Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, Republic of Korea.
Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum, Turkey.
Am J Chin Med. 2020;48(4):967-985. doi: 10.1142/S0192415X20500469. Epub 2020 May 20.
Inflammation and endoplasmic reticulum (ER) stress have been documented to contribute to the development of atherosclerosis. Ginsenoside Rb2 has been reported to exhibit antidiabetic effects. However, the effects of Rb2 on atherosclerotic responses such as inflammation and ER stress in endothelial cells and monocytes remain unclear. In this study, the expression of inflammation and ER stress markers was determined using a Western blotting method. Concentrations of tumor necrosis factor alpha (TNF[Formula: see text]) and monocyte chemoattractant protein-1 (MCP-1) in culture media were assessed by enzyme-linked immunosorbent assay (ELISA) and apoptosis was evaluated by a cell viability assay and a caspase-3 activity measurement kit. We found that exposure of HUVECs and THP-1 monocytes to Rb2 attenuated inflammation and ER stress, resulting in amelioration of apoptosis and THP-1 cell adhesion to HUVECs under lipopolysaccharide (LPS) condition. Increased AMPK phosphorylation and heme oxygenase (HO)-1 expression, including GPR120 expression were observed in Rb2-treated HUVECs and THP-1 monocytes. Downregulation of both, AMPK phosphorylation and HO-1expression rescued these observed changes. Furthermore, GPR120 siRNA mitigated Rb2-induced AMPK phosphorylation. These results suggest that Rb2 inhibits LPS-mediated apoptosis and THP-1 cell adhesion to HUVECs by GPR120/AMPK/HO-1-associated attenuating inflammation and ER stress. Therefore, Rb2 can be used as a potential therapeutic molecule for treatment of atherosclerosis.
炎症和内质网（ER）应激已被证明有助于动脉粥样硬化的发展。已报道人参皂苷 Rb2 具有抗糖尿病作用。然而，Rb2 对内皮细胞和单核细胞中炎症和 ER 应激等动脉粥样硬化反应的影响尚不清楚。在这项研究中，使用 Western blot 方法确定了炎症和 ER 应激标志物的表达。通过酶联免疫吸附测定（ELISA）测定培养基中肿瘤坏死因子 alpha（TNF[Formula: see text]）和单核细胞趋化蛋白-1（MCP-1）的浓度，并通过细胞活力测定和半胱天冬酶-3 活性测定试剂盒评估细胞凋亡。我们发现，暴露于 Rb2 的 HUVECs 和 THP-1 单核细胞减轻了炎症和 ER 应激，从而改善了脂多糖（LPS）条件下的细胞凋亡和 THP-1 细胞与 HUVECs 的黏附。在 Rb2 处理的 HUVECs 和 THP-1 单核细胞中观察到 AMPK 磷酸化和血红素加氧酶（HO）-1 表达增加，包括 GPR120 表达增加。下调 AMPK 磷酸化和 HO-1 表达可挽救这些观察到的变化。此外，GPR120 siRNA 减轻了 Rb2 诱导的 AMPK 磷酸化。这些结果表明，Rb2 通过 GPR120/AMPK/HO-1 相关途径抑制 LPS 介导的凋亡和 THP-1 细胞与 HUVECs 的黏附，从而抑制炎症和 ER 应激。因此，Rb2 可作为治疗动脉粥样硬化的潜在治疗分子。
