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Sophoraflavanone M, a prenylated flavonoid from Sophora flavescens Ait., suppresses pro-inflammatory mediators through both NF-κB and JNK/AP-1 signaling pathways in LPS-primed macrophages
European Journal of Pharmacology ( IF 4.2 ) Pub Date : 2021-06-09 , DOI: 10.1016/j.ejphar.2021.174246
Yixin Han 1 , Xiaoyu Zhang 1 , Yuan Kang 1 , Yuan Gao 1 , Ximeng Li 1 , Ruijuan Qi 1 , Runlan Cai 1 , Yun Qi 1
Affiliation  

(2R)-3α,7,4′-trihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone is a prenylated flavonoid isolated from the anti-inflammatory herb Sophora flavescens Ait. We firstly named it sophoraflavanone M (SFM) in accordance with trivial names of related constitutes from this plant. Although various studies investigated the anti-inflammatory properties of prenylated flavonoids from Sophora flavescens Ait., that of SFM remains unclear and is yet to be determined. In the current study, we assessed the anti-inflammatory effects of SFM in LPS-induced in vivo and in vitro models. In the serum of endotoxemia mice, SFM significantly suppressed LPS-elevated inflammatory cytokines. Furthermore, at nontoxic concentrations, SFM reduced LPS-induced production of inflammatory mediators NO, IL-6, TNF-α, and MCP-1 in mouse primary peritoneal macrophages. Accordingly, in LPS-primed RAW264.7 cell line, it also inhibited these mediators' expression at both transcriptional and translational levels without cytotoxicity. Mechanistically, SFM is found to concurrently inhibit two important inflammatory signaling pathways, NF-κB and JNK/AP-1. SFM restrained phosphorylation and degradation of IκBα as well as the subsequent p65 translocation to dampen NF-κB activity. Meanwhile, it also suppressed JNK phosphorylation to inhibit the transcriptional activity of AP-1. These results provide material basis for traditional application of the anti-inflammatory herb Sophora flavescens Ait. and suggest SFM is a promising natural candidate for alleviating inflammatory conditions.



中文翻译:


Sophoraflavanone M 是一种来自苦参的异戊二烯化黄酮类化合物,可通过 LPS 引发的巨噬细胞中的 NF-κB 和 JNK/AP-1 信号通路抑制促炎介质



(2 R )-3α,7,4'-三羟基-5-甲氧基-8-(γ,γ-二甲基烯丙基)-flavanone 是一种异戊二烯化黄酮类化合物,从抗炎药草苦参(Sophora flavescens Ait) 中分离出来。我们首先根据该植物相关成分的俗名将其命名为槐黄酮M(SFM)。尽管多项研究调查了苦参异戊二烯化黄酮类化合物的抗炎特性,但 SFM 的抗炎特性仍不清楚且尚未确定。在当前的研究中,我们评估了 SFM 在 LPS 诱导的体内体外模型中的抗炎作用。在内毒素血症小鼠的血清中,SFM 显着抑制 LPS 升高的炎症细胞因子。此外,在无毒浓度下,SFM 减少了 LPS 诱导的小鼠原代腹膜巨噬细胞中炎症介质 NO、IL-6、TNF-α 和 MCP-1 的产生。因此,在LPS引发的RAW264.7细胞系中,它也在转录和翻译水平上抑制这些介质的表达,而没有细胞毒性。从机制上讲,SFM 可同时抑制两个重要的炎症信号通路:NF-κB 和 JNK/AP-1。 SFM 抑制 IκBα 的磷酸化和降解以及随后的 p65 易位,从而抑制 NF-κB 活性。同时,它还抑制JNK磷酸化,从而抑制AP-1的转录活性。这些结果为抗炎药材苦参的传统应用提供了物质基础。并表明 SFM 是一种有前景的缓解炎症的天然候选药物。

更新日期:2021-06-15
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