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川芎乙醇提取物对链脲佐菌素诱导的糖尿病肾病小鼠的保护作用。

Protective effect of the ethanol extract from Ligusticum chuanxiong rhizome against streptozotocin-induced diabetic nephropathy in mice.

机构信息

Key Lab of Chemical Biology (MOE), School of Pharmaceutical Sciences, Shandong University, Jinan, People's Republic of China.

Shandong Institute for Food and Drug Control, Jinan, People's Republic of China.

出版信息

J Ethnopharmacol. 2018 Dec 5;227:166-175. doi: 10.1016/j.jep.2018.08.037. Epub 2018 Sep 1.

DOI:10.1016/j.jep.2018.08.037
PMID:30176347
Abstract

ETHNOPHARMACOLOGY RELEVANCE

Rhizome of Ligusticum chuanxiong Hort. (Abbreviated as LC) is a frequently prescribed component in plenty of traditional Chinese medicine (TCM) formulas which are used to treat diabetic nephropathy (DN). The aims of the present study are to investigate the protective effect of the ethanol extract of LC rhizome (EEL) against DN in vivo, evaluate its potential mechanism, and find the evidence supporting its enthopharmacological use as an anti-DN agent.

MATERIALS AND METHODS

Hepa 1c1c7 murine hepatoma cells, human breast carcinoma MDA-MB-231 cells, human renal glomerular endothelial cells (HRGEC), and RAW 264.7 murine macrophages were adopted to test the effects of EEL and its active constituents on inhibitions of oxidative stress and inflammation in vitro. A streptozotocin (STZ) -induced DN C57BL/6 mice model was established and used to investigate the preventive effect of EEL against DN in vivo.

RESULTS

EEL demonstrated potential inhibitory effects against oxidative stress and inflammation in vitro. Using a STZ-induced DN mice model, it has been found that EEL treatment significantly prevented STZ-induced increases of urine production, urinary albumin excretion (UAE) and urine albumin-to-creatinine ratio (UACR), and markedly attenuated STZ-induced renal damages (e.g. glomerulosclerosis and fibrosis). The predominant bioactive constituents, Z-ligustilide (LGT), ferulic acid (FA), and tetramethylpyrazine (TMP), were inhibitors of oxidative stress and inflammation through acting with Nrf2 and NF-κB pathways.

CONCLUSIONS

EEL attenuates structural and functional damages of kidney in STZ-induced DN model in vivo, which might be related to the functions of EEL on inhibitions of oxidative stress and inflammation. These finding definitely supports the ethnopharmacological use of LC as an anti-DN agent.

摘要

民族药理学相关性

川芎根茎(简称 LC)是许多中药配方中常用的一种成分,用于治疗糖尿病肾病(DN)。本研究旨在探讨 LC 根茎乙醇提取物(EEL)对体内 DN 的保护作用,评估其潜在机制,并寻找支持其作为抗 DN 药物的民族药理学应用的证据。

材料与方法

采用 Hepa 1c1c7 小鼠肝癌细胞、人乳腺癌 MDA-MB-231 细胞、人肾小球内皮细胞(HRGEC)和 RAW 264.7 小鼠巨噬细胞体外测试 EEL 及其活性成分对氧化应激和炎症抑制的作用。建立链脲佐菌素(STZ)诱导的 DN C57BL/6 小鼠模型,用于体内研究 EEL 对 DN 的预防作用。

结果

EEL 显示出体外潜在的抗氧化应激和抗炎作用。使用 STZ 诱导的 DN 小鼠模型,发现 EEL 治疗可显著预防 STZ 诱导的尿量增加、尿白蛋白排泄(UAE)和尿白蛋白/肌酐比(UACR)增加,并显著减轻 STZ 诱导的肾脏损伤(如肾小球硬化和纤维化)。主要生物活性成分 Z-藁本内酯(LGT)、阿魏酸(FA)和四甲基吡嗪(TMP)通过与 Nrf2 和 NF-κB 途径相互作用,抑制氧化应激和炎症。

结论

EEL 可减轻体内 STZ 诱导的 DN 模型的结构和功能损伤,这可能与 EEL 抑制氧化应激和炎症的功能有关。这些发现肯定支持将川芎作为抗 DN 药物的民族药理学应用。

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