Abstract
Abstract
Background
Obesity is associated with many comorbidities including inflammatory bowel disease (IBD). We investigated prophylactic effects of an herbal extract (HE) on the DSS-induced colitis mice challenged with high AGEs-fat diet 60% (HFD).
Methods
Six-week-old C57BL/6 male mice were fed with either HFD (8 groups, 6 mice in each group), or normal diet (ND) (8 groups, 6 mice in each group). After 6 weeks, animals received HE (combination of turmeric, ginger, boswellia and cat’s claw extract) for 7 weeks in three doses (high dose (0.6 mg/g); low dose (0.15 mg/g) and mid dose (0.3 mg/g)). Next, mice were subjected to 2.5% DSS in drinking water. Control mice received ND and instead of HE and DSS they received distilled water. Obesity index markers were determined, H&E staining and TUNEL assay evaluated apoptosis. Colonic expressions of IL-6, RAGE, AGER1, Sirt1, Bax, Bcl2, ZO-1 and P53 were determined.
Results
HE ameliorated colitis in HFD mice by reducing colonic myeloperoxidase activity (by 2.3-fold), macrophage accumulation (by 2.6-fold) and mRNA expression of IL-6 (by 2.3-fold) in HFD mice. Moreover, HE restored ZO-1 (by 2.7-fold), prevented apoptosis and maintained immune homeostasis. HE reduced activation of NF-κB protein (by 1.3-fold) through decreasing RAGE (by 1.93-fold) and up-regulation of Sirt1 (by 7.71-fold) and prevented down-regulation of DDOST (by 6.6-fold) in HFD mice.
Conclusions
HE ameliorated colitis in prophylactic in HFD mice and it was, at least partly, due to the restoration of the gut integrity, suppression of inflammation and apoptosis via modulation of colonic Sirt1, RAGE and DDOST signaling.
Graphic abstract
Publisher
Springer Science and Business Media LLC
Subject
Nutrition and Dietetics,Endocrinology, Diabetes and Metabolism,Medicine (miscellaneous)
Reference53 articles.
1. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity among adults and youth: United States, 2015–2016. 2017.
2. Organization WH. (2020, April 1). A report about Obesity and overweight.
3. Ding S, Chi MM, Scull BP, Rigby R, Schwerbrock NM, Magness S, et al. High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. J PloS ONE. 2010;5(8).
4. Zen K, Chen CX-J, Chen Y-T, Wilton R, Liu YJ. Receptor for advanced glycation endproducts mediates neutrophil migration across intestinal epithelium. J Immunol. 2007;178(4):2483–90.
5. Kato S, Itoh K, Ochiai M, Iwai A, Park Y, Hata S, et al. Increased pentosidine, an advanced glycation end-product, in urine and tissue reflects disease activity in inflammatory bowel diseases. J Gastroenterol Hepatol. 2008;23:S140–5.