Coleus vettiveroides Root Extract Protects Against Thioacetamide‐Induced Chronic Liver Injury by Inhibiting NF‐κB Signaling Pathway

IF 4.4 3区 医学 Q2 ENVIRONMENTAL SCIENCES
Kadmad Abdul Hameed Mohamed Azar, Devaraj Ezhilarasan, Munusamy Karthick, Karthik Shree Harini, Venkatesan Kumar
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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.
鹅掌楸根提取物通过抑制 NF-κB 信号通路保护硫代乙酰胺诱导的慢性肝损伤
香草的根(CV)传统上被用于印度的医疗系统,如阿育吠陀和悉达,因为它具有抗氧化、抗炎和抗糖尿病的作用。本研究考察了CV乙醇根提取物(CVERE)对硫代乙酰胺(TAA)诱导的Wistar大鼠肝纤维化的抗纤维化潜力。TAA经腹腔注射,每周3次,连续11周诱导大鼠肝纤维化。各组大鼠给予TAA,同时给予CVERE 125 mg/kg、CVERE 250 mg/kg和水飞蓟素(SIL) 100 mg/kg。分析肝毒性标志物酶、氧化应激标志物、促炎标志物基因表达(TNF - α、NF - κB、COX和il)、纤维化标志物基因表达(胶原I和III)、纤维化标志物蛋白免疫组化表达和组织病理学变化。TAA管理导致了显著的(p <;0.001)血清肝毒性标记酶水平升高。TAA治疗组显示更高的水平(p <;肝脏中SOD和CAT活性降低。TAA增加了大鼠肝脏中CYP2E1表达、促炎和纤维化标记基因表达。肝脏组织病理学证实TAA诱导的结构扭曲和纤维化改变。CVERE和SIL同时治疗可显著防止TAA诱导的氧化应激、炎症和肝纤维化。综上所述,CVERE通过下调TAA代谢激活、氧化还原失衡和抑制NF - κB通路的炎症来抑制TAA诱导的肝纤维化。
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来源期刊
Environmental Toxicology
Environmental Toxicology 环境科学-毒理学
CiteScore
7.10
自引率
8.90%
发文量
261
审稿时长
4.5 months
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.
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