Investigating the Antidiabetic Effects of Calotropis procera : Preclinical Assessment

ABSTRACT

Diabetes mellitus (DM) is a metabolic disease characterized by persistent hyperglycemia, oxidative stress, and inflammation, often leading to severe complications. Current antidiabetic drugs exhibit efficacy; however, they are limited by adverse effects and diminishing long‐term benefits. Natural products, including Calotropis procera , are promising alternatives with minimal side effects: This study investigates the antidiabetic and protective effects of the methanolic extract of C. procera (CMECP) against diabetes and its complications using in vitro and in vivo models. in vitro antioxidant, anti‐inflammatory, and hypoglycemic activities of the extract were conducted using established procedures while experimental rats were induced into diabetes with streptozotocin (STZ) and treated with distilled water, CMECP [150 and 300 mg/kg body weight (BW)] or 100 mg/kg b.wt metformin and assessed for their effects against diabetes and diabetes‐related complications. The extract exhibited dose‐dependent in vitro antioxidant, anti‐inflammatory, and hypoglycemic activities. Treatment with the extract resulted in a 65% decrease in the fasting blood glucose levels of the diabetic rats at 300 mg/kg BW after the treatment period. The extract also improved insulin secretion, reversed dyslipidemia, ameliorated alterations in liver and kidney function biomarkers, reduced oxidative stress markers, and enhanced antioxidant defenses in STZ‐induced diabetic rats. Inflammatory biomarkers such as cyclooxyegase‐2 and nuclear factor‐kappa B were suppressed, with improved hematological parameters and body weight. Additionally, CMECP mitigated diabetic‐induced neuronal cholinesterase activity without affecting neurotransmitter levels. The extract of C. procera demonstrated potent antidiabetic effects by modulating oxidative stress, inflammation, and biochemical dysfunctions in diabetes. These findings support its potential as a natural therapeutic agent for diabetes management. Further studies are ongoing to identify the constituents of the extract and elucidate their mechanisms of action for possible hit compounds identification for future antidiabetic drug development purposes.