Department of Pharmacology, Johannes Gutenberg University Medical Center, Mainz, Germany.
Institute for Biotechnology and Drug Research (IBWF gGmbH), Kaiserslautern, Germany.
J Ethnopharmacol. 2020 Apr 6;251:112534. doi: 10.1016/j.jep.2019.112534. Epub 2019 Dec 29.
Red fruit (Pandanus conoideus Lam) oil (RFO) is utilized by inhabitants of the Papua Island to treat diseases such as infections, cancer, and cardiovascular disease, but the mechanism of action is unknown.
We have recently shown that RFO stimulates nitric oxide (NO) production in endothelial cells. The present study was conducted to investigate the molecular mechanism of endothelial NO synthase (eNOS) activation by RFO.
NO production by endothelial cells was determined with electron paramagnetic resonance. The vascular function of isolated mouse aorta was examined using a wire myograph system. Phosphorylation of eNOS was studied with Western blot analyses.
RFO induced concentration-dependent vasodilation in isolated mouse aorta. The vasodilator effect of RFO was lost in endothelium-denuded aorta and in aorta from mice deficient in eNOS. Treatment of human EA.hy 926 endothelial cells with RFO led to an enhancement of eNOS phosphorylation at serine 1177 and NO production. The RFO-induced eNOS phosphorylation and NO production were reduced by inhibitors of Akt or AMPK, but not by an inhibitor of CaMKII. The effects of RFO were decreased by pharmacological inhibition of PI3K, indicating an involvement of the PI3K-Akt pathway. Moreover, acetone-soluble fractions and oily fractions of RFO showed higher efficacies than the RFO polar fraction in activating eNOS.
RFO contains highly active compounds that enhance NO production through Akt- or AMPK-mediated eNOS phosphorylation. The increase in endothelial NO production is likely to represent one of the molecular mechanisms responsible for the therapeutic effects of RFO.
巴布亚岛的居民使用红色果实（露兜树）油（RFO）来治疗感染、癌症和心血管疾病等疾病，但作用机制尚不清楚。
我们最近表明，RFO 可刺激内皮细胞中一氧化氮（NO）的产生。本研究旨在探讨 RFO 激活内皮型一氧化氮合酶（eNOS）的分子机制。
通过电子顺磁共振测定内皮细胞中 NO 的产生。使用线描测功仪系统检查分离的小鼠主动脉的血管功能。通过 Western blot 分析研究 eNOS 的磷酸化。
RFO 诱导分离的小鼠主动脉浓度依赖性血管舒张。RFO 的血管舒张作用在去内皮的主动脉和缺乏 eNOS 的主动脉中消失。用 RFO 处理人 EA.hy 926 内皮细胞可增强 eNOS 在丝氨酸 1177 处的磷酸化和 NO 的产生。RFO 诱导的 eNOS 磷酸化和 NO 产生被 Akt 或 AMPK 的抑制剂减少，但不被 CaMKII 的抑制剂减少。RFO 的作用通过 PI3K 的药理学抑制而降低，表明 PI3K-Akt 途径的参与。此外，RFO 的丙酮可溶部分和油性部分比 RFO 的极性部分在激活 eNOS 方面具有更高的功效。
RFO 含有高活性化合物，通过 Akt 或 AMPK 介导的 eNOS 磷酸化增强 NO 的产生。增加内皮细胞 NO 的产生可能是 RFO 治疗效果的分子机制之一。
