Integrated metabolomics, network pharmacology and biological verification to reveal the mechanisms of Nauclea officinalis treatment of LPS-induced acute lung injury

被引：8
作者：
Xu, Han [1 ]
Xu, Sicong [3 ]
Li, Liyan [1 ]
Wu, Yuhuang [1 ]
Mai, Shiying [1 ]
Xie, Yiqiang [4 ]
Tan, Yinfeng [1 ]
Li, Ailing [2 ]
Xue, Fengming [2 ]
He, Xiaoning [2 ]
Li, Yonghui [1 ,2 ]
机构：
[1] Hainan Med Univ, Coll Pharm, Key Lab Trop Translat Med, Hainan Prov Key Lab R&D Trop Herbs,Minist Educ, 3 Xueyuan Rd, Haikou 571199, Hainan, Peoples R China
[2] Hainan Med Univ, Affiliated Hosp 2, 368 Yehai Av, Haikou 571199, Hainan, Peoples R China
[3] Hainan Med Univ, Coll Biomed Informat & Engn, Key Lab Trop Translat Med, Minist Educ, 3 Xueyuan Rd, Haikou 571199, Hainan, Peoples R China
[4] Hainan Med Univ, Coll Chinese Med, 3 Xueyuan Rd, Haikou 571199, Hainan, Peoples R China
来源：
CHINESE MEDICINE | 2022年 / 17卷 / 01期
基金：
海南省自然科学基金; 中国国家自然科学基金;
关键词：
Acute lung injury; Nauclea officinalis; Metabolomics; Network pharmacology; Mechanisms; NF-KAPPA-B; GROWTH-FACTOR; INFLAMMATION; STRICTOSAMIDE; JAK2/STAT3; MEDIATORS; APOPTOSIS;
D O I：
10.1186/s13020-022-00685-6
中图分类号：
R [医药、卫生];
学科分类号：
10 ;
摘要：
Background: Acute lung injury (ALI) is a severe inflammatory disease, underscoring the urgent need for novel treatments. Nauclea officinalis Pierre ex Pitard (Danmu in Chinese, DM) is effective in treating inflammatory respiratory diseases. However, there is still no evidence of its protective effect against ALI. Methods: Metabolomics was applied to identify the potential biomarkers and pathways in ALI treated with DM. Further, network pharmacology was introduced to predict the key targets of DM against ALI. Then, the potential pathways and key targets were further verified by immunohistochemistry and western blot assays. Results: DM significantly improved lung histopathological characteristics and inflammatory response in LPS-induced ALI. Metabolomics analysis showed that 16 and 19 differential metabolites were identified in plasma and lung tissue, respectively, and most of these metabolites tended to recover after DM treatment. Network pharmacology analysis revealed that the PI3K/Akt pathway may be the main signaling pathway of DM against ALI. The integrated analysis of metabolomics and network pharmacology identified 10 key genes. These genes are closely related to inflammatory response and cell apoptosis of lipopolysaccharide (LPS)-induced ALI in mice. Furthermore, immunohistochemistry and western blot verified that DM could regulate inflammatory response and cell apoptosis by affecting the PI3K/Akt pathway, and expression changes in Bax and Bcl-2 were also triggered. Conclusion: This study first integrated metabolomics, network pharmacology and biological verification to investigate the potential mechanism of DM in treating ALI, which is related to the regulation of inflammatory response and cell apoptosis. And the integrated analysis can provide new strategies and ideas for the study of traditional Chinese medicines in the treatment of ALI.
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页数：23
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共 62 条
[21]   Surfactant protein B inhibits secretory phospholipase A2 hydrolysis of surfactant phospholipids [J].
Hite, R. Duncan ;
Grier, Bonnie L. ;
Waite, B. Moseley ;
Veldhuizen, Ruud A. ;
Possmayer, Fred ;
Yao, Li-Juan ;
Seeds, Michael C. .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2012, 302 (02) :L257-L265
[22]   Contribution of lectin-like oxidized low-density lipoprotein receptor-1 and LOX-1 modulating compounds to vascular diseases [J].
