{"title":"Coleus vettiveroides Root Extract Protects Against Thioacetamide‐Induced Chronic Liver Injury by Inhibiting NF‐κB Signaling Pathway","authors":"Kadmad Abdul Hameed Mohamed Azar, Devaraj Ezhilarasan, Munusamy Karthick, Karthik Shree Harini, Venkatesan Kumar","doi":"10.1002/tox.24465","DOIUrl":null,"url":null,"abstract":"The roots of <jats:italic>Coleus vettiveroides</jats:italic> (CV) have been traditionally used in Indian medicinal systems such as Ayurveda and Siddha for its antioxidant, anti‐inflammatory, and antidiabetic effects. This study examines the antifibrotic potential of CV ethanolic root extract (CVERE) against thioacetamide (TAA)‐induced liver fibrosis in Wistar rats. TAA was administered via i.p., thrice weekly for 11 weeks to induce liver fibrosis in rats. In separate groups, rats were administered with TAA and were concurrently treated with CVERE 125 mg/kg, CVERE 250 mg/kg, and silymarin (SIL) 100 mg/kg. Liver marker enzymes of hepatotoxicity, oxidative stress markers, proinflammatory marker gene expression (TNF‐α, NF‐κB, COX, and ILs), fibrotic marker gene expression (collagen I and III), immune histochemical expression of fibrosis marker proteins, and histopathologic changes were analyzed. TAA administration led to a significant (<jats:italic>p</jats:italic> < 0.001) increase in the serum level of hepatotoxic marker enzymes. The TAA‐treated group showed higher levels (<jats:italic>p</jats:italic> < 0.001) of MDA and reduced activities of SOD and CAT in the liver. TAA administration increased CYP2E1 expression, proinflammatory, and fibrotic marker gene expressions in rat liver. The histopathology of the liver confirms TAA‐induced architectural distortion and fibrotic changes. CVERE and SIL simultaneous treatments significantly protected against TAA‐induced oxidative stress, inflammation, and liver fibrosis. In conclusion, CVERE inhibited TAA‐induced liver fibrosis through downregulation of TAA metabolic activation, redox imbalance, and inflammation through repression of the NF‐κB pathway.","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"24 1","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environmental Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/tox.24465","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
The roots of Coleus vettiveroides (CV) have been traditionally used in Indian medicinal systems such as Ayurveda and Siddha for its antioxidant, anti‐inflammatory, and antidiabetic effects. This study examines the antifibrotic potential of CV ethanolic root extract (CVERE) against thioacetamide (TAA)‐induced liver fibrosis in Wistar rats. TAA was administered via i.p., thrice weekly for 11 weeks to induce liver fibrosis in rats. In separate groups, rats were administered with TAA and were concurrently treated with CVERE 125 mg/kg, CVERE 250 mg/kg, and silymarin (SIL) 100 mg/kg. Liver marker enzymes of hepatotoxicity, oxidative stress markers, proinflammatory marker gene expression (TNF‐α, NF‐κB, COX, and ILs), fibrotic marker gene expression (collagen I and III), immune histochemical expression of fibrosis marker proteins, and histopathologic changes were analyzed. TAA administration led to a significant (p < 0.001) increase in the serum level of hepatotoxic marker enzymes. The TAA‐treated group showed higher levels (p < 0.001) of MDA and reduced activities of SOD and CAT in the liver. TAA administration increased CYP2E1 expression, proinflammatory, and fibrotic marker gene expressions in rat liver. The histopathology of the liver confirms TAA‐induced architectural distortion and fibrotic changes. CVERE and SIL simultaneous treatments significantly protected against TAA‐induced oxidative stress, inflammation, and liver fibrosis. In conclusion, CVERE inhibited TAA‐induced liver fibrosis through downregulation of TAA metabolic activation, redox imbalance, and inflammation through repression of the NF‐κB pathway.
期刊介绍:
The journal publishes in the areas of toxicity and toxicology of environmental pollutants in air, dust, sediment, soil and water, and natural toxins in the environment.Of particular interest are:
Toxic or biologically disruptive impacts of anthropogenic chemicals such as pharmaceuticals, industrial organics, agricultural chemicals, and by-products such as chlorinated compounds from water disinfection and waste incineration;
Natural toxins and their impacts;
Biotransformation and metabolism of toxigenic compounds, food chains for toxin accumulation or biodegradation;
Assays of toxicity, endocrine disruption, mutagenicity, carcinogenicity, ecosystem impact and health hazard;
Environmental and public health risk assessment, environmental guidelines, environmental policy for toxicants.