{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:14:50Z","timestamp":1790691290748,"version":"4.1.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"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:p>This study investigated the gastroprotective effect of <jats:italic>Piper sarmentosum<\/jats:italic> (PS) on stress-induced gastric ulcers in rats by measuring its effect on oxidative stress, gastric mucosal nitric oxide (NO), and inflammatory biomarkers. Twenty-eight male Wistar rats were randomly divided into four groups; two control groups (non-stress and stress) and two treated groups supplemented with either methanolic PS extract (500\u00a0mg\/kg body weight) or omeprazole (OMZ; 20\u00a0mg\/kg) orally. After 28\u00a0days of treatment, the stress control, PS, and OMZ groups were subjected to water-immersion restrain stress (WIRS) for 3.5\u00a0h. Gastric tissue malondialdehyde (MDA), NO, superoxide dismutase (SOD), inducible NO synthase (iNOS), SOD mRNA, tumor necrosis factor (TNF)-\u03b1, interleukin (IL)-1\u03b2, and IL-6 levels were measured. WIRS significantly increased gastric MDA, NO, and pro-inflammatory cytokine levels compared to the non-stressed control group. PS and omeprazole supplementation significantly reduced WIRS-exposure-induced gastric ulcers and MDA, iNOS, and IL-1\u03b2 levels. However, only PS reduced NO, TNF-\u03b1, and IL-6 levels, which were upregulated in this ulcer model. In conclusion, the gastroprotection afforded by PS is possibly mediated by gastric mucosal NO normalization through reduced iNOS expression and attenuation of inflammatory cytokines. PS showed a greater protective effect than omeprazole in reducing gastric lesions and NO, TNF-\u03b1, and IL-6 levels, and iNOS expression.<\/jats:p>","DOI":"10.3389\/fphar.2022.971443","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T04:59:50Z","timestamp":1673499590000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Piper sarmentosum Roxb. methanolic extract prevents stress-induced gastric ulcer by modulating oxidative stress and inflammation"],"prefix":"10.3389","volume":"13","author":[{"given":"Muhamad Nurul","family":"Akmal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Abdel Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohd Fahami","family":"Nur Azlina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/1476-511X-9-44","article-title":"Aqueous extract of Piper sarmentosum decreases atherosclerotic lesions in high cholesterolemic experimental rabbits","volume":"9","author":"Amran","year":"2010","journal-title":"Lipids Health Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18553\/jmcp.2013.19.s9.1","article-title":"NSAIDs for musculoskeletal pain management:current perspectives and novel strategies to improve safety","volume":"19","author":"Atchison","year":"2013","journal-title":"J. Manag. Care Pharm. JMCP"},{"key":"B3","doi-asserted-by":"publisher","first-page":"01393488","DOI":"10.1371\/journal.pone.0139348","article-title":"Preventive effects of tocotrienol on stress-induced gastric mucosal lesions and its relation to oxidative and inflammatory biomarkers","volume":"10","author":"Azlina","year":"2015","journal-title":"PLoS ONE"},{"key":"B4","doi-asserted-by":"publisher","first-page":"223","DOI":"10.5114\/aoms.2016.63156","article-title":"In vivo effect of Piper sarmentosum methanolic extract on stress-induced gastric ulcers in rats","volume":"15","author":"Azlina","year":"2019","journal-title":"Archives Med. Sci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"5887","DOI":"10.3748\/wjg.v23.i32.5887","article-title":"Comparison between tocotrienol and omeprazole on gastric growth factors in stress-exposed rats","volume":"23","author":"Azlina","year":"2017","journal-title":"World J. Gastroenterology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.5530\/pj.2019.11.167","article-title":"LC-MS analysis of phytocomponents in the methanol extract of piper sarmentosum leaves","volume":"11","author":"Bactiar","year":"2019","journal-title":"Pharmacogn. J."},{"key":"B7","doi-asserted-by":"publisher","first-page":"251","DOI":"10.2174\/1567205016666190228124630","article-title":"Piper sarmentosum Roxb. Root extracts confer neuroprotection by attenuating beta amyloid-induced pro-inflammatory cytokines released from microglial cells","volume":"16","author":"Chan","year":"2019","journal-title":"Curr. Alzheimer Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.foodchem.2004.07.035","article-title":"Screening of antioxidant activity and antioxidant compounds of some edible plants of Thailand","volume":"92","author":"Chanwitheesuk","year":"2005","journal-title":"Food Chem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/S0928-4257(01)00034-1","article-title":"Current roles of nitric oxide in gastrointestinal disorders","volume":"95","author":"Cho","year":"2001","journal-title":"J. Physiology Paris"},{"key":"B10","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.numecd.2005.05.003","article-title":"A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress","volume":"15","author":"Del Rio","year":"2005","journal-title":"Nutr. Metabolism Cardiovasc. Dis."