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基于糖苷的标准化胡芦巴籽提取物通过调节内源性酶改善博来霉素诱导的大鼠肝纤维化。

Glycosides Based Standardized Fenugreek Seed Extract Ameliorates Bleomycin-induced Liver Fibrosis in Rats Via Modulation of Endogenous Enzymes.

作者信息

Kandhare Amit D, Bodhankar Subhash Laxmanrao, Mohan Vishwaraman, Thakurdesai Prasad A

机构信息

Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Pune, Maharashtra, India.

Department of Scientific Affairs and Quality Assurance, Indus Biotech Private Limited, Kondhwa, Pune, Maharashtra, India.

出版信息

J Pharm Bioallied Sci. 2017 Jul-Sep;9(3):185-194. doi: 10.4103/0975-7406.214688.

Abstract

BACKGROUND

Liver fibrosis a complex process of excess collagen deposition resulted in disturbance of hepatic cellar function. Glycosides based standardized fenugreek seed extract (SFSE-G) has potent anti-inflammatory, antioxidant, and anti-fibrotic properties.

OBJECTIVE

The aim of this study is to evaluate the hepatoprotective potential of SFSE-G against bleomycin (BLM)-induced liver fibrosis in laboratory animals.

MATERIALS AND METHODS

Sprague-Dawley rats (180-220 g) were assigned to various groups, namely, normal, sham, BLM control, SFSE-G (5, 10, 20, and 40 mg/kg, p.o.), methylprednisolone (10 mg/kg, p.o.), and sildenafil (25 mg/kg, p.o.). Liver fibrosis was induced in various groups (except normal and sham) by single intratracheal BLM (6 IU/kg) injection. Various biochemical, molecular (reverse transcription polymerase chain reaction) and histological parameters were evaluated.

RESULTS

Intratracheal BLM administration caused significant induction ( < 0.001) of hepatotoxicity and liver fibrosis reflected by elevated levels of serum aspartate transaminase (AST), alanine transaminase (ALT), total as well as direct bilirubin, and gamma-glutamyl transferase (GGT). Administration of SFSE-G (20 and 40 mg/kg, p.o.) significantly reduced ( < 0.001) levels of AST, ALT, and GGT and significantly increased ( < 0.001) the level of serum albumin. BLM-induced elevated liver oxidative stress and decreased total antioxidant capacity was significantly restored ( < 0.001) by SFSE-G (20 and 40 mg/kg) treatment. It also significantly inhibited BLM-induced alteration in liver Farnesoid X receptor (FXR) mRNA expression. SFSE-G treatment reduced histopathological alteration induced by BLM in liver.

CONCLUSION

SFSE-G exerts its hepatoprotective potential via inhibition of oxido-nitrosative stress and modulation of FXR mRNA expression thus ameliorates BLM-induced liver fibrosis.

摘要

背景

肝纤维化是一个复杂的过程,其特征为过量胶原蛋白沉积导致肝细胞功能紊乱。基于糖苷的标准化胡芦巴籽提取物(SFSE-G)具有强大的抗炎、抗氧化和抗纤维化特性。

目的

本研究旨在评估SFSE-G对实验动物博来霉素(BLM)诱导的肝纤维化的肝脏保护潜力。

材料与方法

将体重180 - 220克的Sprague-Dawley大鼠分为不同组,即正常组、假手术组、BLM对照组、SFSE-G组(5、10、20和40毫克/千克,口服)、甲泼尼龙组(10毫克/千克,口服)和西地那非组(25毫克/千克,口服)。除正常组和假手术组外,其他各组通过气管内单次注射BLM(6国际单位/千克)诱导肝纤维化。评估各种生化、分子(逆转录聚合酶链反应)和组织学参数。

结果

气管内给予BLM导致显著的肝毒性和肝纤维化诱导(<0.001),表现为血清天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、总胆红素以及直接胆红素和γ-谷氨酰转移酶(GGT)水平升高。给予SFSE-G(20和40毫克/千克,口服)可显著降低(<0.001)AST、ALT和GGT水平,并显著升高(<0.001)血清白蛋白水平。SFSE-G(20和40毫克/千克)治疗可显著恢复(<0.001)BLM诱导的肝脏氧化应激升高和总抗氧化能力降低。它还显著抑制BLM诱导的肝脏法尼醇X受体(FXR)mRNA表达改变。SFSE-G治疗减少了BLM诱导的肝脏组织病理学改变。

结论

SFSE-G通过抑制氧化-亚硝化应激和调节FXR mRNA表达发挥其肝脏保护潜力,从而改善BLM诱导的肝纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4b6/5621181/3ac87b330ee5/JPBS-9-185-g003.jpg

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