{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:06:35Z","timestamp":1791986795144,"version":"4.4.0"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T00:00:00Z","timestamp":1597104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Obesity and hyper-intestinal permeability are interconnected. This study is designed to evaluate the ability of Mangifera indica seed kernel extract (MESK) in restoring the intestinal barrier and preventing obesity and associated metabolic complications in a high-fat diet-induced obese mouse model. Four groups of Swiss albino mice: (1) normal diet (ND), (2) high-fat diet (HFD), (3) HFD + Orlistat (100 \u00b5g\/kg), and (4) HFD + MESK (75 \u00b5g\/kg), were used to monitor various biochemical parameters associated with metabolic syndrome (glucose, total cholesterol, triglycerides) and body weight in an eight-week-long study. In vivo intestinal permeability was determined by the FITC-dextran method. Interestingly, MESK significantly reduced HFD-induced body weight gain, hepatic lipid accumulation, hepatic fibrosis, hyperglycemia, and dyslipidemia. Additionally, MESK treatment restored the expression of tight junction protein Zonula Occludens-1 (ZO-1) and Claudin-1 and hence prevented increased intestinal permeability induced by a high-fat diet. Moreover, it also increased the expression of potent satiety molecule Nesfatin-1 in the mouse jejunum. Our results, for the first time, establish MESK as a nutraceutical which prevents disruption of the intestinal barrier and thereby intercepts the adverse consequences of compromised intestinal permeability such as obesity, hyperglycemia, dyslipidemia, and systemic inflammation.<\/jats:p>","DOI":"10.3390\/ph13080190","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T09:28:57Z","timestamp":1597138137000},"page":"190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Reversal of Increase in Intestinal Permeability by Mangifera indica Seed Kernel Extract in High-Fat Diet-Induced Obese Mice"],"prefix":"10.3390","volume":"13","author":[{"given":"Pavan Kumar","family":"Mujawdiya","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Hyderabad 500078, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pravesh","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Hyderabad 500078, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashwat","family":"Sharad","sequence":"additional","affiliation":[{"name":"Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suman","family":"Kapur","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Hyderabad 500078, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health & disease","volume":"9","author":"Turner","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1097\/MOL.0b013e3283347ebb","article-title":"Gut microbiota as a regulator of energy homeostasis and ectopic fat deposition: Mechanisms and implications for metabolic disorders","volume":"21","author":"Musso","year":"2010","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11955","DOI":"10.1038\/s41598-017-12109-9","article-title":"Effect of caloric restriction on gut permeability, inflammation markers, and fecal microbiota in obese women","volume":"7","author":"Ott","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.biochi.2017.05.019","article-title":"Impact of high-fat diet on the intestinal microbiota and small intestinal physiology before and after the onset of obesity","volume":"141","author":"Tomas","year":"2017","journal-title":"Biochimie"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8905","DOI":"10.3748\/wjg.v22.i40.8905","article-title":"Effects of a high fat diet on intestinal microbiota and gastrointestinal diseases","volume":"22","author":"Zhang","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"533","DOI":"10.2147\/DMSO.S146339","article-title":"Obesity and non-alcoholic fatty liver disease: Current perspectives","volume":"11","author":"Sarwar","year":"2018","journal-title":"Diabet. Metab. Syndr. Obes."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1590\/S0102-86502011000800006","article-title":"A high-fat diet as a model of fatty liver disease in rats","volume":"26","author":"Picchi","year":"2011","journal-title":"Acta Cir. Bras."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"703","DOI":"10.4103\/1119-3077.163288","article-title":"Non-alcoholic fatty liver disease: Synopsis of current developments","volume":"18","author":"Onyekwere","year":"2015","journal-title":"Niger. J. Clin. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Poeta, M., Pierri, L., and Vajro, P. (2017). Gut-Liver axis derangement in non-alcoholic fatty liver disease. Children, 4.","DOI":"10.3390\/children4080066"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2165\/00002018-200831010-00005","article-title":"Orlistat-associated adverse effects and drug interactions: A critical review","volume":"31","author":"Filippatos","year":"2008","journal-title":"Drug Saf."},{"key":"ref_11","first-page":"2050","article-title":"Medicinal plants for the treatment of obesity: Ethnopharmacological approach and chemical and biological studies","volume":"9","year":"2017","journal-title":"Am. J. Transl. