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1Traditional Medicine Research  2020, Vol. 5 Issue (3): 167-177    DOI: 10.12032/TMR20190814130
Special Issue on Infectious Diseases and Public Health     
The role of natural products in regulating pyroptosis
Yi-Zhen Bai1, Ke-Wu Zeng1,*()
1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
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Highlights

This manuscript categorizes and concludes research results on the correlation between different natural products and pyroptosis in recent years.

Traditionality

The present review summarizes many natural products coming from traditional Chinese medicine that play the role in regulating pyroptosis, such as Chuanxinlian [Andrographis paniculata (Burm. f.) Nees.], Gancao (Glycyrrhiza uralensis Fisch.), Huanglian (Coptis chinensis Franch.), Tusizi (Cuscuta chinensis Lam.), Heizhima (Sesamum indicum L.), etc. The first record about Gancao (Glycyrrhiza uralensis Fisch.) and Huanglian (Coptis chinensis Franch) is in the ancient book of Chinese medicine named Shennongbencaojing (Donghan dynasty of China).

Abstract

In recent years, large numbers of novel cell death types have been reported such as autophagic death, paraptosis, mitosis, oncosis and pyroptosis. As a new type of proinflammatory programmed cell death, pyroptosis has attracted increasing attentions gradually, and its morphological characteristics and molecular mechanisms are significantly different from other cell death types such as necrosis and apoptosis. Many research groups have demonstrated the association between pyroptosis and various human diseases including immunological disease, cancer, atherosclerosis, infectious disease, and cardiovascular and cerebrovascular disease. Natural products are small molecules synthetized in organisms including primary and secondary metabolites. Natural products are important sources of modern innovative drugs discovery and can be used as key tools to explore the molecular mechanism of cell fate. The aim of this study is to review the molecular mechanisms and pathways of pyroptosis, and to categorize and conclude research results on the correlation between different natural products and pyroptosis in recent years. In this study, a total of 39 papers were enrolled in analyses. The molecular pathways and mechanisms of pyroptosis were clearly described. Fourteen types of natural products, their sources, effects, mechanisms and therapeutic potentials are categorized and illuminated. It is showed that a variety of natural products and pyroptosis have close correlations. They negatively or positively affect or act on different positions of pyroptosis inflammatory pathways, indicating that they may have certain potential therapeutic effects on pyroptosis-related diseases. Pyroptosis, a relatively new way of cell death, is closely associated with a variety of diseases. Natural products can have obvious effects on the process of pyroptosis as potential sources of new drugs. In-depth studies using natural products to investigate pyroptosis will help to enhance our understandings of human diseases and establish effective prevention and treatment strategies.



Key wordsNatural products      Pyroptosis      Programmed cell death      Gasdermin-D      Inflammasome     
Published: 13 April 2020
Fund:  This study was supported by the National Natural Science Foundation of China [Nos. 81773932, 30873072 and 81530097] and the National Key Technology R&D Program “New Drug Innovation” of China [No. 2018ZX09711001-008-003]
Corresponding Authors: Ke-Wu Zeng   
E-mail: ZKW@bjmu.edu.cn
Cite this article:

Yi-Zhen Bai, Ke-Wu Zeng. The role of natural products in regulating pyroptosis. 1Traditional Medicine Research, 2020, 5(3): 167-177. doi: 10.12032/TMR20190814130

URL:

https://www.tmrjournals.com/tmr/EN/10.12032/TMR20190814130

Structure types Compounds Sources Effects in Pyroptosis Pathways
Inflammasome formation Caspase activation GSDMD cleavage Cytokine release
Flavonoids Dihydromyricetin Tianchateng [Ampelopsis grossedentata (Hand. -Mazz.) W. T. Wang]
Scutellarin Dengzhanhua [Erigeron breviscapus (Vant.) Hand. -Mazz.]
Taxifolin Luoyesong [Larix gmelinii (Rupr.) Kuzen.]
Saponins Celastrol Nansheteng [Celastrus orbiculatus Thunb.]
Chikusetsu saponin IVa Zhuzishen [Panax japonicus C. A. Mey. var. major (Burk.) C. Y. Wu et K. M. Feng]
Glycyrrhizin Gancao (Glycyrrhiza uralensis Fisch.)
Organic phenol Gossypol Mianhua (Gossypium barbadense L.)
Alkaloids Piperine Hujiao (Piper nigrum L.)
Berberine Huanglian (Coptis chinensis Franch.)
Lipids Vitamin E Vegetable oil & green vegetables
Quinones Emodin Huzhang (Polygonum cuspidatum Sieb. et Zucc.)
Thymoquinone Heizhongcao (Nigella glandulifera Freyn)
Heavy Metals Mercury & Arsenic Shuiyin (Mercury) & Pishuang (As2O3)/ Xionghuang (α-As4S4)
Table1 The classifications, plant origins and functions of compounds in pyroptosis pathway
Figure 1 Chemical structures of Dihydromyricetin, Scutellarin and Taxifolin
Figure 2 Chemical structures of Andrographolide, Celastrol, Chikusetsu saponin Iva and Glycyrrhizin
Figure 3 Chemical structures of Gossypol, Piperine and Berberine
Figure 4 Chemical structures of Vitamin E, Emodin and Thymoquinone
Figure 5 Schematic diagram of pyroptosis pathway and part of the natural products
NLRP, Nucleotide-binding oligomerization domain-like receptor protein; ASC, Apoptosis-associated speck-like protein containing CARD; GSDMD, Gasdermin-DCARD.
1.   Aglietti RA, Dueber EC. Recent Insights into the Molecular Mechanisms Underlying Pyroptosis and Gasdermin Family Functions. Trends Immunol 2017, 38: 261-271.
2.   Ramos-Junior ES, Morandini AC. Gasdermin: A new player to the inflammasome game. Biomed J 2017, 40: 313-316.
3.   Shi J, Gao W, Shao F. Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death. Trends Biochem Sci 2017, 42: 245-254.
4.   Evavold CL, Ruan J, Tan Y, et al. The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages. Immunity 2018, 48: 35-44.
5.   Shi J, Zhao Y, Wang K, et al. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 2015, 526: 660-665.
6.   Monteleone M, Stanley AC, Chen KW, et al. Interleukin-1beta Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion. Cell Rep 2018, 24: 1425-1433.
7.   Chu Q, Jiang Y, Zhang W, et al. Pyroptosis is involved in the pathogenesis of human hepatocellular carcinoma. Oncotarget 2016, 7: 84658-84665.
8.   Dong Z, Pan K, Pan J, et al. The Possibility and Molecular Mechanisms of Cell Pyroptosis After Cerebral Ischemia. Neurosci Bull 2018, 34: 1131-1136.
9.   Ye J, Zhang R, Wu F, et al. Non-apoptotic cell death in malignant tumor cells and natural compounds. Cancer Lett 2018, 420: 210-227.
10.   Yuan YY, Xie KX, Wang S, et al. Inflammatory caspase-related pyroptosis: mechanism, regulation and therapeutic potential for inflammatory bowel disease. Gastroenterol Rep (Oxf) 2018, 6: 167-176.
11.   Liu X, Zhang Z, Ruan J, et al. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature 2016, 535: 153-158.
12.   Knodler LA, Crowley SM, Sham HP, et al. Noncanonical inflammasome activation of caspase-4/caspase-11 mediates epithelial defenses against enteric bacterial pathogens. Cell Host Microbe 2014, 16: 249-256.
