Effect of Ethyl acetate Fraction of Silybum marianum and Ficus Carica Leaves Extract on Glucose Hemostasis, Oxidative Stress Biomarkers and Inflammatory markers in Streptozotocin-induced T2DM Rats

Abstract

Background: Considering diabetes mellitus type two (T2DM) is a persistent metabolic syndrome, it can produce hyperglycemia, which in turn can develop substantial adverse effects such as retinopathy, neuropathy, nephropathy and cardiovascular disease. Plant-based medicine has a significant role to play since it is safe, affordable, and readily available. Synthetic drugs used for diabetic treatment also have identifiable negative side effects and worsened the diabetic condition, and since they are costly in developing countries due to poverty as well as limited availability of medical care in these countries, phytotherapy has an important role to play. The aim of this work was to evaluate the anti-diabetic, anti-oxidant and anti-inflammatory effects of ethyl acetate fraction of Silybum marianum and Ficus carica leaves extract in Streptozotocin-induced T2DM Rats.

Methods: eighty (80) apparently healthy male Wister rats weighing between (180-250 gm.) were utilized in the current study which was stared at July, 2022. To induce type 2 diabetes mellitus (T2DM), animals were fed a high-fat diet (HDF) for 2 weeks before injected intraperitoneally with 40 mg/kg of Streptozotocin (except healthy control group).  Rats were divided into 8 groups ( each group include 10 rats)  and used for 4 weeks as following G1: Healthy control group , G2: Negative control group ( induced T2DM; rats were left without any treatment) , G3: Positive control group ( induced T2DM, rats were treated with 22.5 mg/kg metformin ) , G4: Rats were treated with 250 mg/kg  ethyl acetate fraction of Silybum marianum , G5: Rats were treated with 250 mg/kg  ethyl acetate fraction of Silybum Marianum + 22.5 mg/kg metformin. G6: Rats were treated with 250 mg/kg ethyl acetate fraction of Ficus carica, G7: Rats were treated with 250 mg/kg ethyl acetate fraction of Ficus carica + 22.5 mg/kg metformin, G8: Rats were treated with 250 mg/kg ethyl acetate fraction of Silybum marianum + 250 mg/kg Ficus carica leaves extract Blood samples were taken for the assay of biochemical parameters, oxidative stress and inflammatory markers measurements.

Results: Phytochemical investigation of the current study show that silymarin being a predominant in ethyl acetate fraction of silybum marianum extract and Isoqurcetin is being predominant in ethyl acetate fraction of Ficus carica using HPLC analyses these bioactive compounds regulates blood glucose and improves insulin sensitivity, demonstrating positive effects in the prevention and therapy of associated disorders; which mean these extracts used for treatments were have effectiveness in reduced hyperglycemic state by enhancement insulin secretion from regeneration cells in pancreas. Also ethyl acetate fraction of Silybum marianum and Ficus carica leaves extract improved oxidative stress state in Streptozotocin-induced T2DM rats; where CAT, SOD and GSH were significantly increased in treated groups to provide antioxidant effect with significant reduced in MDA levels. While IL-6 and TNF-α were significantly higher in negative control group with significant dropping in treated groups; hence in the present study investigations indicate that ethyl acetate fraction of silybum marianum and ficus carica leaves extracts both had varying capacity in improve enzymatic activity, anti-diabetic, anti-oxidant and anti-inflammatory effects and aid in limiting free radicals in blood plasma.

Conclusion: The ethyl acetate fraction of silybum marianum and ficus carica leaves extract as a plant-derived product may be of major value in the treatment of diabetes mellitus and its consequences due to its anti-hyperglycemic, anti-inflammatory and antioxidant characteristics. Further experimental research is recommended to improve the transport and absorption of these plant extracts to increase their medicinal efficacy.