Li Jiaqi, Hu Jiaqi, Zhuo Dongliang, Yang Li, Wang Lan, Yang Bin
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China.
State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China.
Phytomedicine. 2025 Jun 11;145:156971. doi: 10.1016/j.phymed.2025.156971.
The complex pathophysiology of asthma and the lack of effective therapies have driven research into natural product remedies. Ginger-processed Magnoliae Officinalis Cortex (GMOC), a traditional Chinese medicine, has been used for asthma treatment, but the lack of its potential mechanism of action limits the clinical application of GMOC.
To investigate the mechanism of action of GMOC in asthmatic mice based on the gut-lung axis.
The anti-asthma effects of GMOC were evaluated in an ovalbumin (OVA)-induced mouse model of asthma. The lung and gut microbiota were analysed via 16S rRNA gene sequencing and short-chain fatty acids (SCFAs) were determined using GC/MS. Protein expression was evaluated by western blotting. Additionally, the chemical profile of GMOC was elucidated using LC/MS. Candidate compounds targeting target proteins were screened using in silico analysis, and an in vitro experiment was used to preliminarily verify the results.
GMOC mitigated lung inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR) in asthmatic mice. It modulated the lung and gut microbiota and increased the levels of SCFAs in the colon, resulting in a reduction in inflammatory responses. In addition, GMOC downregulated transient receptor potential (TRP) channels and key proteins in the PI3K/AKT pathway in the lung and colon. The communication between TRPs and the PI3K/AKT pathway was further investigated in vitro using honokiol, the main compound in GMOC. Further, GMOC upregulated the expression of junction proteins in the lungs and colon to protect the epithelial barrier.
Crosstalk between organs (lung-gut-microbiota) and proteins (TRPs, junction proteins, and proteins in the PI3K/AKT pathway) contributes to the anti-inflammatory activities of GMOC in asthmatic mice.
哮喘复杂的病理生理学以及缺乏有效的治疗方法推动了对天然产物疗法的研究。姜厚朴,一种传统中药,已被用于哮喘治疗,但其潜在作用机制的缺乏限制了姜厚朴的临床应用。
基于肠-肺轴研究姜厚朴在哮喘小鼠中的作用机制。
在卵清蛋白(OVA)诱导的哮喘小鼠模型中评估姜厚朴的抗哮喘作用。通过16S rRNA基因测序分析肺和肠道微生物群,并使用气相色谱/质谱法测定短链脂肪酸(SCFA)。通过蛋白质印迹法评估蛋白质表达。此外,使用液相色谱/质谱法阐明姜厚朴的化学特征。使用计算机分析筛选靶向目标蛋白的候选化合物,并通过体外实验初步验证结果。
姜厚朴减轻了哮喘小鼠的肺部炎症、黏液高分泌和气道高反应性(AHR)。它调节了肺和肠道微生物群,并增加了结肠中SCFA的水平,从而减少了炎症反应。此外,姜厚朴下调了肺和结肠中瞬时受体电位(TRP)通道和PI3K/AKT途径中的关键蛋白。使用姜厚朴中的主要化合物厚朴酚在体外进一步研究了TRP与PI3K/AKT途径之间的通信。此外,姜厚朴上调了肺和结肠中连接蛋白的表达以保护上皮屏障。
器官(肺-肠-微生物群)和蛋白质(TRP、连接蛋白和PI3K/AKT途径中的蛋白质)之间的相互作用有助于姜厚朴在哮喘小鼠中的抗炎活性。