New Opportunities and Challenges of Natural Products Research: When Target Identification Meets Single-cell Multiomics

Overview

Journal Acta Pharm Sin B

Publisher Elsevier

Specialty Pharmacology

Date 2022 Nov 17

PMID 36386472

Authors

Yuyu Zhu

Zijun Ouyang

Haojie Du

Meijing Wang

Jiaojiao Wang

Haiyan Sun

Lingdong Kong

Qiang Xu

Hongyue Ma

Yang Sun

Affiliations

Soon will be listed here.

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.

Citing Articles

MLKL as an emerging machinery for modulating organelle dynamics: regulatory mechanisms, pathophysiological significance, and targeted therapeutics.

Wang Y, Wei W, Zhang Y, Miao J, Bao X, Lu C Front Pharmacol. 2025; 16:1512968.

PMID: 40070567 PMC: 11893596. DOI: 10.3389/fphar.2025.1512968.

Potential mechanism of traditional Chinese medicine intervention in gastric cancer: targeted regulation of autophagy.

Sun S, Yu W, Zhang G, Li X, Song L, Lv Y Front Pharmacol. 2025; 16:1548672.

PMID: 40066330 PMC: 11891941. DOI: 10.3389/fphar.2025.1548672.

Carabrone Attenuates Metabolic Dysfunction-Associated Steatohepatitis by Targeting STAT3 in Mice.

Pan A, Jin J, Wu Y, Zhang Q, Chen H, Hu Y MedComm (2020). 2025; 6(3):e70145.

PMID: 40066227 PMC: 11892021. DOI: 10.1002/mco2.70145.

Advances and mechanisms of traditional Chinese medicine and its active ingredients against antibiotic-resistant infections.

Yang S, Su P, Li L, Liu S, Wang Y J Pharm Anal. 2025; 15(2):101117.

PMID: 40026356 PMC: 11871446. DOI: 10.1016/j.jpha.2024.101117.

High Rosmarinic Acid Content L. Phytocomplex Modulates Microglia Neuroinflammation Induced by High Glucose.

Videtta G, Sasia C, Galeotti N Antioxidants (Basel). 2025; 14(2).

PMID: 40002348 PMC: 11851730. DOI: 10.3390/antiox14020161.

References

Hou M, Wang R, Zhao S, Wang Z . Ginsenosides in genus and their biosynthesis. Acta Pharm Sin B. 2021; 11(7):1813-1834. PMC: 8343117. DOI: 10.1016/j.apsb.2020.12.017. View

Duckert H, Pries V, Khedkar V, Menninger S, Bruss H, Bird A . Natural product-inspired cascade synthesis yields modulators of centrosome integrity. Nat Chem Biol. 2011; 8(2):179-84. DOI: 10.1038/nchembio.758. View

Barreca M, Stathis A, Barraja P, Bertoni F . An overview on anti-tubulin agents for the treatment of lymphoma patients. Pharmacol Ther. 2020; 211:107552. DOI: 10.1016/j.pharmthera.2020.107552. View

Wu J, Shao Y, Liu J, Chen G, Ho P . The medicinal use of realgar (As₄S₄) and its recent development as an anticancer agent. J Ethnopharmacol. 2011; 135(3):595-602. DOI: 10.1016/j.jep.2011.03.071. View

Reynolds G, Vegh P, Fletcher J, Poyner E, Stephenson E, Goh I . Developmental cell programs are co-opted in inflammatory skin disease. Science. 2021; 371(6527). PMC: 7611557. DOI: 10.1126/science.aba6500. View

Chan H, Shan H, Dahoun T, Vogel H, Yuan S . Advancing Drug Discovery via Artificial Intelligence. Trends Pharmacol Sci. 2019; 40(8):592-604. DOI: 10.1016/j.tips.2019.06.004. View

Shen Z, Zhu M, Zhao A . [Comparative observation on efficacy of jieyu pill and maprotiline in treating depression]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004; 24(5):415-7. View

Wang K, Chen Y, Gao S, Wang M, Ge M, Yang Q . Norlichexanthone purified from plant endophyte prevents postmenopausal osteoporosis by targeting ER to inhibit RANKL signaling. Acta Pharm Sin B. 2021; 11(2):442-455. PMC: 7893202. DOI: 10.1016/j.apsb.2020.09.012. View

Fattori V, Hohmann M, Rossaneis A, Pinho-Ribeiro F, Verri W . Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses. Molecules. 2016; 21(7). PMC: 6273101. DOI: 10.3390/molecules21070844. View

10.

