Contents lists available at ScienceDirect Complementary Therapies in Medicine journal homepage: www.elsevier.com/locate/ctim Sugarcane molasses enhances TGF-β secretion and FOXP3 gene expression by Bifidobacterium Animalis Subsp. Lactis stimulated PBMCs of Ulcerative Colitis patients Abdolhussein Shakurnia a,1 , Abdolkarim Sheikhi b, * ,1 , Majeed Mirzapour c , Vahid Baharifar a , Narges Baharifar b , Nima Aghamohammadi d , Mehdi Sheikhi e , Mehdi Matinrad c , S. Nouraddin Mousavinasab f , Sepideh Sheikhi g , Razieh Sheikhi h a Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran b Department of Immunology, Faculty of Medicine, Dezful University of Medical Sciences, Dezful, Iran c Caruncane co., Dezful, Iran d Department of Internal Medicine, Faculty of Medicine, Dezful University of Medical Sciences, Dezful, Iran e Faculty of Medicine, Kazeroon Azad University, Kazeroon, Iran f Department of Social Medicine, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran g Faculty of Nursing and Midwifery, Islamic Azad University of Dezful, Dezful, Iran h Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran ARTICLE INFO Keywords: Sugarcane molasses Ulcerative colitis B. lactis Immunomodulation TGF-β TNF-α ABSTRACT Ulcerative colitis (UC) is one of the inflammatory diseases of the gut with frequent bloody diarrhea leads to increased rates of anemia. Evidences indicate the immunomodulation disorders in the response to intestinal microbiota in UC. Although sugarcane molasses, rich in necessary minerals and vitamins, could be a good support nutrient but its effect on immune system of UC patients is unknown. To determine how the immune system of UC patients responds to molasses this study was planned. Bifidobacterium lactis were cultivated on MRS broth. PBMCs of 12 UC patients were separated by Ficoll- Hypaque centrifugation and co-cultured with different concentrations of UV killed bacteria and/or molasses in RPMI-1640 plus 10 % FCS. The gene expression of FoxP3 was measured by real-time PCR. TGF-β and TNF-α were measured in supernatant of PBMCs by ELISA. Sugarcane molasses and B. lactis significantly augmented TGF-β compared to control (p < 0.01 and p < 0.001 respectively). The secretion levels of TGF-β by B. lactis plus molasses compared to B. lactis stimulated PBMCs was significantly higher (p < 0.05) but the level of TNF-α by PBMCs after 2/4/12 h incubation with B. lactis plus molasses compared to B. lactis alone was not changed (p > 0.2). The level of FOXP3 expression after treatment with molasses was increased significantly (p < 0.05). These data show that if sugarcane molasses added to B. lactis, not only do not increase the pro-inflammatory cytokine, TNF-α, but also augments the anti-inflammatory cytokine, TGF-β by PBMCs. Therefore, these results pave the way for further investigation to show sugarcane molasses as a safe support to compensate the lost nutrients in UC patients. 1. Introduction Ulcerative colitis (UC) a major form of inflammatory bowel disease (IBD), is a cause of significant morbidity worldwide and its incidence and prevalence appear to be increasing with time. Patients with UC frequently experience episodes of bloody diarrhea with or without mucous, abdominal pain, fever and weight loss. 1 UC is assumed to be result of a breakdown of tolerance to intestinal environmental antigens such as resident enteric bacteria and altered barrier properties of the mucous and epithelial layers. These alterations can allow luminal an- tigens to penetrate the intestinal mucosa and elicit an overproduction of pro-inflammatory cytokines and trafficking of effector leukocytes into https://doi.org/10.1016/j.ctim.2019.102210 Received 23 May 2019; Received in revised form 3 October 2019; Accepted 4 October 2019 ⁎ Corresponding author at: Department of Immunology and Microbiology, Faculty of Medicine, Dezful University of Medical Sciences, Dezful, 6461945914, Iran. E-mail addresses: sheikhi.a@dums.ac.ir, sheikhi@queensu.ca (A. Sheikhi). 1 The first and second author are of equal rights. Complementary Therapies in Medicine 47 (2019) 102210 Available online 23 October 2019 0965-2299/ © 2019 Elsevier Ltd. All rights reserved. T