su NW. Biologically active compo- Drug Metab Rev. 2004;36(1):57–104.
nents and nutraceuticals in the Monascus-fermented rice: a review. 22. Paquot N, Scheen AJ. Which HbA and lipid targets in patients with Appl Microbiol Biotechnol. 2008;77(5):965–973.
type 2 diabetes? Rev Med Liege. 2012;67(2):98–103. French.
14. Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes 23. Porte D Jr. Clinical importance of insulin secretion and its interaction mellitus. Metabolism. 2008;57(5):712–717.
with insulin resistance in the treatment of type 2 diabetes mellitus and 15. Zhang H, Wei J, Xue R, et al. Berberine lowers blood glucose in type 2 its complications. Diabetes Metab Res Rev. 2001;17(3):181–188.
diabetes mellitus patients through increasing insulin receptor expression. 24. Liu L, Yu YL, Yang JS, et al. Berberine suppresses intestinal Metabolism. 2010;59(2):285–292.
disaccharidases with beneficial metabolic effects in diabetic states, 16. Yin J, Zhang H, Ye J. Traditional Chinese medicine in treatment of evidences from in vivo and in vitro study. Naunyn Schmiedebergs Arch metabolic syndrome. Endocr Metab Immune Disord Drug Targets. Pharmacol. 2010;381(4):371–381.
25. Zhang BJ, Xu D, Guo Y, Ping J, Chen LB, Wang H. Protection by 17. Chen W, Miao YQ, Fan DJ, et al. Bioavailability study of berberine and and anti-oxidant mechanism of berberine against rat liver fibrosis the enhancing effects of TPGS on intestinal absorption in rats. AAPS induced by multiple hepatotoxic factors. Clin Exp Pharmacol Physiol. Pharm Sci Tech. 2011;12(2):705–711.
18. Pan GY, Wang GJ, Liu XD, Fawcett JP, Xie YY. The involvement of P-glycoprotein in berberine absorption. Pharmacol Toxicol. 2002;91(4):193–197.
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