An Explorative Study on Renoprotective and Hypolipidemic Role of Punica Granatum in Diabetic Rodent Model

Background: Diabetes is a serious threat to global health that neither regards socioeconomic status nor national boundaries. Diabetes and its complications, if not well managed, can lead to frequent hospital admissions and premature death. Globally, diabetes is one of the top 10 causes of death. However, if appropriate management of diabetes is achieved, different serious complications can be delayed or prevented. Therefore, searching of new and safe medicine for the control of diabetes and its complications is a thrust area of research. Aim: Evaluation of efficacy of standardized extract of pomegranate fruit pulp in hypertension, blood lipid profile and renal function of diabetic animal models (induced by streptozotocin and high fat diet). Type of the study: experimental observational study. Place: Department of Pharmacology of R.G. Kar Medical College and Hospital, MRU of Biochemistry department of R.G. Kar Medical College and Hospital. Duration: 19months (April 2021to October 2022). The test drug was prepared with the ethanolic extraction of fruit pulp of P. granatum (PGE) and chemically standardized by different chromatographic techniques. Diabetic animal model (36 rats were distributed in 6 groups and each group contain 6 rats) was created by injecting streptozotocin at the dose of 60 mg/kg in adult male Wistar rats (except normal control).They were fed with High Fat Diet (except normal control and diabetic control). [1] After completion of treatment with metformin and pomegranate fruit pulp extract according to respective group (Normal Control, Diabetic Control, Diabetic with fat diet, diabetic with fat diet and treated with metformin, diabetic with fat diet and treated with chemically standardized Punica granatum extract @ 125mg/kg/day, diabetic with fat diet and treated with chemically standardized Punica granatum @ 250mg/kg/day) all animals(adult male wistar rats) was placed in metabolic cages for collection of urine samples for urea and creatinine and finally sacrificed under deep anesthesia on day 29th (after 29days of intervention). Body weight, Blood Pressure, Blood Glucose were evaluated every week. The blood was analyzed for blood glucose, lipid profile, renal function and cytokines (IL-1 beta, IL-6 and TNF-alpha) at day 28. The histopathological evaluation was done in liver, kidney, pancreas and myocardium tissues. All groups were statistically analyzed and compared within and between groups by t-test, one way ANOVA and post hoc tukey test. Results: 1) Metformin lowered the body weight 4.52% within 14 days and 5.98% within 28 days compared to High fat diet in STZ diabetic rats. Test drug, PPE at the oral dose of 125 mg/kg significantly lowered the body weight 6.12% in 14 days and 9.81% in 28 days. Moreover, at higher dose, PPE (250 mg/kg) lowered the body weight at 7.2% in 14 days and 10.84% in 28 days compared to High fat diet in STZ diabetic rats. 2) Within 14 days the blood glucose level was reduced to 24% (p=0.009) and it was lowered to 49% (p=0.003) within 28 days compared to high fat diet induced diabetic animals by metformin. PPE at the dose of 125 mg/kg down regulate 16.6% (p=0.03) in 14 days and 41.7% in 28 days (p=0.004). While, PPE at the dose of 250 mg/kg diminished blood glucose concentration to 20.8% (p=0.015) and 44.5% (p=0.002) in respective days. 3) PPE at the dose of 125 mg/kg reduced the systolic BP to 8.3% within 14 days and 23% within 28 days. PPE at the same dose, diastolic BP was reduced to 11.9% and 11.68% in 28 days. PPE at 250 mg/kg lowered the systolic BP to 9.4% in 14 days and 26.7% in 28 days. The diastolic BP was reduced by PPE (250 mg/kg) to 17% in 14 days and 21% in 28 days. 4) Metformin reduced 31% LDL, 48% VLDL and 22.54% triglycerides compared to high fat diet induced diabetic rats. PPE at the dose of 125 mg/kg lowered LDL up to 15.5%, VLDL 62.7% and triglycerides to 27.5%. Moreover, PPE at the dose of 250 mg/kg significantly diminished blood LDL to 40.9%, VLDL to 59.5% and triglycerides to 38.4%. 5) Metformin at the dose of 500 mg/kg reduced urine volume (50.6%), blood urea (33%) and blood creatinine (53%) concentration compared to high fat diabetic rats. PPE at the dose of 125 mg/kg, lowered 32% urine volume, 30.5% blood urea and 46.6% blood creatinine level in rats compared to high fat diabetic rats. Moreover, PPE at the dose of 250 mg/kg, reduced 43% urine volume, 42% blood urea and 61% blood creatinine level in rats compared to high fat diabetic rats. Conclusion & Implication: Phenolic acids, specially quercetin, catechin, rutin, ellagic acid and gallic acids present in PGE are used medicinally for health benefits, particularly in diabetes and its complications. PGE has the capacity to regulate blood sugar, blood lipids, hypertension and renal functions in high fat diet induced insulin resistance diabetic animals.