{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:52:48Z","timestamp":1786560768756,"version":"build-2736575974"},"reference-count":110,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009104","name":"Department of Health Research, India","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic syndrome (MetS), a cluster of biochemical and physiological alterations leading to the development of cardiovascular disease and type 2 diabetes (T2DM), is a major health concern worldwide. Recently, elevated level of proprotein subtilisin\/kexin type-9 (PCSK-9) along with dyslipidemia, high blood pressure, blood sugar, and triglycerides have been linked to the establishment and advancement of Mets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim of this study<\/jats:title>\n                    <jats:p>In this study, we explored the protective effects of diallyl trisulfide (DATS), a natural organosulfur compound derived from garlic, in a high-carbohydrate high-fat (HCHF) diet-induced rat model of MetS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Herein, we report that DATS improves MetS parameters\n                      <jats:italic>via<\/jats:italic>\n                      significantly downregulating the mRNA expression of PCSK-9 (1.59-fold when compared with HCHF control) and its transcriptional activator, HNF-1\u03b1. Similarly, the mRNA expression (\u22123.19-fold) and the\n                      <jats:italic>ex-vivo<\/jats:italic>\n                      enzymatic activity of 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase (HMG-R) were attenuated in DATS-treated rats. In contrast, DATS significantly increased the low-density lipoprotein-receptor (LDL-R) mRNA expression by 1.98-fold. This unique regulation of PCSK-9\/LDL-R axis, HNF1\u03b1, and HMG-R was well corroborated by the reduced plasma level of PCSK-9, low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs). Furthermore, the mRNA expression and circulatory level of inflammatory cytokines\n                      <jats:italic>i.e<\/jats:italic>\n                      ., interleukin (IL)-1, IL-6, tumor necrosis factor-\u03b1 (TNF-\u03b1) and chemokines\n                      <jats:italic>i.e<\/jats:italic>\n                      ., Chemokine (C-X-C motif) ligand (CXCL)-1, CXCL-2, and monocyte chemoattractant protein-1 (MCP-1) were also ameliorated after DATS intervention. The expression of peroxisome proliferator-activated receptors (PPAR)-\u03b1, \u03b2, and \u03b3 was also upregulated after treatment with DATS, when compared to untreated HCHF group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This comprehensive investigation demonstrates that DATS mitigates HCHF diet-induced MetS by targeting molecular regulators of cholesterol homeostasis, oxidative stress, glycemic indices, and inflammation. These findings suggest that DATS may serve as a promising therapeutic agent in preventing and managing MetS and associated cardiometabolic risks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1781950","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:57:14Z","timestamp":1780030634000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Diallyl trisulfide attenuates metabolic syndrome via integrated modulation of PCSK-9\/LDL-R axis, redox homeostasis, and inflammatory cytokine networks in high-carbohydrate high-fat (HCHF) diet-fed rats"],"prefix":"10.3389","volume":"17","author":[{"given":"Parvej","family":"Ahmad","sequence":"first","affiliation":[{"name":"Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral Information and Research Center (IIRC-5), Integral University","place":["Lucknow, Uttar Pradesh, India"]},{"name":"Department of Hematology, Stem Cell Research Center, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)","place":["Lucknow, Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunim","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Hematology, Stem Cell Research Center, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)","place":["Lucknow, Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahir Sultan","family":"Alvi","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral Information and Research Center (IIRC-5), Integral University","place":["Lucknow, Uttar Pradesh, India"]},{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, The Avera Health and Science Center, South Dakota State University","place":["Brookings, SD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandra Prakash","family":"Chaturvedi","sequence":"additional","affiliation":[{"name":"Department of Hematology, Stem Cell Research Center, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS)","place":["Lucknow, Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saheem","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, College