Novel findings of 18β-glycyrrhetinic acid on sRAGE secretion through inhibition of transient receptor potential canonical channels in high-glucose environment
Novel findings of 18β-glycyrrhetinic acid on sRAGE secretion through inhibition of transient receptor potential canonical channels in high-glucose environment
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DOI：
10.1002/biof.1517
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发表时间：
2019-07-01
期刊：
影响因子：
6
通讯作者：
Yen, Gow-Chin
中科院分区：
文献类型：
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作者：
Li, Zih-Ying;Tung, Yu-Tang;Yen, Gow-Chin
增强糖基化终产物可溶性受体（sCRP）被认为是治疗糖尿病的有效策略。钙离子和瞬时受体电位典型（TRPC）通道调节胰岛素分泌。然而，TRPC通道在糖尿病中的作用仍然未知。18 β-大黄次酸（18 β-GA），从大黄中产生，已显示出抗糖尿病的特性。本研究旨在研究18 β-GA对高糖诱导的THP-1细胞分泌唾液的影响。HG处理增强TRPC 3和TRPC 6的表达，从而引起活性氧（ROS）的积累，这是通过p47烟酰胺腺嘌呤二核苷酸磷酸氧化酶和诱导型一氧化氮合酶（iNOS）介导的，与解偶联蛋白2（UCP 2）的下降和低分泌相关。有趣的是，18 β-GA表现出类似于Pyr 3或2-氨基乙基二苯基硼酸酯抑制剂的显著作用，并有效地逆转了HG引起的机制，包括阻断TRPC 3和TRPC 6蛋白表达，抑制细胞内[Ca 2 +]浓度，降低ROS、p47 s和iNOS的表达，但增加UCP 2水平，促进分泌。因此，18 β-GA对糖尿病及其并发症提供了潜在的意义。
Enhancing soluble receptor for advanced glycation endproducts (sRAGE) is considered as a potent strategy for diabetes therapy. sRAGE secretion is regulated by calcium and transient receptor potential canonical (TRPC) channels. However, the role of TRPC channels in diabetes remains unknown. 18 beta-Glycyrrhetinic acid (18 beta-GA), produced from liquorice, has shown antidiabetic properties. This study was aimed to investigate the effect of 18 beta-GA on sRAGE secretion via TRPC channels in high glucose (HG)-induced THP-1 cells. HG treatment enhanced TRPC3 and TRPC6 expression and consequently caused reactive oxygen species (ROS) accumulation mediated through p47 nicotinamide-adenine dinucleotide phosphate oxidase and inducible nitric oxide synthase (iNOS) associated with uncoupling protein 2 (UCP2) decline and lower sRAGE secretion. Interestingly, 18 beta-GA showed the dramatic effects similar to Pyr3 or 2-aminoethyl diphenyl borinate inhibitors and effectively reversed HG-elicited mechanisms including that blocking TRPC3 and TRPC6 protein expressions, suppressing intracellular [Ca2+] concentration, decreasing expressions of ROS, p47s, and iNOS, but increasing UCP2 level and promoting sRAGE secretion. Therefore, 18 beta-GA provides a potential implication to diabetes mellitus and its complications.