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代谢组学与转录组学的整合揭示了白屈菜治疗过敏性哮喘的潜在治疗机制。

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

作者信息

Wang Renguang, Sui Xintong, Dong Xin, Hu Liming, Li Zhimeng, Yu Hang, Li Cuicui, Ji Guoxin, Wang Shumin

机构信息

College of Pharmacy, Changchun University of Chinese Medicine, Changchun, 130117, China.

Jilin Zhong Ke Bio-Engineering Co., Ltd, Changchun, 130012, China.

出版信息

Chin Med. 2024 Apr 26;19(1):65. doi: 10.1186/s13020-024-00932-y.

DOI:10.1186/s13020-024-00932-y
PMID:38671520
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11055330/
Abstract

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

背景

白屈菜是一种著名的传统中药,已有报道称其具有止咳平喘作用。然而,其作用机制尚不清楚。

方法

首先通过卵清蛋白(OVA)激发使SD大鼠致敏并建立哮喘模型。随后,进行苏木精-伊红(H&E)染色、Masson三色染色、过碘酸-希夫(PAS)染色以及白细胞介素(IL)-4、IL-6、IL-17炎症细胞因子检测,以评估白屈菜对哮喘的保护作用。然后,基于转录组学和代谢组学分析的整合,检测白屈菜对哮喘的作用及其分子作用机制。

结果

给予白屈菜后,肺部炎症、胶原沉积和黏液分泌的组织学损伤减轻,血清炎症细胞因子紊乱也得到改善。此外,综合分析显示,白屈菜治疗后,发现7个差异表达基因(DEGs)(Alox15、P4ha1、Pla2g16、Pde3a、Nme1、Entpd8和Adcy9)和9种代谢生物标志物(ADP、黄嘌呤核苷、次黄嘌呤、肌苷、前列腺素E2(PGE2)、前列腺素F2α(PGF2α)、磷脂酰丝氨酸、肌酸和溶血磷脂酰胆碱(10:0))与嘌呤代谢、花生四烯酸代谢、精氨酸和脯氨酸代谢以及甘油磷脂代谢等富集代谢途径相关。获得的代谢生物标志物和DEGs主要与能量代谢和炎症相关,可能是潜在的治疗靶点。

结论

白屈菜通过调节Alox15、P4ha1、Pla2g16、Pde3a、Nme1、Entpd8和Adcy9基因表达,恢复能量代谢和炎症紊乱,从而缓解OVA诱导的大鼠哮喘。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/15c5e8d6c504/13020_2024_932_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/5713b16d59d8/13020_2024_932_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/3d14aae6457c/13020_2024_932_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/37e7302b3614/13020_2024_932_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/1624ce948e79/13020_2024_932_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/aed325d39b47/13020_2024_932_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/15c5e8d6c504/13020_2024_932_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/5713b16d59d8/13020_2024_932_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/3d14aae6457c/13020_2024_932_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/37e7302b3614/13020_2024_932_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/1624ce948e79/13020_2024_932_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/aed325d39b47/13020_2024_932_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb2/11055330/15c5e8d6c504/13020_2024_932_Fig6_HTML.jpg

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