of Applied Medical Sciences, University of Hail","place":["Hail, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodor","family":"Bin Sheeha","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Sciences, College of Health and Rehabilitation Sciences, Princess Nourah Bint Abdulrahman University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paridhi","family":"Puri","sequence":"additional","affiliation":[{"name":"University Centre for Research and Development, Chandigarh University","place":["Mohali, Punjab, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar W.","family":"Alothamali","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy, College of Applied Medical Sciences, University of Ha\u2019il","place":["Ha\u2019il, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Salman","family":"Khan","sequence":"additional","affiliation":[{"name":"Clinical Biochemistry and Natural Product Research Lab, Department of Biosciences, Integral Information and Research Center (IIRC-5), Integral University","place":["Lucknow, Uttar Pradesh, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1007\/s11883-014-0439-8","article-title":"Living the PCSK9 adventure: from the identification of a new gene in familial hypercholesterolemia towards a potential new class of anticholesterol drugs","volume":"16","author":"Abifadel","year":"2014","journal-title":"Curr. Atheroscler. Rep."},{"key":"B2","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/978-981-13-7154-7_20","article-title":"Functioning of organosulfur compounds from garlic (Allium sativum Linn) in targeting risk factor-mediated atherosclerosis: a cross talk between alternative and modern medicine","volume-title":"Natural bio-active compounds: volume 1: production and applications","author":"Ahmad","year":"2019"},{"key":"B3","doi-asserted-by":"publisher","first-page":"117756","DOI":"10.1016\/j.lfs.2020.117756","article-title":"Insights into pharmacological mechanisms of polydatin in targeting risk factors-mediated atherosclerosis","volume":"254","author":"Ahmad","year":"2020","journal-title":"Life Sci."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1007\/s00044-021-02799-2","article-title":"Identification and evaluation of natural organosulfur compounds as potential dual inhibitors of \u03b1-amylase and \u03b1-glucosidase activity: an in-silico and in-vitro approach","volume":"30","author":"Ahmad","year":"2021","journal-title":"Med. Chem. Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1007\/s43450-022-00330-1","article-title":"Target-based virtual and biochemical screening against HMG-CoA reductase reveals Allium sativum-derived organosulfur compound N-Acetyl cysteine as a cardioprotective agent","volume":"32","author":"Ahmad","year":"2022","journal-title":"Rev. Bras. Farmacogn."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3924","DOI":"10.1080\/14786419.2023.2269465","article-title":"Naturally occurring organosulfur compounds effectively inhibits PCSK-9 activity and restrict PCSK-9-LDL-receptor interaction via in-silico and in-vitro approach","volume":"38","author":"Ahmad","year":"2024","journal-title":"Nat. Prod. Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"5413","DOI":"10.1002\/ptr.8323","article-title":"Organosulfur compounds, S-Allyl-L-cysteine and S-ethyl-L-cysteine, target PCSK-9\/LDL-R-axis to ameliorate cardiovascular, hepatic, and metabolic changes in high carbohydrate and high fat diet-induced metabolic syndrome in rats","volume":"39","author":"Ahmad","year":"2025","journal-title":"Phyther. Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1158\/1535-7163.MCT-25-0097","article-title":"Ubiquitination of oncogenic mutant p53 via attenuation of ribosome biogenesis machinery effectively inhibits pancreatic tumor growth","volume":"25","author":"Ahmad","year":"","journal-title":"Mol. Cancer Ther."},{"key":"B9","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s12247-025-10349-1","article-title":"Repurposing of FDA-approved drugs identifies glipizide as a potent HMG-CoA reductase inhibitor: a high-throughput virtual screening and molecular dynamics approach for targeting hypercholesterolemia","volume":"21","author":"Ahmad","year":"","journal-title":"J. Pharm. Innov."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1172\/JCI61919","article-title":"Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice","volume":"122","author":"Ai","year":"2012","journal-title":"J. Clin. Invest."},{"key":"B11","doi-asserted-by":"publisher","first-page":"3293","DOI":"10.15419\/bmrat.v6i7.556","article-title":"Therapeutic efficacy of Boerhaavia diffusa (Linn.) root methanolic extract in attenuating streptozotocin-induced diabetes, diabetes-linked hyperlipidemia and oxidative-stress in rats","volume":"6","author":"Akhter","year":"2019","journal-title":"Biomed. Res. Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"10519","DOI":"10.3390\/ijms221910519","article-title":"ROS\/TNF-\u03b1 crosstalk triggers the expression of IL-8 and MCP-1 in human monocytic THP-1 cells via the NF-\u03baB and ERK1\/2 mediated signaling","volume":"22","author":"Akhter","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2297456","DOI":"10.1080\/16583655.2023.2297456","article-title":"A molecular informatics and in-vitro approach to evaluate the HMG-CoA reductase inhibitory efficacy of monoterpenes, carvacrol and geraniol","volume":"18","author":"Almalki","year":"2024","journal-title":"J. Taibah Univ. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1080\/14786419.2015.1108977","article-title":"Molecular rationale delineating the role of lycopene as a potent HMG-CoA reductase inhibitor: in vitro and in silico study","volume":"30","author":"Alvi","year":"2016","journal-title":"Nat. Prod. Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1016\/j.biopha.2017.11.116","article-title":"Lycopene amends LPS induced oxidative stress and hypertriglyceridemia via modulating PCSK-9 expression and Apo-CIII mediated lipoprotein lipase activity","volume":"96","author":"Alvi","year":"","journal-title":"Biomed. Pharmacother."},{"key":"B16","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.freeradbiomed.2017.04.012","article-title":"Potential role of lycopene in targeting proprotein convertase subtilisin\/kexin type-9 to combat hypercholesterolemia","volume":"108","author":"Alvi","year":"","journal-title":"Free Radic. Biol. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1007\/s00204-016-1892-7","article-title":"Dietary fructose as a risk factor for non-alcoholic fatty liver disease (NAFLD)","volume":"91","author":"Alwahsh","year":"2017","journal-title":"Arch. Toxicol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e9039","DOI":"10.1590\/1414-431x20199039","article-title":"A high-carbohydrate diet induces greater inflammation than a high-fat diet in mouse skeletal muscle","volume":"53","author":"Antunes","year":"2020","journal-title":"Braz. J. Med. Biol. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/360438","article-title":"Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1161\/01.ATV.19.2.330","article-title":"Serum paraoxonase after myocardial infarction","volume":"19","author":"Ayub","year":"1999","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.atherosclerosis.2013.12.020","article-title":"Severe heterozygous familial hypercholesterolemia and risk for cardiovascular disease: a study of a cohort of 14,000 mutation carriers","volume":"233","author":"Besseling","year":"2014","journal-title":"Atherosclerosis"},{"key":"B22","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.mjafi.2019.12.001","article-title":"Metabolic syndrome: the Indian public health perspective","volume":"76","author":"Bhalwar","year":"2020","journal-title":"Med. J. Armed Forces India"},{"key":"B24","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1210\/er.2018-00064","article-title":"Molecular actions of PPAR\u03b1 in lipid metabolism and inflammation","volume":"39","author":"Bougarne","year":"2018","journal-title":"Endocr. Rev."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1172\/JCI23705","article-title":"PPARs in atherosclerosis: the clot thickens","volume":"114","author":"Castrillo","year":"2004","journal-title":"J. Clin. Invest."},{"key":"B26","doi-asserted-by":"publisher","first-page":"13248","DOI":"10.1038\/s41598-017-13251-0","article-title":"Hydrogen sulphide treatment increases insulin sensitivity and improves oxidant metabolism through the CaMKKbeta-AMPK pathway in PA-Induced IR C2C12 cells","volume":"7","author":"Chen","year":"2017","journal-title":"Sci. Rep."},{"key":"B27","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1055\/s-0042-1757712","article-title":"NAFLD in cardiovascular diseases: a contributor or comorbidity?","volume":"42","author":"Chen","year":"2022","journal-title":"Semin. Liver Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.apsb.2024.10.004","article-title":"Oxidative stress and inflammation in the pathogenesis of neurological disorders: mechanisms and implications","volume":"15","author":"Dash","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"B29","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1089\/met.2020.0116","article-title":"A high-fat diet induces lower systemic inflammation than a high-carbohydrate diet in mice","volume":"19","author":"de