<i>Peganum harmala </i>Extracts as a Hypoglycemic and Hepatoprotective Agent in Diabetes-Induced Liver Damage

Abstract

Background: Liver disorders associated with type II diabetes result in cellular death, highlighting the importance of exploring protective mechanisms such as apoptosis to mitigate tissue damage. Antioxidant agents are promising options to address this issue, and plant secondary metabolites, such as the alkaloids of Peganum harmala, are considered among the most effective factors for treating liver disorders. Objectives: This study aimed to examine apoptosis, along with biochemical and histopathological parameters, in the liver of diabetic Wistar rats using methanolic extracts of P. harmala from seeds and leaves. Methods: Peganum harmala was collected from Zahedan. Phytochemical analysis of the leaf and seed extracts was conducted via high-performance liquid chromatography (HPLC) and DPPH tests. Sixty-four male Wistar rats (250 - 300 g) were organized into eight groups of eight individuals. Diabetes was induced by a 70 mg/kg streptozotocin (STZ) injection. The treatment groups were administered 150 mg/kg of leaf or seed extracts, or 6.5 mg/kg of harmine, a P. harmala alkaloid, daily for four weeks. Samples were then collected from anesthetized rats for biochemical, histopathological, and flow cytometry analyses. Results: The results indicated that methanolic extracts of P. harmala seed reduced plasma cholesterol and triglyceride levels in both healthy and diabetic groups. Biochemical tests also demonstrated that the seed extracts and harmine significantly reduced the plasma levels of liver enzymes. The leaf extracts and harmine significantly reduced apoptosis among diabetic groups, while seed extracts induced more apoptosis. The group treated with the seed extracts showed significant levels of healing and recovery in the liver tissue in histopathological evaluations. Conclusions: The significant antioxidant characteristics of the seed extract of P. harmala suggest its potential as a hypoglycemic medicine to moderate complications associated with diabetes.