Application of omics- and multi-omics-based techniques for natural product target discovery

Zhang, Hongwei; Lv, Chao; Zhang, Lijun; Guo, Xin; Shen, Yiwen; Nagle, Dale G.; Zhou, Yifeng; Liu, Sanhong; Zhang, Guoqing; Luan, Xin

doi:10.1016/j.biopha.2021.111833

Cited by 44 publications

(26 citation statements)

References 130 publications

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“…The discovery of new targets of natural active small molecules will also open up a broad research space for the treatment of related diseases. At present, the identification of natural product targets is becoming increasingly important in the biomedical field, and the identification methods are also diverse, each with its own advantages and disadvantages 301 . The current identification methods can be used both independently and complementarily, and their combined use may be more conducive to the identification of natural product targets.…”

Section: Target Identification and Validation Of Natural Productsmentioning

confidence: 99%

New opportunities and challenges of natural products research: When target identification meets single-cell multiomics

Zhu

Ouyang

et al. 2022

Acta Pharmaceutica Sinica B

176

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Section: Target Identification and Validation Of Natural Productsmentioning

confidence: 99%

New opportunities and challenges of natural products research: When target identification meets single-cell multiomics

Zhu

Ouyang

et al. 2022

Acta Pharmaceutica Sinica B

176

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“…Their unique structures and biological activities are not only of great interest to the research community that aims to discover natural product-based medicines, but also to chemists, biochemists, microbiologists, and metabolic engineers that aim to understand the mechanisms for the generation of these complex molecules and their ecological role and that search for heterologous hosts to efficiently produce these compounds ( Keller, 2019 ; Mattern et al., 2015 ; Tsukada et al., 2020 ). The discovery of novel pathways, gene clusters, and enzymes involved in the biosynthesis of secondary metabolites is still rising due to the progress of various systems biology methodologies from genome sequencing to transcriptomics, proteomics, metabolomics, and bioinformatics ( Baltz, 2019 ; Zhang et al., 2021 ). A successful example of this approach has been recently published for another clade of fungi (early diverging fungi), in which a series of polyketide synthases – enzymes involved in the biosynthesis of secondary metabolites – and a large diversity of natural products have been identified ( Swift et al., 2021 ).…”

Section: Biotechnological Opportunities Of Wrfmentioning

confidence: 99%

Systems biology-guided understanding of white-rot fungi for biotechnological applications: A review

Kijpornyongpan¹,

Schwartz²,

Yaguchi³

et al. 2022

iScience

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“…It is a promising approach to discovering the underlying mechanisms between the multiple-component drug such as herbal extract and their putative targets ( Li and Zhang, 2013 ; Wang et al, 2021a ). Besides, the multi-omics techniques, including genomics, transcriptomics, proteomics, and metabolomics, could directly reflect the changes after drug treatment and have become effective tools to discover potential targets of natural products or TCM ( Zhang et al, 2021 ). Therefore, in the current study, we first demonstrated the antitumor effects of dandelion extract against TNBC in vitro and in vivo .…”

Section: Introductionmentioning

confidence: 99%

Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism

et al. 2022

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Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. TNBC exists widely reprogrammed lipid metabolism, and its metabolic-associated proteins and oncometabolites are promising as potential therapeutic targets. Dandelion (Taraxacum mongolicum) is a classical herbal medicine used to treat breast diseases based on traditional Chinese medicine theory and was reported to have antitumor effects and lipid regulatory capacities. Our previous study showed that dandelion extract was effective against TNBC. However, whether dandelion extract could regulate the lipid metabolisms of TNBC and exert its antitumor effects via interfering with lipids metabolism remained unclear. In this study, an integrated approach combined with network pharmacology and multi-omics techniques (including proteomics, metabolomics, and lipidomics) was performed to investigate the potential regulatory mechanisms of dandelion extract against TNBC. We first determined the antitumor effects of dandelion extract in vitro and in vivo. Then, network pharmacology analysis speculated the antitumor effects involving various metabolic processes, and the multi-omics results of the cells, tumor tissues, and plasma revealed the changes in the metabolites and metabolic-associated proteins after dandelion extract treatment. The alteration of glycerophospholipids and unsaturated fatty acids were the most remarkable types of metabolites. Therefore, the metabolism of glycerophospholipids and unsaturated fatty acids, and their corresponding proteins CHKA and FADS2, were considered the primary regulatory pathways and biomarkers of dandelion extract against TNBC. Subsequently, experimental validation showed that dandelion extract decreased CHKA expression, leading to the inhibition of the PI3K/AKT pathway and its downstream targets, SREBP and FADS2. Finally, the molecular docking simulation suggested that picrasinoside F and luteolin in dandelion extract had the most highly binding scores with CHKA, indicating they may be the potential CHKA inhibitors to regulate glycerophospholipids metabolisms of TNBC. In conclusion, we confirmed the antitumor effects of dandelion extract against TNBC cells in vitro and demonstrated that dandelion extract could interfere with glycerophospholipids and unsaturated fatty acids metabolism via downregulating the CHKA expression and inhibiting PI3K/AKT/SREBP/FADS2 axis.

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Application of omics- and multi-omics-based techniques for natural product target discovery

Cited by 44 publications

References 130 publications

New opportunities and challenges of natural products research: When target identification meets single-cell multiomics

New opportunities and challenges of natural products research: When target identification meets single-cell multiomics

Systems biology-guided understanding of white-rot fungi for biotechnological applications: A review

Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism

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