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Review
. 2022 Nov;12(11):4011-4039.
doi: 10.1016/j.apsb.2022.08.022. Epub 2022 Aug 27.

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

Yuyu Zhu  1 , Zijun Ouyang  2 , Haojie Du  3 , Meijing Wang  3 , Jiaojiao Wang  1 , Haiyan Sun  2 , Lingdong Kong  3 , Qiang Xu  3 , Hongyue Ma  1 , Yang Sun  3   4
Affiliations
Review

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

Yuyu Zhu et al. Acta Pharm Sin B. 2022 Nov.

Abstract

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization.

Keywords: Biosynthesis; Cancer; Inflammatory diseases; Molecular mechanism; Natural products; Single-cell multiomics; Target identification; Traditional Chinese medicine.

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Figures

Image 1
Graphical abstract
Figure 1
Figure 1
Schematic representation of natural products (in white) improving inflammatory diseases and cancer (in blue). This figure is created with biorender.com.
Figure 2
Figure 2
Milestones in the discovery of typical natural products for the treatment of inflammatory diseases and cancer. This figure is created with biorender.com.
Figure 3
Figure 3
Molecular mechanisms of natural products ameliorating inflammatory diseases and cancer through inducing cell death, inhibiting inflammatory signaling and affecting gut microbiota. This figure is created with biorender.com.
Figure 4
Figure 4
Heatmap of literature scores of TCM for treating several diseases.
Figure 5
Figure 5
Natural product–centric target identification strategies. (A) Covalent binding to affinity magnetic beads; (B) Biotin modification; (C) Bioorthogonal chemical reactions; (D) Probes for photoaffinity groups. This figure is created with biorender.com.
Figure 6
Figure 6
Method for target identification of natural products with Label-free. (A) Drug Affinity Responsive Target Stability (DARTS); (B) Cellular Thermal Shift Assay (CETSA); (C) Target-Responsive Accessibility Profiling (TRAP); (D) Target Identification by Chromatographic Co-Elution (TICC). This figure is created with biorender.com.
Figure 7
Figure 7
Strategies for research on mechanism of natural products based on deciphering target protein. This figure is created with biorender.com.
See this image and copyright information in PMC

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