Sravathi Vemula, Doppalapudi Madhuri, Yadala Ravi Kumar, Banothu Anilkumar, Anumolu Vijaya Kumar, Veera Hanuman Donga Durga, Debbarma Bhaskar
Department of Veterinary Pathology, P.V. Narsimha Roa Telangana Veterinary University, Hyderabad, Telangana, India.
Department of Pharmacology and Toxicology, P.V. Narsimha Roa Telangana Veterinary University, Hyderabad, Telangana, India.
Front Vet Sci. 2025 May 28;12:1558092. doi: 10.3389/fvets.2025.1558092. eCollection 2025.
Ulcerative colitis (UC), is a chronic inflammatory bowel disease characterized by recurrent episodes of inflammation and ulceration of the colonic mucosa. This study aimed to explore the therapeutic potential effects of visnagin (VIS), a natural furanochromone using a murine model, focusing on tight junction protein expression, oxidative stress, apoptosis and associated inflammation in a dextran sodium sulfate (DSS) induced UC model. A total of 36 male C57BL/6 mice were divided randomly into six groups ( = 6): Group 1 served as the control, group 2, treated with DSS (2% with three 5-day cycles diluted in distilled water administered orally). Group 3 (VIS) alone (60 mg/kg b. wt), orally for 31 days, Group 4-low dose of VIS (30 mg/kg b. wt for 31 days with DSS, group 5-high dose VIS (60 mg/kg b. wt) for 31 days with DSS and Group 6 Dexamethasone sodium @ 1 mg/kg b. wt-IP with DSS for 31 days. Disease progression and therapeutic outcomes were assessed by monitoring clinical symptoms, body weight changes, colon length, Disease activity index (DAI), oxidative stress indices, gross and histopathological analysis, inflammatory cytokine levels and immunohistochemical expression. Results demonstrated that VIS co-administration, particularly at high doses, significantly mitigated DSS-induced weight loss, colon shortening. This protective effect was further supported by a significant reduction in oxidative and nitrosative stress which was evident from decreased levels of nitrite and Malondialdehyde (MDA) in VIS treated groups 4 and 5. Further, VIS suppressed pro-inflammatory cytokines (TNF-, IL-1, IL-6, IFN-, NF-κB, IL-17, MPO and TGF-β) while increasing anti-inflammatory IL-10 levels in colon tissues. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed significantly reduced mRNA expression of TNF- and IL-17 along with increased occludin expression in groups 4, 5 and 6. VIS also improves intestinal barrier by increasing the expression of tight junction occludin, as confirmed through RT-PCR. Immunohistochemical analysis showed strong positive immunoreactivity for NF-κB, COX-2, NLRP3 and TNF- in DSS group, which wa notably reduced in VIS-treated groups. Additionally, VIS improved intestinalbarrier integrity by upregulating occluding expression. Histopathological analysis further confirmed that VIS attenuated DSS-induecdcolonic lesions. In conclusion, VIS exhibits potent anti-inflammatory and mucosal-protective properties, making it a promising therapeutic candidate for managing UC. Its ability to modulate inflammatory pathways and enhance intestinal barrier function suggests its potential as an alternative treatment for UC.
溃疡性结肠炎（UC）是一种慢性炎症性肠病，其特征为结肠黏膜反复出现炎症和溃疡。本研究旨在利用小鼠模型探索天然呋喃色酮维斯纳金（VIS）的治疗潜在效果，重点关注葡聚糖硫酸钠（DSS）诱导的UC模型中紧密连接蛋白表达、氧化应激、细胞凋亡及相关炎症。总共36只雄性C57BL/6小鼠被随机分为六组（每组n = 6）：第1组作为对照组，第2组用DSS处理（2%，分三个5天周期，用蒸馏水稀释后口服）。第3组单独给予VIS（60 mg/kg体重），口服31天，第4组低剂量VIS（30 mg/kg体重，与DSS一起给药31天），第5组高剂量VIS（60 mg/kg体重，与DSS一起给药31天），第6组地塞米松钠1 mg/kg体重腹腔注射，与DSS一起给药31天。通过监测临床症状、体重变化、结肠长度、疾病活动指数（DAI）、氧化应激指标、大体和组织病理学分析、炎症细胞因子水平及免疫组化表达来评估疾病进展和治疗结果。结果表明，VIS联合给药，尤其是高剂量时，显著减轻了DSS诱导的体重减轻和结肠缩短。VIS处理的第4组和第5组中亚硝酸盐和丙二醛（MDA）水平降低，氧化和亚硝化应激显著降低，进一步支持了这种保护作用。此外，VIS抑制了结肠组织中促炎细胞因子（TNF-α、IL-1β、IL-6、IFN-γ、NF-κB、IL-17、MPO和TGF-β），同时提高了抗炎性IL-10水平。逆转录聚合酶链反应（RT-PCR）分析显示，第4、5和6组中TNF-α和IL-17的mRNA表达显著降低，而闭合蛋白表达增加。如RT-PCR所证实，VIS还通过增加紧密连接蛋白闭合蛋白的表达改善了肠道屏障。免疫组化分析显示，DSS组中NF-κB、COX-2、NLRP3和TNF-α呈强阳性免疫反应，而在VIS处理组中显著降低。此外，VIS通过上调闭合蛋白表达改善了肠道屏障完整性。组织病理学分析进一步证实，VIS减轻了DSS诱导的结肠病变。总之，VIS具有强大的抗炎和黏膜保护特性，使其成为治疗UC的有前景的候选药物。其调节炎症途径和增强肠道屏障功能的能力表明其作为UC替代治疗方法的潜力。
