当前位置: X-MOL 学术Eur. J. Pharmacol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
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 是来自 Sophora flavescens Ait. 的异戊二烯化黄酮类化合物,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)-黄烷酮是一种从抗炎药草苦参Ait中分离出来的异戊二烯化黄酮类化合物。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)。尽管各种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,尚待确定。在目前的研究中,我们评估了 SFM 在 LPS 诱导的体内体外抗炎作用楷模。在内毒素血症小鼠的血清中,SFM 显着抑制 LPS 升高的炎性细胞因子。此外,在无毒浓度下,SFM 减少了 LPS 诱导的小鼠原发性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,它还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 被发现同时抑制两种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 易位以抑制 NF-κB 活性。同时,它还抑制 JNK 磷酸化以抑制 AP-1 的转录活性。苦参Ait。并表明 SFM 是缓解炎症的有希望的天然候选物。

更新日期:2021-06-15
down
wechat
bug