Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Pathology, School of Basic Medical Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Curr Med Sci. 2019 Aug;39(4):526-533. doi: 10.1007/s11596-019-2069-4. Epub 2019 Jul 25.
Activation of macrophages is a key event for the pathogenesis of various inflammatory diseases. Notch signaling pathway recently has been found to be a critical pathway in the activation of proinflammatory macrophages. Salidroside (Sal), one of main bioactive components in Rhodiola crenulata (Hook. F. et Thoms) H. ohba, reportedly possesses anti-inflammatory activity and ameliorates inflammation in alcohol-induced hepatic injury. However, whether Sal regulates the activation of proinflammatory macrophages through Notch signaling pathway remains unknown. The present study investigated the effects of Sal on macrophage activation and its possible mechanisms by using both alcohol and lipopolysaccharide (LPS) to mimic the microenvironment of alcoholic liver. Detection of THP-1-derived macrophages exhibited that Sal could significantly decrease the expression of tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and IL-6 in the macrophages at both mRNA and protein levels. Furthermore, Sal significantly suppressed NF-κB activation via Notch-Hes signaling pathway in a dose-dependent manner. Moreover, in the microenvironment of alcoholic liver, the expression of Notch-dependent pyruvate dehydrogenase phosphatase 1 (PDP1) was elevated, and that of M1 gene expression [inducible NO synthase (NOS2)] was up-regulated. These changes could all be effectively ameliorated by Sal. The aforementioned findings demonstrated that Sal could inhibit LPS-ethanol-induced activation of proinflammatory macrophages via Notch signaling pathway.
巨噬细胞的激活是各种炎症性疾病发病机制的关键事件。最近发现，Notch 信号通路是促炎巨噬细胞激活的关键途径。红景天苷（Sal）是红景天（Rhodiola crenulata（Hook. F. et Thoms）H. ohba）的主要生物活性成分之一，据报道具有抗炎活性，并改善酒精性肝损伤中的炎症。然而，Sal 是否通过 Notch 信号通路调节促炎巨噬细胞的激活仍不清楚。本研究通过使用酒精和脂多糖（LPS）模拟酒精性肝的微环境，研究了 Sal 对巨噬细胞激活的影响及其可能的机制。对 THP-1 衍生的巨噬细胞的检测表明，Sal 可显著降低巨噬细胞中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的表达，无论是在 mRNA 水平还是在蛋白水平。此外，Sal 还可通过 Notch-Hes 信号通路呈剂量依赖性方式显著抑制 NF-κB 的激活。此外，在酒精性肝的微环境中，Notch 依赖性丙酮酸脱氢酶磷酸酶 1（PDP1）的表达升高，M1 基因表达（诱导型一氧化氮合酶（NOS2））上调。Sal 可有效改善这些变化。上述发现表明，Sal 可通过 Notch 信号通路抑制 LPS-乙醇诱导的促炎巨噬细胞的激活。