Almeida-Souza","year":"2021","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2023\/5431615","article-title":"The role of the gut microbiome and the hepatic axis in the pathogenesis of metabolic syndrome and therapeutics","volume":"2023","author":"Divya","year":"2023","journal-title":"Adv. Gut Microbiome Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.atherosclerosis.2015.01.013","article-title":"High-fructose feeding promotes accelerated degradation of hepatic LDL receptor and hypercholesterolemia in hamsters via elevated circulating PCSK9 levels","volume":"239","author":"Dong","year":"2015","journal-title":"Atherosclerosis"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2611","DOI":"10.1016\/j.numecd.2024.04.005","article-title":"Modulation of the antioxidant enzyme paraoxonase-1 for protection against cardiovascular diseases","volume":"34","author":"Dornas","year":"2024","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"B33","doi-asserted-by":"publisher","first-page":"23667","DOI":"10.1074\/jbc.M112.350181","article-title":"Peroxisome proliferator-activated receptor \u03b3 activation by ligands and dephosphorylation induces proprotein convertase subtilisin Kexin type 9 and low density lipoprotein receptor expression","volume":"287","author":"Duan","year":"2012","journal-title":"J. Biol. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1161\/01.HYP.0000182697.39687.34","article-title":"Fructose feeding increases insulin resistance but not blood pressure in sprague-dawley rats","volume":"46","author":"D\u2019Angelo","year":"2005","journal-title":"Hypertension"},{"key":"B35","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/0003-9861(59)90090-6","article-title":"Tissue sulfhydryl groups","volume":"82","author":"Ellman","year":"1959","journal-title":"Arch. Biochem. Biophys."},{"key":"B36","doi-asserted-by":"publisher","first-page":"106730","DOI":"10.1016\/j.intimp.2020.106730","article-title":"Potential anti-inflammatory effect of dapagliflozin in HCHF diet-induced fatty liver degeneration through inhibition of TNF-\u03b1, IL-1\u03b2, and IL-18 in rat liver","volume":"86","author":"ElMahdy","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.dsx.2018.08.017","article-title":"Serum cystatin C as an indicator for early detection of diabetic nephropathy in type 2 diabetes mellitus","volume":"13","author":"Elsayed","year":"2019","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"B38","doi-asserted-by":"publisher","first-page":"868934","DOI":"10.3389\/fcvm.2022.868934","article-title":"Inflammatory mediators in atherosclerotic vascular remodeling","volume":"9","author":"Evans","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"113526","DOI":"10.1016\/j.biopha.2022.113526","article-title":"Rosuvastatin and co-enzyme Q10 improve high-fat and high-fructose diet-induced metabolic syndrome in rats via ameliorating inflammatory and oxidative burden","volume":"153","author":"Fahmy","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"B40","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1159\/000506899","article-title":"Amelioration of high fructose diet-induced insulin resistance, hyperuricemia, and liver oxidative stress by combined use of selective agonists of PPAR-\u03b1 and PPAR-\u03b3 in rats","volume":"3","author":"Farag","year":"2020","journal-title":"Dubai Med. J."},{"key":"B41","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/j.bbrc.2008.07.023","article-title":"Inflammation stimulates the expression of PCSK9","volume":"374","author":"Feingold","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B42","doi-asserted-by":"publisher","first-page":"300","DOI":"10.3390\/nu16020300","article-title":"The garlic compound, Diallyl Trisulfide, attenuates Benzo[a]Pyrene-Induced precancerous effect through its antioxidant effect, AhR inhibition, and increased DNA repair in human breast epithelial cells","volume":"16","author":"Ferguson","year":"2024","journal-title":"Nutrients"},{"key":"B43","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"B44","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin. Chem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"9420020","DOI":"10.26599\/fmh.2024.9420020","article-title":"Inflammation and gut microbiota in the alcoholic liver disease","volume":"1","author":"Gao","year":"2024","journal-title":"Food Med. Homol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"e199139","DOI":"10.1001\/jamanetworkopen.2019.9139","article-title":"Association between Clinical Practice group adherence to quality measures and adverse outcomes among adult patients with diabetes","volume":"2","author":"Gilstrap","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"B47","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.cell.2015.01.036","article-title":"A century of cholesterol and coronaries: from plaques to genes to statins","volume":"161","author":"Goldstein","year":"2015","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"21117","DOI":"10.1038\/s41598-020-78342-x","article-title":"Saroglitazar in patients with non-alcoholic fatty liver disease and diabetic dyslipidemia: a prospective, observational, real world study","volume":"10","author":"Goyal","year":"2020","journal-title":"Sci. Rep."