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lauricella, M., Emanuele, S., Calvaruso, G., Giuliano, M., and D\u2019Anneo, A. (2017). Multifaceted health benefits of Mangifera indica L. (Mango): The inestimable value of orchards recently planted in sicilian rural areas. Nutrients, 9.","DOI":"10.20944\/preprints201704.0161.v1"},{"key":"ref_13","first-page":"4974","article-title":"Ethanolic extract of Mangiferaindica seed kernel ameliorates visceral fat via improvement in lipid metabolism in high fat diet inducedobese mice","volume":"5","author":"Kankanampati","year":"2012","journal-title":"J. Pharm. Res."},{"key":"ref_14","first-page":"38","article-title":"Triphalaand its constituents ameliorate visceral adiposity in high fat diet \u2013induced obese mice","volume":"18","author":"Gurjar","year":"2012","journal-title":"Altern. Ther. Health Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"503139","DOI":"10.1155\/2015\/503139","article-title":"Development of HPLC protocol and simultaneous quantification of four free flavonoids from dracocephalum heterophyllum benth","volume":"2015","author":"Numonov","year":"2015","journal-title":"Int. J. Anal. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Segnani, C., Ippolito, C., Antonioli, L., Pellegrini, C., Blandizzi, C., Dolfi, A., and Bernardini, N. (2015). Histochemical detection of collagen fibers by sirius red\/fast green is more sensitive than van gieson or sirius red alone in normal and inflamed rat colon. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0144630"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1590\/S0102-86502004000700005","article-title":"Experimental model for collagen estimation in cell culture","volume":"19","author":"Keira","year":"2004","journal-title":"Acta Cir. Bras."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Woting, A., and Blaut, M. (2018). Small intestinal permeability and gut-transit time determined with low and high molecular weight fluorescein isothiocyanate-dextrans in C3H mice. Nutrients, 10.","DOI":"10.3390\/nu10060685"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.etp.2014.07.004","article-title":"Immunohistological characterization of intercellular junction proteins in rhesus macaque intestine","volume":"66","author":"Gumber","year":"2014","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18390","DOI":"10.3748\/wjg.v20.i48.18390","article-title":"Increased expression of tumor necrosis factor-\u03b1 is associated with advanced colorectal cancer stages","volume":"20","author":"Alkhayal","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"145","DOI":"10.2174\/1573408016666200414153108","article-title":"Screening of antioxidant and \u03b1-glucosidase inhibitory activities of Indian medicinal plants","volume":"16","author":"Mujawdiya","year":"2020","journal-title":"Curr. Enzym. Inhib."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.jhep.2010.04.031","article-title":"Hepatocellular ballooning in NASH","volume":"53","author":"Caldwell","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1097\/MCO.0b013e3283478727","article-title":"Role of intestinal inflammation as an early event in obesity and insulin resistance","volume":"14","author":"Ding","year":"2011","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bischoff, S.C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J.D., Serino, M., Tilg, H., Watson, A., and Wells, J.M. (2014). Intestinal permeability\u2013A new target for disease prevention and therapy. BMC Gastroenterol., 14.","DOI":"10.1186\/s12876-014-0189-7"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.2337\/db06-1491","article-title":"Metabolic endotoxemia initiates obesity and insulin resistance","volume":"56","author":"Cani","year":"2007","journal-title":"Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3945\/ajcn.116.148338","article-title":"Gut permeability, obesity, and metabolic disorders: Who is the chicken and who is the egg?","volume":"105","author":"Alessio","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1002\/path.5134","article-title":"Increased jejunal permeability in human obesity is revealed by a lipid challenge and is linked to inflammation and type 2 diabetes","volume":"246","author":"Genser","year":"2018","journal-title":"J. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"G518","DOI":"10.1152\/ajpgi.00024.2006","article-title":"Increased intestinal permeability in obese mice: New evidence in the pathogenesis of nonalcoholic steatohepatitis","volume":"292","author":"Paola","year":"2007","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sambolin-Escobales, L., Nazario, M., Torres-Aguiar, R., Cruz, M.L., Yamamura, Y., Appleyard, C.B., and Chompre, G. (2016). High fat diet induces decreased levels of colonic tight junctions and inflammatory cytokine expression in sprague dawley rats. FASEB J., 30.","DOI":"10.1096\/fasebj.30.1_supplement.lb698"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Sung, Y.Y., Kim, S.H., Yoo, B.W., and Kim, H.K. (2015). The nutritional composition and anti-obesity effects of an herbal mixed extract containing Allium fistulosum and Viola mandshurica in high-fat-diet-induced obese mice. