PMID- 32504994 OWN - NLM STAT- MEDLINE DCOM- 20210421 LR - 20231213 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 85 DP - 2020 Aug TI - 3,4,5-Trihydroxycinnamic acid exerts a protective effect on pulmonary inflammation in an experimental animal model of COPD. PG - 106656 LID - S1567-5769(20)30477-X [pii] LID - 10.1016/j.intimp.2020.106656 [doi] AB - 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-alpha (TNF-alpha) 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-kappaB (NF-kappaB) 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-kappaB signaling and upregulation of NQO1 and SIRT1 expression. CI - Copyright (c) 2020 Elsevier B.V. All rights reserved. FAU - Min, Jae-Hong AU - Min JH AD - 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. FAU - Kim, Min-Gu AU - Kim MG AD - 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. FAU - Kim, Seong-Man AU - Kim SM AD - 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. FAU - Park, Ji-Won AU - Park JW AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Cheongju 28116, Republic of Korea. FAU - Chun, Wanjoo AU - Chun W AD - Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Kangwon 24341, Republic of Korea. FAU - Lee, Hee Jae AU - Lee HJ AD - Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Kangwon 24341, Republic of Korea. FAU - Oh, Sei-Ryang AU - Oh SR AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Cheongju 28116, Republic of Korea. FAU - Ahn, Kyung-Seop AU - Ahn KS AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Cheongju 28116, Republic of Korea. Electronic address: ksahn@kribb.re.kr. FAU - Lee, Jae-Won AU - Lee JW AD - Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Cheongju 28116, Republic of Korea. Electronic address: suc369@kribb.re.kr. LA - eng PT - Journal Article DEP - 20200605 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (3,4,5-trihydroxycinnamic acid) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antioxidants) RN - 0 (Cinnamates) RN - 0 (Cytokines) RN - 0 (Smoke) SB - IM MH - Animals MH - Anti-Inflammatory Agents/pharmacology/*therapeutic use MH - Antioxidants/pharmacology/*therapeutic use MH - Bronchoalveolar Lavage Fluid/cytology MH - Cell Line MH - Cinnamates/pharmacology/*therapeutic use MH - Cytokines/immunology MH - Humans MH - Inflammation/drug therapy/immunology/pathology MH - Lung/drug effects/immunology/pathology MH - Mice, Inbred C57BL MH - Models, Animal MH - Pulmonary Disease, Chronic Obstructive/*drug therapy/immunology/pathology MH - Smoke/adverse effects MH - Nicotiana OTO - NOTNLM OT - Airway inflammation OT - COPD OT - Cigarette smoke OT - NF-kappaB OT - NQO1 OT - THCA COIS- Declaration of Competing Interest The authors declare that they have no competing interest. EDAT- 2020/06/07 06:00 MHDA- 2021/04/22 06:00 CRDT- 2020/06/07 06:00 PHST- 2020/02/20 00:00 [received] PHST- 2020/05/12 00:00 [revised] PHST- 2020/05/29 00:00 [accepted] PHST- 2020/06/07 06:00 [pubmed] PHST- 2021/04/22 06:00 [medline] PHST- 2020/06/07 06:00 [entrez] AID - S1567-5769(20)30477-X [pii] AID - 10.1016/j.intimp.2020.106656 [doi] PST - ppublish SO - Int Immunopharmacol. 2020 Aug;85:106656. doi: 10.1016/j.intimp.2020.106656. Epub 2020 Jun 5.