Foenumoside B isolated from Lysimachia foenum-graecum extract suppresses LPS-induced inflammatory response via NF-κB/AP-1 inactivation in murine macrophages and in endotoxin-induced shock model
Foenumoside B isolated from Lysimachia foenum-graecum extract suppresses LPS-induced inflammatory response via NF-κB/AP-1 inactivation in murine macrophages and in endotoxin-induced shock model
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DOI：
10.1016/j.ejphar.2018.05.022
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发表时间：
2018-08-05
影响因子：
5
通讯作者：
Cheon, Hyae Gyeong
中科院分区：
文献类型：
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作者：
Choi, Hye-Eun;Kwak, Hyun Jeong;Cheon, Hyae Gyeong
Foenumoside B （FSB）是从Lysimachia foenum-graecum提取物（LFE）中分离得到的一种生物活性成分，已被证明具有抗炎作用，但其分子机制尚未阐明。因此，作者研究了FSB在LPS激活的小鼠巨噬细胞中抗炎作用的机制。FSB在蛋白和mRNA水平上抑制lps诱导的iNOS和COX-2的表达，从而降低RAW264.7和原代巨噬细胞NO和PGE2的产生。FSB还能在蛋白和mRNA水平上降低lps诱导的tnf - α、IL-6和IL-1 β的表达。对FSB抗炎作用分子机制的研究表明，FSB通过抑制AKT、p38和STAT3的磷酸化，抑制NF-kappa B和AP-1的转录活性，并抑制NF-kappa B的核易位。在脓毒症模型中，FSB预处理可抑制lps刺激下血浆和肝脏中iNOS、COX-2、tnf - α、IL-6和IL-1 β等促炎介质的mRNA和蛋白水平。重要的是，在lps诱导的脓毒症模型中，FSB提高了小鼠的存活率。综上所述，这些结果表明，FSB对lps诱导的炎症的抗炎作用与抑制AKT、p38和STAT3的磷酸化有关，随后抑制NF-kappa B和AP-1的转录，从而降低促炎基因的表达。
Foenumoside B (FSB), a bioactive component isolated from the Lysimachia foenum-graecum extract (LFE), has been shown to possess anti-inflammatory effects, but the underlying molecular mechanisms involved have not been elucidated. Accordingly, the authors investigated the mechanisms responsible for the anti-inflammatory effects of FSB in murine macrophages activated by LPS. FSB suppressed the LPS-induced expressions of iNOS and COX-2 at protein and mRNA levels and consequently decreased NO and PGE2 production in RAW264.7 and primary macrophages. FSB also reduced the LPS-induced inductions of TNF-alpha, IL-6 and IL-1 beta at protein and mRNA levels. Studies of the molecular mechanisms involved in the anti-inflammatory effects of FSB showed that it inhibited the transcriptional activities of NF-kappa B and AP-1, and the nuclear translocation of NF-kappa B via inhibition of the phosphorylations of AKT, p38 and STAT3. In a sepsis model, pretreatment with FSB inhibited the LPS-stimulated mRNA and protein levels of proinflammatory mediators, such as, iNOS, COX-2, TNF-alpha, IL-6 and IL-1 beta in plasma and liver. Importantly, FSB increased the survival rate of mice in the LPS-induced sepsis model. Taken together, these results show that the anti-inflammatory effects of FSB against LPS-induced inflammatory conditions are associated with inhibitions of the phosphorylations of AKT, p38 and STAT3 followed by the transcriptional suppressions of NF-kappa B and AP-1, and thus, reduced expressions of pro-inflammatory genes.