Liuweibuqi capsules improve pulmonary function in stable chronic obstructive pulmonary disease with lung-qi deficiency syndrome by regulating STAT4/STAT6 and MMP-9/TIMP-1

Pharm Biol. 2019 Dec;57(1):744-752. doi: 10.1080/13880209.2019.1666151.

Abstract

Context: Liuweibuqi (LWBQ) capsule has been reported to influence symptoms of patients with chronic obstructive pulmonary disease (COPD); however, specific function of LWBQ capsules in COPD with lung-qi deficiency syndrome remains elusive.Objective: This study investigates effect of LWBQ capsules on STAT4/STAT6 and MMP-9/TIMP-1 expression and pulmonary function in stable COPD with lung-qi deficiency syndrome.Materials and methods: Totally, 429 patients diagnosed with stable COPD and lung-qi deficiency syndrome were treated with starch capsules (each time for 9 capsules), or different doses: low (each dose for 8 capsules and 1 LWBQ capsules), medium (each time for 6 capsules and 3 LWBQ capsules), or high (each time for 9 LWBQ capsules) of LWBQ capsules for 30 days, 3 times a day. Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC% and DLco%pred were evaluated by pulmonary function meter. STAT4/STAT6 and MMP-9/TIMP-1 expression was assessed by RT-qPCR and western blot analysis, and serum concentrations of IL-4, IFN-γ and IL-6 by ELISA.Results: Spearman rank correlation analysis and ROC curve showed that STAT4/STAT6 and MMP-9/TIMP-1 affected pulmonary functions and curative effect of stable COPD with lung-qi deficiency syndrome. After LWBQ capsule treatment, FEV1, FVC, FEV1/FVC% and DLco%pred elevated; STAT4/STAT6, MMP-9/TIMP-1, IFN-γ and IL-6 expression declined whereas IL-4 expression increased (p < 0.05). Logistic regression analysis demonstrated that FEV1/FVC was negatively correlated with STAT4/STAT6 and MMP-9/TIMP-1 expression in COPD patients.Conclusions: LWBQ capsules play a beneficial role in pulmonary function of stable COPD with lung-qi deficiency syndrome via STAT4/STAT6 and MMP-9/TIMP-1.

Keywords: IFN-γ; IL-4; IL-6; forced expiratory volume; forced vital capacity; matrix metalloproteinase; signal transducer and activator of transcription.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Capsules
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Qi*
  • Respiratory Function Tests
  • STAT4 Transcription Factor / metabolism
  • STAT6 Transcription Factor / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Treatment Outcome
  • Vital Capacity

Substances

  • Capsules
  • Drugs, Chinese Herbal
  • STAT4 Transcription Factor
  • STAT4 protein, human
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • MMP9 protein, human
  • Matrix Metalloproteinase 9

Grants and funding

This study was supported by Taicang Application of Basic Research Project [No. TC2015YYYLO2] and Suzhou Science and Technology Development Plan [No. SYS02015150].