{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:33:24Z","timestamp":1792064004679,"version":"4.4.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Gynura procumbens<\/jats:italic>, known as longevity spinach, is a plant traditionally used in tropical Asian countries for its anti-inflammatory, hepatoprotective, anti-hypertensive, and anti-hyperglycemic properties. The current study aimed to enhance the hepatorenal protective activity of <jats:italic>Gynura procumbens<\/jats:italic> leaf extract (GLE) by developing a self-microemulsifying drug delivery system (SMEDDS). SMEDDS-GLE exhibited the formation of small micelles with a mean droplet size of 231\u2009nm. This resulted in a significant enhancement in the dispersion of GLE in water, as evidenced by a dispersibility that was at least 4.8 times greater than that of GLE alone. In the rat model of hepatic injury induced by cisplatin (7.5\u2009mg\/kg, <jats:italic>i.p.<\/jats:italic>), the administration of SMEDDS-GLE (75 mg-GLE\/kg, <jats:italic>p.o.<\/jats:italic>) significantly reduced liver damage, observed by histological examination and reduced levels of plasma biomarkers associated with hepatic injury. Furthermore, according to histological examination findings and plasma biomarkers assessment, SMEDDS-GLE enhanced the nephroprotective benefits of GLE in the rat model of acute kidney injury. Based on these findings, a strategic application of the SMEDDS-based approach could be a viable choice to enhance GLE\u2019s nutraceutical properties.<\/jats:p>","DOI":"10.1371\/journal.pone.0304435","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T18:40:38Z","timestamp":1740422438000},"page":"e0304435","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Gynura procumbens leaf extract-loaded self-microemulsifying drug delivery system offers enhanced protective effects in the hepatorenal organs of the experimental rats"],"prefix":"10.1371","volume":"20","author":[{"given":"Manik Chandra","family":"Shill","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. 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study","volume":"20","author":"R Shafiezadeh","year":"2020","journal-title":"Hepat Mon"},{"issue":"2","key":"pone.0304435.ref003","doi-asserted-by":"crossref","first-page":"2236","DOI":"10.18632\/oncotarget.23368","article-title":"The prevalence and association of chronic kidney disease and diabetes in liver cirrhosis using different estimated glomerular filtration rate equation","volume":"9","author":"CY Chen","year":"2018","journal-title":"Oncotarget"},{"key":"pone.0304435.ref004","doi-asserted-by":"crossref","first-page":"19","DOI":"10.4103\/0976-0105.128253","article-title":"A current challenge","volume":"5","author":"DS Bennadi","year":"2014","journal-title":"J Basic Clin Pharm"},{"issue":"15","key":"pone.0304435.ref005","doi-asserted-by":"crossref","first-page":"7902","DOI":"10.1074\/jbc.M115.711564","article-title":"Membrane oxidation enables the cytosolic entry of polyarginine cell-penetrating peptides","volume":"291","author":"TY Wang","year":"2016","journal-title":"J Biol 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agents","volume":"17","author":"S Mushtaq","year":"2018","journal-title":"EXCLI J"},{"key":"pone.0304435.ref015","doi-asserted-by":"crossref","first-page":"694","DOI":"10.3389\/fphys.2020.00694","article-title":"Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of chronic diseases","volume":"11","author":"M Sharifi-Rad","year":"2020","journal-title":"Front Physiol"},{"issue":"1","key":"pone.0304435.ref016","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.tifs.2015.07.005","article-title":"Recent developments in nanoformulations of lipophilic functional foods","volume":"46","author":"GH Shin","year":"2015","journal-title":"Trends Food Sci Technol"},{"issue":"12","key":"pone.0304435.ref017","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1093\/jn\/132.12.3772","article-title":"Functional foods: benefits, concerns and challenges\u2014a position paper from the american council on science and health","volume":"132","author":"CM Hasler","year":"2002","journal-title":"J Nutr"},{"issue":"10","key":"pone.0304435.ref018","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.3390\/molecules28104186","article-title":"Phytochemical and biological investigation of an indigenous plant of bangladesh, gynura procumbens (lour.) merr.: drug discovery from nature","volume":"28","author":"MA Jobaer","year":"2023","journal-title":"Molecules"},{"key":"pone.0304435.ref019","first-page":"802","article-title":"Gynura procumbens nanoencapsulation: a novel promising approach to combat dengue infection","volume":"16","author":"AP Wardana","year":"2023","journal-title":"Rasayan J Chem"},{"key":"pone.0304435.ref020","doi-asserted-by":"crossref","first-page":"504624","DOI":"10.3389\/fphar.2020.504624","article-title":"Antioxidant and anti-inflammatory effects of genus Gynura: a systematic review","volume":"11","author":"JN Tan","year":"2020","journal-title":"Front 