Chemical Constituents from the Rhizome of Ligusticum chuanxiong Hort. and Their Nrf2 Inducing Activity,Chemistry & Biodiversity

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Chemical Constituents from the Rhizome of Ligusticum chuanxiong Hort. and Their Nrf2 Inducing Activity
Chemistry & Biodiversity ( IF 2.3 ) Pub Date : 2021-08-26 , DOI: 10.1002/cbdv.202100302
Kan Zhang ₁ , Kai-Li Fang ₁ , Tian Wang ₁ , Lin-Tao Xu ₁ , Yu Zhao ₁ , Xiao-Ning Wang ₁ , Lan Xiang ₁ , Tao Shen ₁

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The rhizome of Ligusticum chuanxiong Hort. has been widely used for the therapy of diabetic nephropathy (DN) in traditional Chinese medicine (TCM). The nuclear transcription factor erythroid 2-related factor (Nrf2) is a potential target for treating DN. The purpose of this research was to study the chemical constituents from the rhizome of L. chuanxiong, evaluate their Nrf2 inducing activity, and find the molecules with potential therapeutic effect against DN. In this study, two new phthalides (1–2) along with twenty-seven known constituents were obtained from the rhizome of L. chuanxiong. Their structures were elucidated through various spectroscopic methods. Twelve constituents, including eight phthalides (2, 5, 6,10–13, 14) and four other compounds (17, 18, 20,28), stimulated NAD(P)H: quinone reductase (QR) activity, suggesting that these bioactive constituents were potential Nrf2 activators. Among the isolated compounds, phthalide levistolide A (LA, 14) upregulated the protein levels of Nrf2, NQO1, and γ-GCS in a dose-dependent manner. Our results implied that the clinical application of the rhizome of L. chuanxiong as an anti-DN drug in TCM might be attributed to the Nrf2 inducing effect of phthalides. Thus, phthalides is a group of promising leading molecules for discovering anti-DN agents.

中文翻译：

川芎黄芩根茎的化学成分。及其 Nrf2 诱导活性

川芎的根茎。在中医药（TCM）中已广泛用于治疗糖尿病肾病（DN）。核转录因子红细胞2相关因子（Nrf2）是治疗DN的潜在靶点。本研究的目的是研究川芎根茎的化学成分，评估其Nrf2诱导活性，并寻找具有潜在治疗DN作用的分子。在这项研究中，两个新的苯酞（1 - 2）从根茎获得具有27已知的成分沿L.川芎. 通过各种光谱方法阐明了它们的结构。十二组分，包括8个苯酞（2，5，6，10 - 13，14）以及其它四种化合物（17，18，20，28），受激NAD（P）H：醌还原酶（QR）的活性，这表明这些生物活性成分是潜在的 Nrf2 激活剂。在分离的化合物中，苯酞左旋内酯 A (LA, 14 ) 以剂量依赖性方式上调 Nrf2、NQO1 和 γ-GCS 的蛋白质水平。我们的研究结果表明川芎根茎的临床应用作为中药中的抗DN药物可能归因于苯酞的Nrf2诱导作用。因此，苯酞是一组有前途的主要分子，可用于发现抗 DN 药物。

更新日期：2021-08-26

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