Effect of Liuweibuqi capsule, a Chinese patent medicine, on the JAK1/STAT3 pathway and MMP9/TIMP1 in a chronic obstructive pulmonary disease rat model

• Published in: Journal of traditional Chinese medicine Vol. 35; no. 1; pp. 54 - 62
• Main Authors: Wang, Chengyang, Li, Zegen, Liu, Xiangguo, Peng, Qinghe, Li, Fang, Li, Da, Wang, Chuanbo
• Format: Journal Article
• Language: English
• Published: China 01.02.2015
• Subjects: Animals; Capsules - administration & dosage; Disease Models, Animal; Drugs, Chinese Herbal - administration & dosage; Humans; Janus Kinase 1 - genetics; Janus Kinase 1 - metabolism; Male; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - enzymology; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction; STAT3; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - metabolism; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; 中国专利; 基质金属蛋白酶抑制剂; 大鼠模型; 慢性阻塞性肺疾病; 炎性细胞因子; 胶囊; 酶联免疫吸附测定法
• ISSN: 0255-2922
• DOI: 10.1016/S0254-6272(15)30009-1

OBJECTIVE： To observe effect of Liuweibuqi Capsule, a Traditional Chinese Medicine （TCM）, on the janus kinase （JAK）/signal transducer and activator of transcription （STAT） pathway and matrix metalloproteinases （MMPs） in a chronic obstructive pulmonary disease （COPD） rat model with lung deficiency in terms of TCM＇s pattern differentiation. METHODS： Rats were randomly divided into a normal group, model group, Liuweibuqi group, Jinshuibao group, and spleen aminopeptidase group （n= 10）. Aside from the normal group, all rats were ex-posed to smoke plus lipopolysaccharide tracheal instillation to establish the COPD model with lung deficiency. Models were established after 28 days and then the normal and model groups were given normal saline （0.09 g/kg）, Liuweibuqi group was given Liuweibuqi capsule （0.35 g/kg）, Jinshuibao group was given Jinshuibao capsules （0.495 g/kg）, and the spleen group was given spleen aminopeptidase （0.33 mg/kg）, once a day for 30 days. Changes in symptoms, signs, and lung histology were observed. Lung function was measured with a spirometer. Serum cytokines were detected using enzyme-linked immunosorbent assay, and changes in the JAK/STAT pathway, MMP-9, and MMPs inhibitor 1 （TIMP1） were detected by immunohistochemistry, RT-PCR, and western blotting, respectively.RESULTS： Compared with the normal group, lung tissue was damaged, and lung function was reduced in the model control group. Additionally, the levels of interleukin （IL）-1β, y interferon （IFN-γ）, and IL-6 were higher, while IL-4 and IL-10 were lower in the model control group than those in the normal group. The expressions of JAK1, STAT3, ρ-STAT3, and MMP-9 mRNA and protein in lung tissue were higher, and TIMP1 mRNA and protein was lower in the model group compared with the normal group. After treatment, compared with the model group, the expression of inflammatory cytokines was lower in each treatment group, and expressions of JAK/ STAT pathway, MMPs were lower. Compared with the positive control groups, the Jinshuibao and spleen aminopeptidase groups, lung function was better, and JAK1, STAT3, and p-STAT3 protein were lower and TIMP1 was higher in the Liuweibuqi group.CONCLUSION： Liuweibuqi capsules can improve the symptoms of COPD possibly by regulating the expression of the JAK1/STAT3 pathway and MMP9/ TIMP1.