},{"key":"B49","doi-asserted-by":"publisher","first-page":"7130","DOI":"10.1016\/S0021-9258(19)42083-8","article-title":"Glutathione S transferases. The first enzymatic step in mercapturic acid formation","volume":"249","author":"Habig","year":"1974","journal-title":"J. Biol. Chem."},{"key":"B50","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1093\/jn\/104.5.580","article-title":"Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat","volume":"104","author":"Hafeman","year":"1974","journal-title":"J. Nutr."},{"key":"B51","doi-asserted-by":"publisher","first-page":"2697","DOI":"10.36721\/PJPS.2019.32.6.REG.2697-2708.1","article-title":"Phyllanthus virgatus forst extract and it\u2019s partially purified fraction ameliorates oxidative stress and retino-nephropathic architecture in streptozotocin-induced diabetic rats","volume":"32","author":"Hashim","year":"2019","journal-title":"Pak. J. Pharm. Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1186\/s13690-021-00749-3","article-title":"Comparison of metabolic syndrome prevalence using four different definitions \u2013 a population-based study in Finland","volume":"79","author":"Haverinen","year":"2021","journal-title":"Arch. Public Heal."},{"key":"B53","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1093\/ajcp\/34.4_ts.381","article-title":"Revised spectrophotometric methods for the determination of glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase, and lactic acid dehydrogenase","volume":"34","author":"Henry","year":"1960","journal-title":"Am. J. Clin. Pathol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1001\/jama.2020.4501","article-title":"Trends in the prevalence of metabolic syndrome in the United States, 2011-2016","volume":"323","author":"Hirode","year":"2020","journal-title":"J. Am. Med. Assoc."},{"key":"B55","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.tibs.2006.12.008","article-title":"Molecular biology of PCSK9: its role in LDL metabolism","volume":"32","author":"Horton","year":"2007","journal-title":"Trends biochem. Sci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1080\/13813455.2017.1415938","article-title":"Dietary phenolic acids reverse insulin resistance, hyperglycaemia, dyslipidaemia, inflammation and oxidative stress in high-fructose diet-induced metabolic syndrome rats","volume":"124","author":"Ibitoye","year":"2018","journal-title":"Arch. Physiol. Biochem."},{"key":"B57","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.ajme.2017.09.001","article-title":"First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): their fundamental role in the entire antioxidant defence grid","volume":"54","author":"Ighodaro","year":"2018","journal-title":"Alex. J. Med."},{"key":"B58","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1186\/s10020-024-01019-y","article-title":"The interplay of factors in metabolic syndrome: understanding its roots and complexity","volume":"30","author":"Islam","year":"2024","journal-title":"Mol. Med."},{"key":"B59","doi-asserted-by":"publisher","first-page":"100184","DOI":"10.1016\/j.prmcm.2022.100184","article-title":"Berberis aristata and its secondary metabolites: insights into nutraceutical and therapeutical applications","volume":"5","author":"Jahan","year":"2022","journal-title":"Pharmacol. Res. - Mod. Chin. Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"e00136","DOI":"10.1002\/prp2.136","article-title":"Saroglitazar, a novel PPAR \u03b1\/\u03b3 agonist with predominant PPAR \u03b1 activity, shows lipid\u2010lowering and insulin\u2010sensitizing effects in preclinical models","volume":"3","author":"Jain","year":"2015","journal-title":"Pharmacol. Res. Perspect."},{"key":"B61","first-page":"130","article-title":"A modified spectrophotometric assay of superoxide dismutase","volume":"21","author":"Kakkar","year":"1984","journal-title":"Indian J. biochem. Biophys."