Abstract

Context

Among the plants in the genus Barringtonia (Lecythidaceae) used as traditional medicines to treat arthralgia, chest pain, and haemorrhoids in Indonesia, Barringtonia racemosa L. and Barringtonia acutangula (L.) Gaertn. have demonstrated anti-inflammatory activity in systemic inflammatory models.

Objective

The anti-inflammatory activity of Barringtonia angusta Kurz has not been investigated. We prepared a methanol extract of the leaves and stems of B. angusta (Ba-ME) and systemically evaluated its anti-inflammatory effects in vitro and in vivo.

Materials and methods

RAW264.7 cells stimulated with LPS or Pam3CSK4 for 24 h were treated with Ba-ME (12.5, 25, 50, 100, and 150 µg/mL), and NO production and mRNA levels of inflammatory genes were evaluated. Luciferase reporter gene assay, western blot analysis, overexpression experiments, and cellular thermal shift assay were conducted to explore the mechanism of Ba-ME. In addition, the anti-gastritis activity of Ba-ME (50 and 100 mg/kg, administered twice per day for two days) was evaluated using an HCl/EtOH-induced gastritis mouse model.

Results

Ba-ME dose-dependently suppressed NO production [IC₅₀ = 123.33 µg/mL (LPS) and 46.89 µg/mL (Pam3CSK4)] without affecting cell viability. Transcriptional expression of iNOS, IL-1β, COX-2, IL-6, and TNF-α and phosphorylation of Src, IκBα, p50/105, and p65 were inhibited by Ba-ME. The extract specifically targeted the Src protein by binding to its SH2 domain. Moreover, Ba-ME significantly ameliorated inflammatory lesions in the HCl/EtOH-induced gastritis model.

Discussion and Conclusions

The anti-inflammatory activity of Ba-ME is mediated by targeting of the Src/NF-κB signalling pathway, and B. angusta has potential as an anti-inflammatory drug.

中文翻译：

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Barringtonia angusta 甲醇提取物的抗炎作用是通过靶向 NF-κB 信号通路中的 Src 介导的

摘要

语境

在印度尼西亚用作传统药物治疗关节痛、胸痛和痔疮的Barringtonia (Lecythidaceae)属植物中，Barringtonia racemosa L. 和Barringtonia acutangula (L.) Gaertn。已在全身炎症模型中显示出抗炎活性。

客观的

尚未研究Barringtononia angusta Kurz的抗炎活性。我们制备了B. angusta (Ba-ME)叶和茎的甲醇提取物，并在体外和体内系统地评估了其抗炎作用。

材料和方法

用 LPS 或 Pam3CSK4 刺激 24 小时的 RAW264.7 细胞用 Ba-ME（12.5、25、50、100 和 150 µg/mL）处理，并评估 NO 产生和炎症基因的 mRNA 水平。进行荧光素酶报告基因检测、蛋白质印迹分析、过表达实验和细胞热位移检测以探索 Ba-ME 的机制。此外，使用 HCl/EtOH 诱导的胃炎小鼠模型评估 Ba-ME（50 和 100 mg/kg，每天给药两次，持续两天）的抗胃炎活性。

结果

Ba-ME 剂量依赖性地抑制 NO 的产生 [IC ₅₀ = 123.33 µg/mL (LPS) 和 46.89 µg/mL (Pam3CSK4)]，而不影响细胞活力。Ba-ME 抑制iNOS、IL-1β、COX-2、IL-6和TNF-α 的转录表达以及 Src、IκBα、p50/105 和 p65 的磷酸化。该提取物通过与其 SH2 结构域结合来特异性靶向 Src 蛋白。此外，Ba-ME 显着改善了 HCl/EtOH 诱导的胃炎模型中的炎症病变。

讨论和结论

Ba-ME 的抗炎活性是通过靶向 Src/NF-κB 信号通路介导的，而B. angusta具有作为抗炎药的潜力。