Hofmann, Anja ;
Brunssen, Coy ;
Morawietz, Henning .
VASCULAR PHARMACOLOGY, 2018, 107 :1-11
[23]   An untargeted metabolomics approach to investigate the wine-processed mechanism of Scutellariae radix in acute lung injury [J].
Hu, Lianqi ;
Wang, Yaqi ;
Sun, Haojie ;
Xiong, You ;
Zhong, Lingyun ;
Wu, Zhenfeng ;
Yang, Ming .
JOURNAL OF ETHNOPHARMACOLOGY, 2020, 253
[24]   Network Pharmacology Integrated Molecular Docking Revealed the Mechanism of Jianpi Yiqi Taohua Decoction Against Ulcerative Colitis [J].
Jia, Lin ;
Zhou, Haiyan ;
Li, Wenhao ;
Lv, Zhantai .
MEDICAL SCIENCE MONITOR, 2022, 28
[25]   MiR-216a alleviates LPS-induced acute lung injury via regulating JAK2/STAT3 and NF-κB signaling [J].
Kong, Fanpo ;
Sun, Yanqi ;
Song, Wenke ;
Zhou, Yongqin ;
Zhu, Siliang .
HUMAN CELL, 2020, 33 (01) :67-78
[26]   Editorial: Network Pharmacology and Traditional Medicine [J].
Lai, Xinxing ;
Wang, Xin ;
Hu, Yuanjia ;
Su, Shibing ;
Li, Wenqing ;
Li, Shao .
FRONTIERS IN PHARMACOLOGY, 2020, 11
[27]   An Integrative Metabolomic and Network Pharmacology Study Revealing the Regulating Properties of Xihuang Pill That Improves Anlotinib Effects in Lung Cancer [J].
Li, Chunyu ;
Wang, Zhihong ;
Chen, Wei ;
Cao, Bo ;
Zhang, Mingyu ;
Gu, Qiong ;
Qi, Shuya ;
Fei, Xiaofei ;
Shi, Yafei ;
Li, Xingjie ;
Li, RuiSheng ;
Wang, Jiabo ;
Li, Guohui .
FRONTIERS IN ONCOLOGY, 2021, 11
[28]   Anti-inflammatory effect of the six compounds isolated from Nauclea officinalis Pierre ex Pitard, and molecular mechanism of strictosamide via suppressing the NF-κB and MAPK signaling pathway in LPS-induced RAW 264.7 macrophages [J].
Li, DongYu ;
Chen, JiaQuan ;
Ye, JiQing ;
Zhai, XiaoTing ;
Song, Jie ;
Jiang, CuiHua ;
Wang, Jing ;
Zhang, Hao ;
Jia, XiaoBin ;
Zhu, FenXia .
JOURNAL OF ETHNOPHARMACOLOGY, 2017, 196 :66-74
[29]   In vivo anti-inflammatory and analgesic activities of strictosamide from Nauclea officinalis [J].
Li, Na ;
Cao, Liang ;
Cheng, Yue ;
Meng, Zhao-Qing ;
Tang, Zhao-Hui ;
Liu, Wen-Jun ;
Wang, Zhen-Zhong ;
Ding, Gang ;
Xiao, Wei .
PHARMACEUTICAL BIOLOGY, 2014, 52 (11) :1445-1450
[30]   Integrated metabolomics and network pharmacology to reveal the mechanisms of hydroxysafflor yellow A against acute traumatic brain injury [J].
Li, Teng ;
Zhang, Wei ;
Hu, En ;
Sun, Zhengji ;
Li, Pengfei ;
Yu, Zhe ;
Zhu, Xiaofei ;
Zheng, Fei ;
Xing, Zhihua ;
Xia, Zian ;
He, Feng ;
Luo, Jiekun ;
Tang, Tao ;
Wang, Yang .
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL, 2021, 19 :1002-1013
1234567