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罗望子叶对硫代乙酰胺诱导大鼠肝纤维化和纤维溶解变化的调节作用。

Modulatory effect of Prosopis juliflora leaves on hepatic fibrogenic and fibrolytic alterations induced in rats by thioacetamide.

机构信息

Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.

Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.

出版信息

Biomed Pharmacother. 2019 Jul;115:108788. doi: 10.1016/j.biopha.2019.108788. Epub 2019 Apr 28.

Abstract

This study investigated the antifibrotic effect of Prosopis juliflora leaves crude methanolic extract (PJEL) against thioacetamide (TAA)-induced liver fibrosis. The phytochemical analysis of PJEL was performed via HPLC/MS in association with evaluating its free radical scavenging and cytotoxic activities. The antifibrotic activity of PJEL was assessed by dividing Wistar rats into 8 groups: normal control, PJEL1-administered rats (2 mg/ Kg b.w.), PJEL2-administered rats (4 mg/ Kg b.w.), PJEL3-administered rats (8 mg/Kg b.w.), TAA-induced hepatic fibrosis, TTA + PJEL1, TAA + PJEL2, and TAA + PJEL3. Results indicated that PJEL crude methanolic extract is rich in polyphenolic compounds and alkaloids. PJEL exerted free radical scavenging activity with IC of 123.5 μg/mL and cytotoxic activity against a well-differentiated hepatocellular cell line (IC = 11.1 μg/mL). PJEL at a dose of 4 mg/Kg b.w. ameliorated serum ALT activity and improved serum albumin level and hepatic hydroxyproline content in association with a reduction in the fibrosis stage. PJEL elevated hepatic tumor necrosis factor-α and interleukin-6 contents with less necrosis grade. PJEL post-therapy ameliorated the relative expression of Bcl-2, Col1A1, Mmp-9, and Mmp-2 genes in liver. CONCLUSION: PJEL possesses a good therapeutic activity against TAA-induced liver fibrosis via enhancing extracellular matrix removal and stimulating hepatic regeneration to decrease hepatic necrosis.

摘要

本研究旨在探讨洋麻叶粗甲醇提取物(PJEL)对硫代乙酰胺(TAA)诱导的肝纤维化的抗纤维化作用。通过 HPLC/MS 分析 PJEL 的植物化学成分,并评估其自由基清除和细胞毒性活性。通过将 Wistar 大鼠分为 8 组来评估 PJEL 的抗纤维化活性:正常对照组、PJEL1 给药组(2mg/kg b.w.)、PJEL2 给药组(4mg/kg b.w.)、PJEL3 给药组(8mg/kg b.w.)、TAA 诱导的肝纤维化组、TAA+PJEL1 组、TAA+PJEL2 组和 TAA+PJEL3 组。结果表明,PJEL 粗甲醇提取物富含多酚类化合物和生物碱。PJEL 具有自由基清除活性,IC 为 123.5μg/mL,对分化良好的肝细胞系具有细胞毒性活性(IC=11.1μg/mL)。PJEL 在 4mg/kg b.w.的剂量下可改善血清 ALT 活性,提高血清白蛋白水平和肝羟脯氨酸含量,并降低纤维化程度。PJEL 增加了肝肿瘤坏死因子-α和白细胞介素-6 的含量,且坏死程度降低。PJEL 治疗后可改善肝脏中 Bcl-2、Col1A1、Mmp-9 和 Mmp-2 基因的相对表达。结论:PJEL 通过增强细胞外基质的去除和刺激肝再生来减少肝坏死,对 TAA 诱导的肝纤维化具有良好的治疗作用。

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