},{"key":"B62","doi-asserted-by":"publisher","first-page":"118","DOI":"10.4103\/jfmpc.jfmpc_10_17","article-title":"Prevalence of metabolic syndrome crossing 40% in northern India: time to act fast before it runs out of proportions","volume":"7","author":"Khan","year":"2018","journal-title":"J. Fam. Med. Prim. Care"},{"key":"B63","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41392-022-00955-7","article-title":"Inflammation and atherosclerosis: signaling pathways and therapeutic intervention","volume":"7","author":"Kong","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"B64","doi-asserted-by":"publisher","first-page":"742","DOI":"10.3390\/life11080742","article-title":"High-sensitivity c-reactive protein relationship with metabolic disorders and cardiovascular diseases risk factors","volume":"11","author":"Koziarska-Ro\u015bciszewska","year":"2021","journal-title":"Life"},{"key":"B65","doi-asserted-by":"publisher","first-page":"e22051","DOI":"10.1016\/j.heliyon.2023.e22051","article-title":"Effect of herbal extracts and saroglitazar on high-fat diet-induced obesity, insulin resistance, dyslipidemia, and hepatic lipidome in C57BL\/6J mice","volume":"9","author":"Kumari","year":"2023","journal-title":"Heliyon"},{"key":"B66","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.ijcard.2012.09.080","article-title":"Diallyl trisufide (DATS) suppresses high glucose-induced cardiomyocyte apoptosis by inhibiting JNK\/NF\u03baB signaling via attenuating ROS generation","volume":"168","author":"Kuo","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"B67","first-page":"2338","article-title":"The polymorphic paraoxonase\/arylesterase isozymes of human serum","volume":"43","author":"La Du","year":"1984","journal-title":"Fed. Proc."},{"key":"B68","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/j.cotox.2017.11.002","article-title":"NF-\u03baB in oxidative stress","volume":"7","author":"Lingappan","year":"2018","journal-title":"Curr. Opin. Toxicol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2-\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B70","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1016\/j.ijbiomac.2018.05.115","article-title":"Antiglycation study of HMG-R inhibitors and tocotrienol against glycated BSA and LDL: a comparative study","volume":"116","author":"Nabi","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"213","DOI":"10.2174\/1573399814666180924113442","article-title":"Glycation and HMG-CoA reductase inhibitors: implication in diabetes and associated complications","volume":"15","author":"Nabi","year":"2019","journal-title":"Curr. Diabetes Rev."},{"key":"B72","doi-asserted-by":"publisher","first-page":"108373","DOI":"10.1016\/j.abb.2020.108373","article-title":"A biochemical and biophysical study on in-vitro anti-glycating potential of iridin against D-Ribose modified BSA","volume":"686","author":"Nabi","year":"2020","journal-title":"Arch. Biochem. Biophys."},{"key":"B73","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1080\/13813455.2021.1874996","article-title":"Ezetimibe attenuates experimental diabetes and renal pathologies via targeting the advanced glycation, oxidative stress and AGE-RAGE signalling in rats","volume":"129","author":"Nabi","year":"2023","journal-title":"Arch. Physiol. Biochem."},{"key":"B74","article-title":"Effects and issues of diet fat on cardiovascular metabolism","volume-title":"New Insights into Metabolic Syndrome","author":"Nishikawa","year":"2020"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.2337\/diabetes.44.9.1054","article-title":"Elevated levels of authentic plasma hydroperoxides in IDDM","volume":"44","author":"Nourooz-Zadeh","year":"1995","journal-title":"Diabetes"},{"key":"B76","doi-asserted-by":"publisher","first-page":"9831","DOI":"10.3390\/ijms25189831","article-title":"Diallyl trisulfide and cardiovascular health: evidence and potential molecular mechanisms","volume":"25","author":"Novakovic","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"B78","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1097\/FJC.0b013e3181feb90a","article-title":"High-carbohydrate high-fat diet\u2013induced metabolic syndrome and cardiovascular remodeling in rats","volume":"57","author":"Panchal","year":"2011","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.3945\/jn.111.157263","article-title":"Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in diet-induced metabolic syndrome in rats","volume":"142","author":"Panchal","year":"2012","journal-title":"J. Nutr."},{"key":"B80","doi-asserted-by":"publisher","first-page":"273","DOI":"10.26502\/aimr.0184","article-title":"Etiology, pathophysiology, and treatment strategies in the prevention and management of metabolic syndrome","volume":"7","author":"Patial","year":"2024","journal-title":"Arch. Intern. Med. Res."},{"key":"B81","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1089\/met.2019.0005","article-title":"The role of visceral adiposity index levels in predicting the presence of metabolic syndrome and insulin resistance in overweight and obese patients","volume":"17","author":"Pekgor","year":"2019","journal-title":"Metab. Syndr. Relat. Disord."