Wang H, Mu W, Zhai J, Xing D, Miao S, Wang J . The key role of Shenyan Kangfu tablets, a Chinese patent medicine for diabetic nephropathy: study protocol for a randomized, double-blind and placebo-controlled clinical trial. Trials. 2013; 14:165. PMC: 3679981. DOI: 10.1186/1745-6215-14-165. View

11.

Hu M, Luo Q, Alitongbieke G, Chong S, Xu C, Xie L . Celastrol-Induced Nur77 Interaction with TRAF2 Alleviates Inflammation by Promoting Mitochondrial Ubiquitination and Autophagy. Mol Cell. 2017; 66(1):141-153.e6. PMC: 5761061. DOI: 10.1016/j.molcel.2017.03.008. View

12.

Xu M, Su W, Xu Q, Huang W . Effect of Xingnaojing injection on cerebral edema and blood-brain barrier in rats following traumatic brain injury. Chin J Traumatol. 2010; 13(3):158-62. View

13.

Cai Y, Xin Q, Lu J, Miao Y, Lin Q, Cong W . A New Therapeutic Candidate for Cardiovascular Diseases: Berberine. Front Pharmacol. 2021; 12:631100. PMC: 8010184. DOI: 10.3389/fphar.2021.631100. View

14.

Yang L, Xu B, Yuan C, Dai Z, Wang Y, Li Q . The Antioxidative Action of ZTP by Increasing Nrf2/ARE Signal Pathway. Evid Based Complement Alternat Med. 2019; 2019:5421528. PMC: 6431467. DOI: 10.1155/2019/5421528. View

15.

Yang H, Liu Y, Zhao M, Guo Q, Zheng X, Liu D . Therapeutic potential of targeting membrane-spanning proteoglycan SDC4 in hepatocellular carcinoma. Cell Death Dis. 2021; 12(5):492. PMC: 8121893. DOI: 10.1038/s41419-021-03780-y. View

16.

Yao Y, Liu Y, Zeng Z, Zhao Y, Li T, Chen R . Identification of Target Genes of Antiarrhythmic Traditional Chinese Medicine Wenxin Keli. Cardiovasc Ther. 2020; 2020:3480276. PMC: 7284932. DOI: 10.1155/2020/3480276. View

17.

Li X, Ba Q, Liu Y, Yue Q, Chen P, Li J . Dihydroartemisinin selectively inhibits PDGFRα-positive ovarian cancer growth and metastasis through inducing degradation of PDGFRα protein. Cell Discov. 2018; 3:17042. PMC: 5787695. DOI: 10.1038/celldisc.2017.42. View

18.

Cheng Z, Wu J, Chen J . Clinical observation on the treatment of male neoplastic anemia with Yixuesheng capsule combined with recombination human erythropoietin. Chin J Integr Med. 2009; 15(1):63-5. DOI: 10.1007/s11655-009-0063-3. View

19.

Wang L, Wang B, Gasek N, Zhou Y, Cohn R, Martin D . Targeting p21 highly expressing cells in adipose tissue alleviates insulin resistance in obesity. Cell Metab. 2021; 34(1):75-89.e8. PMC: 8732323. DOI: 10.1016/j.cmet.2021.11.002. View

20.

Zhu H, Hu J, Lo-Coco F, Jin J . The simpler, the better: oral arsenic for acute promyelocytic leukemia. Blood. 2019; 134(7):597-605. DOI: 10.1182/blood.2019000760. View