溃疡性结肠炎(UC)是一种临床上普遍存在的持久和复杂的炎症性肠病,进步,和衰弱。截至目前,少数有效的UC药物治疗具有令人无法接受的高副作用.找到更安全,更有效的UC治疗方法至关重要。Nodakenin通过抑制几种促炎介质而具有抗炎和抗氧化活性。在本研究中,我们旨在评估nodakenin通过NF-κB介导的NLRP3炎性体途径对抗结肠炎的结肠保护作用.在老鼠身上,UC由2,4,6-三硝基苯磺酸(TNBS)诱导。Nodakenin(10、20和40mg/kg)被引入胃内,计算疾病活动指数(DAI)评分。丙二醛(MDA),髓过氧化物酶(MPO),超氧化物歧化酶(SOD),一氧化氮(NO)水平,肿瘤坏死因子-α(TNF-α),在结肠匀浆中评估白细胞介素-6(IL-6)浓度。结肠样本用于组织病理学研究和涉及核因子κB(NF-κB)的mRNA表达研究,环氧合酶-2(COX-2),诱导型一氧化氮(iNOS),核苷酸结合受体结构域3(NLRP3),白细胞介素-1β(IL-1β),和白细胞介素-18(IL-18)。发现Nodakenin治疗可有效降低DAI评分,组织学评分,MPO,MDA,与模型对照组相比,在升高SOD水平的同时,展示其抗炎和抗氧化性能。Nodakenin(40mg/kg)显着下调TNF-α的表达,IL-6,NF-κB(1.24倍),iNOS(1.2倍),COX-2(1.98倍),NLRP3(1.78倍),IL-1β(1.29倍),和IL-18(1.17倍)赋予其对抗结肠炎的巨大抗炎潜力。一起,nodakenin可能通过NF-B介导的NLRP3炎性体途径缓解TNBS诱导的结肠炎,并通过下调各种转录基因和促炎介质减少结肠损伤。
Ulcerative colitis (UC) is an enduring and complex inflammatory bowel disease that is clinically prevalent, progressive, and debilitating. As of now, the few effective medical treatments for UC have unacceptably high side effects. It is crucial to find safer and more effective UC treatments. Nodakenin possesses anti-inflammatory and antioxidant activity by suppressing several pro-inflammatory mediators. In the present study, we aimed to evaluate the colonoprotective effect of nodakenin in combating colitis through the NFƙB-mediated NLRP3 inflammasome pathway. In mice, UC was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Nodakenin (10, 20, and 40 mg/kg) was introduced intragastrically, and disease activity index (DAI) score was calculated. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), nitric oxide (NO) levels, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) concentration were evaluated in colon homogenate. Colon samples were used for histopathological investigation and mRNA expression studies involving nuclear factor kappa B (NFƙB), cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), nucleotide-binding receptor domain 3 (NLRP3), interleukin-1β (IL-1β), and interleukin-18 (IL-18). Nodakenin treatment was found effective in lowering the DAI score, histological score, MPO, MDA, and NO levels while elevating SOD levels as compared to the model control group, showcasing its anti-inflammatory and antioxidant properties. Nodakenin (40 mg/kg) significantly downregulated the expression of TNF-α, IL-6, NFƙB (1.24-fold), iNOS (1.2-fold), COX-2 (1.98-fold), NLRP3 (1.78-fold), IL-1β (1.29-fold), and IL-18 (1.17-fold) conferring its great anti-inflammatory potential in combating colitis. Taking together, nodakenin presumably alleviated TNBS-induced colitis by NFƙB-mediated NLRP3 inflammasome pathway and reduced colon damage by downregulating various transcriptional genes and pro-inflammatory mediators.