Anti-Ulcerative Effect of Curcumin-Galactomannoside Complex on Acetic Acid-Induced Experimental Model by Inhibiting Inflammation and Oxidative Stress.
- 作者列表："Sheethal S","Ratheesh M","Jose SP","Asha S","Krishnakumar IM","Sandya S","Girishkumar B","Grace J
:Ulcerative colitis (UC) is a chronic inflammatory bowel disease that affects the mucosa and submucosa of colon. The pathogenesis of ulcerative colitis (UC) is related to reduced antioxidant capacity and increased inflammatory processes. Reactive oxygen metabolites are the potent inflammatory mediators that may be involved in tissue injury in inflammatory bowel disease. Conventional drug therapies for UC come with a myriad of side effects which further raise the need for natural bioactive agents. Curcumin has proven to be beneficial in the prevention and treatment of a number of inflammatory diseases, but due its poor bioavailability, the therapeutic applications are limited. Thus, to enhance its bioavailability, a new formulation - curcumin-galactomannoside (CGM)- was made by complexing curcumin with galactomannans derived from fenugreek. The present study aims to evaluate the effects of CGM on experimental UC model. Adult male Wistar rats were divided into 5 groups: normal control rats (NC); ulcerative colitis control rats (UC); UC + sulfasalazine (SS) treated; UC + curcumin (CM) treated; and UC + CGM supplemented for 21 days. The colonic mucosal injury was assessed by macroscopic and histological examination, along with evaluation of antioxidant status, inflammatory mediators, and gene expressions. Administration of CGM significantly enhanced antioxidant activities and decreased the level of inflammatory mediators and also suppressed the expression of inflammatory markers as compared with other groups. In conclusion, findings from these results reveal that CGM exerts marked curative effects on acute experimental colitis, possibly by regulating the antioxidant status and modulating inflammatory cascade.
: 溃疡性结肠炎 (Ulcerative colitis，UC) 是一种影响结肠粘膜和粘膜下层的慢性炎症性肠病。溃疡性结肠炎 (UC) 的发病机制与抗氧化能力降低和炎症过程增加有关。活性氧代谢产物是可能参与炎症性肠病组织损伤的强效炎症介质。UC 的常规药物治疗伴随着无数的副作用，这进一步提高了对天然生物活性药物的需求。姜黄素已被证明在许多炎症性疾病的预防和治疗中是有益的，但由于其生物利用度差，其治疗应用受到限制。因此，为了提高其生物利用度，通过将姜黄素与来源于胡芦巴的半乳甘露聚糖进行络合，制备了一种新的制剂-姜黄素-半乳甘露糖苷 (CGM)。本研究旨在评价 CGM 对实验性 UC 模型的影响。成年雄性 Wistar 大鼠分为 5 组: 正常对照大鼠 (NC); 溃疡性结肠炎对照大鼠 (UC); UC + 柳氮磺胺吡啶 (SS) 处理; UC + 姜黄素 (CM) 治疗; 和 UC + CGM 补充 21 天。通过肉眼和组织学检查评估结肠黏膜损伤，同时评估抗氧化状态、炎症介质和基因表达。与其他组相比，给予 CGM 可显著增强抗氧化活性，降低炎症介质水平，并抑制炎症标志物的表达。总之，这些结果揭示了 CGM 对急性实验性结肠炎的显著疗效，可能是通过调节抗氧化状态和调节炎症级联反应。
METHODS::Chronic diseases, including inflammatory bowel disease (IBD) urgently need new biomarkers as a significant proportion of patients, do not respond to current medications. Inflammation is a common factor in these diseases and microbial sensing in the intestinal tract is critical to initiate the inflammation. We have identified ELMO1 (Engulfment and Cell Motility Protein-1) as a microbial sensor in epithelial and phagocytic cells that turns on inflammatory signals. Using a stem-cell-based "gut-in-a-dish" coculture model, we studied the interactions between microbes, epithelium and monocytes in the context of IBD. To mimic the in-vivo cell physiology, enteroid-derived monolayers (EDMs) were generated from the organoids isolated from WT and ELMO1-/- mice and colonic biopsies of IBD patients. The EDMs were infected with the IBD-associated microbes to monitor the inflammatory responses. ELMO1-depleted EDMs displayed a significant reduction in bacterial internalization, a decrease in pro-inflammatory cytokine productions and monocyte recruitment. The expression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria of IBD patients where the higher expression is positively correlated with the elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. MCP-1 is released from the epithelium and recruits monocytes to the site of inflammation. Once recruited, monocytes require ELMO1 to engulf the bacteria and propagate a robust TNF-α storm. These findings highlight that the dysregulated epithelial ELMO1→MCP-1 axis can serve as an early biomarker in the diagnostics of IBD and other inflammatory disorders.
METHODS:BACKGROUND:Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS:We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS:Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS:Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.
METHODS::Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex pathogenesis, affecting people of all ages. They are characterized by alternating phases of clinical relapse and remission, depending on the fine balance between immune cells and the gut microbiota. The cross talk between cells of the immune system and the gut microbiota can result in either tolerance or inflammation, according to multifactorial triggers, ranging from environmental factors to genetic susceptibility. Glucocorticoid (GC) administration remains the first-line treatment for IBDs, although long-term use is limited by development of serious adverse effects. Recently, new alternative pharmacological therapies have been developed, although these are not always effective in IBD patients. There is a constant demand for effective new drug targets to guarantee total remission and improve the quality of life for IBD patients. The glucocorticoid-induced leucine zipper (GILZ) has been implicated as a promising candidate for this purpose, in view of its powerful anti-inflammatory effects that mimic those of GCs while avoiding their unwanted adverse reactions. Here we present and discuss the latest findings about the involvement of GILZ in IBDs.