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翠云草叶片的植物成分及其通过激活实验性肝纤维化大鼠模型中的 NRF2/ARE 信号通路的肝保护作用。

Phytoconstituents of Sansevieria suffruticosa N.E.Br. Leaves and Its Hepatoprotective Effect via Activation of the NRF2/ARE Signaling Pathway in an Experimentally Induced Liver Fibrosis Rat Model.

机构信息

Pharmacology Department, Medicine and Clinical Studies Research Institute, National Research Center, Giza, 12622, Egypt.

Department of Biochemistry, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.

出版信息

Chem Biodivers. 2022 Apr;19(4):e202100960. doi: 10.1002/cbdv.202100960. Epub 2022 Mar 24.

Abstract

Sansevieria species possess antioxidant and hepatoprotective activities. However, the therapeutic potential of Sansevieria suffruticosa N.E.Br. in liver fibrosis was not evaluated yet. Twenty-seven phytoconstituents were tentatively identified in the phytoconstituents profile of Sansevieria suffruticosa N.E.Br. leaves extract (SSLE) using high-performance liquid chromatography coupled with mass spectrometry (HPLC-ESI/MS-MS). Using column chromatography, hesperetin, 4-hydroxybenzoic acid, ginsenoside Rg2, and quinic acid were isolated from SSLE. The hepatoprotective effect of SSLE via the activation of the NRF2 signaling pathway was evaluated using a rat model of thioacetamide-induced liver fibrosis. Five groups of 6 male adult Wistar rats were used. All animals except the normal control were injected with 200 mg/kg of TAA intraperitoneally twice weekly for 6 weeks. SSLE-treated groups were orally administered 200 and 100 mg/kg/day of the extract, two weeks before the liver fibrosis induction and were continued concomitantly with TAA injection. A reference group received 100 mg/kg b.wt of silymarin orally. SSLE treated groups exhibited a marked reduction in serum alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) levels compared with the TAA group. The levels of reduced glutathione (GSH) content and hepatic mRNA levels of Nrf2 and HO-1 were significantly increased. Histological findings further confirmed the protective role of SSLE against TAA. In conclusion, the aforementioned results indicated that the hepatoprotective mechanism of SSLE was exerted via activating the Nrf2 pathway to counteract oxidative stress.

摘要

龙舌兰属植物具有抗氧化和保肝活性。然而,还没有评估过龙舌兰属植物在肝纤维化中的治疗潜力。采用高效液相色谱-电喷雾串联质谱法(HPLC-ESI/MS-MS)对龙舌兰属植物叶提取物(SSLE)的植物成分谱进行了初步鉴定,共鉴定出 27 种植物成分。采用柱色谱法,从 SSLE 中分离出橙皮苷、4-羟基苯甲酸、人参皂苷 Rg2 和奎宁酸。采用硫代乙酰胺诱导的大鼠肝纤维化模型,评价了 SSLE 通过激活 NRF2 信号通路的保肝作用。使用 6 只成年雄性 Wistar 大鼠的 5 组。除正常对照组外,所有动物均每周两次腹腔注射 200mg/kg TAA 共 6 周。SSLE 处理组在肝纤维化诱导前两周开始口服 200 和 100mg/kg/天的提取物,并与 TAA 注射同时进行。参考组给予 100mg/kg b.wt 的水飞蓟素口服。与 TAA 组相比,SSLE 处理组的血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和丙二醛(MDA)水平明显降低,还原型谷胱甘肽(GSH)含量和肝组织中 Nrf2 和 HO-1 的 mRNA 水平显著升高。组织学发现进一步证实了 SSLE 对 TAA 的保护作用。综上所述,上述结果表明 SSLE 的保肝机制是通过激活 Nrf2 通路来抵抗氧化应激。

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