},{"key":"B11","first-page":"369","article-title":"Gastric mucosa injury associated with oxidative stress","author":"Dinu","year":"2009","journal-title":"Lucr. Stiintife Med. Veterinaara"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e51537","DOI":"10.1371\/journal.pone.0051537","article-title":"Acute toxicity and gastroprotection studies of a new schiff base derived copper (II) complex against ethanol-induced acute gastric lesions in rats","volume":"7","author":"Hajrezaie","year":"2012","journal-title":"PLoS ONE"},{"key":"B13","doi-asserted-by":"publisher","first-page":"22","DOI":"10.5114\/aoms.2012.27276","article-title":"The effects of palm vitamin E on stress hormone levels and gastric lesions in stress-induced rats","volume":"8","author":"Ibrahim","year":"2012","journal-title":"Archives Med. Sci."},{"key":"B14","first-page":"118","article-title":"Palm tocotrienol-rich fraction supplementation suppressed stress-induced gastric oxidative stress in rats","volume":"1","author":"Kamisah","year":"2011","journal-title":"J. Appl. Pharm. Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"e59296","DOI":"10.1371\/journal.pone.0059296","article-title":"Acute toxicity and gastroprotection studies with a newly synthesized steroid","volume":"8","author":"Ketuly","year":"2013","journal-title":"PLoS ONE"},{"key":"B16","doi-asserted-by":"publisher","first-page":"123","DOI":"10.15171\/bi.2015.20","article-title":"Reliability of malondialdehyde as a biomarker of oxidative stress in psychological disorders","volume":"5","author":"Khoubnasabjafari","year":"2015","journal-title":"BioImpacts"},{"key":"B17","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1111\/j.1600-079X.2007.00543.x","article-title":"Day\/night differences in stress-induced gastric lesions in rats with an intact pineal gland or after pinealectomy","volume":"44","author":"Konturek","year":"2008","journal-title":"J. Pineal Res."},{"key":"B42","first-page":"1301","article-title":"Omeprazole and regulation of cytokine profile in Helicobacter pylori-infected patients with duodenal ulcer disease","volume":"47","author":"Kountouras","year":"2000","journal-title":"Hepatogastroenterology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"217039","DOI":"10.1155\/2014\/217039","article-title":"Pharmacological correction of stress-induced gastric ulceration by novel small-molecule agents with antioxidant profile","volume":"2014","author":"Kudryavtsev","year":"2014","journal-title":"Sci. World J."},{"key":"B19","first-page":"39","article-title":"Effects of reactive oxygen species action on gastric mucosa in various models of mucosal injury","volume":"53","author":"Kwiecie\u0144","year":"2002","journal-title":"J. Physiology Pharmacol."},{"key":"B20","first-page":"515","article-title":"Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, interacts with gastric oxidative metabolism and enhances stress-induced gastric lesions","volume":"63","author":"Kwiecien","year":"2012","journal-title":"J. Physiology Pharmacol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1186\/ar2465","article-title":"Role of nitric oxide in the gastrointestinal tract","volume":"10","author":"Lanas","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"B22","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/0009-8981(86)90247-0","article-title":"The relationship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atherosclerosis","volume":"155","author":"Ledwoz","year":"1986","journal-title":"Clin. Chim. Acta"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive oxygen species in inflammation and tissue injury","volume":"20","author":"Mittal","year":"2014","journal-title":"Antioxidants Redox Signal."},{"key":"B24","doi-asserted-by":"publisher","first-page":"27986","DOI":"10.1039\/c4ra13315c","article-title":"Free radicals, natural antioxidants, and their reaction mechanisms","volume":"5","author":"Nimse","year":"2015","journal-title":"RSC Adv."},{"key":"B25","doi-asserted-by":"publisher","first-page":"804796","DOI":"10.1155\/2013\/804796","article-title":"Tocotrienol attenuates stress-induced gastric lesions via activation of prostaglandin and upregulation of COX-1 mRNA","volume":"2013","author":"Nur Azlina","year":"2013","journal-title":"Evidence-Based Complementary Altern. