Dissection of the Functional Mechanism of Human Gut Bacterial Strain AD16 by Secondary Metabolites’ Identification, Network Pharmacology, and Experimental Validation

Gut microbiota plays important roles in several metabolic processes, such as appetite and food intake and absorption of nutrients from the gut. It is also of great importance in the maintenance of the health of the host. However, much remains unknown about the functional mechanisms of human gut micr...

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Autores principales: Qin Wang, Yao Wang, Ya-Jing Wang, Nan Ma, Yu-Jie Zhou, He Zhuang, Xing-Hua Zhang, Chang Li, Yue-Hu Pei, Shu-Lin Liu
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/f3d7b5e190c7476fac7a0403fc4e0447
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spelling oai:doaj.org-article:f3d7b5e190c7476fac7a0403fc4e04472021-11-05T14:09:51ZDissection of the Functional Mechanism of Human Gut Bacterial Strain AD16 by Secondary Metabolites’ Identification, Network Pharmacology, and Experimental Validation1663-981210.3389/fphar.2021.706220https://doaj.org/article/f3d7b5e190c7476fac7a0403fc4e04472021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.706220/fullhttps://doaj.org/toc/1663-9812Gut microbiota plays important roles in several metabolic processes, such as appetite and food intake and absorption of nutrients from the gut. It is also of great importance in the maintenance of the health of the host. However, much remains unknown about the functional mechanisms of human gut microbiota itself. Here, we report the identification of one anticancer gut bacterial strain AD16, which exhibited potent suppressive effects on a broad range of solid and blood malignancies. The secondary metabolites of the strain were isolated and characterized by a bioactivity-guided isolation strategy. Five new compounds, streptonaphthalenes A and B (1-2), pestaloficins F and G (3-4), and eudesmanetetraiol A (5), together with nine previously known compounds, were isolated from the effective fractions of AD16. Structures of the new compounds were established by 1D and 2D NMR and MS analysis, and the absolute configurations were determined by the CD method. The analysis of network pharmacology suggested that 3, 2, and 13 could be the key components for the anti-NSCLC activity of AD16. In addition to the PI3K–Akt signaling pathway, the proteoglycans in cancer pathway could be involved in the anti-NSCLC action of AD16.Qin WangYao WangYa-Jing WangNan MaYu-Jie ZhouHe ZhuangXing-Hua ZhangChang LiYue-Hu PeiShu-Lin LiuShu-Lin LiuFrontiers Media S.A.articlegut bacterialsecondary metabolitesnetwork pharmacologyanticancerAD16Therapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic gut bacterial
secondary metabolites
network pharmacology
anticancer
AD16
Therapeutics. Pharmacology
RM1-950
spellingShingle gut bacterial
secondary metabolites
network pharmacology
anticancer
AD16
Therapeutics. Pharmacology
RM1-950
Qin Wang
Yao Wang
Ya-Jing Wang
Nan Ma
Yu-Jie Zhou
He Zhuang
Xing-Hua Zhang
Chang Li
Yue-Hu Pei
Shu-Lin Liu
Shu-Lin Liu
Dissection of the Functional Mechanism of Human Gut Bacterial Strain AD16 by Secondary Metabolites’ Identification, Network Pharmacology, and Experimental Validation
description Gut microbiota plays important roles in several metabolic processes, such as appetite and food intake and absorption of nutrients from the gut. It is also of great importance in the maintenance of the health of the host. However, much remains unknown about the functional mechanisms of human gut microbiota itself. Here, we report the identification of one anticancer gut bacterial strain AD16, which exhibited potent suppressive effects on a broad range of solid and blood malignancies. The secondary metabolites of the strain were isolated and characterized by a bioactivity-guided isolation strategy. Five new compounds, streptonaphthalenes A and B (1-2), pestaloficins F and G (3-4), and eudesmanetetraiol A (5), together with nine previously known compounds, were isolated from the effective fractions of AD16. Structures of the new compounds were established by 1D and 2D NMR and MS analysis, and the absolute configurations were determined by the CD method. The analysis of network pharmacology suggested that 3, 2, and 13 could be the key components for the anti-NSCLC activity of AD16. In addition to the PI3K–Akt signaling pathway, the proteoglycans in cancer pathway could be involved in the anti-NSCLC action of AD16.
format article
author Qin Wang
Yao Wang
Ya-Jing Wang
Nan Ma
Yu-Jie Zhou
He Zhuang
Xing-Hua Zhang
Chang Li
Yue-Hu Pei
Shu-Lin Liu
Shu-Lin Liu
author_facet Qin Wang
Yao Wang
Ya-Jing Wang
Nan Ma
Yu-Jie Zhou
He Zhuang
Xing-Hua Zhang
Chang Li
Yue-Hu Pei
Shu-Lin Liu
Shu-Lin Liu
author_sort Qin Wang
title Dissection of the Functional Mechanism of Human Gut Bacterial Strain AD16 by Secondary Metabolites’ Identification, Network Pharmacology, and Experimental Validation
title_short Dissection of the Functional Mechanism of Human Gut Bacterial Strain AD16 by Secondary Metabolites’ Identification, Network Pharmacology, and Experimental Validation
title_full Dissection of the Functional Mechanism of Human Gut Bacterial Strain AD16 by Secondary Metabolites’ Identification, Network Pharmacology, and Experimental Validation
title_fullStr Dissection of the Functional Mechanism of Human Gut Bacterial Strain AD16 by Secondary Metabolites’ Identification, Network Pharmacology, and Experimental Validation
title_full_unstemmed Dissection of the Functional Mechanism of Human Gut Bacterial Strain AD16 by Secondary Metabolites’ Identification, Network Pharmacology, and Experimental Validation
title_sort dissection of the functional mechanism of human gut bacterial strain ad16 by secondary metabolites’ identification, network pharmacology, and experimental validation
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/f3d7b5e190c7476fac7a0403fc4e0447
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