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Govaniadine Ameliorates Oxidative Stress, Inflammation, and Kupffer Cell Activation in Carbon Tetrachloride-Induced Hepatotoxicity in Rats
ACS Omega ( IF 4.1 ) Pub Date : 2021-01-21 , DOI: 10.1021/acsomega.0c02261
Azra Jahan 1 , Sumaira Shams 1 , Safdar Ali 2 , Samrana Samrana 3 , Amjad Ali 4 , Achyut Adhikari 5, 6 , Muhammad Sajid 7 , Abid Ali 3 , Hamid Ali 8
Affiliation  

Liver diseases such as hepatic carcinoma are one of the main health problems worldwide. Herbal drugs are largely used to treat liver injury in the indigenous system of medicine and may provide lead compounds for hepatoprotective drug discovery. The present study is investigated to test the Corydalis govaniana Wall. extract, fraction, and isolate therapeutically active constituents to explore their hepatoprotective, anti-inflammatory, and antioxidant activities. For this purpose, the antioxidant activity of govaniadine, caseadine, caseamine, and protopine was performed by assessing the scavenging events of the stable 2,2-diphenyl-1-picrylhydrazyl. Hepatoprotection of govaniadine was assessed in terms of reduction in serum enzymes (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase) caused by CCl4-induced liver injury in rats and by histopathological techniques. All the compounds showed significant antioxidant activity with a percentage inhibition of 92.2, 86.7, 85.3, and 79.7, respectively, compared to propyl gallate 90.3%. Treatment with govaniadine reduced the serum enzyme level down to normal levels in the CCl4-treated group while inhibiting the increase of malondialdehyde, and the induction of superoxide dismutase and the glutathione level was upregulated. Histopathology showed ∼47% damage to the liver cells in the CCl4-treated group; reduction in this damaged area was found to be better upon using govaniadine. Immunohistochemistry results showed that govaniadine as compared to silymarin has exceedingly decreased the inflammation by halting the CCl4-induced activation of hepatic macrophages. In carrageenan-induced paw edema assay, govaniadine significantly alleviated the edema after 1–5 h at a dose of 20 mg/kg (26.00 and 28.5%), 50 mg/kg (22.05 and 27.0%), and 100 mg/kg (20.02 and 25.30%), respectively. The results of our experiments suggest that govaniadine showed antioxidant and hepatoprotective activity in liver injury. The hepatoprotective function of govaniadine may be associated to the scavenging of the free radical and attenuation of oxidative stress as well as inflammatory responses in the liver. Hence, govaniadine may be a lead compound for the hepatoprotective drug discovery process and further research is needed to find out their molecular mechanism of protection.

中文翻译:

Govaniadine改善四氯化碳诱导的大鼠肝毒性中的氧化应激,炎症和Kupffer细胞活化

肝病等肝病是全球主要的健康问题之一。在本地医学系统中,草药主要用于治疗肝损伤,并且可能为发现保肝药物提供先导化合物。本研究进行了调查,以测试延胡索壁。提取,分离和分离治疗活性成分,以探索其肝保护,抗炎和抗氧化活性。为此,通过评估稳定的2,2-二苯基-1-吡啶并肼基清除事件,进行了govaniadine,caseadine,caseamine和protopine的抗氧化活性。通过降低由CCl 4引起的血清酶(丙氨酸转氨酶,天冬氨酸转氨酶和碱性磷酸酶)的降低来评估对鸟氨酸的肝保护作用。致大鼠肝损伤和组织病理学技术。与90.3%的没食子酸丙酯相比,所有化合物均显示出显着的抗氧化活性,抑制百分比分别为92.2、86.7、85.3和79.7。用戈维那定治疗将CCl 4处理组的血清酶水平降低至正常水平,同时抑制丙二醛的增加,并且超氧化物歧化酶的诱导和谷胱甘肽水平被上调。组织病理学显示,在CCl 4处理组中,肝细胞受到约47%的损害;人们发现,使用govaniadine可以更好地减少受损区域。免疫组织化学结果显示,与水飞蓟素相比,地戈那定通过停止CCl 4大大减少了炎症-诱导的肝巨噬细胞活化。在角叉菜胶诱发的爪水肿试验中,在1–5 h时,地戈那定可以分别减轻20 mg / kg(26.00和28.5%),50 mg / kg(22.05和27.0%)和100 mg / kg( 20.02和25.30%)。我们的实验结果表明,地戈那定在肝损伤中具有抗氧化和保肝作用。govaniadine的保肝功能可能与自由基的清除,氧化应激的减弱以及肝脏中的炎症反应有关。因此,govaniadine可能是保肝药物发现过程中的先导化合物,需要进一步研究以发现其保护分子机制。
更新日期:2021-02-02
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