Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Cheongju 28116, Republic of Korea; College of Pharmacy, Chungbuk National University, Cheongju-si, Chungcheongbuk-do 28160, Republic of Korea.
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Cheongju 28116, Republic of Korea; College of Pharmacy, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, Republic of Korea.
Int Immunopharmacol. 2020 Aug;85:106656. doi: 10.1016/j.intimp.2020.106656. Epub 2020 Jun 5.
3,4,5-Trihydroxycinnamic acid (THCA), a derivative of hydroxycinnamic acid, has been reported to exert anti-inflammatory and antioxidant activities. However, its anti-inflammatory effects in chronic obstructive pulmonary disease (COPD) have not yet been elucidated. Therefore, we explored the protective effects of THCA on pulmonary inflammation in an experimental COPD model elicited by cigarette smoke (CS) and lipopolysaccharide (LPS). Oral administration of THCA significantly inhibited the activity of elastase, the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO) and the numbers of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) of experimental COPD mice. THCA also exerted inhibitory effects on the recruitment of inflammatory cells, the levels of PAS positive cells and cAMP-response-element-binding protein (CREB) activation, and the expression of phosphodiesterase 4 (PDE4) in the lungs of experimental COPD mice. In addition, THCA exerted a regulatory effect on the activation of p38, ERK and nuclear factor-κB (NF-κB) in the lungs of experimental COPD mice. THCA also significantly upregulated the expression of NAD(P)H dehydrogenase (quinone 1) 1 (NQO1) and the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) in the lungs of mice. Furthermore, THC restored the reduction of NAD-dependent protein deacetylase sirtuin-1 (SIRT1) in the lungs of experimental COPD mice. In phorbol myristate acetate (PMA)-stimulated A549 or H292 airway epithelial cells, pretreatment of THCA dose-dependently inhibited the generation of IL-6. THCA also led to increased NQO1 expression in H292 cells. Collectively, these protective effects of antioxidant THCA were notably excellent and are thought to be associated with the downregulation of MAPK (partial)/NF-κB signaling and upregulation of NQO1 and SIRT1 expression.
3,4,5-三羟基肉桂酸（THCA）是羟基肉桂酸的衍生物，已被报道具有抗炎和抗氧化活性。然而，其在慢性阻塞性肺疾病（COPD）中的抗炎作用尚未阐明。因此，我们在香烟烟雾（CS）和脂多糖（LPS）诱导的实验性 COPD 模型中探讨了 THCA 对肺炎症的保护作用。THCA 口服给药可显著抑制弹性蛋白酶活性，抑制白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和单核细胞趋化蛋白-1（MCP-1）、髓过氧化物酶（MPO）以及实验性 COPD 小鼠支气管肺泡灌洗液（BALF）中中性粒细胞和巨噬细胞的数量释放。THCA 还对实验性 COPD 小鼠肺部炎症细胞募集、PAS 阳性细胞和 cAMP 反应元件结合蛋白（CREB）激活水平以及磷酸二酯酶 4（PDE4）表达水平产生抑制作用。此外，THCA 对实验性 COPD 小鼠肺部 p38、ERK 和核因子-κB（NF-κB）的激活也具有调节作用。THCA 还显著上调了 NAD（P）H 脱氢酶（醌 1）1（NQO1）的表达，并激活了小鼠肺部的核因子红细胞衍生 2 相关因子 2（Nrf2）。此外，THCA 恢复了实验性 COPD 小鼠肺部 NAD 依赖性蛋白去乙酰化酶沉默调节因子 1（SIRT1）的减少。在佛波醇肉豆蔻酸乙酸酯（PMA）刺激的 A549 或 H292 气道上皮细胞中，THCA 预处理呈剂量依赖性抑制 IL-6 的产生。THCA 还导致 H292 细胞中 NQO1 表达增加。综上所述，抗氧化剂 THCA 的这些保护作用非常显著，被认为与 MAPK（部分）/NF-κB 信号下调和 NQO1 和 SIRT1 表达上调有关。