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0875-1"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ohashi, T., Nakade, Y., Ibusuki, M., Kitano, R., Yamauchi, T., Kimoto, S., Inoue, T., Kobayashi, Y., Sumida, Y., and Ito, K. (2019). Conophylline inhibits high fat diet-induced non-alcoholic fatty liver disease in mice. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0210068"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3313","DOI":"10.1007\/s00018-018-2860-6","article-title":"Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease","volume":"75","author":"Ipsen","year":"2018","journal-title":"Cell Mol. Life Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1586\/egh.11.8","article-title":"Hepatocellular ballooning in nonalcoholic steatohepatitis: The pathologist\u2019s perspective","volume":"5","author":"Lackner","year":"2011","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s40635-018-0203-4","article-title":"Tight junction structure, function, and assessment in the critically ill: A systematic review","volume":"6","author":"Vermette","year":"2018","journal-title":"Intensive Care Med. Exp."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s10695-019-00701-x","article-title":"Inhibition of intestinal lipases alleviates the adverse effects caused by high-fat diet in Nile tilapia","volume":"46","author":"Zhang","year":"2020","journal-title":"Fish Physiol. Biochem."},{"key":"ref_36","first-page":"4","article-title":"Nesfatin-1 and its effects on different systems","volume":"19","author":"Ayada","year":"2015","journal-title":"Hippokratia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1159\/000496731","article-title":"Nucleobindin-2\/nesfatin-1 in the human hypothalamus is reduced in obese subjects and colocalizes with oxytocin, vasopressin, melanin-concentrating hormone, and cocaine- and amphetamine-regulated transcript","volume":"108","author":"Psilopanagioti","year":"2019","journal-title":"Neuroendocrinology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"331","DOI":"10.12717\/DR.2018.22.4.331","article-title":"Tissue-specific localization NUCB2\/nesfatin-1 in the liver and heart of mouse fetus","volume":"22","author":"Sun","year":"2018","journal-title":"Dev. Reprod."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3892\/etm.2011.199","article-title":"Effect of exercise and high-fat diet on plasma adiponectin and nesfatin levels in mice","volume":"2","author":"Chaolu","year":"2011","journal-title":"Exp. Ther. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.3748\/wjg.v16.i14.1735","article-title":"Expression of nesfatin-1\/NUCB2 in rodent digestive system","volume":"16","author":"Zhang","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_41","unstructured":"Cerit, K.K., Turkan, K., Damla, Y., Eyuboglu, I.P., Sirvanci, S., Akkiprik, M., Iksu, B., Dagli, E.T., and Yegan, B.C. (2020). Nesfatin-1 ameliorates oxidative bowel injury in rats with necrotizing enterocolitis: The role of the microbiota composition and claudin-3 expression. J. Pediatric Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/S1734-1140(13)71044-2","article-title":"Long-term inhibition of intestinal lipase by orlistat improves release of gut hormones increasing satiety in obese women","volume":"65","author":"Janowska","year":"2013","journal-title":"Pharmacol. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6897","DOI":"10.3748\/wjg.v20.i22.6897","article-title":"Expression of gastrointestinal nesfatin-1 and gastric emptying in ventromedial hypothalamic nucleus and ventrolateral hypothalamic nucleus-lesioned rats","volume":"20","author":"Tian","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_44","first-page":"765","article-title":"Anti-inflammatory effects of nesfatin-1 on acetic acid-induced gastric ulcer in rats: Involvement of cyclo-oxygenase pathway","volume":"68","author":"Kolgazi","year":"2017","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"G367","DOI":"10.1152\/ajpgi.00173.2003","article-title":"TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation","volume":"286","author":"Ma","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.1016\/j.ajpath.2013.09.001","article-title":"TNF-\u03b1 modulation of intestinal epithelial tight junction barrier is regulated by ERK1\/2 activation of Elk-1","volume":"183","author":"Guo","year":"2013","journal-title":"Am. J. Pathol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/8\/190\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:59:02Z","timestamp":1760176742000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/13\/8\/190"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,11]]},"references-count":46,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,8]]}},"alternative-id":["ph13080190"],"URL":"https:\/\/doi.org\/10.3390\/ph13080190","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,11]]}}}