Yang Xin-Xin, Wang Shuai, Cui Lin-Lin, Li Tian-Jiao, Bai Gang, Bao Yong-Rui, Meng Xian-Sheng
College of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, China.
Liaoning Multi-Dimensional Analysis of Traditional Chinese Medicine Technical Innovation Center, Dalian, China.
Front Pharmacol. 2022 Dec 15;13:1090345. doi: 10.3389/fphar.2022.1090345. eCollection 2022.
This work was performed to determine the pharmacological effects of Bufei Jianpi granules on chronic obstructive pulmonary disease and its metabolism in rats. Chronic obstructive pulmonary disease (COPD), ranked as the third leading cause of death worldwide, is seriously endangering human health. At present, the pathogenesis of COPD is complex and unclear, and the drug treatment mainly aims to alleviate and improve symptoms; however, they cannot achieve the purpose of eradicating the disease. Bufei Jianpi granule (BJG) is a Chinese medicine developed by the First Affiliated Hospital of Henan University of Traditional Chinese Medicine for treating COPD. This study focuses on the pharmacological effects of BJG on COPD and its metabolism in rats, aiming to provide a scientific basis for developing BJG against COPD. A total of 72 Sprague-Dawley (SD) rats were divided into the blank group, model group, positive control group, and BJG groups (2.36, 1.18, and 0.59 g/kg). Except for the blank group, rats in other groups were administered lipopolysaccharide (LPS) combined with smoking for 6 weeks to establish the COPD model. After another 6 weeks of treatment, the therapeutic effect of BJG on COPD rats was evaluated. In the BJG (2.36 g/kg) group, the cough condition of rats was significantly relieved and the body weight was close to that of the blank group. Compared with the mortality of 16.7% in the model group, no deaths occurred in the BJG (2.36 g/kg) and (1.18 g/kg) groups. The lung tissue damage in the BJG groups was less than that in the COPD group. Compared with the model group, MV, PIF, PEF, and EF50 in the BJG groups were observably increased in a dose-dependent manner, while sRaw, Raw, and FRC were obviously decreased. Also, the contents of IL-6, IL-8, TNF-α, PGE2, MMP-9, and NO in the serum and BALF were lowered dramatically in all BJG groups. All indicators present an obvious dose-effect relationship. On this basis, the UPLC-QTOF-MS/MS technology was used to analyze characteristic metabolites in rats under physiological and pathological conditions. A total of 17 prototype and 7 metabolite components were detected, and the concentration of most components was increased in the COPD pathologic state. It is suggested that BJG has a pharmacological effect in the treatment of COPD and the absorption and metabolism of chemical components of BJG in rats exhibited significant differences under physiological and pathological conditions.
本研究旨在探讨补肺健脾颗粒对大鼠慢性阻塞性肺疾病的药理作用及其代谢情况。慢性阻塞性肺疾病(COPD)是全球第三大致死原因,严重威胁人类健康。目前,COPD的发病机制复杂且尚不明确,药物治疗主要以缓解和改善症状为主,但无法达到根治疾病的目的。补肺健脾颗粒(BJG)是河南中医药大学第一附属医院研制的用于治疗COPD的中药。本研究聚焦于BJG对COPD大鼠的药理作用及其代谢情况,旨在为开发抗COPD的BJG提供科学依据。将72只Sprague-Dawley(SD)大鼠分为空白组、模型组、阳性对照组和BJG组(2.36、1.18和0.59 g/kg)。除空白组外,其他组大鼠采用脂多糖(LPS)联合烟熏6周以建立COPD模型。再经6周治疗后,评估BJG对COPD大鼠的治疗效果。在BJG(2.36 g/kg)组中,大鼠的咳嗽症状明显缓解,体重接近空白组。与模型组16.7%的死亡率相比,BJG(2.36 g/kg)组和(1.18 g/kg)组未出现死亡情况。BJG组的肺组织损伤小于COPD组。与模型组相比,BJG组的分钟通气量(MV)、吸气峰流量(PIF)、呼气峰流量(PEF)和50%用力呼气流量(EF50)明显呈剂量依赖性增加,而比气道阻力(sRaw)、气道阻力(Raw)和功能残气量(FRC)明显降低。此外,所有BJG组血清和支气管肺泡灌洗液(BALF)中白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、前列腺素E2(PGE2)、基质金属蛋白酶-9(MMP-9)和一氧化氮(NO)的含量均显著降低。所有指标均呈现明显的剂量效应关系。在此基础上,采用超高效液相色谱-四极杆飞行时间串联质谱(UPLC-QTOF-MS/MS)技术分析大鼠在生理和病理条件下的特征性代谢产物。共检测到17种原型成分和7种代谢产物成分,且大多数成分在COPD病理状态下的浓度升高。提示BJG对COPD具有药理作用,且BJG化学成分在大鼠体内的吸收和代谢在生理和病理条件下存在显著差异。