Elsevier

Biomedicine & Pharmacotherapy

Volume 103, July 2018, Pages 539-545
Biomedicine & Pharmacotherapy

Ameliorating effect of berbamine on hepatic key enzymes of carbohydrate metabolism in high-fat diet and streptozotocin induced type 2 diabetic rats

https://doi.org/10.1016/j.biopha.2018.04.066Get rights and content

Abstract

Background

Aberrations in the activities of key enzymes of carbohydrate metabolism is well documented in diabetes mellitus. Previous studies have shown that active ingredients in the extracts of Berberis aristata exhibits diverse pharmacological activities in animal models.

Objective

The present study was undertaken to investigate whether berbamine (BBM), an alkaloid from the roots of Berberis aristata can ameliorate the altered activities of carbohydrate metabolic enzymes in high fat diet (HFD)/streptozotocin (STZ) induced diabetic rats.

Results

Supplementation of HFD for 4 weeks followed by intraperitonial administration of single low dose of STZ (40 mg/kg b.w.) to Sprague Dawley rats resulted in significant hyperglycemia with a decline in plasma insulin levels. The rats also exhibited decreased hemoglobin with an increase in glycated hemoglobin levels. The activities of hexokinase, glucose-6-phosphate dehydrogenase were decreased whereas increases in the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase were observed in the hepatic tissues of diabetic control rats. Glycogen content in the hepatic and skeletal muscle tissues were found to be decreased in diabetic rats. Oral administration of BBM for 56 days, dose dependently (50, 100, 200 mg/kg b.w.) improved insulin secretion in diabetic treated rats. Immunohistochemical studies on pancreas revealed a strong immunoreactivity to insulin in BBM treated rats. At the effective dose of 100 mg/kg b.w., BBM restored the altered activities of carbohydrate metabolic enzymes and also improved glycogen content in insulin dependent tissues.

Conclusion

From the biochemical and histochemical data obtained in this study we conclude that BBM ameliorated the activities of metabolic enzymes and maintained glucose homeostasis in HFD/STZ induced diabetic rats and it can be used as a potential phytomedicine for the management of diabetes mellitus.

Introduction

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemic results from the total absence or insufficient secretion/ action of insulin. Though the etiology is multifaceted, genetic predisposition associated with an intake of ill-balanced diet play a vital role in the incidence of diabetes. Sedentary lifestyle, increasing availability of energy dense food and lack of exercise have led to dramatic rise in type 2 diabetes mellitus (T2DM). It is estimated that a global prevalence of 382 million people with diabetes in 2013, is expected to double by 2035 [1].

Nutrition plays an important role in the development and also in the prevention of diabetes mellitus. A diet rich in fat can induce metabolic disorders like insulin resistance, dyslipidemia and hypertension in rodents and humans [2]. Administration of high fat diet and streptozotocin (HFD/STZ) to experimental animals lead to β-cell dysfunction, defective insulin function and persistent hyperglycemia that mimics the natural stages of progression of diabetes in humans [3]. An aberration in insulin action causes derangement in carbohydrate metabolism resulting from altered activities of enzymes that control glycolysis, gluconeogenesis in liver and muscle and produces hyperglycemia. Presently available oral hypoglycemic drugs have limitations and hence a search for newer drugs is warranted.

Medicinal plants and their bioactive constituents are commonly used worldwide to control diabetes and its complications due to their non-toxic nature, availability and affordability. Hence WHO has recommended the use of traditional plants for the treatment of chronic and life threatening diseases including diabetes mellitus. Berberis aristata is a well known medicinal plant whose fruits, stem, bark and root are used in ayurvedic preparations for their diverse medicinal properties. Berbamine (BBM) is a bis-benzylisoquinoline alkaloid derived from the roots of Berberis aristata, possess antioxidant, anti-inflammatory, immunomodulatory and cardiovascular effects [4,5]. However there was no study in the literature on the possible antidiabetic effects of BBM. In this context, the present study was designed to evaluate the effect of BBM on the activities of carbohydrate metabolic enzymes in HFD/STZ induced diabetic rats.

Section snippets

Chemicals and drugs

BBM and STZ were purchased from Sigma Aldrich Pvt. Ltd., (St. Louis, MO, USA). Insulin kit was purchased from Bioassay Technology Laboratory (Korain Biotech Co. Ltd, China). Diagnostic kits for glucose, hemoglobin (Hb) and glycated hemoglobin (HbA1c) were purchased from Agappe diagnostics Ltd, Kerala, India. All other chemicals used in this study were of analytical grade and obtained from SD fine and HIMEDIA, India.

Ethical statement for animal experimentation

Forty two male Sprague-dawley rats with body weight ranging from 160 to 180 g

Dose dependent effect of BBM on plasma glucose and insulin levels

An increase in plasma glucose with a significant decrease in insulin levels were observed in diabetic rats (Table 1). Oral administration of BBM at three different doses (50, 100 and 200 mg/kg b.w.) for 56 days resulted in significant improvement in plasma insulin with a fall in glucose levels at the end of the treatment period. There was no significant change in normal rats treated with BBM. The effect of BBM was compared with metformin, a standard drug.

Effect of BBM on changes in body weight, food and fluid intake of control and diabetic treated rats

Table 2 shows the changes in the body

Discussion

Type 2 diabetes mellitus is the most common metabolic disorder across the world and is becoming the major cause of morbidity and mortality in human populations. Intake of excess dietary fat blunts insulin mediated glucose utilization and promotes insulin resistance under diabetic conditions [17]. Further, administration of low dose of STZ (40 mg/kg b.w.) to HFD fed rats causes mild destruction of pancreatic β-cells by necrosis resulting in insulin deficiency [18]. Studies by Srinivasan et al. [

Conclusion

From the results of the present study, we conclude that administration of BBM dose dependently to diabetic rats improved insulin secretion and exhibited pancreatic β-cell protective activity. It ameliorated the activities of carbohydrate metabolic enzymes and restored glucose homeostasis in HFD/STZ induced diabetic rats. The molecular actions of BBM on improving insulin secretion and resistance are warranted.

Conflict of interest

The authors declare no conflict of interests.

Acknowledgement

The Indian Council of Medical Research (ICMR), New Delhi is gratefully acknowledged for the financial support in the form of Major Research Project. The authors gratefully thank UGC, DST for the financial support to the department.

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