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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Frontiers Media S.A.
2021
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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) |
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gut bacterial secondary metabolites network pharmacology anticancer AD16 Therapeutics. Pharmacology RM1-950 |
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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 |
work_keys_str_mv |
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