Anti-colitic effects of Oldenlandia umbellata L. through NF-κB pathway inhibition in a DSS-induced mouse model.

IF 4.6 2区 医学 Q2 IMMUNOLOGY
X Janet Bertilla, S Rupachandra
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引用次数: 0

Abstract

Background: Ulcerative colitis (UC) is an inflammatory bowel disease marked by epithelial barrier dysfunction and hyperactivation of immune signaling, particularly in the NF-κB pathway. Conventional therapies are limited by side effects and relapse risk, highlighting the need for safer, plant-based interventions. Oldenlandia umbellata L., a traditional herb, has demonstrated anti-inflammatory potential but remains underexplored in gastrointestinal disorders.

Objective: This study investigates the therapeutic efficacy of a methanolic extract of O.umbellata L. (MEOU) in a dextran sulfate sodium (DSS)-induced mouse model of colitis, focusing on its effects on clinical symptoms, histopathology, intestinal permeability, cytokine expression, and NF-κB signaling.

Methods: Acute colitis was induced in BALB/c mice with 5% DSS for 7 days, followed by oral treatment with MEOU (100, 200 or 400 mg/kg) and prednisolone (5 mg/kg) for another 7 days. Clinical parameters (body weight, Disease Activity Index (DAI), colon and spleen morphology, and histopathology were evaluated. Intestinal permeability was measured by FITC-dextran assay, while TNF-α, IL-6 mRNA levels, and NF-κB p65 protein levels were analyzed by RT-qPCR and Western blot, respectively.

Results: MEOU significantly attenuated weight loss, reduced DAI scores, and reversed colon shortening and splenomegaly in a dose-dependent manner. Histological analysis revealed preserved mucosal structure and reduced inflammatory infiltration. FITC-dextran assays confirmed improved barrier integrity. Molecular analyses showed that MEOU downregulated pro-inflammatory cytokines and suppressed NF-κB p65 activation.

Conclusion: MEOU exhibits potent anti-colitic activity through anti-inflammatory and barrier-protective mechanisms by NF-κB pathway inhibition, supporting its potential as a plant-based therapeutic for UC.

通过抑制NF-κB通路对dss诱导小鼠模型的抗结肠炎作用。
背景:溃疡性结肠炎(UC)是一种炎症性肠病,其特征是上皮屏障功能障碍和免疫信号过度激活,尤其是NF-κB通路。传统疗法受到副作用和复发风险的限制,因此需要更安全、基于植物的干预措施。大黄,一种传统的草药,已经证明了抗炎的潜力,但在胃肠道疾病方面仍未得到充分的开发。目的:探讨伞叶甲醇提取物(MEOU)对右旋糖酐硫酸钠(DSS)诱导的小鼠结肠炎模型的治疗作用,重点观察其对结肠炎小鼠临床症状、组织病理学、肠道通透性、细胞因子表达及NF-κB信号通路的影响。方法:以5% DSS诱导BALB/c小鼠急性结肠炎7 d后,分别给予MEOU(100、200、400 mg/kg)和强的松龙(5 mg/kg)口服7 d。评估临床参数(体重、疾病活动指数(DAI)、结肠和脾脏形态及组织病理学)。采用fitc -葡聚糖法检测大鼠肠通透性,RT-qPCR和Western blot分别检测大鼠TNF-α、IL-6 mRNA和NF-κB p65蛋白水平。结果:MEOU显著减轻体重减轻,降低DAI评分,并以剂量依赖性方式逆转结肠缩短和脾肿大。组织学分析显示粘膜结构保留,炎症浸润减少。fitc -葡聚糖检测证实屏障完整性得到改善。分子分析显示,MEOU下调促炎细胞因子,抑制NF-κB p65的激活。结论:MEOU通过抑制NF-κB通路的抗炎和屏障保护机制显示出强大的抗结肠炎活性,支持其作为UC的植物性治疗药物的潜力。
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来源期刊
Inflammopharmacology
Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY
CiteScore
8.00
自引率
3.40%
发文量
200
期刊介绍: Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]
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