},{"key":"B82","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.jnutbio.2010.11.011","article-title":"Lipid redistribution by \u03b1-linolenic acid-rich chia seed inhibits stearoyl-CoA desaturase-1 and induces cardiac and hepatic protection in diet-induced obese rats","volume":"23","author":"Poudyal","year":"2012","journal-title":"J. Nutr. Biochem."},{"key":"B83","doi-asserted-by":"publisher","first-page":"690707","DOI":"10.3389\/fchem.2021.690707","article-title":"Permeability data of organosulfur garlic compounds estimated by immobilized artificial membrane chromatography: correlation across several biological barriers","volume":"9","author":"Ramirez","year":"2021","journal-title":"Front. Chem."},{"key":"B84","doi-asserted-by":"publisher","first-page":"208","DOI":"10.22270\/jddt.v10i2.3941","article-title":"The clinical aspects of saroglitazar and its side effects","volume":"10","author":"Ratna Sai","year":"2020","journal-title":"J. Drug Deliv. Ther."},{"key":"B85","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1093\/ajcp\/28.1.56","article-title":"A colorimetric method for the determination of Serum Glutamic oxalacetic and Glutamic Pyruvic transaminases","volume":"28","author":"Reitman","year":"1957","journal-title":"Am. J. Clin. Pathol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1016\/j.metabol.2006.02.022","article-title":"Oxidative stress and dysregulation of NAD(P)H oxidase and antioxidant enzymes in diet-induced metabolic syndrome","volume":"55","author":"Roberts","year":"2006","journal-title":"Metabolism"},{"key":"B87","doi-asserted-by":"publisher","first-page":"295","DOI":"10.3390\/nu11020295","article-title":"Immunomodulatory effects of glutathione, garlic derivatives, and hydrogen sulfide","volume":"11","author":"Rodrigues","year":"2019","journal-title":"Nutrients"},{"key":"B88","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1038\/pr.2014.170","article-title":"Understanding the role of gut microbiome in metabolic disease risk","volume":"77","author":"Sanz","year":"2015","journal-title":"Pediatr. Res."},{"key":"B89","doi-asserted-by":"publisher","first-page":"e3502","DOI":"10.1002\/dmrr.3502","article-title":"Metabolic syndrome and cardiovascular diseases: going beyond traditional risk factors","volume":"38","author":"Silveira Rossi","year":"2022","journal-title":"Diabetes. Metab. Res. Rev."},{"key":"B90","doi-asserted-by":"publisher","first-page":"9503","DOI":"10.1158\/0008-5472.CAN-08-1677","article-title":"Garlic constituent diallyl trisulfide prevents development of poorly differentiated prostate cancer and pulmonary metastasis multiplicity in TRAMP mice","volume":"68","author":"Singh","year":"2008","journal-title":"Cancer Res."},{"key":"B91","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/0003-2697(72)90132-7","article-title":"Colorimetric assay of catalase","volume":"47","author":"Sinha","year":"1972","journal-title":"Anal. Biochem."},{"key":"B92","doi-asserted-by":"publisher","first-page":"116466","DOI":"10.1016\/j.biopha.2024.116466","article-title":"Hydrogen sulfide dysfunction in metabolic syndrome-associated vascular complications involves cGMP regulation through soluble guanylyl cyclase persulfidation","volume":"174","author":"Smimmo","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"B93","doi-asserted-by":"publisher","first-page":"754","DOI":"10.3389\/fimmu.2018.00754","article-title":"Role of C-reactive protein at sites of inflammation and infection","volume":"9","author":"Sproston","year":"2018","journal-title":"Front. Immunol."},{"key":"B94","doi-asserted-by":"publisher","first-page":"e0255","DOI":"10.1097\/MD.0000000000010255","article-title":"Anti-hyperlipidemia of garlic by reducing the level of total cholesterol and low-density lipoprotein","volume":"97","author":"Sun","year":"2018","journal-title":"Med. (United States)"},{"key":"B95","doi-asserted-by":"publisher","first-page":"79","DOI":"10.5455\/oams.240716.rv.025","article-title":"The potential role of S-allylcysteine as antioxidant against various disorders in animal models","volume":"5","author":"Uddandrao","year":"2016","journal-title":"Oxid. Antioxid. Med. Sci."},{"key":"B96","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1093\/clinchem\/21.10.1523","article-title":"Indirect assessment of hydroxymethylglutaryl CoA reductase (NADPH) activity in liver tissue","volume":"21","author":"Venugopala Rao","year":"1975","journal-title":"Clin. Chem."},{"key":"B97","doi-asserted-by":"publisher","first-page":"47","DOI":"10.17179\/excli2021-4453","article-title":"Potential dual inhibitors of PCSK-9 and HMG-R from natural sources in cardiovascular risk management","volume":"21","author":"Waiz","year":"2022","journal-title":"EXCLI J."