A chinese herbal formula ameliorates COPD by inhibiting the inflammatory response via downregulation of p65, JNK, and p38

Abstract

BackgroundBufei Yishen formula (BYF), a traditional Chinese medicine (TCM), is an effective therapeutic strategy for patients with chronic obstructive pulmonary disease (COPD). PurposeTo evaluate the efficacy of BYF and investigate its therapeutic mechanisms. MethodsA total of 134 patients completed the study: 68 patients treated by BYF combined with conventional Western medicine in the trial group; and 66 patients treated using conventional Western medicine in the control group. The efficacy of BYF was evaluated by a subgroup analysis of data obtained from a four-center, open-label, randomized controlled trial of comprehensive TCM interventions. A rat model of COPD was treated with the key active molecules (KAM) of BYF for 8 weeks. An in vitro model of COPD was also treated with KAM. ResultsPatients treated with BYF had reduced frequency of acute exacerbation of COPD (p < 0.001) and duration (p = 0.028), dyspnea scale (p = 0.007), 6-min walking distance (p = 0.048). There were no differences observed in forced vital capacity in one second (FVC), forced expiratory volume in one second (FEV1), and FEV1 percentage of the predicted value (FEV1%). The five KAM of BYF (KAM-BYF) improved lung function, including tidal volume, minute ventilation, peak expiratory flow, FVC, FEV0.1, and FEV0.3, and pathological changes in COPD rats. Treatment with KAM-BYF markedly decreased the levels of interleukin 6 (IL6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP9), and MMP12 in serum and bronchial alveolar lavage fluid. In airway epithelial cells, KAM-BYF decreased the levels of TNF-α-induced IL8 and IL6. Finally, we discovered that the anti-inflammatory effects of KAM-BYF in COPD rats and BEAS-2Bs were mediated through inhibition of nuclear factor-kappaB (NF-κB) p65, c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase signaling. ConclusionsBYF exerts beneficial effects in patients with COPD via inhibition of inflammation.