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华中科技大学方进波团队——神香草提取物抑制卵清蛋白致敏的过敏性哮喘

花匠小妙招
2026-06-23 09:09

Zhang Y, Peng H, Li J, et al. Hyssopus cuspidatusextract inhibited OVA-sensitized allergic asthma through PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation [J].Chin Herb Med, 2025, 17(3): 539-547.

神香草提取物通过PI3K/JNK/P38信号通路和脂质稳态调节抑制卵清蛋白致敏的过敏性哮喘

过敏性哮喘是一种以气道炎症和高反应性为特征的慢性呼吸系统疾病，全球范围内都面临着这一重大的健康挑战。目前的治疗方法包括皮质类固醇和支气管扩张剂等，但却常常伴随着严重的副作用，且需要长期应用，极易产生耐受。在这一背景下，探索替代疗法，如传统的中医药疗法显示出极大的优势。

神香草提取物来源于维吾尔族传统医学使用的一种药材-神香草。研究发现，神香草对于过敏性哮喘小鼠具有良好的治疗效果，但其分子机制却并不明确。该研究旨在探究神香草提取物在卵清蛋白诱导的过敏性哮喘小鼠模型中的治疗作用和机制。

本文使用超高效液相色谱-四极杆-飞行时间质谱，鉴定得到神香草提取物中的52种化合物，主要是萜类和黄酮类。体内药效实验发现，神香草提取物显著降低了哮喘小鼠的气道阻力、肺组织中嗜酸性粒细胞的浸润，以及OVA致敏小鼠体内的免疫球蛋白E（IgE）、白细胞介素-4（IL-4）、白细胞介素-5（IL-5）和白细胞介素-13（IL-13）的水平。网络药理学分析表明，磷脂酰肌醇3激酶（PI3K）、c-Jun N末端激酶（JNK）和p38丝裂原活化蛋白激酶（P38）是HCE在治疗过敏性哮喘中靶向的关键蛋白。Western blot结果证实，HCE治疗下调了这些蛋白的磷酸化水平，表明了在过敏性哮喘发病机制中PI3K/JNK/P38信号通路居于核心地位。

此外，非靶向脂质组学分析结果表明，神香草提取物显著上调了神经酰胺（Cer）和鞘磷脂（SM）的水平，同时下调了磷脂酰胆碱（PC）的水平。这些发现表明HCE可能调节脂质稳态，这在哮喘的病理生理学中发挥着重要作用。

本次研究结果提供了有力的证据，表明神香草提取物可能是一个有前景的过敏性哮喘治疗剂。通过调节PI3K/JNK/P38信号通路和脂质稳态，HCE为治疗这一复杂的呼吸系统疾病提供了新方法。这些发现突出了传统医学在现代治疗策略中的潜力，并值得进一步研究HCE的临床应用。

关于神香草提取物对过敏性哮喘影响的研究不仅强调了探索传统医药资源的重要性，也为全球哮喘患者开发更有效、更安全的治疗方法开辟了新途径。

图1 神香草提取物治疗卵清蛋白致敏过敏性哮喘的分子机制

Hyssopus cuspidatusextract inhibited OVA-sensitized allergic asthma through PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation

Yali Zhanga,1, Huiming Pengb,1, Jingjing Lic,1, Pan Lvd,1, Mengru Zhanga, Xu Wanga, Siyu Wanga, Siying Zhua, Jiankang Lua, Xuepeng Fane,f,*, Jinbo Fanga,*

Allergic asthma, characterized by airway inflammation and hyperresponsiveness, is a chronic respiratory disease that poses a significant health challenge worldwide. Current treatment methods, including corticosteroids and bronchodilators, often come with severe side effects and can lead to tolerance when used long-term. Against this backdrop, the exploration of alternative therapies, such as traditional Chinese medicine, shows great promise.

Hyssopus cuspidatusextract (HCE) originates from a medicinal herb used in Uyghur traditional medicine, known as "Zupaqini." Studies have found that this extract has a beneficial therapeutic effect on mice with allergic asthma, although its molecular mechanisms are not well understood. This research aims to investigate the therapeutic effects and mechanisms of HCE in a mouse model of allergic asthma induced by ovalbumin (OVA).

This study utilized ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC Q-TOF MS) to identify 52 compounds in Hyssopus cuspidatus extract, primarily terpenoids and flavonoids. In vivo pharmacological experiments found that the extract significantly reduced airway resistance, eosinophil infiltration in lung tissues, and levels of immunoglobulin E (IgE), interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) in OVA-sensitized asthmatic mice. Network pharmacology analysis indicated that phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (P38) are key proteins targeted by HCE in the treatment of allergic asthma. Western blot results confirmed that HCE treatment downregulated the phosphorylation levels of these proteins, highlighting the central role of the PI3K/JNK/P38 signaling pathway in the pathogenesis of allergic asthma.

Furthermore, untargeted lipidomics analysis revealed that HCE treatment significantly upregulated the levels of ceramide (Cer) and sphingomyelin (SM) while downregulating the level of phosphatidylcholine (PC). These findings suggest that HCE may modulate lipid homeostasis, which plays a crucial role in asthma pathophysiology.

The study’s results provide compelling evidence that HCE could be a promising therapeutic agent for allergic asthma. By modulating the PI3K/JNK/P38 signaling pathways and lipid homeostasis, HCE offers a novel approach to treating this complex respiratory disease. The findings highlight the potential of traditional medicine in modern therapeutic strategies and warrant further investigation into the clinical applications of HCE.

In conclusion, the research on HCE's effects on allergic asthma not only underscores the importance of exploring traditional medicinal resources but also opens new avenues for the development of more effective and safer treatments for asthma sufferers worldwide.

方进波

方进波，华中科技大学同济药学院副教授，硕士/博士研究生导师。主要从事创新中药导向的药效物质、作用机制及品质评价研究。先后赴美国UCLA、UIC、英国曼切斯特大学等校访学进修，兼任世界中联李时珍医药研究与应用专业委员会常务理事，世界中联中药分析专业委员会理事，中国民族医药学会药用资源分会常务理事，湖北省药品监督管理局新药、医疗器械审评及现场核查专家。国家自然科学基金通讯评审专家，教育部硕士学位论文评审专家，人民卫生出版社药学统编教材《生药学》第7、8版编委，《生药学学习指导与习题集》（第1，2版）副主编。主持国家自然科学基金2项、参与国家重点研发计划、国家重大新药创制专项等国家级项目多项，申请/授权发明专利5项。任Chinese Medicine, Chinese Herbal Medicines及Science of Traditional Chinese Medicine(STCM)青年编委，在Phytomedicine, Journal of Natural Products, Acta Pharmacologica Sinica等期刊发表论文30余篇。

张亚丽

张亚丽，2021年毕业于沈阳药科大学获中药学硕士学位，以第一作者在Journal of Ethnopharmacology发表论文2篇。

彭会明

彭会明，博士，华中科技大学同济基础医学院讲师，2003获得华中科技大学同济医学院临床医学学士，2006年获得人体解剖学与组织胚胎学硕士学位，2016年获得德国Duisberg-Essen University分子生物学博士学位，主要从事分子细胞药理学研究，研究成果以第一作者发表在Advanced Science等期刊上。