State Key Laboratory of Functions and Applications of Medicinal Plants, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guiyang, 550004, China.
Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, 550004, China; School of Pharmacy, Guizhou Medical University, Guiyang, 550004, China.
J Ethnopharmacol. 2024 May 10;325:117852. doi: 10.1016/j.jep.2024.117852. Epub 2024 Feb 1.
Gerberae Piloselloides Herba (GPH) is derived from Gerbera piloselloides (Linn.) Cass. It is a commonly used traditional medicine in China, featured by its special bioactivities as antitussive, expectorant, anti-asthma, anti-bacterial and anti-tumor. It is often used as an effective treatment for cough and sore throat as well as bronchial asthma (BA) in China. It was demonstrated in our previous studies that GPH exerted significant effects on the treatment of BA, but its underlying mechanism remains unclear.
This study was aimed at revealing the mechanism through which GPH protects against BA.
The protective effect of GPH against BA was evaluated in a mouse model of BA induced by ovalbumin. Through integrated metabolomics and transcriptomics analysis, the most critical pathways were discovered. The effects of GPH in regulating these pathways was verified through molecular biology experiments and molecular docking.
GPH have anti-BA effects. In plasma and lung tissue, 5 and 17 differentially expressed metabolites (DEMs), respectively, showed a reversed tendency in the GPH group compared with the model group; apart from gamma-aminobutyric acid and butyrylcarnitine, these DEMs might aid in BA diagnosis. The DEMs were involved primarily in the regulation of lipid metabolism, followed by glucose metabolism and amino acid metabolism. Transcriptomic analysis indicated that GPH modulated 268 differentially expressed genes (DEGs). Integration analysis of metabolomics and transcriptomics revealed that GPH might regulate the PPAR signaling pathway, thus affecting the expression of key gene targets such as Cyp4a12a, Cyp4a12b, Adh7, Acaa1b and Gpat2; controlling fatty acid degradation, unsaturated fatty acid biosynthesis, glycerophospholipid metabolism and other lipid metabolic pathways; and ameliorating BA. This possibility was confirmed through reverse-transcription quantitative polymerase chain reaction, western blotting, immunofluorescence and molecular docking.
GPH was found to activate the PPAR signaling pathway, decrease the levels of Cyp4a12a and Cyp4a12b, and increase the levels of Adh7, Acaa1b and Gpat2, thereby regulating lipid metabolism disorder, decreasing the generation of inflammatory mediators and limiting lung injury.
Gerbera piloselloides Herba（GPH）源自Gerbera piloselloides（Linn.）Cass。它是中国常用的传统药物，具有镇咳、祛痰、平喘、抗菌、抗肿瘤等特殊的生物活性。在中国，它通常被用作治疗咳嗽和喉咙痛以及支气管哮喘（BA）的有效药物。我们之前的研究表明，GPH 对治疗 BA 有显著效果，但具体机制尚不清楚。
本研究旨在揭示 GPH 防治 BA 的作用机制。
采用卵白蛋白诱导的 BA 小鼠模型评价 GPH 的防治作用。通过整合代谢组学和转录组学分析，发现关键途径。通过分子生物学实验和分子对接验证 GPH 对这些途径的调节作用。
GPH 具有防治 BA 的作用。在血浆和肺组织中，GPH 组与模型组相比，分别有 5 种和 17 种差异表达代谢物（DEMs）呈现出相反的趋势；除γ-氨基丁酸和丁酰肉碱外，这些 DEMs 可能有助于 BA 的诊断。DEMs 主要参与脂质代谢的调节，其次是葡萄糖代谢和氨基酸代谢。转录组分析表明，GPH 调节了 268 个差异表达基因（DEGs）。代谢组学和转录组学的整合分析表明，GPH 可能调节过氧化物酶体增殖物激活受体信号通路，从而影响 Cyp4a12a、Cyp4a12b、Adh7、Acaa1b 和 Gpat2 等关键基因靶标的表达；控制脂肪酸降解、不饱和脂肪酸生物合成、甘油磷脂代谢等脂质代谢途径；改善 BA。通过逆转录定量聚合酶链反应、western blot、免疫荧光和分子对接实验证实了这一可能性。
GPH 被发现可激活过氧化物酶体增殖物激活受体信号通路，降低 Cyp4a12a 和 Cyp4a12b 的水平，增加 Adh7、Acaa1b 和 Gpat2 的水平，从而调节脂质代谢紊乱，减少炎症介质的产生，限制肺损伤。
