Callicarpa japonica Thunb. attenuates cigarette smoke-induced neutrophil inflammation and mucus secretion.
BACKGROUND
Callicarpa japonica Thunb. (CJT) is traditionally used as an herbal remedy for the treatment of inflammatory diseases in Korea, China, and Japan. In this study, we evaluated the effects of C. japonica Thunb. (CJT) on the development of COPD using a Cigarette smoke (CS)-induced murine model and cigarette smoke condensate (CSC)-stimulated H292 cells, human pulmonary mucoepidermoid cell line.


METHODS
C. japonica Thunb. was isolated from the leaves and stem of C. japonica. The methanol extract profile was obtained by UPLC Q-TOF-MS analysis. In in vivo experiment, the mice received 1h of cigarette smoke for 10 days. C. japonica Thunb. was administered to mice by oral gavage 1h before cigarette smoke exposure for 10 days. In in vitro experiment, we evaluated the effect of C. japonica Thunb. on the expression of MUC5AC and proinflammatory cytokines in H292 cells stimulated with CSC.


RESULTS
CJT treatment effectively suppressed the infiltration of neutrophils, and decreased the production of ROS and the activity of neutrophil elastase in the bronchoalveolar lavage fluid (BALF) induced by CS. CJT also significantly attenuated production of proinflammatory cytokines such as IL-6 and TNF-α in the BALF, and reduced the infiltration of inflammatory cells and the production of mucus in lung tissue induced by CS. In in vitro experiments, CJT decreased the expression of MUC5AC and proinflammatory cytokines in CSC-stimulated H292 cells. Furthermore, CJT attenuated the phosphorylation of ERK induced by CSC in H292 cells. Taken together, CJT effectively reduced the neutrophil airway inflammation and mucus secretion induced by CS in murine model, and inhibited the expression of MUC5AC in CSC-stimulated H292 human lung cell line. These findings suggest that CJT has a therapeutic potential for the treatment of COPD.
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea.
Jae-Won
JW
Lee
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea.
Na-Rae
NR
Shin
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea; Department of Life Sciences and Biotechnology, Korea University, 5-1 Anam-dong, Sungbuk-gu, Seoul 136-701, Republic of Korea.
Ji-Won
JW
Park
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea.
So-Yeon
SY
Park
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea.
Ok-Kyoung
OK
Kwon
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea.
Han-Sol
HS
Lee
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea.
Jung
J
Hee Kim
Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Kangwon 200-701, Republic of Korea.
Hee Jae
HJ
Lee
International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
Joongku
J
Lee
State Key Labtoratory of Systematic and Evolutionary Botany (LSEB) Institute of Botany, The Chinese Academy of Sciences, 20 Nanxincun, Xiangshan, Beijing 100093, PR China.
Zhi-yun
ZY
Zhang
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea.
Sei-Ryang
SR
Oh
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gu, Chungju-si, Chungbuk 363-883, Republic of Korea; Department of Life Sciences and Biotechnology, Korea University, 5-1 Anam-dong, Sungbuk-gu, Seoul 136-701, Republic of Korea; Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon, Kangwon 200-701, Republic of Korea; International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea; State Key Labtoratory of Systematic and Evolutionary Botany (LSEB) Institute of Botany, The Chinese Academy of Sciences, 20 Nanxincun, Xiangshan, Beijing 100093, PR China. Electronic address: ksahn@kribb.re.kr.
Kyung-Seop
KS
Ahn
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D032408:Callicarpa; D002460:Cell Line; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D019272:Leukocyte Elastase / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use*; D018515:Plant Leaves; D018547:Plant Stems; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D015850:Interleukin-6; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D019272:Leukocyte Elastase
Callicarpa japonica Thunb.; Cigarette smoke; Inflammation; MUC5AC; Neutrophil