Ko Han-Jik, Ahn Eun-Kyung, Oh Joa Sub
College of Pharmacy, Dankook University, Cheonan, Chungnam 330‑714, Republic of Korea.
Bio Center, Gyeonggi Institute of Science and Technology Promotion, Yeongtong-gu, Suwon-si, Gyeonggi-do 443‑270, Republic of Korea.
Int J Mol Med. 2015 Oct;36(4):1042-8. doi: 10.3892/ijmm.2015.2301. Epub 2015 Aug 3.
Inflammation is induced by the expression of cyclooxygenase‑2 (COX‑2), which is an important mediator of chronic inflammatory diseases, such as rheumatoid arthritis, asthma and inflammatory bowel disease. Tribulus terrestris (T. terrestris) is known to have a beneficial effect on inflammatory diseases. In this study, we investigated the effects of N‑trans‑ρ‑caffeoyl tyramine (CT) isolated from T. terrestris on the production of nitric oxide (NO), and the expression of pro‑inflammatory cytokines and COX‑2 in lipopolysaccharide (LPS)‑stimulated RAW 264.7 cells. We also aimed to elucidate the molecular mechanisms involved. We found that the ethanolic extract of T. terrestris (EETT) and CT inhibited the production of NO, tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑6 and IL‑10 in the LPS‑stimulated RAW 264.7 cells in a dose‑dependent manner. They were determined by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). In addition, CT markedly suppressed the expression of COX‑2 and the production of prostaglandin E2 (PGE2) in response to LPS stimulation. Furthermore, CT markedly decreased p‑c‑Jun N‑terminal kinase (p‑JNK) protein expression in LPS‑stimulated RAW 264.7 cells. COX-2 and p-JNK were measured by western blot analysis. Taken together, these findings indicate that CT isolated from T. terrestris is a novel and potent modulator of inflammatory responses. Thus, it may prove benefiical to further evaluate CT as a possible treatment for chronic inflammatory diseases.
炎症是由环氧化酶-2(COX-2)的表达所诱导的,COX-2是类风湿性关节炎、哮喘和炎症性肠病等慢性炎症性疾病的重要介质。已知刺蒺藜对炎症性疾病具有有益作用。在本研究中,我们研究了从刺蒺藜中分离出的N-反式-ρ-咖啡酰酪胺(CT)对脂多糖(LPS)刺激的RAW 264.7细胞中一氧化氮(NO)产生、促炎细胞因子表达和COX-2表达的影响。我们还旨在阐明其中涉及的分子机制。我们发现刺蒺藜乙醇提取物(EETT)和CT以剂量依赖性方式抑制LPS刺激的RAW 264.7细胞中NO、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6和IL-10的产生。它们通过逆转录-聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)来测定。此外,CT显著抑制COX-2的表达以及LPS刺激后前列腺素E2(PGE2)的产生。此外,CT显著降低LPS刺激的RAW 264.7细胞中磷酸化c-Jun氨基末端激酶(p-JNK)蛋白的表达。通过蛋白质印迹分析来检测COX-2和p-JNK。综上所述,这些发现表明从刺蒺藜中分离出的CT是一种新型且有效的炎症反应调节剂。因此,进一步评估CT作为慢性炎症性疾病的一种可能治疗方法可能是有益的。