Evaluation of anti-diabetic and immunomodulatory activity of polyphenols derived from Cassia auriculata L. on induced diabetic rat

Diabetes mellitus (DM) is considered as an immuno-metabolic disease as the immune system impairment is leads to the progression of the disease. In this study we have examined the potential effect of Cassia auriculata flowers derived polyphenols (CAP) in modulating immune integrity and antidiabetic activity on experimentally induced (Streptazocin induced & Streptazocin+ Nicotinamide induced ) diabetic rats. Normal and diabetic induced Sprague Dawley male rats at age of ~12 weeks were orally administrated with various CAP doses (10, 25, 50 &100 mg/kg) and observed for 28 days. Upon sacrifice measurement of glucose, insulin and HbA1c levels were done to assess the responses to therapy that facilitate reaching antidiabetic effect. Splenocytes were consumed to measure the expression of total T, B and NK and regulatory Tcells through flow cytometer analysis. The functional assay for Tcells and neutrophils were conducted using tritiated thymidine assay and oxidative burst assay respectively. In addition, biochemical parameters (cholesterol, triglyceride & albumin) and haematological parameters (Leukocyte count, haemoglobin level, neutrophils& lymphocytes counts) were also analysed. Supplementation of CAP in all dosages had reduced the blood glucose and increased the insulin level towards the normal in both rat models. Despite gaining of body weight, CAP supplementation also significantly normalised the biochemical and haematological parameters of diabetic rats in comparison to normal control. Flow cytometer analysis revealed that the CAP supplementation reduced the percentages of pan splenic T and B cells; however a gradual increase in T helper cell sub-population along with reduction in T cytotoxic cells were noted. Although, the percentage of T cells was reduced yet, their ability of respond to mitogen (Lipopolysaccharide) and cellular expansion was enhanced when treated with CAP. Such expansion was not confined to T cells only, but also extends towards regulatory T cells, whose expression was escalated in the presence of CAP supplementation. In term of innate immune cell activity, CAP treatment reduced the oxidative burst activity of neutrophils indicating abridged oxidative stress in diabetes. The results collectively showed that CAP supplementation has normalised the diabetic indicators by reducing glycaemic level and inducing insulin secretion. This anti-diabetic activity of CAP also imposed an immunomodulatory function on adaptive and innate immune cells. The enhanced proliferation of T cells; specific expansion of T helper sub-population and reduced oxidative burst activity of neutrophils are important to prevent the macromolecular damages that related to diabetes. Thus CAP could serves as holistic treatment that exerts anti-diabetic and immunomodulatory activity and maintains a protective mechanism by minimising complications in long term treatment for diabetes.

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