Hossen Muhammad Jahangir, Kim Seung Cheol, Son Young-Jin, Baek Kwang-Soo, Kim Eunji, Yang Woo Seok, Jeong Deok, Park Jae Gwang, Kim Han Gyung, Chung Woo-Jae, Yoon Keejung, Ryou Chongsuk, Lee Sang Yeol, Kim Jong-Hoon, Cho Jae Youl
Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea ; Department of Animal Science, Patuakhali Science and Technology University, Patuakhali 8602, Bangladesh.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Ewha Womans University Mokdong Hospital College of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea.
Evid Based Complement Alternat Med. 2015;2015:608126. doi: 10.1155/2015/608126. Epub 2015 Mar 23.
In traditional Chinese medicine, Persicaria chinensis L. has been prescribed to cure numerous inflammatory disorders. We previously analyzed the bioactivity of the methanol extract of this plant (Pc-ME) against LPS-induced NO and PGE2 in RAW264.7 macrophages and found that it prevented HCl/EtOH-induced gastric ulcers in mice. The purpose of the current study was to explore the molecular mechanism by which Pc-ME inhibits activator protein- (AP-) 1 activation pathway and mediates its hepatoprotective activity. To investigate the putative therapeutic properties of Pc-ME against AP-1-mediated inflammation and hepatotoxicity, lipopolysaccharide- (LPS-) stimulated RAW264.7 and U937 cells, a monocyte-like human cell line, and an LPS/D-galactosamine- (D-GalN-) induced acute hepatitis mouse model were employed. The expression of LPS-induced proinflammatory cytokines including interleukin- (IL-) 1β, IL-6, and tumor necrosis factor-α (TNF-α) was significantly diminished by Pc-ME. Moreover, Pc-ME reduced AP-1 activation and mitogen-activated protein kinase (MAPK) phosphorylation in both LPS-stimulated RAW264.7 cells and differentiated U937 cells. Additionally, we highlighted the hepatoprotective and curative effects of Pc-ME pretreated orally in a mouse model of LPS/D-GalN-intoxicated acute liver injury by demonstrating the significant reduction in elevated serum AST and ALT levels and histological damage. Therefore, these results strongly suggest that Pc-ME could function as an antihepatitis remedy suppressing MAPK/AP-1-mediated inflammatory events.
在传统中医中，拳参已被用于治疗多种炎症性疾病。我们之前分析了该植物甲醇提取物（Pc-ME）对RAW264.7巨噬细胞中脂多糖（LPS）诱导的一氧化氮（NO）和前列腺素E2（PGE2）的生物活性，发现它可预防小鼠盐酸/乙醇诱导的胃溃疡。本研究的目的是探索Pc-ME抑制活化蛋白-（AP-）1激活途径并介导其肝保护活性的分子机制。为了研究Pc-ME对AP-1介导的炎症和肝毒性的潜在治疗特性，使用了脂多糖（LPS）刺激的RAW264.7细胞和U937细胞（一种单核细胞样人细胞系）以及LPS/D-半乳糖胺（D-GalN）诱导的急性肝炎小鼠模型。Pc-ME显著降低了LPS诱导的促炎细胞因子白细胞介素-（IL-）1β、IL-6和肿瘤坏死因子-α（TNF-α）的表达。此外，Pc-ME降低了LPS刺激的RAW264.7细胞和分化的U937细胞中AP-1的激活以及丝裂原活化蛋白激酶（MAPK）的磷酸化。此外，我们通过证明血清AST和ALT水平升高以及组织学损伤的显著降低，突出了口服预处理Pc-ME在LPS/D-GalN中毒急性肝损伤小鼠模型中的肝保护和治疗作用。因此，这些结果强烈表明Pc-ME可以作为一种抗肝炎药物，抑制MAPK/AP-1介导的炎症事件。
