Integration of metabolomics and transcriptomics reveals the therapeutic mechanism underlying Chelidonium majus L. in the treatment of allergic asthma

IF 5.3 3区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Renguang Wang, Xintong Sui, Xin Dong, Liming Hu, Zhimeng Li, Hang Yu, Cuicui Li, Guoxin Ji, Shumin Wang
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Abstract

Chelidonium majus is a well-known traditional Chinese medicine, and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown. Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, Hematoxylin and eosin (H&E) staining, Masson’s trichrome (Masson) staining, Periodic acid-Schiff (PAS) staining and inflammatory cytokines assay of interleukin (IL)-4, IL-6, IL-17 were implemented to evaluate the protective effects of Chelidonium majus on asthma. Then, the effects of Chelidonium majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses. After administration with Chelidonium majus, the histological injuries of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after Chelidonium majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC (10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs were mainly related to energy metabolism and inflammation, and may be potential therapeutic targets. Chelidonium majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation.
代谢组学和转录组学的整合揭示了马钱子治疗过敏性哮喘的机制
诃子是一种著名的传统中药,据报道具有止咳平喘的功效。然而,其作用机制尚不清楚。哮喘 SD 大鼠首先通过卵清蛋白(OVA)激发而致敏。随后,通过血栓素和伊红(H&E)染色、马森氏三色染色(Masson)、过硫酸希夫(PAS)染色以及白细胞介素(IL)-4、IL-6、IL-17等炎症细胞因子检测,评估毛叶车轴草对哮喘的保护作用。然后,基于转录组学和代谢组学的整合分析,检测了车前子对哮喘的影响及其分子作用机制。结果表明,服用诃子后,肺部炎症、胶原沉积和粘液分泌的组织学损伤减轻,血清炎症细胞因子的扰动也得到了转化。此外,综合分析表明,经毛胆皂苷治疗后,7个不同表达基因(DEGs)(Alox15、P4ha1、Pla2g16、Pde3a、Nme1、Entpd8和Adcy9)和9个代谢生物标志物(ADP、黄嘌呤核苷、次黄嘌呤核苷、肌苷、前列腺素E2(PGE2)、前列腺素F2a(PGF2a)、磷脂酰丝氨酸、肌酸和LysoPC(10:0))与丰富的代谢途径有关,包括嘌呤代谢、花生四烯酸代谢、精氨酸和脯氨酸代谢以及甘油磷脂代谢。所获得的代谢生物标志物和DEGs主要与能量代谢和炎症有关,可能是潜在的治疗靶点。通过调节Alox15、P4ha1、Pla2g16、Pde3a、Nme1、Entpd8和Adcy9基因的表达,恢复能量代谢和炎症反应的紊乱,从而缓解OVA诱导的大鼠哮喘。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Chinese Medicine
Chinese Medicine INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY
CiteScore
7.90
自引率
4.10%
发文量
133
审稿时长
31 weeks
期刊介绍: Chinese Medicine is an open access, online journal publishing evidence-based, scientifically justified, and ethical research into all aspects of Chinese medicine. Areas of interest include recent advances in herbal medicine, clinical nutrition, clinical diagnosis, acupuncture, pharmaceutics, biomedical sciences, epidemiology, education, informatics, sociology, and psychology that are relevant and significant to Chinese medicine. Examples of research approaches include biomedical experimentation, high-throughput technology, clinical trials, systematic reviews, meta-analysis, sampled surveys, simulation, data curation, statistics, omics, translational medicine, and integrative methodologies. Chinese Medicine is a credible channel to communicate unbiased scientific data, information, and knowledge in Chinese medicine among researchers, clinicians, academics, and students in Chinese medicine and other scientific disciplines of medicine.
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