Dharmapuri Gangappa, Kotha Anil Kumar, Kalangi Suresh K, Reddanna Pallu
Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
Department of Microbiology, Faculty of Allied Health Sciences, SGT University, Gurugram 122505,India.
ACS Pharmacol Transl Sci. 2024 Apr 29;7(5):1270-1277. doi: 10.1021/acsptsci.3c00323. eCollection 2024 May 10.
Inflammatory bowel diseases (IBD), an inflammatory disease, include Crohn's disease and ulcerative colitis. Dysregulated autoimmune response to gut dysbiosis is mainly involved in the pathogenesis of IBD and is triggered by various inciting environmental factors. With its rising prevalence in every continent, IBD has evolved into a global disease, which is on the rise, affecting people of all ages. There is a growing incidence of IBD in the elderly population, as evidenced by epidemiological data. IBD is characterized by an inflammatory process that requires a lifelong treatment. The main challenge in IBD management is the adverse side effects associated with almost all of the currently available drugs. Hence, there is a search for drugs with more efficacy and fewer side effects. Natural products with great structural diversity and ease of modification chemically are being explored, as they were shown to control IBD by safely suppressing pro-inflammatory pathways. The present study aims at understanding the role of mangiferin, a COX-2 inhibitor isolated from tubers of in the treatment of IBD and colon cancer, on the Caco-2 human colon cancer cell line and in the acetic acid-induced IBD mouse model. In the acetic acid-induced colitis model, it prevented the decrease in length of the colon, mucosal erosion, and cellular infiltration in a dose-dependent manner. The expression levels of various pro-inflammatory markers like COX-2, IL1β, TNF-α, INF-γ, IL-6, NLRP3, and caspase-1 were downregulated in an acetic acid-induced mouse model on treatment with mangiferin in a dose dependent manner. Mangiferin also showed anticancer effects on Caco-2 cells by increasing the expression of Fas ligand, Fas receptor, FADD, caspase-8, and caspase-3 proteins, whereas Bid and Bcl-2 proteins showed decreased expression. These data suggest that mangiferin, an inhibitor of COX, induces apoptosis in colon cancer cells and protects mice from acetic acid-induced colitis .
炎症性肠病（IBD）是一种炎症性疾病，包括克罗恩病和溃疡性结肠炎。对肠道微生物群失调的自身免疫反应失调主要参与IBD的发病机制，并由各种诱发环境因素触发。随着其在各大洲的患病率不断上升，IBD已演变成一种全球性疾病，且呈上升趋势，影响着各个年龄段的人群。流行病学数据表明，老年人群中IBD的发病率在不断增加。IBD的特征是炎症过程，需要终身治疗。IBD管理中的主要挑战是几乎所有现有药物都存在的不良副作用。因此，人们正在寻找疗效更高、副作用更少的药物。具有高度结构多样性且易于化学修饰的天然产物正在被探索，因为它们已被证明可通过安全抑制促炎途径来控制IBD。本研究旨在了解从[具体植物名称]块茎中分离出的COX-2抑制剂芒果苷在治疗IBD和结肠癌中对Caco-2人结肠癌细胞系以及在乙酸诱导的IBD小鼠模型中的作用。在乙酸诱导的结肠炎模型中，它以剂量依赖的方式预防了结肠长度的减少、黏膜糜烂和细胞浸润。在用芒果苷治疗的乙酸诱导小鼠模型中，各种促炎标志物如COX-2、IL1β、TNF-α、INF-γ、IL-6、NLRP3和caspase-1的表达水平以剂量依赖的方式下调。芒果苷还通过增加Fas配体、Fas受体、FADD、caspase-8和caspase-3蛋白的表达对Caco-2细胞显示出抗癌作用，而Bid和Bcl-2蛋白的表达则降低。这些数据表明，COX抑制剂芒果苷可诱导结肠癌细胞凋亡，并保护小鼠免受乙酸诱导的结肠炎。
