Ryu Hyung Won, Lee Su Ui, Lee Seoghyun, Song Hyuk-Hwan, Son Tae Hyun, Kim Yeah-Un, Yuk Heung Joo, Ro Hyunju, Lee Chong-Kil, Hong Sung-Tae, Oh Sei-Ryang
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, Republic of Korea.
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang, Cheongju, Chungbuk 28116, Republic of Korea; College of Bioscience and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea.
Cytokine. 2017 Mar;91:57-64. doi: 10.1016/j.cyto.2016.12.006. Epub 2016 Dec 21.
Pseudolysimachion rotundum var. subintegrum is utilized as a traditional herbal remedy to treat cough, bronchitis, and asthma in Korea, Russia, China, and Europe. Here, we show that 3-methoxy-catalposide, a novel iridoide glycoside isolated from P. rotundum var. subintegrum has the anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated macrophages. The chemical structure of 3-methoxy-catalposide was determined by NMR, optical rotation and HRESIMS. In in vitro experiment, RAW264.7 cells were treated with 3-methoxy-catalposide for 2h before exposure to LPS for different times. Inflammatory gene and protein expressions were assayed using RT-PCR and ELISA. Activities of signal proteins were examined using western analysis. Our results demonstrated that 3-methoxy-catalposide significantly inhibits the expression of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in RAW264.7 cells stimulated by LPS, thereby suppressing the release of prostaglandin E2 (PGE) and nitric oxide (NO). Moreover, 3-methoxy-catalposide markedly reduced the LPS-induced expression of pro-inflammatory genes, such as interleukin (IL)-6, IL-1β, and TNF-α. Further, 3-methoxy-catalposide inhibited both LPS-induced activation of three MAP kinases (ERK 1/2, JNK, and p38) and the nuclear translocation of NF-κB and AP-1. These results support that 3-methoxy-catalposide may be a promising candidate for inflammation treatment.
圆叶假泽兰变种全缘叶在韩国、俄罗斯、中国和欧洲被用作治疗咳嗽、支气管炎和哮喘的传统草药。在此，我们表明，从圆叶假泽兰变种全缘叶中分离出的一种新型环烯醚萜苷3-甲氧基梓醇苷在脂多糖（LPS）刺激的巨噬细胞中具有抗炎活性。通过核磁共振（NMR）、旋光度和高分辨电喷雾电离质谱（HRESIMS）确定了3-甲氧基梓醇苷的化学结构。在体外实验中，RAW264.7细胞在暴露于LPS不同时间之前，先用3-甲氧基梓醇苷处理2小时。使用逆转录聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）检测炎症基因和蛋白表达。使用蛋白质免疫印迹分析检测信号蛋白的活性。我们的结果表明，3-甲氧基梓醇苷显著抑制LPS刺激的RAW264.7细胞中环氧化酶（COX）-2和诱导型一氧化氮合酶（iNOS）的表达，从而抑制前列腺素E2（PGE）和一氧化氮（NO）的释放。此外，3-甲氧基梓醇苷显著降低LPS诱导的促炎基因如白细胞介素（IL）-6、IL-1β和肿瘤坏死因子-α（TNF-α）的表达。此外，3-甲氧基梓醇苷抑制LPS诱导的三种丝裂原活化蛋白激酶（ERK 1/2、JNK和p38）的激活以及核因子κB（NF-κB）和活化蛋白-1（AP-1）的核转位。这些结果支持3-甲氧基梓醇苷可能是一种有前途的炎症治疗候选药物。
