Inflammatory responses bridge comorbid cardiac disorder in experimental model of IBD induced by DSS: protective effect of the trigonelline
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Pathogenesis of the inflammatory bowel disease (IBD) involves the combination of immunological and inflammatory factors. IBD is associated with several extra-intestinal manifestations. The exact underlying bridge between the probable cardiac diseases in IBD patients is undetermined. Trigonelline is an alkaloid with several therapeutic potential properties. In this study, we aimed to assess the probable underlying mechanisms of this comorbidity as well as protective effect of trigonelline focusing inflammatory response and oxidative state in mouse model of colitis. Dextran sodium sulfate (DSS) was used for induction of colitis in mice. Trigonelline (10, 50 and 100 mg/kg) was administrated via intraperitoneal rout (i.p.) for 14 continuous days. Heart, intestine and serum samples were taken for assessment of total antioxidant capacity, malondialdehyde (MDA), gene expressions of inflammatory markers including tumor necrosis factor alpha (Tnf-α), interleukin 1-beta (Il/1β), toll- like receptor 4 (Tlr4) as well as for evaluation of histopathological alterations. Results demonstrated that trigonelline effectively attenuated the cellular/molecular and histopathological adverse effects of colitis in the intestine and heart tissues. In this regards, we found that trigonelline decreased the MDA level, attenuated the expression of Tnf-α, Il/1β and, Tlr4 as well as modulated the histopathological alterations in the intestine. Furthermore, trigonelline increased the antioxidant capacity in the related experimental groups. We concluded that IBD (colitis) is associated with comorbid cellular/molecular modifications in the heart and for the first time, we found that trigonelline has potential therapeutic effects (at least partially) to attenuate the cardiac manifestations of the colitis.
KeywordsInflammatory bowel disease Cardiac complications Comorbidity Trigonelline Mice
This work was supported by a grant from Shahrekord University of Medical Sciences (SKUMS) with grant number of “2363”. The authors would like to thank Dr. Mahmoud Rafieian kopaei, Dr. Gholam Reza Mobini, Dr. Elham Saghaei and Mrs. Elham Bijad for their collaboration on this study.
- Amini-Khoei H, Haghani-Samani E, Beigi M, Soltani A, Mobini GR, Balali-Dehkordi S, Haj-Mirzaian A, Rafieian-Kopaei M, Alizadeh A, Hojjati MR (2019) On the role of corticosterone in behavioral disorders, microbiota composition alteration and neuroimmune response in adult male mice subjected to maternal separation stress. Int Immunopharmacol 66:242–250CrossRefGoogle Scholar
- Arlt A, Sebens S, Krebs S, Geismann C, Grossmann M, Kruse M, Schreiber S, Schäfer H (2013) Inhibition of the Nrf2 transcription factor by the alkaloid trigonelline renders pancreatic cancer cells more susceptible to apoptosis through decreased proteasomal gene expression and proteasome activity. Oncogene 32:4825CrossRefGoogle Scholar
- Dutta M, Ghosh AK, Mohan V, Mishra P, Rangari V, Chattopadhyay A, Das T, Bhowmick D, Bandyopadhyay D (2014) Antioxidant mechanism (s) of protective effects of Fenugreek 4-hydroxyisoleucine and trigonelline enriched fraction [TF4H (28%)] Sugaheal® against copper-ascorbate induced injury to goat cardiac mitochondria in vitro. J Pharm Res 8:798–811Google Scholar
- Haj-Mirzaian A, Amiri S, Amini-Khoei H, Hosseini M-J, Haj-Mirzaian A, Momeny M, Rahimi-Balaei M, Dehpour AR (2017) Anxiety-and depressive-like behaviors are associated with altered hippocampal energy and inflammatory status in a mouse model of Crohn’s disease. Neuroscience 366:124–137CrossRefGoogle Scholar
- Kristensen SL, Ahlehoff O, Lindhardsen J, Erichsen R, Lamberts M, Khalid U, Nielsen OH, Torp-Pedersen C, Gislason GH, Hansen PR (2014) Inflammatory bowel disease is associated with an increased risk of hospitalization for heart failure: a Danish Nationwide Cohort Study. Circ Heart Fail 7:717–722CrossRefGoogle Scholar
- Luque-Sierra A, Alvarez-Amor L, Kleemann R, Martín F, Varela LM (2018) Extra-virgin olive oil with natural phenolic content exerts an anti-inflammatory effect in adipose tissue and attenuates the severity of atherosclerotic lesions in ldlr–/–.Leiden Mice. Mol Nutr Food Res 62:1800295CrossRefGoogle Scholar
- Popivanova BK, Kitamura K, Wu Y, Kondo T, Kagaya T, Kaneko S, Oshima M, Fujii C, Mukaida N (2008) Blocking TNF-α in mice reduces colorectal carcinogenesis associated with chronic colitis. J Clin Investig 118:560–570Google Scholar
- Wong S, Knight J, Hopfer S, Zaharia O, Leach CN, Sunderman F (1987) Lipoperoxides in plasma as measured by liquid-chromatographic separation of malondialdehyde-thiobarbituric acid adduct. Clin Chem 33:214–220Google Scholar