Introduction

Diabetes mellitus is an endocrine disease characterized by unusual lipid and sugar metabolisms. The global prevalence of diabetes has been rising rapidly. It is one of the leading causes of death in in low- and middle-income countries [2, 3]. There is an association between diabetes, metabolic syndrome and Cardiovascular Disease (CVD). Increased plasma level of Low-Density Lipoprotein (LDL) and Very-Low-Density Lipoprotein (VLDL) during metabolic syndrome, contribute to the pathogenesis of atherosclerosis [6-9]. Patients with diabetes are 2-4 times more at risk of CVD morbidity and mortality than individuals without diabetes. This study aimed to evaluate the effect of bioflora probiotic and aqueous extract of cinnamon plant on the amelioration of metabolic syndrome symptoms in rat model of diabetes. Bioflora is a commercial probiotic containing four probiotic strains include Lactobacillus acidophilus, Bifidobacterium longum, Bifidobacterium lactis, and Bifidobacterium bifidum.

Materials and Methods

In this study, 35 four-week-old male Wistar rats were purchased from Pasteur Institute of Iran. During the experiments, the animals were fed ad-libitum and had access to water all the times and kept under standard conditions. After 10 days of adaptation, rats were randomly divided into 5 groups of negative control (n=7, healthy rats), positive control (n=7, untreated diabetic rats), probiotic group (n=7, diabetic rats treated with bioflora probiotic 3.2×108 CFUs/day), cinnamon group (n=7, diabetic rats treated with 200 mg/kg cinnamon aqueous extract daily), and probiotic + cinnamon (n=7). A single high dose (60 mg/kg body weight) intra-peritoneal injection of Streptozotocin (STZ) was used to induce diabetes in rats. Only rats with a basal blood glucose level above 300 mg/dL were considered diabetic. After development of diabetes, rats were orally gavaged by 1 ml suspension of probiotic, cinnamon aqueous extract, or both for four weeks. At the end of experiment, the animals were anesthetized and 5 ml of blood samples were then extracted directly from their heart. The serum was separated from the clot by centrifugation and kept at -20° C. The glucose levels and lipid profile were assessed by using a specific assay kit (colorimetric). Quantitative immunoturbidimetric assay was used for identifying the high sensitivity C-Reactive Protein (hs-CRP) as a cardiovascular risk marker. Atherosclerosis Index (AI) was defined as log (Triglyceride/HDL-C).

Results 

The STZ-induced diabetes caused a significant reduction in the body weight of animals where it was greater in animals treated with cinnamon aqueous extract (Table 1).

The administration of bioflora probiotic increased the weight of rats in the probiotic group compared to other diabetic groups. It seems that the probiotic caused improvement in feed conversion ratio and feed uptake. Treatment with both bioflora probiotic and cinnamon extract led to a reduction in blood glucose, and also in cholesterol and triglyceride levels. The induction of diabetes had no any significant effect on the HDL-cholesterol (HDL-C) concentration. The LDL-Cholesterol (LDL-C) concentration, however, increased significantly with the diabetes induction. Bioflora probiotic reduced the LDL-cholesterol level while the cinnamon extract had no significant effect on this blood factor. The AI value was increased in rats due to bioflora probiotic administration. The hs-CRP, which is one the most important indicators of the risk of developing CVD, was increased in the positive control group. This factor significantly decreased in the probiotic group but its level in the cinnamon groups was not different from that in the positive control group. There was no reliable evidence of synergy between Bioflora probiotic and aqueous extract of cinnamon in amelioration of diabetes symptoms in rats. 

Discussion

Insulin is a key hormone in  glucose  and lipid metabolisms. Insulin can regulate the production of a number of proteins affecting the circulating levels of lipoproteins. Insulin deficiency or insulin resistance in diabetes can lead to the development of dyslipidemia. Hence, people with diabetes are at high risk of CVDs. The results of this study showed that the blood glucose level in the groups treated with bioflora probiotic and cinnamon extract decreased by 19.65% and 29.81%, respectively. The most important antidiabetic components of cinnamon are cinnamaldehyde, cinnamate, cinnamic acid, and eugenol. Procyanidin type A is an important polymer in cinnamon which increases the glucose absorption and glycogen synthesis in tissue while reduces the glucose uptake by intestinal epithelial cells [26, 27]. Some probiotic strains increase the glucagon gene expression and cause glucose hemostasis by upregulating the Peroxisome Proliferator Activated Receptor γ (PPAR-γ) transcription factor [28-30].

The cinnamon extract improves lipid profile by inhibiting the ß-hydroxy-ß-methylglutaryl-coenzyme-A (HMG Co-A) reductase and reducing the oxidative stress. It is well documented that some bioflora probiotic strains can deconjugate the bile salts and lead to cholesterol reduction. The short-chain fatty acids produced by bioflora probiotic strains also inhibit the cholesterol synthesis in liver. Our results showed that bioflora reduced the risk of atherosclerosis by improvement of lipid profile. The hs-CRP level, as an indicator of CVD, is high in diabetic patients. The concentration of this factor increases 1000 times during infectious diseases and CVDs. Some strains of bioflora especially bifidobacteria, by inhibiting oxygen free radicals and reducing IL-6 gene expression, inhibit the increase of hs-CRP and reduce inflammation. It was concluded that use of bioflora as supplement can prevent and improve metabolic syndrome in diabetic patients. 

Ethical Considerations

Compliance with ethical guidelines

This study ethically approved in Research Centre of Islamic Azad University of Arak (Code: IR.IAU.ARAKREC1397.005). All interventions performed in accordance with the Guide for Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources.

Funding

This article is extracted from a research project approved by research committee of Islamic Azad university of arak (Code: 266). Research deputy of this University financially suppoted part of this study.

Authors' contributions

Conceptualization: Parvaneh Jafari, Fatemeh Shahrestan; Methodology: Fatemeh Shahrestan, Aram Gharebaghi, Esmaeil Shahrestan; Data analysis: Parvaneh Jafari, Aram Gharebaghi; Investigation: All authors. 

Conflicts of interest

The authors declared no conflict of interests.

Acknowledgements

The authors gratefully acknowledge the financial support of the Islamic Azad University of Arak and Tak Gene Company for kindy providing us with probiotic product.

 

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