{"title":"多重免疫代谢组学挖掘：通过抑制亮氨酸/PI3K/Akt/mTOR信号通路，NP可预防ALI中的高免疫。","authors":"Mantong Zhao, Jiazi Lin, Xiao Wang, Chengkai Chen, Jianhua Li, Jiamin Yu, Tong Zhou, Yefang Liang, Xuejuan Shen, Ruixiang Shi, Simin Yang, Shuting Zeng, Yongan Deng, Xiaodong Duan, Lichang Zhou, Xiaobo Sun, Yi Wang, Zunpeng Shu","doi":"10.1016/j.freeradbiomed.2024.09.053","DOIUrl":null,"url":null,"abstract":"<p><p>Acute lung injury (ALI) is currently a global health concern. Nicandra physalodes (L.) Gaertn. (NP) holds an important position in traditional Chinese medicine and nutrition. The potential protective mechanisms of NP against ALI remain unknown. The purpose of this study was to investigate the protective effects and molecular mechanisms of NP extract (NPE) on lipopolysaccharide (LPS)-induced ALI in mice. By utilizing network pharmacology to forecast the active ingredients in NP as well as possible signaling pathways. The composition of the NPE was analyzed using UPLC-Q-TOF-MS/MS. In addition, <sup>1</sup>H-NMR immunometabolomics was employed to identify alterations in primary metabolic pathways and metabolites in the lung, serum, and fecal tissues. Finally, the protein and gene expression of key pathways were verified by IHC, IF, RT-qPCR, and ELISA. It was found that the main ingredients of NPE were revealed to be nicandrenone, withanolide A, and baicalin. NPE significantly improved lung injury, pulmonary edema, and inflammatory cell infiltration in mice with ALI. In addition, NPE improved autophagic activity and alleviated Th1 and Th17 cell-induced lung inflammation by suppressing the PI3K/Akt/mTOR signaling pathway. Importantly, immunometabolomic analysis of fecal, serum, and lung tissues revealed that NPE reversed ALI-induced leucine resistance by remodeling immunometabolism. We confirmed NPE prevents ALI by remodeling immunometabolism, regulating the Leucine/PI3K/Akt/mTOR signaling pathway, inhibiting Th1/Th17 cell differentiation, and providing a scientific immunological basis for the clinical application of NPE.</p>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":null,"pages":null},"PeriodicalIF":7.1000,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Multi-immunometabolomics mining: NP prevents hyperimmune in ALI by inhibiting Leucine/PI3K/Akt/mTOR signaling pathway.\",\"authors\":\"Mantong Zhao, Jiazi Lin, Xiao Wang, Chengkai Chen, Jianhua Li, Jiamin Yu, Tong Zhou, Yefang Liang, Xuejuan Shen, Ruixiang Shi, Simin Yang, Shuting Zeng, Yongan Deng, Xiaodong Duan, Lichang Zhou, Xiaobo Sun, Yi Wang, Zunpeng Shu\",\"doi\":\"10.1016/j.freeradbiomed.2024.09.053\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Acute lung injury (ALI) is currently a global health concern. Nicandra physalodes (L.) Gaertn. (NP) holds an important position in traditional Chinese medicine and nutrition. The potential protective mechanisms of NP against ALI remain unknown. The purpose of this study was to investigate the protective effects and molecular mechanisms of NP extract (NPE) on lipopolysaccharide (LPS)-induced ALI in mice. By utilizing network pharmacology to forecast the active ingredients in NP as well as possible signaling pathways. The composition of the NPE was analyzed using UPLC-Q-TOF-MS/MS. In addition, <sup>1</sup>H-NMR immunometabolomics was employed to identify alterations in primary metabolic pathways and metabolites in the lung, serum, and fecal tissues. Finally, the protein and gene expression of key pathways were verified by IHC, IF, RT-qPCR, and ELISA. It was found that the main ingredients of NPE were revealed to be nicandrenone, withanolide A, and baicalin. NPE significantly improved lung injury, pulmonary edema, and inflammatory cell infiltration in mice with ALI. In addition, NPE improved autophagic activity and alleviated Th1 and Th17 cell-induced lung inflammation by suppressing the PI3K/Akt/mTOR signaling pathway. Importantly, immunometabolomic analysis of fecal, serum, and lung tissues revealed that NPE reversed ALI-induced leucine resistance by remodeling immunometabolism. We confirmed NPE prevents ALI by remodeling immunometabolism, regulating the Leucine/PI3K/Akt/mTOR signaling pathway, inhibiting Th1/Th17 cell differentiation, and providing a scientific immunological basis for the clinical application of NPE.