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艾叶精油通过调节5-脂氧合酶-白三烯和吲哚胺2,3-双加氧酶-犬尿氨酸途径缓解哮喘:代谢组学见解

Artemisia argyi essential oil alleviates asthma by regulating 5-LOX-CysLTs and IDO-1-KYN pathways: Insights from metabolomics.

作者信息

Rong Ying, Tang Mengqi, Liu Luyao, Ma Xiaoge, Liu Mengge, Qu Lingbo, Liao Xinglin, Jiang Qiman, Zhang Nan, Xu Xia

机构信息

Department of Medical Analysis, School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, Henan, 450001, PR China.

Nanyang LANHAISENYUAN Medical Technology Ltd.,CO, Nanyang, Henan, 473000, PR China.

出版信息

J Ethnopharmacol. 2024 Oct 28;333:118458. doi: 10.1016/j.jep.2024.118458. Epub 2024 Jun 11.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Artemisia argyi essential oil (AAEO) is a traditional herbal remedy for asthma. However, the potential effect of AAEO on asthma has not been elucidated.

AIM OF THE STUDY

To investigate the protective properties of AAEO upon asthma and elucidate its mechanism.

MATERIALS AND METHODS

The effects of AAEO in asthma were assessed by histology and biochemical analysis. Then, we integrated real-time reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry and metabolomics analysis to reveal its mechanism.

RESULTS

In vivo, AAEO reduced the counts of white blood cells (WBCs) and cytokines in bronchoalveolar lavage fluid (BALF), ameliorated pathologic alterations in lung tissues, and inhibited secretion of OVA-sIgE and muc5ac. Metabolomics results showed that AAEO can exert therapeutic effects on asthmatic mice by regulating disordered arachidonic acid metabolism and tryptophan metabolism. Further studies shown that AAEO inhibited the expression of 5-LOX and reduced the accumulation of CysLTs in mice. Meanwhile, AAEO promoted the activity of IDO-1, facilitated the conversion of tryptophan to kynurenine, and regulated the imbalance of Treg/Th17 immunity. Immunohistochemical results showed that AAEO promoted the expression of IDO-1. RT-qPCR results showed that AAEO promoted the expression of IL-10 and Foxp3 mRNA, and inhibited the expression of IL-17A and RORγt mRNA, thus regulated the imbalance of Treg/Th17 immunity and exerted its therapeutic effects.

CONCLUSION

AAEO treatment not only attenuates the clinical symptoms of asthma but is also involved in regulating lung tissue metabolism. The anti-asthmatic activity of AAEO may be achieved by reprogramming 5-LOX-CysLTs and IDO-1-KYN pathways.

摘要

民族药理学相关性

艾叶精油(AAEO)是一种治疗哮喘的传统草药。然而,AAEO对哮喘的潜在作用尚未阐明。

研究目的

研究AAEO对哮喘的保护作用并阐明其机制。

材料与方法

通过组织学和生化分析评估AAEO在哮喘中的作用。然后,我们整合实时逆转录定量聚合酶链反应、酶联免疫吸附测定、免疫组织化学和代谢组学分析来揭示其机制。

结果

在体内,AAEO减少了支气管肺泡灌洗液(BALF)中的白细胞(WBC)计数和细胞因子,改善了肺组织的病理改变,并抑制了OVA-sIgE和muc5ac的分泌。代谢组学结果表明,AAEO可通过调节紊乱的花生四烯酸代谢和色氨酸代谢对哮喘小鼠发挥治疗作用。进一步研究表明,AAEO抑制小鼠中5-LOX的表达并减少半胱氨酰白三烯(CysLTs)的积累。同时,AAEO促进吲哚胺2,3-双加氧酶-1(IDO-1)的活性,促进色氨酸向犬尿氨酸的转化,并调节调节性T细胞(Treg)/辅助性T细胞17(Th17)免疫失衡。免疫组织化学结果表明,AAEO促进IDO-1的表达。逆转录定量聚合酶链反应(RT-qPCR)结果表明,AAEO促进白细胞介素-10(IL-10)和叉头框蛋白3(Foxp3)mRNA的表达,并抑制白细胞介素-17A(IL-17A)和维甲酸相关孤儿受体γt(RORγt)mRNA的表达,从而调节Treg/Th17免疫失衡并发挥其治疗作用。

结论

AAEO治疗不仅减轻哮喘的临床症状,还参与调节肺组织代谢。AAEO的抗哮喘活性可能通过重编程5-LOX-CysLTs和IDO-1-KYN途径来实现。

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