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Patel","year":"2024","journal-title":"Pharmaceuticals (Basel)"},{"key":"pone.0304435.ref026","doi-asserted-by":"crossref","first-page":"153890","DOI":"10.1016\/j.phymed.2021.153890","article-title":"Herbal nanomedicines: Recent advancements, challenges, opportunities and regulatory overview","volume":"96","author":"PK Teja","year":"2022","journal-title":"Phytomedicine"},{"key":"pone.0304435.ref027","first-page":"65","article-title":"Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs","volume":"274","author":"B Ki","year":"2004"},{"issue":"6","key":"pone.0304435.ref028","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S1773-2247(12)50092-4","article-title":"The influence of the ratio of lipid to surfactant and the presence of cosolvent on phase behaviour during aqueous dilution of lipid-based drug delivery systems","volume":"22","author":"K Mohsin","year":"2012","journal-title":"J Drug 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Studies","volume":"21","author":"M Chandra Shill","year":"2024","journal-title":"Chem Biodivers"},{"key":"pone.0304435.ref032","first-page":"2019","article-title":"Structural characterization, antimicrobial activity, and in vitro cytotoxicity effect of black seed oil. evidence-based complement","author":"SJ Mohammed","year":"2019","journal-title":"Altern Med"},{"key":"pone.0304435.ref033","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1016\/j.sjbs.2022.01.052","article-title":"Hesperidin ameliorates cisplatin induced hepatotoxicity and attenuates oxidative damage, cell apoptosis, and inflammation in rats","volume":"29","author":"DM Aboraya","year":"2022","journal-title":"Saudi J Biol Sci"},{"key":"pone.0304435.ref034","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/15593258221124728","article-title":"The hepatoprotective and anti-nephrotoxic potential of methanolic extract of a polyherbal preparation in ccl4-induced liver injury model of wistar rats","volume":"20","author":"M Boota","year":"2022","journal-title":"Dose-Response"},{"issue":"4","key":"pone.0304435.ref035","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1093\/ilar.43.4.244","article-title":"Guidelines for the design and statistical analysis of experiments using laboratory animals","volume":"43","author":"MFW Festing","year":"2002","journal-title":"ILAR J"},{"key":"pone.0304435.ref036","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1590\/S0102-86502007000100013","article-title":"Histological study of the liver and biochemistry of the blood of Wistar rats following ligature of right hepatic duct","volume":"22","author":"AB Quaresma","year":"2007","journal-title":"Acta Cir Bras"},{"key":"pone.0304435.ref037","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2024\/9441968","article-title":"Polyphenol-standardized aphanamixis polystachya leaf extract ameliorates diabetes, oxidative stress, inflammation, and fibrosis in streptozotocin-induced diabetic rats","author":"M Chandra Shill","year":"2024","journal-title":"J Food Biochem"},{"issue":"3","key":"pone.0304435.ref038","doi-asserted-by":"crossref","first-page":"308","DOI":"10.4103\/jpbs.JPBS_268_20","article-title":"Date seed extract-loaded oil-in-water nanoemulsion: Development, characterization, and antioxidant activity as a delivery model for rheumatoid arthritis","volume":"12","author":"A Qadir","year":"2020","journal-title":"J Pharm Bioallied Sci"},{"key":"pone.0304435.ref039","doi-asserted-by":"crossref","first-page":"104391","DOI":"10.1016\/j.jff.2021.104391","article-title":"Self-emulsifying drug delivery system of black seed oil with improved hypotriglyceridemic effect and enhanced hepatoprotective function","volume":"78","author":"S Halder","year":"2021","journal-title":"J Funct Foods"},{"issue":"10","key":"pone.0304435.ref040","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1007\/s11095-012-0704-x","article-title":"Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) I: Use of Poloxamer 188 as both solidifying and emulsifying agent for lipids","volume":"29","author":"A V Shah","year":"2012","journal-title":"Pharm Res"},{"key":"pone.0304435.ref041","doi-asserted-by":"crossref","first-page":"249","DOI":"10.4103\/0250-474X.159596","article-title":"Role of components in the formation of self-microemulsifying drug delivery systems","volume":"77","author":"AK Gurram","year":"2015","journal-title":"Indian J Pharm Sci"},{"key":"pone.0304435.ref042","doi-asserted-by":"crossref","first-page":"120814","DOI":"10.1016\/j.molliq.2022.120814","article-title":"Microemulsion and interfacial properties of anionic\/nonionic surfactant mixtures based on sulfonate surfactants: The influence of alcohol","volume":"371","author":"J Wu","year":"2023","journal-title":"J Mol Liq"},{"key":"pone.0304435.ref043","article-title":"Toxicological profile for propylene glycol","author":"M Ed","year":"2002","journal-title":"ATSDR\u2019s Toxicol Profiles"},{"key":"pone.0304435.ref044","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.addr.2016.04.007","article-title":"50 