Dai Chuanhao, Liu Dewen, Qin Cuiying, Fang Jingya, Cheng Guangqing, Xu Chunhong, Wang Qixin, Lu Tianming, Guo Zuchang, Wang Jigang, Zhong Tianyu, Guo Qiuyan
Department of Clinical Laboratory, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
J Ethnopharmacol. 2025 Jan 31;340:119124. doi: 10.1016/j.jep.2024.119124. Epub 2024 Dec 16.
Chronic asthma caused by allergies is a lung illness marked by airway remodeling and hyperresponsiveness. Guben Kechuan (GK) granule is a clinically proven formula for treating lung disease. It relieves cough and helps to clear phlegm, but the mechanisms underlying its treatment for asthma are not clear.
We aimed to elucidate the efficacy and potential mechanisms by which GK ameliorates allergic asthma.
Ultra-performance liquid chromatography (UHPLC-LTQ-Orbitrap-MS) identified the main chemical components of GK. The efficacy of GK was studied in an ovalbumin/alum (OVA)/AL(OH)-sensitized rat model of bronchial asthma by measuring cytokine concentrations in serum and alveolar lavage samples, examining tissue pathology, and performing leukocyte counts. The mechanisms underlying its effectiveness in asthma were investigated by both transcriptomic and proteomic analyses.
GK relieved asthma-induced airway inflammation and remodeling, reduced inflammatory cell infiltration, and decreased the levels of the inflammatory cytokines TNF-α, IL-4, IL-5, IL-6, and IL-10. Analysis of the transcriptomic and proteomic results found that asthma activated the transcription factors STAT3 and NF-κB and induced oxidative-stress damage and apoptosis. GK was found to reduce Bax and caspase-3 expression, increase Bcl-2 expression, and inhibit asthma-induced apoptosis. GK downregulated the expression of the transcription factors STAT3 and NF-kB, which decreased the inflammatory response. Decreases in CAT, SOD, and GSH reduced asthma-induced oxidative-stress damage.
Our findings provide evidence that GK alleviates bronchial asthma by inhibiting apoptosis and oxidative stress damage mediated by the NF-κB/STAT3 signaling pathway.
由过敏引起的慢性哮喘是一种以气道重塑和高反应性为特征的肺部疾病。固本咳喘(GK)颗粒是一种经临床验证的治疗肺部疾病的方剂。它能缓解咳嗽并有助于祛痰,但其治疗哮喘的机制尚不清楚。
我们旨在阐明GK改善过敏性哮喘的疗效和潜在机制。
采用超高效液相色谱法(UHPLC-LTQ-Orbitrap-MS)鉴定GK的主要化学成分。通过测量血清和肺泡灌洗样本中的细胞因子浓度、检查组织病理学以及进行白细胞计数,研究GK在卵清蛋白/明矾(OVA)/氢氧化铝致敏的支气管哮喘大鼠模型中的疗效。通过转录组学和蛋白质组学分析研究其治疗哮喘有效性的潜在机制。
GK减轻了哮喘诱导的气道炎症和重塑,减少了炎性细胞浸润,并降低了炎性细胞因子TNF-α、IL-4、IL-5、IL-6和IL-10的水平。对转录组学和蛋白质组学结果的分析发现,哮喘激活了转录因子STAT3和NF-κB,并诱导了氧化应激损伤和细胞凋亡。发现GK可降低Bax和caspase-3的表达,增加Bcl-2的表达,并抑制哮喘诱导的细胞凋亡。GK下调了转录因子STAT3和NF-κB的表达,从而降低了炎症反应。CAT、SOD和GSH的减少减轻了哮喘诱导的氧化应激损伤。
我们的研究结果提供了证据,表明GK通过抑制NF-κB/STAT3信号通路介导的细胞凋亡和氧化应激损伤来减轻支气管哮喘。