Macrophage plays a critical part in host defense, tissue repair, and anti-inflammation; Macrophage reprogramming is responsible for disease development or regression. We aimed to clarify the effect of sinomenine-4-hydroxy-palmitate (C16), on macrophage reprogramming and anti-inflammatory in endotoxemia model. According to a structure modification of SIN (Sinomenine), C16 was found. Then, based on the endotoxin model, the mice liver and kidney toxicity was evaluated and serum cytokines level of IL-6 (Interleukin-6), TNF-α (Tumor necrosis factor-α), and IL-1β (Interleukin-1β) were measured by ELISA (Enzyme linked immunosorbent assay). Then, we confirmed the effect of C16 on macrophages reprogramming, we used the flow cytometry to test the effect of C16 on macrophages apoptosis in vitro. Then, iNOS (Inducible nitric oxide synthase), M1-type related cytokines, such as IL-1β, TNF-α, and M2-type related cytokines, such as Arg-1 (Arginase-1), CD206, Fizz1, and Ym1 was detected, which expressed in ANA-1 and primary peritoneal macrophages. To further explore the molecular mechanism of C16 in reprogramming of macrophages from M1 toward M2 phenotype, the expression of STAT1 (signal transducer and activator of Transcription 1), STAT3, ERK1/2 (extracellular signal regulated kinase1/2), AKT, p38, and its corresponding phosphorylation were determined by western blot. Our results demonstrated that C16 improved the survival rate of LPS- (lipopolysaccharide) challenged mice and decreased the inflammatory cytokines expression; After C16 treatment, the expression of M1 phenotype correlation factors decreased significantly, while the expression of M2 phenotype correlation factors increased significantly at different levels compared with normal group. It indicated that C16 reprogram macrophages phenotype from M1 toward M2 following LPS stimulus. Furthermore, the results also showed that C16 showed anti-inflammatory effect by inhibiting LPS-induced p38, AKT and STAT1 phosphorylation and contributing ERK1/2 activation. C16 promoted macrophage reprogramming toward M2-like phenotype via p-p38/p-AKT or STAT1 signals pathway and C16 might be a valid candidate for inflammatory disease.

巨噬细胞在宿主防御、组织修复和抗炎中起关键作用；巨噬细胞重编程负责疾病的发展或消退。我们旨在阐明青藤碱-4-羟基-棕榈酸酯 (C16) 在内毒素血症模型中对巨噬细胞重编程和抗炎的影响。根据SIN（青藤碱）的结构修饰，发现了C16。然后，基于内毒素模型，评估小鼠肝肾毒性和血清细胞因子IL-6（Interleukin-6）、TNF-α（Tumor necrosis factor-α）和IL-1β（Interleukin-1β）的水平。通过ELISA（酶联免疫吸附测定）测量。然后，我们证实了C16对巨噬细胞重编程的影响，我们使用流式细胞仪在体外测试了C16对巨噬细胞凋亡的影响。然后，iNOS（诱导型一氧化氮合酶），检测到 M1 型相关细胞因子，如 IL-1β、TNF-α 和 M2 型相关细胞因子，如 Arg-1（Arginase-1）、CD206、Fizz1 和 Ym1，它们在 ANA-1 和原发性腹腔巨噬细胞。为了进一步探索 C16 在巨噬细胞从 M1 向 M2 表型重编程中的分子机制，STAT1（信号转导和转录激活因子 1）、STAT3、ERK1/2（细胞外信号调节激酶1/2）、AKT、p38、通过蛋白质印迹测定其相应的磷酸化。我们的研究结果表明，C16 提高了 LPS-（脂多糖）攻击小鼠的存活率并降低了炎性细胞因子的表达；C16处理后，M1表型相关因子的表达明显下降，而M2表型相关因子的表达与正常组相比有不同程度的增加。它表明 C16 在 LPS 刺激后将巨噬细胞表型从 M1 重编程为 M2。此外，结果还表明，C16 通过抑制 LPS 诱导的 p38、AKT 和 STAT1 磷酸化并促进 ERK1/2 活化而显示出抗炎作用。C16 通过 p-p38/p-AKT 或 STAT1 信号通路促进巨噬细胞重编程为 M2 样表型，C16 可能是炎症性疾病的有效候选者。AKT 和 STAT1 磷酸化并促进 ERK1/2 激活。C16 通过 p-p38/p-AKT 或 STAT1 信号通路促进巨噬细胞重编程为 M2 样表型，C16 可能是炎症性疾病的有效候选者。AKT 和 STAT1 磷酸化并促进 ERK1/2 活化。C16 通过 p-p38/p-AKT 或 STAT1 信号通路促进巨噬细胞重编程为 M2 样表型，C16 可能是炎症性疾病的有效候选者。