eng Science and Education Publishing American Journal of Food and Nutrition 2374-1163 2025-07-28 13 4 138 153 10.12691/ajfn-13-4-3 AJFN20251343 article Yousif A. Elhassaneen yousif12@hotmail.com 1 Basma A. El-khateeb 1 Esraa S. Abd El-Aty 1 Department of Nutrition and Food science, Faculty of Home Economics, Menoufia University, Shebin El-Kom, Egypt This study examined the chemical composition, bioactive compounds, antioxidant activity of Acacia nilotica seed powder (ANS), and its effects on hypercholesterolemic rats over four weeks. Thirty-six rats were acclimated on a basal diet (BD) for two weeks, then divided into groups: a negative control on BD, a positive control fed a hypercholesterolemic diet (HCD) for 3 weeks, followed by BD, and three treatment groups receiving BD with 5%, 7%, and 9% ANS. Proximate analysis of ANS revealed 8.27% moisture, 9.43% crude fat, 27.13% protein, and 39.44% carbohydrates, indicating high nutritional value. Bioactive compounds included polysaccharides, polyphenols, saponins, alkaloids, flavonoids, and kaempferol, with low oxalates and tannins within safe limits. Antioxidant activity was 66.89%, comparable to standard antioxidants. ANS treatment improved metabolic parameters dose-dependently. Body weight gain (BWG), reduced by ~40% in untreated rats, improved by 10%, 20%, and 43% at 3, 6, and 9 g/100 g ANS, respectively. Feed intake and feed efficiency ratio similarly recovered. Liver enzymes AST, ALT, and ALP, elevated in the model by 39.8%, 61.8%, and 16.6%, decreased significantly with 9 g ANS by 22.1%, 95.5%, and 10.7%. Serum triglycerides and total cholesterol, increased by ~181% and 38%, declined dose-dependently with ANS, with TG dropping by ~260% and TC by ~22.7% at 9 g. HDL cholesterol rose by 25%, 37%, and 72%, while LDL and VLDL cholesterol fell by up to 44% and 41%. Glutathione levels (GSH and GSSG) improved, reversing 23.14% and 19.84% declines in controls. Erythrocyte antioxidant enzymes (GSH-Px, GSH-Rd, SOD, CAT) decreased by 25¨C38% in controls but increased by 23¨C45% with ANS. Oxidative stress markers ROS and MDA, elevated by 45% and 62.48%, were reduced dose-dependently, with MDA decreasing by 42.89% at the highest dose. These results demonstrate ANS¡¯s potent antioxidant and lipid-lowering effects in hypercholesterolemic rats. https://pubs.sciepub.com/ajfn/13/4/3/ajfn-13-4-3.pdf Hypercholesterolemia liver functions serum lipid profile antioxidant enzymes oxidative stress