Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China; National and Local Joint Engineering Laboratory for Energy Plant Bio-Oil Production and Application, Chengdu, China.
Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu, China.
J Ethnopharmacol. 2021 Mar 25;268:113617. doi: 10.1016/j.jep.2020.113617. Epub 2020 Dec 8.
Penthorum chinense Pursh is used for promoting diuresis and alleviating "heat"-associated disorders, which were considered to be related to diabetic in Traditional Chinese Medicine (TCM).
Here, we aimed to evaluate the ability and underlying mechanism of the ethyl acetate fraction of Penthorum chinense Pursh stems (PSE) to inhibit vascular inflammation in high glucose (HG)-induced human umbilical vein endothelial cells (HUVEC cells).
HUVEC cells were pre-treated with PSE following HG treatment. The cell viability, mitochondrial membrane potential (MMP), lactate dehydrogenase (LDH) levels, reactive oxygen species (ROS) generation were analyzed. Inflammatory, and antioxidant,-related proteins were analyzed using western blotting. Molecular docking and drug affinity targeting experiments (DARTS) were utilized to analyze and verify the binding of the Keap1 protein and polyphenols of PSE.
HG can significantly increase the activity of lactic dehydrogenase (LDH), destroy the mitochondrial membrane potential (MMP), and promote the generation of reactive oxygen species (ROS), while PSE treatment reversed these changes. Mechanistically, PSE inhibited NF-κB and inflammatory cytokines activation induced by HG through activating the expression of Nrf2 and its downstream antioxidant proteins Heme oxygenase-1 (HO-1), NAD (P)H Quinone Dehydrogenase 1 (NQO1), Glutamate cysteine ligase catalytic subunit (GCLC), Glutamate-cysteine ligase modifier (GCLM). Further study indicated that PSE activated Nrf2 antioxidant pathway mainly by the binding of primary polyphenols from PSE and the Keap1 protein.
Taken together, the present data highlight the health benefits of polyphenols from Penthorum chinense Pursh. regarding diabetes, proving it to be an important source of health care products. Besides, binding of the Keap1 protein may be an effective strategy to activate Nrf2 antioxidant pathway and prevent diabetes.
在中国传统医学（TCM）中，贯叶连翘被用于利尿和缓解与“热”相关的疾病，这些疾病被认为与糖尿病有关。
本研究旨在评估贯叶连翘茎乙酸乙酯提取物（PSE）抑制高糖（HG）诱导的人脐静脉内皮细胞（HUVEC 细胞）血管炎症的能力及其潜在机制。
用 PSE 预处理 HUVEC 细胞，然后用 HG 处理。分析细胞活力、线粒体膜电位（MMP）、乳酸脱氢酶（LDH）水平、活性氧（ROS）生成。采用 Western blot 分析炎症和抗氧化相关蛋白。利用分子对接和药物亲和靶标实验（DARTS）分析和验证 Keap1 蛋白与 PSE 多酚的结合。
HG 可显著增加乳酸脱氢酶（LDH）的活性，破坏线粒体膜电位（MMP），促进活性氧（ROS）的产生，而 PSE 处理可逆转这些变化。机制上，PSE 通过激活 NF-κB 和炎症细胞因子的表达，抑制 HG 诱导的 NF-κB 和炎症细胞因子的激活，从而抑制 Nrf2 和其下游抗氧化蛋白血红素加氧酶-1（HO-1）、NAD（P）H 醌氧化还原酶 1（NQO1）、谷胱甘肽半胱氨酸连接酶催化亚基（GCLC）、谷胱甘肽-cysteine 连接酶修饰亚基（GCLM）。进一步的研究表明，PSE 主要通过 PSE 中主要多酚与 Keap1 蛋白的结合来激活 Nrf2 抗氧化途径。
综上所述，本研究数据强调了贯叶连翘多酚在糖尿病方面的健康益处，证明了其作为保健品的重要来源。此外，Keap1 蛋白的结合可能是激活 Nrf2 抗氧化途径和预防糖尿病的有效策略。