</p>\",\"PeriodicalId\":12407,\"journal\":{\"name\":\"Free Radical Biology and Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.1000,\"publicationDate\":\"2024-10-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Free Radical Biology and Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.freeradbiomed.2024.09.053\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Free Radical Biology and Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.freeradbiomed.2024.09.053","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
急性肺损伤（ALI）是目前全球关注的健康问题。Nicandra physalodes (L.) Gaertn.（NP）在传统中药和营养学中占有重要地位。NP 对 ALI 的潜在保护机制仍然未知。本研究旨在探讨 NP 提取物（NPE）对脂多糖（LPS）诱导的小鼠 ALI 的保护作用和分子机制。通过利用网络药理学预测 NPE 中的活性成分以及可能的信号通路。利用 UPLC-Q-TOF-MS/MS 分析了 NPE 的成分。此外，还采用 1H-NMR 免疫代谢组学来确定肺、血清和粪便组织中主要代谢途径和代谢物的变化。最后，通过 IHC、IF、RT-qPCR 和 ELISA 验证了关键通路的蛋白质和基因表达。研究发现，NPE 的主要成分是烟碱酮、香叶醇内酯 A 和黄芩苷。NPE 能明显改善 ALI 小鼠的肺损伤、肺水肿和炎症细胞浸润。此外，NPE 还通过抑制 PI3K/Akt/mTOR 信号通路，改善了自噬活性，减轻了 Th1 和 Th17 细胞诱导的肺部炎症。重要的是，粪便、血清和肺组织的免疫代谢组学分析表明，NPE 通过重塑免疫代谢逆转了 ALI 诱导的亮氨酸抵抗。我们证实 NPE 可通过重塑免疫代谢、调节亮氨酸/PI3K/Akt/mTOR 信号通路、抑制 Th1/Th17 细胞分化来预防 ALI，并为 NPE 的临床应用提供了科学的免疫学依据。
Multi-immunometabolomics mining: NP prevents hyperimmune in ALI by inhibiting Leucine/PI3K/Akt/mTOR signaling pathway.
Acute lung injury (ALI) is currently a global health concern. Nicandra physalodes (L.) Gaertn. (NP) holds an important position in traditional Chinese medicine and nutrition. The potential protective mechanisms of NP against ALI remain unknown. The purpose of this study was to investigate the protective effects and molecular mechanisms of NP extract (NPE) on lipopolysaccharide (LPS)-induced ALI in mice. By utilizing network pharmacology to forecast the active ingredients in NP as well as possible signaling pathways. The composition of the NPE was analyzed using UPLC-Q-TOF-MS/MS. In addition, 1H-NMR immunometabolomics was employed to identify alterations in primary metabolic pathways and metabolites in the lung, serum, and fecal tissues. Finally, the protein and gene expression of key pathways were verified by IHC, IF, RT-qPCR, and ELISA. It was found that the main ingredients of NPE were revealed to be nicandrenone, withanolide A, and baicalin. NPE significantly improved lung injury, pulmonary edema, and inflammatory cell infiltration in mice with ALI. In addition, NPE improved autophagic activity and alleviated Th1 and Th17 cell-induced lung inflammation by suppressing the PI3K/Akt/mTOR signaling pathway. Importantly, immunometabolomic analysis of fecal, serum, and lung tissues revealed that NPE reversed ALI-induced leucine resistance by remodeling immunometabolism. We confirmed NPE prevents ALI by remodeling immunometabolism, regulating the Leucine/PI3K/Akt/mTOR signaling pathway, inhibiting Th1/Th17 cell differentiation, and providing a scientific immunological basis for the clinical application of NPE.
期刊介绍：
Free Radical Biology and Medicine is a leading journal in the field of redox biology, which is the study of the role of reactive oxygen species (ROS) and other oxidizing agents in biological systems. The journal serves as a premier forum for publishing innovative and groundbreaking research that explores the redox biology of health and disease, covering a wide range of topics and disciplines. Free Radical Biology and Medicine also commissions Special Issues that highlight recent advances in both basic and clinical research, with a particular emphasis on the mechanisms underlying altered metabolism and redox signaling. These Special Issues aim to provide a focused platform for the latest research in the field, fostering collaboration and knowledge exchange among researchers and clinicians.
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