Bufei Yishen granules suppress oxidative stress in rats with chronic obstructive pulmonary disease via Nrf2 signaling

OBJECTIVE To explore the antioxidant effect of Bufei Yishen granules on chronic obstructive pulmo⁃nary disease(COPD)and investigate its underlying mechanism.METHODS Forty-eight rats were randomly divided into normal,model,Bufei Yishen granules(BY)and N-acetylcysteine(NAC)groups,12 rats in each group.The stable COPD rat model was duplicated by using repeated cigarette smoke exposure combined with Klebsiella bacterial infection for 12 weeks(week 1-12),and the corresponding drugs were administered for the next 8 weeks(week 13-20).Minute volume(MV),tidal volume(TV)and peak expiratory flow(PEF)were measured by whole body plethysmography(WBP)system every 4 weeks.Before sacrificed,forced vital capacity(FVC)and forced expiratory volume 0.1(FEV0.1)were measured byPFT system.The pathological changes of lung tissue were observed by pathological techniques.Heme oxygenase 1(HO-1),superoxide dismutase 1(SOD1)and Nrf2 in lung tissue were measured by immunohisto-hemical method.The total anti oxidizing capability(T-AOC),lipid peroxide(LPO)in rat serum were measured.The expression of Nrf2,HO-1 andγ-glutamyl cysteine synthetase(γ-GCS)mRNA in lung tissue was detected by quantitative polymerase chain reac⁃tion(qPCR).The protein expression of Keap1,Nrf2 and HO-1 in lung tissue were detected by Western blotting.RESULTS①Lung function:compared with normal group,the MV in model group was significantly decreased at week 8(P<0.01),the TV and PEF were significantly decreased at week 4(P<0.01).At week 20,compared with model group,MV,TV,and PEF in the BY and NAC groups were significantly increased(P<0.01);compared with the NAC group,MV,TV,and PEF in BY group were significantly increased(P<0.01).At the end of week 20,the FVC and FEV0.1 in model group were significantly lower than that in normal group(P<0.01).Compared with model group,the FVC and FEV0.1 in the BY and NAC groups were significantly increased(P<0.05).②Oxidative indexes:Compared with Normal group,T-AOCin serum was significantly decreased in Model group,while LPO was significantly increased(P<0.01).Compared with the Model,T-AOC in BY and NAC groups was significantly increased(P<0.01),and the LPO was significantly decreased(P<0.05,P<0.01).There were no difference between the BTG and NAC.③Nrf2 signaling:Nrf2 and HO-1 in lung tissue were mainly expressed in the cytoplasm and part of the nucleus of alveolar epithelial cells.SOD1 protein was mainly distributed in bronchial epithelial cells and alveolar septa.Compared with normal group,the expression of Nrf2 in the model group was increased(P<0.01),and HO-1 and SOD1 were decreased(P<0.01).Compared with the model,the expression of Nrf2 in the BY group was significantly increased(P<0.05),and HO-1 and SOD1 in BY and NAC groups were both increased(P<0.01).Compared with the NAC group,the expression of HO-1 in BY group was increased(P<0.01).Compared with normal group,the Nrf2 mRNA expression of lung tissue in the model was significantly increased(P<0.01),the HO-1 andγ-GCS mRNA was decreased(P<0.01).Compared with model group,the Nrf2,HO-1,andγ-GCS mRNA in the BY group were increased(P<0.01),the HO-1,andγ-GCS mRNA in NAC group were increased(P<0.01).Compared with normal group,the Nrf2 protein expression of lung tissue in the model group was significantly increased(P<0.01),and HO-1 protein expression was significantly decreased(P<0.01).Compared with the model,the Nrf2 and HO-1 protein in NAC and BY groups was significantly increased(P<0.01).CONCLUSION Bufei Yishen gran⁃ules has beneficial curative effect in COPD rats,and has the same antioxidation effect as NAC,the mechanism may be involved in upregulating Nrf2 signaling.

Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis:A Multi-center,Double-Blinded and Randomized Controlled Trial

Objective: To assess the efficacy and safety of Bufei Jiedu(BFJD) Granules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis(MDR-PTB). Methods: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups(1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months(6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life(QoL) of patients. Adverse reactions were monitored during and after the trial. Results: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo(58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion(5 months vs. 11 months). The cavity closure rate of the BFJD Granules group(50.6%, 43/85) was higher than that of the placebo group(32.1%, 26/81;P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group(all P<0.01). Overall, the death rates in the two groups were not significantly different;5.1%(8/156) in the BFJD Granules group and 2.6%(4/156) in the placebo group. Conclusions: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rate, and rapidly improved QoL of patients with MDR-PTB(Registration No. ChiCTR-TRC-12002850)

Effect of Bufei granule on stable chronic obstructive pulmonary disease: a randomized, double blinded, placebo-controlled, and multicenter clinical study

OBJECTIVE: To study the therapeutic effect Bufei granule, which is a traditional Chinese drug that can enhance the immune function of the lung, on patients with stable chronic obstructive pulmonary disease(COPD).METHODS: This is a randomized, double blinded,placebo-controlled, and multicenter clinical study.Three medical centers in Tianjin, China, participated in the trial. A total of 140 patients with stable COPD were enrolled and randomized into two groups, with 70 patients in each. The treatment group was treated with Bufei granule, while the control group received Bufei placebo. The pharmacological treatment lasted for 12 weeks from the date of enrollment. Then, the indexes of patients were observed. Data were analyzed to study the effect of Bufei granule, with the frequency of acute exacerbation as the primary outcome. Traditional Chinese Medicine syndromes,Modified British Medical Research Council dyspnea scale score, St.George's respiratory questionnaire scores, pulmonary function, and serum inflammatory marker levels [including interleukin-6(IL-6), interleukin-8, tumor necrosis factor-α, and transformation growth factor-β1]were the secondary outcomes.RESULTS: During the 12-week treatment, treatment and control groups had no adverse reactions.The analysis of the indexes obtained from all patients showed that the therapeutic effect in the treatment group was significantly better than that in the control group because most of the similar probabilities of primary and secondary outcomes were less than 0.05,except for the level of IL-6.CONCLUSION: Bufei granule can treat patients with stable COPD by lowering the frequency of acute exacerbation, improving the quality of life,and alleviating the severity of inflammation.