Anti-inflammatory, anti-colitis, and antioxidant effects of columbianadin against DSS-induced ulcerative colitis in rats via alteration of HO-1/Nrf2 and TLR4-NF-κB signaling pathway.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2025-01-05 DOI:10.1007/s10787-024-01630-9

Yanping Zhang, Ping Cao, Dongyuan Qin, Ying Zhao, Xing Chen, Peng Ma

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引用次数: 0

Abstract

Background: Ulcerative colitis (UC) is a significant inflammatory bowel disease (IBD) that typically arises from chronic inflammation of the intestinal tract. Report suggest that anti-inflammatory drug plays a crucial role in the protection of UC. The recent study demonstrated that columbianadin has a protective effect against UC induced by dextran sulfate sodium (DSS) in rats through the modulation of HO-1/Nrf2 and TLR4-NF-κB signaling pathways.

Material and methods: In this study, Swiss Wistar rats were utilized, and UC was induced using 2% DSS. The treatment regimen included oral administration of columbianadin (5, 10 and 15 mg/kg) and sulfasalazine to the rats. The body weight, spleen index, disease activity index (DAI), colon length, food and water intake were estimated. Moreover, antioxidant, cytokines, inflammatory and apoptosis parameters were determined. mRNA expression levels were also quantitatively analyzed.

Results: Columbianadin treatment significantly (P < 0.001) boosted the body weight and suppressed the DAI. Columbianadin significantly (P < 0.001) enhanced the colon length and repressed the spleen index along with enhanced food and water intake. Columbianadin significantly (P < 0.001) suppressed the level of lactate dehydrogenase (LDH), myeloperoxidase (MPO) and altered the level of oxidative stress parameters such as catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), malonaldehyde (MDA), nitric oxide (NO), SA; cytokines level such as interleukin (IL)-1, 1β, 6, 10, 17, 18, TNF-α; inflammatory parameters viz., cyclooxygenase-2 (COX-2), prostaglandin (PGE₂), inducible nitric oxide synthetase (iNOS), nuclear factor kappa B (NF-κB), transforming growth factor (TGF-β); apoptosis parameters include Bax, Bcl-2, Bcl-2/Bax ratio, caspase-1 and A-caspase-3 activity, respectively. Columbianadin significantly altered the mRNA expression of IFN-γ, IL-6, IL-1β, IL-8, TNF-α, NF-κB, TLR4, Bcl-2, caspase-9, Bax, p38, ASC, MCP-1, ZO-1, and Ocln. While this study focused on COX-2 modulation as a marker of inflammatory response, no direct measurements or inferences were made regarding leukotriene activity, which involves a separate lipoxygenase pathway.

Conclusion: Columbianadin exhibited the protective effect against DSS-induced UC via alteration of HO-1/Nrf2 and TLR4-NF-κB signaling pathway.

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来源期刊

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 [...]