Bruceine A protects against diabetic kidney disease via inhibiting galectin-1
Bruceine A protects against diabetic kidney disease via inhibiting galectin-1
复制标题
布鲁斯碱 A 通过抑制半乳糖凝集素 1 预防糖尿病肾病
DOI：
10.1016/j.kint.2022.04.020
复制
发表时间：
2022-08-18
影响因子：
19.6
通讯作者：
Wang, Zhen
中科院分区：
文献类型：
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作者：
Li, Huiying;Zhao, Xiaoli;Wang, Zhen
鸦胆子碱A是从中药鸦胆子（Brucea javanica（L.）Merr.它具有各种各样的生物活性。然而，该化合物是否对糖尿病肾病具有保护作用仍然未知。半乳凝素-1积极参与多种与慢性炎症相关的人类疾病，包括糖尿病肾病。在这里，我们确定了马钱子碱A作为一种肾脏保护分子，对糖尿病肾病模型的db/db小鼠在体外和体内具有有效的抗炎活性。机制上，通过选择性结合半乳糖凝集素-1保守的碳水化合物识别结构域，破坏半乳糖凝集素-1和活化蛋白C激酶1受体之间的相互作用，发现马钱子碱A抑制高糖应激下大鼠系膜HBZY-1细胞半乳糖凝集素-1介导的炎症信号转导。因此，我们的研究结果表明，马钱子碱A作为一种身份不明的半乳糖凝集素-1抑制剂，提供显着的保护，对糖尿病肾病，并可能提供新的药物治疗的疾病。
Bruceine A is a natural quassinoid compound extracted from the fruit of the Traditional Chinese Medicine Brucea javanica (L.) Merr. that has various types of various biological activities. However, whether the compound has a protective effect on diabetic kidney disease remains unknown. Galectin-1 is actively involved in a variety of chronic inflammation-relevant human diseases including diabetic kidney disease. Here, we identified Bruceine A as a kidney protective molecule against a model of diabetic kidney disease in db/db mice with potent anti-inflammatory activity both in vitro and in vivo. Mechanistically, by selectively binding to the conserved carbohydraterecognition domain of galectin-1 and disrupting the interaction between galectin-1 and the receptor for activated protein C kinase 1, Bruceine A was found to inhibit galectin-1-mediated inflammatory signal transduction under high glucose stress in rat mesangial HBZY-1 cells. Thus, our findings reveal Bruceine A as an unidentified galectin-1 inhibitor affording significant protection against diabetic kidney disease and may provide novel pharmacological therapeutics for the disease.