Department of Medical Analysis, School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, Henan, 450001, China.
Nanyang LANHAISENYUAN Medical Technology Ltd, CO. Nanyang, Henan, 473000, China.
Food Funct. 2024 Apr 22;15(8):4292-4309. doi: 10.1039/d3fo04078j.
Asthma is a chronic inflammatory disorder in airways with typical pathologic features of airway inflammation and mucus hypersecretion. α-Terpineol is a monocyclic terpene found in many natural plants and foods. It has been reported to possess a wide range of pharmacological activities including anti-inflammatory and expectorant effects. However, the role of α-terpineol in asthma and its potential protective mechanism have not been well elucidated. This study is designed to investigate the pharmacological effect and mechanism of α-terpineol on asthmatic mice using the metabolomics platform. A murine model of asthma was established using ovalbumin (OVA) sensitization and then challenged for one week. The leukocyte count and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), lung histopathology, inflammatory infiltrate and mucus secretion were evaluated. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based metabolomics study was performed on lung tissues and serum to explore endogenous small molecule metabolites affected by α-terpineol in asthmatic mice. After α-terpineol treatment, leukocyte count, inflammatory cytokines in the BALF, and peribronchial inflammation infiltration were significantly downregulated. Goblet cell hyperplasia and mucus secretion were attenuated, with the level of Muc5ac in BALF decreased. These results proved the protective effect of α-terpineol against airway inflammation, mucus hypersecretion and Th1/Th2 immune imbalance. To further investigate the underlying mechanisms of α-terpineol in asthma treatment, UPLC-MS/MS-based metabolomics analysis was performed. 26 and 15 identified significant differential metabolites were found in the lung tissues and serum of the control, model and α-terpineol groups, respectively. Based on the above differential metabolites, enrichment analysis showed that arachidonic acid (AA) metabolism was reprogrammed in both mouse lung tissues and serum. 5-Lipoxygenase (5-LOX) and cysteinyl leukotrienes (CysLTs) are the key enzyme and the end product of AA metabolism, respectively. In-depth studies have shown that pretreatment with α-terpineol can alleviate asthma by decreasing the AA level, downregulating the expression of 5-LOX and reducing the accumulation of CysLTs in mouse lung tissues. In summary, this study demonstrates that α-terpineol is a potential agent that can prevent asthma regulating disordered AA metabolism.
哮喘是一种气道慢性炎症性疾病，具有气道炎症和黏液高分泌的典型病理特征。α-松油醇是一种单环萜烯，存在于许多天然植物和食物中。据报道，它具有广泛的药理活性，包括抗炎和祛痰作用。然而，α-松油醇在哮喘中的作用及其潜在的保护机制尚未得到充分阐明。本研究旨在利用代谢组学平台研究α-松油醇对哮喘小鼠的药理作用及其机制。采用卵清蛋白（OVA）致敏建立哮喘小鼠模型，然后进行一周攻毒。评估支气管肺泡灌洗液（BALF）中的白细胞计数和炎症细胞因子、肺组织病理学、炎症浸润和黏液分泌。对肺组织和血清进行基于超高效液相色谱-串联质谱（UPLC-MS/MS）的代谢组学研究，以探讨α-松油醇对哮喘小鼠影响的内源性小分子代谢物。经过α-松油醇治疗后，白细胞计数、BALF 中的炎症细胞因子和支气管周围炎症浸润明显下调。杯状细胞增生和黏液分泌减弱，BALF 中 Muc5ac 水平降低。这些结果证明了α-松油醇对气道炎症、黏液高分泌和 Th1/Th2 免疫失衡的保护作用。为了进一步探讨α-松油醇治疗哮喘的潜在机制，进行了基于 UPLC-MS/MS 的代谢组学分析。在对照组、模型组和α-松油醇组的肺组织和血清中分别发现了 26 种和 15 种鉴定的显著差异代谢物。基于上述差异代谢物，富集分析表明，花生四烯酸（AA）代谢在小鼠肺组织和血清中均被重新编程。5-脂氧合酶（5-LOX）和半胱氨酰白三烯（CysLTs）分别是 AA 代谢的关键酶和终产物。深入研究表明，α-松油醇预处理可以通过降低 AA 水平、下调 5-LOX 的表达和减少 CysLTs 在小鼠肺组织中的积累来缓解哮喘。综上所述，本研究表明，α-松油醇是一种潜在的预防哮喘的药物，可通过调节紊乱的 AA 代谢发挥作用。
