In Vivo Anti-Atherosclerotic Activity of Ethanolic Leaf Extract of Annona reticulata and Atrabotrys hexapetalus on Albino Rats

Background: Atherosclerosis is a chronic inflammatory and lipid-driven vascular disorder characterized by dyslipidemia, endothelial dysfunction, and plaque formation. Herbal medicines rich in bioactive phytoconstituents are increasingly explored for their cardioprotective potential. Annona reticulata and Artabotrys hexapetalus are traditionally used medicinal plants reported to possess antioxidant and lipid-modulating properties. However, their comparative and synergistic anti-atherosclerotic effects require scientific validation. Aim: To evaluate the in vivo anti-atherosclerotic activity of ethanolic leaf extracts of Annona reticulata and Artabotrys hexapetalus, individually and in combination, in high-fat diet-induced atherosclerotic albino rats. Methods: Atherosclerosis was induced in albino rats using a high-fat diet. Animals were divided into seven groups (n=6): normal control, disease control, atorvastatin (1 mg/kg), Annona reticulata extract (200 mg/kg, p.o.), Artabotrys hexapetalus extract (200 mg/kg, p.o.), combined extract (1:1), and vehicle control. Body weight changes, serum lipid profile parameters (total cholesterol, triglycerides, LDL, HDL), and histopathological examination of aortic tissue were assessed. Phytochemical screening was performed to identify bioactive constituents. Statistical analysis was conducted using one-way ANOVA followed by Dunnett’s test. Results: Phytochemical analysis revealed the presence of flavonoids, alkaloids, glycosides, steroids, and tannins in both extracts. The disease control group showed significant elevation in total cholesterol (279.2 mg/dL) and LDL (134.5 mg/dL) with marked reduction in HDL (23.67 mg/dL) compared to normal controls. Treatment with individual extracts significantly reduced total cholesterol (180 mg/dL) and LDL (100 mg/dL) while increasing HDL levels (63–67 mg/dL) (p < 0.01). The combined extract exhibited the most pronounced lipid-lowering and HDL-elevating effect, nearly comparable to atorvastatin. Histopathological findings demonstrated improved aortic architecture and reduced lipid deposition in treated groups. Conclusion: Ethanolic leaf extracts of Annona reticulata and Artabotrys hexapetalus exhibit significant antiatherosclerotic activity, with synergistic effects observed in combination therapy. The cardioprotective action may be attributed to their rich phytochemical profile and modulation of lipid metabolism. Major Findings:The study demonstrated that ethanolic leaf extracts of Annona reticulata and Artabotrys hexapetalus significantly reduced serum total cholesterol and LDL levels while markedly increasing HDL concentrations in high-fat diet–induced atherosclerotic rats. The combined extract (1:1) exhibited a superior and synergistic lipid-lowering effect compared to individual treatments, producing results nearly comparable to atorvastatin. Phytochemical screening confirmed the presence of flavonoids, alkaloids, glycosides, steroids, and tannins, which likely contributed to antioxidant activity, improved lipid metabolism, and vascular protection. Histopathological analysis further revealed restoration of normal aortic architecture with reduced lipid deposition in treated groups, confirming the anti-atherosclerotic potential of both extracts.