Ginsenoside Rb2 enhances the anti-inflammatory effect of ω-3 fatty acid in LPS-stimulated RAW264.7 macrophages by upregulating GPR120 expression
Ginsenoside Rb2 enhances the anti-inflammatory effect of ω-3 fatty acid in LPS-stimulated RAW264.7 macrophages by upregulating GPR120 expression
复制标题
人参皂苷 Rb2 通过上调 GPR120 表达增强 LPS 刺激的 RAW264.7 巨噬细胞中 omega-3 脂肪酸的抗炎作用
DOI：
10.1038/aps.2016.135
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发表时间：
2017-02-01
影响因子：
8.2
通讯作者：
Wang, He-yao
中科院分区：
文献类型：
--
作者：
Huang, Qi;Wang, Ting;Wang, He-yao
近年来的研究证实慢性低度炎症与代谢综合征密切相关，抗炎治疗是治疗心血管疾病和2型糖尿病的潜在途径。越来越多的证据表明，GPR 120活化是改善慢性炎症和改善糖代谢的可行方案。在这项研究中，我们研究了在葡萄糖和脂质代谢中表现出调节活性的Rb 2（Rb 2）是否影响脂多糖（LPS）激活的小鼠巨噬细胞RAW 264. 7细胞中GPR 120的表达，并检查了GPR 120激活对减少LPS诱导的炎症反应的贡献。LPS（100 ng/mL）激活巨噬细胞，导致TNF-α、IL-6、IL-1 β和NO产生急剧增加。用ω-3脂肪酸α-亚麻酸（ALA，50 μ mol/L）治疗可中度降低LPS刺激的炎性细胞因子和NO产生（TNF-α和IL-6分别降低46%和42%）。在ALA处理前用Rb 2（1或10 μ mol/L）预孵育12 h显著增强ALA的抑制作用（TNF-α和IL-6分别降低74%和86%）。与单独用ALA处理相比，用Rb 2预孵育导致LPS刺激的iNOS和考克斯-2表达以及LPS刺激的IKK/NF-κ B磷酸化和MAPK通路活化的更显著降低。Rb 2（0.1-100 μ mol/L）剂量和时间依赖性地增加RAW264.7细胞中GPR 120的mRNA和蛋白表达，但单独用Rb 2处理对LPS激活的RAW264.7细胞没有抗炎作用。在转染GPR 120 shRNA的RAW264.7细胞中，Rb 2对LPS诱导的炎症的改善作用被取消。总之，Rb 2通过增加GPR 120表达并随后增强omega-3脂肪酸诱导的GPR 120活化在体外LPS刺激的小鼠巨噬细胞RAW 264. 7细胞中发挥抗炎作用。
Recent studies confirm that chronic low-grade inflammation is closely associated with metabolic syndromes, and anti-inflammatory therapy is a potential approach for treating cardiovascular diseases and type 2 diabetes. Accumulating evidence suggests that GPR120 activation is a feasible solution to ameliorating chronic inflammation and improving glucose metabolism. In this study we investigated whether ginsenoside Rb2 (Rb2), which exhibited regulatory activities in glucose and lipid metabolism, affected GPR120 expression in lipopolysaccharide (LPS)-activated mouse macrophage RAW264.7 cells, and examined the contribution of GPR120 activation to reducing the LPS-induced inflammatory response. LPS (100 ng/mL) activated the macrophages, resulting in dramatic increases in TNF-alpha, IL-6, IL-1 beta and NO production. Treatment with a omega-3 fatty acid alpha-linolenic acid (ALA, 50 mu mol/L) produced moderate reduction in LPS-stimulated inflammatory cytokines and NO production (TNF-alpha and IL-6 were decreased by 46% and 42%, respectively). Pre-incubation with Rb2 (1 or 10 mu mol/L) for 12 h before ALA treatment dramatically amplified the inhibitory effects of ALA (TNF-alpha and IL-6 were decreased by 74% and 86%, respectively). Compared to the treatment with ALA alone, pre-incubation with Rb2 resulted in a more prominent reduction in LPS-stimulated expression of iNOS and COX-2 and LPS-stimulated IKK/NF-kappa B phosphorylation and MAPK pathway activation. Rb2 (0.1-100 mu mol/L) dose- and time-dependently increased both mRNA and protein expression of GPR120 in RAW264.7 cells, but treatment with Rb2 alone did not exert anti-inflammatory effect in LPS-activated RAW264.7 cells. In RAW264.7 cells transfected with GPR120 shRNA, the ameliorating effects of Rb2 on LPS-induced inflammation were abolished. In conclusion, Rb2 exerts anti-inflammatory effect in LPS-stimulated mouse macrophage RAW264.7 cells in vitro by increasing GPR120 expression and subsequently enhancing omega-3 fatty acid-induced GPR120 activation.