},{"key":"B98","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1080\/10715762.2023.2237180","article-title":"Association of circulatory PCSK-9 with biomarkers of redox imbalance and inflammatory cascades in the prognosis of diabetes and associated complications: a pilot study in the Indian population","volume":"57","author":"Waiz","year":"2023","journal-title":"Free Radic. Res."},{"key":"B99","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s43162-026-00624-z","article-title":"Prognostic significance and interplay of circulatory PCSK-9\u2013ApoCIII\u2013chemokine axis in type 2 diabetes and its complications: a pilot study in North Indian patients","volume":"38","author":"Waiz","year":"2026","journal-title":"Egypt. J. Intern. Med."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/7284767","article-title":"Ginkgolide B mediated alleviation of inflammatory cascades and altered lipid metabolism in HUVECs via targeting PCSK-9 expression and functionality","volume":"2019","author":"Wang","year":"2019","journal-title":"Biomed. Res. Int."},{"key":"B101","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/s41420-023-01690-w","article-title":"Exogenous H2S initiating Nrf2\/GPx4\/GSH pathway through promoting Syvn1-Keap1 interaction in diabetic hearts","volume":"9","author":"Wang","year":"","journal-title":"Cell Death Discov."},{"key":"B102","doi-asserted-by":"publisher","first-page":"10742484231162249","DOI":"10.1177\/10742484231162249","article-title":"High-Fructose diet induces cardiac dysfunction via macrophage recruitment in adult mice","volume":"28","author":"Wang","year":"","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"B103","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/j.foodchem.2005.05.049","article-title":"A systematic survey of antioxidant activity of 30 Chinese medicinal plants using the ferric reducing antioxidant power assay","volume":"97","author":"Wong","year":"2006","journal-title":"Food Chem."},{"key":"B104","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1055\/s-0043-119352","article-title":"The effects of a modified high-carbohydrate high-fat diet on metabolic syndrome parameters in Male rats","volume":"126","author":"Wong","year":"2018","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"B105","doi-asserted-by":"publisher","first-page":"764038","DOI":"10.3389\/fcvm.2021.764038","article-title":"Regulation of PCSK9 expression and function: mechanisms and therapeutic implications","volume":"8","author":"Xia","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"B106","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.jare.2024.06.016","article-title":"Challenges and advances in the management of inflammation in atherosclerosis","volume":"71","author":"Xing","year":"2025","journal-title":"J. Adv. Res."},{"key":"B107","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/0009-3084(87)90071-5","article-title":"Lipid peroxides and human diseases","volume":"45","author":"Yagi","year":"1987","journal-title":"Chem. Phys. Lipids"},{"key":"B108","doi-asserted-by":"publisher","first-page":"107542","DOI":"10.1016\/j.phrs.2024.107542","article-title":"Protective role of 3-mercaptopyruvate sulfurtransferase (MPST) in the development of metabolic syndrome and vascular inflammation","volume":"211","author":"Zampas","year":"2025","journal-title":"Pharmacol. Res."},{"key":"B109","first-page":"18602","article-title":"Binding of proprotein convertase subtilisin\/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation","volume-title":"J. Biol. Chem.","author":"Zhang","year":"2007"},{"key":"B110","doi-asserted-by":"publisher","first-page":"335","DOI":"10.3390\/nu9040335","article-title":"High dietary fructose: direct or indirect dangerous factors disturbing tissue and organ functions","volume":"9","author":"Zhang","year":"2017","journal-title":"Nutrients"},{"key":"B111","doi-asserted-by":"publisher","first-page":"14700","DOI":"10.3390\/ijms241914700","article-title":"High-Carbohydrate diet consumption poses a more severe liver cholesterol deposition than a high-fat and high-calorie diet in mice","volume":"24","author":"Zhang","year":"2023","journal-title":"Int. J. Mol. Sci."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1781950\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T04:57:16Z","timestamp":1780030636000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1781950\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":110,"alternative-id":["10.3389\/fphar.2026.1781950"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1781950","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1781950"}}