en تخصصي Special پژوهشي Research <strong>Objective:</strong> High-fat diet (HFD) rises the susceptibility of both obesity and consequently Inflammatory Bowel Disease (IBD). We designed a study to investigate the improving effects of herbal extract (HE, the combination of turmeric, ginger, boswellia<em>,</em> and cat&rsquo;s claw extract) on the risk of high AGEs-fat diet 60% (HFD) mice induced colitis and obesity.<br> <strong>Materials and Methods</strong><strong>:</strong> Four-week-old C57BL/6 male mice after 2 weeks adaptation with normal diet were fed with either HFD or normal diets. After 6 weeks of being on diet, animals received HE for 16 weeks. Obesity index markers were determined as well as histological studies using H&E (Hematoxylin-eosin) staining. Colonic expression of<em> IL-1&beta; </em>was determined. Data analysis was performed by utilizing Kruskal-Wallis and Mann-Whitney test for post-hoc comparisons, and SPSS (version 17.0) and GraphPad Prism Software (Version 8.0, USA).<br> <strong>Results:</strong> HE decreased histological scores (by 6-fold) in HFD diet-fed mice, and reduced myeloperoxidase activity (by 2.2-fold), and ratio of colon weight to length (by 4-fold) in HFD diet-fed mice. Moreover, HE prevented intestinal permeability through the restoration of ZO-1 (by 4-fold) and immune homeostasis by modulation of <em>IL-1&beta;</em> (by 2.4-fold) expression.<br> <strong>Conclusion</strong><strong>:</strong> HFD induced obesity-associated colitis. HE decreased the colitis symptoms in HFD diet-fed mice, with the reduction of inflammation.<strong><em><span dir="RTL"></span></em></strong> Colitis, High-fat diet, Herbal extract, Inflammation 37 43 http://ijdo.ssu.ac.ir/browse.php?a_code=A-10-30-337&slc_lang=en&sid=1 Fatemeh Azizian-Farsani 0000-0002-6943-9199 No Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Navid Abedpoor 0000-0003-1676-6951 No Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Maryam Derakhshan 0000-0003-0517-2111 No Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran. Mohammad Hossein Nasr-Esfahani 0000-0003-1983-3435 No Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran. Mohammad Hasan Sheikhha 0000-0002-3734-8970 Yes Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.Biotechnology Research center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Kamran Ghaedi 0000-0002-9790-5644 No Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.