From Toxic Ornamental to Therapeutic Agent: Comprehensive Phytochemical, Toxicological, and Antidiabetic Evaluation of Cascabela thevetia Leaf Extract in Alloxan-Induced Diabetic Rats

Abstract

Background: Globally, the escalating burden of Type 2 Diabetes Mellitus continues to drive demand for safer and more accessible therapeutic alternatives derived from natural sources. Cascabela thevetia (Yellow Oleander), despite its well-documented cardiotoxicity, has long been employed by traditional healers for various ailments, including metabolic disorders. Objective: This study aimed to scientifically evaluate the phytochemical composition, acute toxicity profile, and antidiabetic potential of C. thevetia leaf extracts through a systematic experimental approach. Methods: Leaves were sequentially extracted using petroleum ether, chloroform, ethyl acetate, ethanol, methanol, and water. Phytochemical characterisation included qualitative screening, total phenolic and flavonoid quantification, and TLC profiling. Acute oral toxicity was assessed following OECD 423 guidelines. Antidiabetic activity was evaluated in alloxan-induced (150 mg/kg, i.p.) Swiss albino rats treated with ethanolic and aqueous extracts (500 mg/kg, p.o.) over 14 days, with glibenclamide (10 mg/kg) as the standard comparator. Biochemical parameters encompassing fasting blood glucose, lipid profile, and hepatic transaminase enzymes, as well as pancreatic histopathology, were subsequently analysed. Results: Ethanolic extraction yielded the highest percentage (13.40% w/w), with alkaloids, flavonoids, glycosides, terpenoids, and phenolics detected. Total phenolic and flavonoid contents were 15.16±0.25 mg GAE/g and 16.06±0.30 mg QE/g, respectively. Acute toxicity profiling demonstrated LD₅₀ >5000 mg/kg for both extracts. In diabetic rats, the ethanolic extract (500 mg/kg) produced a statistically significant (p<0.001) reduction in fasting blood glucose from 239±2.10 to 200±1.79 mg/dL within 24 hours of a single dose, approaching the response observed with glibenclamide (182±2.58 mg/dL). Chronic administration over 14 days achieved near-normalisation of blood glucose (100.3±2.99 mg/dL). The extract also markedly attenuated elevated triglycerides (155.9±3.17 vs. 258.9±16.15 mg/dL in diabetic controls) and total cholesterol (132.3±10.05 vs. 189.1±13.96 mg/dL), while restoring HDL levels (52.31±1.19 vs. 28.9±1.82 mg/dL). Histopathological examination revealed remarkable regeneration of pancreatic islets with largely preserved β-cell architecture following extract treatment. Conclusion: Standardised ethanolic extract of C. thevetia leaves demonstrates potent antihyperglycaemic, hypolipidaemic, and pancreatic cytoprotective effects with a wide safety margin, warranting further investigation for bioactive compound isolation and clinical translation.