years of oral lipid-based formulations: provenance, progress and future perspectives","volume":"101","author":"OM Feeney","year":"2016","journal-title":"Adv Drug Deliv Rev"},{"issue":"11","key":"pone.0304435.ref045","doi-asserted-by":"crossref","first-page":"2562","DOI":"10.3390\/pharmaceutics15112562","article-title":"Stabilized astaxanthin nanoparticles developed using flash nanoprecipitation to improve oral bioavailability and hepatoprotective effects","volume":"15","author":"A Ghosh","year":"2023","journal-title":"Pharmaceutics"},{"issue":"6","key":"pone.0304435.ref046","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1002\/jsfa.12329","article-title":"Lysophosphatidylcholine-based liposome to improve oral absorption and nephroprotective effects of astaxanthin","volume":"103","author":"A Ghosh","year":"2023","journal-title":"J Sci Food Agric"},{"issue":"12","key":"pone.0304435.ref047","doi-asserted-by":"crossref","first-page":"5354","DOI":"10.1039\/D3MH00717K","article-title":"Dynamic light scattering and transmission electron microscopy in drug delivery: a roadmap for correct characterization of nanoparticles and interpretation of results. Mater Horizons","volume":"10","author":"SK Filippov","year":"2023","journal-title":"Mater Horiz"},{"issue":"1","key":"pone.0304435.ref048","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.ejpb.2007.11.008","article-title":"Characterization of drug-chitosan interaction by 1H NMR, FTIR and isothermal titration calorimetry","volume":"69","author":"Y Boonsongrit","year":"2008","journal-title":"Eur J Pharm Biopharm"},{"issue":"4","key":"pone.0304435.ref049","first-page":"463","article-title":"Dissolution enhancement of felodipine by amorphous nanodispersions using an amphiphilic polymer: insight into the role of drug\u2013polymer interactions on drug dissolution","volume":"21","author":"MM Pandey","year":"2016","journal-title":"Pharm Dev Technol"},{"issue":"1","key":"pone.0304435.ref050","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.taap.2011.10.016","article-title":"Insights antifibrotic mechanism of methyl palmitate: Impact on nuclear factor kappa B and proinflammatory cytokines","volume":"258","author":"EM Mantawy","year":"2012","journal-title":"Toxicol Appl Pharmacol"},{"key":"pone.0304435.ref051","doi-asserted-by":"crossref","first-page":"104606","DOI":"10.1016\/j.pestbp.2020.104606","article-title":"Pathophysiological impacts of exposure to an endocrine disruptor (tetradifon) onamylase and lipase activities associated metabolic disorders","volume":"167","author":"R Badraoui","year":"2020","journal-title":"Pestic Biochem Physiol"},{"issue":"29","key":"pone.0304435.ref052","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.3748\/wjg.v18.i29.3775","article-title":"Alanine and aspartate aminotransferase and glutamine-cycling pathway: their roles in pathogenesis of metabolic syndrome","volume":"18","author":"S Sookoian","year":"2012","journal-title":"World J Gastroenterol"},{"issue":"1","key":"pone.0304435.ref053","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3109\/10408449509089886","article-title":"Oxygen and xenobiotic reductase activities of cytochrome P450","volume":"25","author":"R Goeptar","year":"1995","journal-title":"Crit Rev Toxicol"},{"key":"pone.0304435.ref054","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/B0-12-475570-4\/00082-2","volume-title":"Encyclopedia of Endocrine Diseases","author":"D Goltzman","year":"2004"},{"issue":"6","key":"pone.0304435.ref055","doi-asserted-by":"crossref","first-page":"103289","DOI":"10.1016\/j.sjbs.2022.103289","article-title":"Gastroprotective, hepatoprotective, and nephroprotective effects of thymol against the adverse effects of acetylsalicylic acid in rats: Biochemical and histopathological studies","volume":"29","author":"SMA El-Sheikh","year":"2022","journal-title":"Saudi J Biol Sci"},{"issue":"4","key":"pone.0304435.ref056","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.ejps.2013.05.014","article-title":"Physicochemical and biopharmaceutical characterization of amorphous solid dispersion of nobiletin, a citrus polymethoxylated flavone, with improved hepatoprotective effects","volume":"49","author":"S Onoue","year":"2013","journal-title":"Eur J Pharm Sci"},{"issue":"1-2","key":"pone.0304435.ref057","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1159\/000365852","article-title":"Protective effects of relaxin against cisplatin-induced nephrotoxicity in rats","volume":"128","author":"T Yoshida","year":"2014","journal-title":"Nephron Exp Nephrol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0304435","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T18:40:56Z","timestamp":1740422456000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0304435"}},"subtitle":[],"editor":[{"given":"Miquel","family":"Vall-llosera Camps","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,2,24]]},"references-count":57,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0304435","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,24]]}}}