* Department of Radiation Oncology, Chung Shan Medical University Hospital, Taichung City 40201, Taiwan.
† Department of Radiation Oncology, School of Medicine, Chung Shan Medical University, Taichung City 40201, Taiwan.
Am J Chin Med. 2019;47(1):153-176. doi: 10.1142/S0192415X19500083. Epub 2019 Jan 7.
Endotoxin lipopolysaccharide (LPS) plays an important role in the acceleration of hepatic inflammation. Natural medicinal plants that can prevent inflammation by targeting LPS have potential therapeutic clinical application. The aim of the study is to examine the anti-inflammatory effects of lotus seedpod extract (LSE), used as a traditional Chinese herbal medicine with hemostasis function and for eliminating bruise, on the LPS-induced hepatic inflammation and its underlying molecular mechanisms in vitro and in vivo. In vitro, LSE and its purified compound (-)-epigallocatechin (EGC) dose-dependently inhibited the expressions of pro-inflammatory cytokines and mediators, including tumor necrosis factor (TNF)- , interleukin (IL)-6, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), without affecting cell viability in LPS-stimulated human hepatoma cell line HepG2. Molecular studies showed the anti-LPS effect of HLP or EGC might be mediated via downregulation of Toll-like receptor 4. (TLR4)-mediated both NF- B and p38 signaling, as demonstrated by the usage of pyrrolidine dithiocarbamate (PDTC), a specific NF- B inhibitor. In vivo, LPS-induced hepatic inflammation was significantly ameliorated in LSE-fed mice as gauged by dose-dependent inhibition of serum levels of biochemical markers of liver damage, the changes of hepatic lobular architecture and the secretion of pro-inflammatory mediators, as well as induction of anti-oxidant enzymes. As a result, our data presented the first evidence of EGC-enriched LSE as an anti-inflammatory agent in LPS-stimulated HepG2 cells and mice, and these findings may open interesting perspectives to the strategy in treatment for hepatic inflammation.
内毒素脂多糖（LPS）在加速肝脏炎症中起着重要作用。能够针对 LPS 预防炎症的天然药用植物具有潜在的临床治疗应用。本研究旨在研究莲房提取物（LSE）作为一种具有止血功能和消除瘀伤的传统中药的抗炎作用，及其在体外和体内对 LPS 诱导的肝炎症及其潜在分子机制的影响。体外实验中，LSE 及其纯化化合物（-）-表没食子儿茶素没食子酸酯（EGC）呈剂量依赖性抑制促炎细胞因子和介质的表达，包括肿瘤坏死因子（TNF）- ，白细胞介素（IL）-6、环氧合酶-2（COX-2）和诱导型一氧化氮合酶（iNOS），而不影响 LPS 刺激的人肝癌细胞系 HepG2 中的细胞活力。分子研究表明，HLP 或 EGC 的抗 LPS 作用可能是通过下调 Toll 样受体 4（TLR4）介导的 NF-κB 和 p38 信号通路来介导的，这是通过使用吡咯烷二硫代氨基甲酸盐（PDTC），一种特定的 NF-κB 抑制剂来证明的。在体内，LSE 喂养的 LPS 诱导的肝炎症在小鼠中得到了显著改善，表现为血清肝损伤生化标志物水平、肝小叶结构变化和促炎介质分泌的剂量依赖性抑制，以及抗氧化酶的诱导。因此，我们的数据首次提供了 EGC 富集的 LSE 作为 LPS 刺激的 HepG2 细胞和小鼠中抗炎剂的证据，这些发现可能为治疗肝炎症的策略开辟了有趣的前景。
