Attenuation of Inflammatory Symptoms by Icariside B2 in Carrageenan and LPS-Induced Inflammation Models via Regulation of MAPK/NF-κB Signaling Cascades
Attenuation of Inflammatory Symptoms by Icariside B2 in Carrageenan and LPS-Induced Inflammation Models via Regulation of MAPK/NF-κB Signaling Cascades
复制标题
DOI：
10.3390/biom10071037
复制
发表时间：
2020-07-01
期刊：
影响因子：
5.5
通讯作者：
Lee, Sang Han
中科院分区：
文献类型：
--
作者：
Alam, Md Badrul;Kwon, Yoon-Gyung;Lee, Sang Han
长期的炎症反应可导致多种慢性疾病的发展，如自身免疫性疾病和自然治疗剂的发展是必要的。采用小鼠模型对大芪甲草甘苷ICSB的抗炎作用进行体外和体内评价。采用lps刺激BV2细胞，检测ICSB体外抗炎作用，并检测炎症基因和细胞因子的蛋白表达水平。小鼠皮下注射1%角叉菜胶（CA）诱导足跖急性期炎症。通过每小时测量爪子体积来评估炎症；随后，将小鼠安乐死，取右后爪皮肤，进行逆转录聚合酶链反应（RT-PCR）和Western blot分析。ICSB通过降低诱导NO合成酶（iNOS）和环氧合酶2 （COX-2）的表达，抑制lps刺激的一氧化氮（NO）和前列腺素E2 （PGE(2)）的产生。ICSB还能抑制COX-2酶，IC50值为7.80 +/- 0.26 μ m。分子对接分析表明，ICSB与小鼠和人COX-2蛋白具有较强的结合亲和力，结合能分别为-8 kcal/mol和-7.4 kcal/mol。ICSB还能在转录和翻译水平上降低促炎细胞因子如tnf - α、IL-6和IL-1 β的表达。ICSB阻碍抑制蛋白kappa B α (I kappa B α)磷酸化，从而终止活化B细胞核因子kappa-轻链增强子（NF-kappa B）核易位。ICSB还抑制丝裂原活化蛋白激酶（MAPKs）信号通路。ICSB （50 mg/kg）对ca诱导小鼠有抗水肿作用，抑制ca诱导的iNOS和COX-2蛋白水平升高。ICSB通过干扰细胞外信号调节激酶（ERK）和p38磷酸化，以及通过调节iNOS、COX-2、tnf - α、IL-1 β和IL-6的表达水平，下调NF-kappa B的表达，从而减轻炎症反应。
Prolonged inflammatory responses can lead to the development of several chronic diseases, such as autoimmune disorders and the development of natural therapeutic agents is required. A murine model was used to assess the anti-inflammatory effects of the megastigmane glucoside, icariside B2 (ICSB), and the assessment was carried out in vitro, and in vivo. The in vitro anti-inflammatory effects of ICSB were tested using LPS-stimulated BV2 cells, and the protein expression levels of inflammatory genes and cytokines were assessed. Mice were subcutaneously injected with 1% carrageenan (CA) to induce acute phase inflammation in the paw. Inflammation was assessed by measuring paw volumes hourly; subsequently, the mice were euthanized and the right hind paw skin was expunged and processed for reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. ICSB inhibits LPS-stimulated nitric oxide (NO) and prostaglandin E2 (PGE(2)) generation by reducing the expression of inducible NO synthase (iNOS) and cyclooxygenase 2 (COX-2). ICSB also inhibits the COX-2 enzyme with an IC50 value of 7.80 +/- 0.26 mu M. Molecular docking analysis revealed that ICSB had a strong binding affinity with both murine and human COX-2 proteins with binding energies of -8 kcal/mol and -7.4 kcal/mol, respectively. ICSB also reduces the manifestation of pro-inflammatory cytokines, such as TNF-alpha, IL-6, and IL-1 beta, at their transcriptional and translational level. ICSB hinders inhibitory protein kappa B alpha (I kappa B alpha) phosphorylation, thereby terminating the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kappa B) nuclear translocation. ICSB also represses the mitogen-activated protein kinases (MAPKs) signaling pathways. ICSB (50 mg/kg) showed an anti-edema effect in CA-induced mice and suppressed the CA-induced increases in iNOS and COX-2 protein levels. ICSB attenuated inflammatory responses by downregulating NF-kappa B expression through interference with extracellular signal-regulated kinase (ERK) and p38 phosphorylation, and by modulating the expression levels of iNOS, COX-2, TNF-alpha, IL-1 beta, and IL-6.