{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:23:52Z","timestamp":1787027032282,"version":"build-2736575974"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      This study aimed to investigate the antioxidant, antihyperlipidemic, antihypercholesterolemic, and hepatoprotective properties of\n                      <jats:italic>Acacia nilotica<\/jats:italic>\n                      (\n                      <jats:italic>A. nilotica<\/jats:italic>\n                      ) pod extracts in male albino Wistar rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>A. nilotica<\/jats:italic>\n                      pod extracts (ANPE) were prepared using ethanol, methanol, acetone, and distilled water. Antioxidant properties were evaluated by determining total phenolic content (TPC), ferric reducing antioxidant power (FRAP) and DPPH (2,2-diphenyl-1-picrylhydrazyl) activity. ANPE were administered at doses of 250, 500, and 750\u00a0mg\/kg\/day to rats with hypercholesterolemia induced by a high-fat diet. Lipid profile, cardiac enzymes (CK-MB and Troponin-I) and oxidative stress markers were measured. In addition, virtual screening and molecular dynamic simulations were performed to assess the potential of\n                      <jats:italic>A. nilotica<\/jats:italic>\n                      pod constituents to inhibit oxidosqualene cyclase (OSC), a key enzyme in cholesterol biosynthesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The ethanolic extract of\n                      <jats:italic>A. nilotica<\/jats:italic>\n                      pods displayed the highest antioxidant activity with a TPC of 61.83 \u00b1 2.60\u00a0mg GAE\/g, FRAP of 1712.9 \u00b1 4.11\u00a0\u00b5g Fe\/g and DPPH inhibition of 79.47% \u00b1 0.66%. The highest dose (750\u00a0mg\/kg) of ANPE significantly decreased serum cholesterol and LDL levels, while improving HDL and HDL\/LDL ratio (p &amp;lt; 0.05). This dose also improved oxidative stress markers, cardiac enzymes, the atherogenic index, and the Castelli index compared with the hypercholesterolemic control group (p &amp;lt; 0.05). Histopathological examination of liver and kidney tissues confirmed that the highest dose of APNE exerted marked hepatoprotective and renoprotective effects (p &amp;lt; 0.05).\n                      <jats:italic>In silico<\/jats:italic>\n                      analyses highlighted a plausible molecular mechanism whereby \u03b2-sitosterol of\n                      <jats:italic>A. nilotica<\/jats:italic>\n                      interacts with the OSC active site, supporting a hypothesis for the observed reduction in cholesterol biosynthesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      ANPE exhibits strong antihypercholesterolemic, antioxidant, hepatoprotective, and nephroprotective effects in a rat model of diet-induced hypercholesterolemia. The long-term safety and efficacy of its bioactive constituents should be evaluated in future preclinical and clinical studies. Computational modelling suggests that \u03b2-sitosterol from\n                      <jats:italic>A. nilotica<\/jats:italic>\n                      may act as a putative OSC inhibitor, providing a mechanistic framework that warrants further\n                      <jats:italic>in vitro<\/jats:italic>\n                      and biochemical validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1831586","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T05:40:42Z","timestamp":1778132442000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Investigating the phytotherapeutic efficacy of Acacia nilotica pod ethanolic extract in modulating lipid profile, oxidative stress and inflammation in diet-induced hypercholesterolemia: in vivo and in silico insights"],"prefix":"10.3389","volume":"17","author":[{"given":"Khurram","family":"Afzal","sequence":"first","affiliation":[{"name":"Department of Human Nutrition, Faculty of Food Science and Nutrition, Bahauddin Zakariya University","place":["Multan, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamna","family":"Khalid","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Faculty of Food Science and Nutrition, Bahauddin Zakariya University","place":["Multan, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asad","family":"Abbas","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Faculty of Food Science and Nutrition, Bahauddin Zakariya University","place":["Multan, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen","place":["Aachen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nudrat","family":"Khursheed","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Faculty of Food Science and Nutrition, Bahauddin Zakariya University","place":["Multan, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bipindra","family":"Pandey","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Madan Bhandari Academy of Health Sciences","place":["Hetauda, Bagmati, Nepal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Raza","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Faculty of Food Science and Nutrition, Bahauddin Zakariya University","place":["Multan, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Malik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Saud University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanmoy","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Chemistry, JIS College of Engineering","place":["Kalyani, West Bengal, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hina","family":"Javed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Bahauddin Zakariya University","place":["Multan, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javaria","family":"Saeed","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Southern Punjab","place":["Multan, Pakistan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"109","DOI":"10.3923\/rjmp.2019.109.118","article-title":"Acute and sub-chronic toxicity evaluation of crude methanolic leaves extract of Acacia nilotica (linn.)","volume":"13","author":"Abdulhamid","year":"2019","journal-title":"Res. 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