Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Department of Endocrinology, Jining No.1 People's Hospital, Jining, Shandong, China.
J Cell Biochem. 2018 Nov;119(10):8547-8554. doi: 10.1002/jcb.27095. Epub 2018 Jul 30.
Baicalin (BAI), one major flavonoid from Scutellaria baicalensis, possesses anticancer and anti-inflammatory properties. However, the effect of BAI on diabetes mellitus has not been investigated. This study explored the antidiabetic effect of BAI on pancreatic β-cell line Min6. Min6 cells were treated with tumor necrosis factor-α (TNF-α) to mimic β-cell destruction in type 1 diabetes mellitus. The effects of BAI on viability and apoptosis of Min6 cells were analyzed by the cell counting kit-8 assay and Annexin V-fluoresceine isothiocyanate/propidium iodide staining method. The insulin secretion of Min6 cells was determined using radioimmunoassay. Expression of apoptosis-associated proteins and inducible nitric oxide synthase (iNOS), and activation of phosphatidylinositol 3'-kinase/protein kinase B (PI3K/AKT) and nuclear factor ΚB (NF-κB) pathways were analyzed by Western blot analysis. Relative microRNA-205 (miR-205) expression was determined by quantitative real time polymerase chain reaction. TNF-α treatment inhibited cell growth and insulin secretion, but promoted iNOS expression. All of these effects were reversed by BAI treatment. BAI promoted viability; suppressed apoptosis; regulated caspase-3, B-cell lymphoma 2 and Bcl-2-associated X protein; decreased iNOS level; and increased insulin production. BAI protected Min6 cells by upregulating miR-205. Besides, the Min6 cell-protective effect of BAI was PI3K/AKT pathway and NF-κB pathway dependent. BAI activated the PI3K/AKT pathway and inhibited the NF-κB pathway by regulating miR-205. In conclusion, BAI protected Min6 cells from TNF-α-induced injury by upregulating miR-205, which acts, at least in part, via activation of the PI3K/AKT pathway and inactivation of the NF-κB pathway.
黄芩苷（BAI）是黄芩中的一种主要黄酮类化合物，具有抗癌和抗炎作用。然而，BAI 对糖尿病的影响尚未得到研究。本研究探讨了 BAI 对胰岛β细胞系 Min6 的抗糖尿病作用。用肿瘤坏死因子-α（TNF-α）处理 Min6 细胞模拟 1 型糖尿病中β细胞的破坏。通过细胞计数试剂盒-8 检测和 Annexin V-荧光素异硫氰酸酯/碘化丙啶染色法分析 BAI 对 Min6 细胞活力和凋亡的影响。使用放射免疫法测定 Min6 细胞的胰岛素分泌。通过 Western blot 分析检测凋亡相关蛋白和诱导型一氧化氮合酶（iNOS）的表达，以及磷酸肌醇 3'-激酶/蛋白激酶 B（PI3K/AKT）和核因子 ΚB（NF-κB）通路的激活。通过定量实时聚合酶链反应测定相对 microRNA-205（miR-205）表达。TNF-α 处理抑制细胞生长和胰岛素分泌，但促进 iNOS 表达。所有这些作用均被 BAI 处理逆转。BAI 促进细胞活力；抑制细胞凋亡；调节半胱天冬酶-3、B 细胞淋巴瘤 2 和 Bcl-2 相关 X 蛋白；降低 iNOS 水平；增加胰岛素生成。BAI 通过上调 miR-205 保护 Min6 细胞。此外，BAI 对 Min6 细胞的保护作用依赖于 PI3K/AKT 通路和 NF-κB 通路。BAI 通过调节 miR-205 激活 PI3K/AKT 通路并抑制 NF-κB 通路。总之，BAI 通过上调 miR-205 保护 Min6 细胞免受 TNF-α 诱导的损伤，至少部分通过激活 PI3K/AKT 通路和抑制 NF-κB 通路发挥作用。