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3923\/ijp.2009.58.64","article-title":"Modulation of restraint induced gastric oxidative changes in rats by tocotrienol and tocopherol","volume":"5","author":"Nur Azlina","year":"2009","journal-title":"Int. J. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/j.imr.2016.07.004","article-title":"Reactive oxygen species and antioxidant defense in human gastrointestinal diseases","volume":"5","author":"Patlevi\u010d","year":"2016","journal-title":"Integr. Med. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"9752826","DOI":"10.1155\/2019\/9752826","article-title":"Preventive effect of naringin on metabolic syndrome and its mechanism of action: A systematic review","volume":"2019","author":"Raja Kumar","year":"2019","journal-title":"Evidence-Based Complementary Altern. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/978-3-211-33303-7_2","article-title":"Robotics and artificial intelligence: Jewish ethical perspectives","volume":"98","author":"Rappaport","year":"2006","journal-title":"Acta Neurochir. Suppl."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.3390\/molecules24071364","article-title":"Piper species: A comprehensive review on their phytochemistry, biological activities and applications","volume":"24","author":"Salehi","year":"2019","journal-title":"Molecules"},{"key":"B31","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.jep.2004.01.014","article-title":"Effects of Piper longum fruit, Piper sarmentosum root and Quercus infectoria nut gall on caecal amoebiasis in mice","volume":"91","author":"Sawangjaroen","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"B32","first-page":"171","article-title":"Protective effect of increasing doses of famotidine, omeprazole, lansoprazole, and melatonin against ethanol-induced gastric damage in rats","volume":"36","author":"Sener","year":"2004","journal-title":"Indian J. Pharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"450840","DOI":"10.1155\/2013\/450840","article-title":"\u03b1 -mangostin from cratoxylum arborescens (vahl) blume demonstrates anti-ulcerogenic property: A mechanistic study","volume":"2013","author":"Sidahmed","year":"2013","journal-title":"Evidence-Based Complementary Altern. Med."},{"key":"B34","first-page":"41","article-title":"Natural antioxidants: Piper sarmentosum (kadok) and Morinda elliptica (mengkudu)","volume":"9","author":"Subramaniam","year":"2003","journal-title":"Malays. J. Nutr."},{"key":"B35","doi-asserted-by":"publisher","first-page":"112897","DOI":"10.1016\/j.jep.2020.112897","article-title":"Piper sarmentosum Roxb: A review on its botany, traditional uses, phytochemistry, and pharmacological activities","volume":"263","author":"Sun","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-17917\/v1","article-title":"Piper sarmentosum extract alleviates inflammatory responses and improves barrier function in porcine intestinal epithelial (IPEC-J2) cells induced by lipopolysaccharide (LPS)","author":"Wang","year":"2020","journal-title":"J. Ethnopharmacol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.canlet.2013.08.016","article-title":"Helicobacter pylori-induced gastric inflammation and gastric cancer","volume":"345","author":"Wang","year":"2014","journal-title":"Cancer Lett."},{"key":"B38","first-page":"971","article-title":"Role of neutrophils in a rat model of gastric ulcer recurrence caused by interleukin-1 beta","volume":"150","author":"Watanabe","year":"1997","journal-title":"Am. J. Pathology"},{"key":"B39","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1136\/gut.48.6.774","article-title":"Acid regulates inflammatory response in a rat model of induction of gastric ulcer recurrence by interleukin 1beta","volume":"48","author":"Watanabe","year":"2001","journal-title":"Gut"},{"key":"B40","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jep.2009.12.021","article-title":"In vivo anti-nociceptive and anti-inflammatory activities of the aqueous extract of the leaves of Piper sarmentosum","volume":"128","author":"Zakaria","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1177\/1087057105277414","article-title":"Small interfering RNA and gene expression analysis using a multiplex branched DNA assay without RNA purification","volume":"10","author":"Zhang","year":"2005","journal-title":"J. Biomol. Screen."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.971443\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T04:59:58Z","timestamp":1673499598000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.971443\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,12]]},"references-count":42,"alternative-id":["10.3389\/fphar.2022.971443"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.971443","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,12]]},"article-number":"971443"}}