13.   Liu Z, Wang C, Rathkey JK, et al. Structures of the Gasdermin D C-Terminal Domains Reveal Mechanisms of Autoinhibition. Structure 2018, 26: 778-784 e773.
14.   Xu B, Jiang M, Chu Y, et al. Gasdermin D plays a key role as a pyroptosis executor of non-alcoholic steatohepatitis in humans and mice. J Hepatol 2018, 68: 773-782.
15.   Yang J, Zhao Y, Shao F. Non-canonical activation of inflammatory caspases by cytosolic LPS in innate immunity. Curr Opin Immunol 2015, 32: 78-83.
16.   Chen Q, Shi P, Wang Y, et al. GSDMB promotes non-canonical pyroptosis by enhancing caspase-4 activity. J Mol Cell Biol 2019, 11: 496-508.
17.   Feng S, Fox D, Man SM. Mechanisms of Gasdermin Family Members in Inflammasome Signaling and Cell Death. J Mol Biol 2018, 430: 3068-3080.
18.   Kovacs SB, Miao EA. Gasdermins: Effectors of Pyroptosis. Trends Cell Biol 2017, 27: 673-684.
19.   Sarhan J, Liu BC, Muendlein HI, et al. Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during Yersinia infection. Proceedings of the National Academy of Sciences of the United States of America 2018, 115: E10888-E10897.
20.   Schneider KS, Gross CJ, Dreier RF, et al. The Inflammasome Drives GSDMD-Independent Secondary Pyroptosis and IL-1 Release in the Absence of Caspase-1 Protease Activity. Cell Rep 2017, 21: 3846-3859.
21.   Tsuchiya K, Nakajima S, Hosojima S, et al. Caspase-1 initiates apoptosis in the absence of gasdermin D. Nature communications 2019, 10: 2091-2091.
22.   Wang Y, Gao W, Shi X, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature 2017, 547: 99-103.
23.   Wang Y, Yin B, Li D, et al. GSDME mediates caspase-3-dependent pyroptosis in gastric cancer. Biochem Biophys Res Commun 2018, 495: 1418-1425.
24.   Wang YC, Liu QX, Zheng Q, et al. Dihydromyricetin Alleviates Sepsis-Induced Acute Lung Injury through Inhibiting NLRP3 Inflammasome-Dependent Pyroptosis in Mice Model. Inflammation 2019, 42: 1301-1310.
25.   Hu Q, Zhang T, Yi L, et al. Dihydromyricetin inhibits NLRP3 inflammasome-dependent pyroptosis by activating the Nrf2 signaling pathway in vascular endothelial cells. Biofactors 2018, 44: 123-136.
26.   Liu Y, Jing YY, Zeng CY, et al. Scutellarin Suppresses NLRP3 Inflammasome Activation in Macrophages and Protects Mice against Bacterial Sepsis. Front Pharmacol 2017, 8: 975.
27.   Ye Y, Wang X, Cai Q, et al. Protective effect of taxifolin on H2O2-induced H9C2 cell pyroptosis. J Cent South Univ (Medical sciences). 2017, 42: 1367-1374. (Chinese)
28.   Li X, Wang T, Zhang D, et al. Andrographolide ameliorates intracerebral hemorrhage induced secondary brain injury by inhibiting neuroinflammation induction. Neuro- pharmacology 2018, 141: 305-315.
29.   Dai W, Wang X, Teng H, et al. Celastrol inhibits microglial pyroptosis and attenuates inflammatory reaction in acute spinal cord injury rats. Int Immunopharmacol 2019, 66: 215-223.
30.   Xin W, Wang Q, Zhang D, et al. A new mechanism of inhibition of IL-1beta secretion by celastrol through the NLRP3 inflammasome pathway. Eur J Pharmacol 2017, 814: 240-247.
31.   Hua S, Ma M, Fei X, et al. Glycyrrhizin attenuates hepatic ischemia-reperfusion injury by suppressing HMGB1 - dependent GSDMD - mediated kupffer cells pyroptosis. Int Immunopharmacol 2019, 68: 145-155.
32.   Lin QR, Li CG, Zha QB, et al. Gossypol induces pyroptosis in mouse macrophages via a non-canonical inflammasome pathway. Toxicol Appl Pharmacol 2016, 292: 56-64.
33.   Peng X, Yang T, Liu G, et al. Piperine ameliorated lupus nephritis by targeting AMPK-mediated activation of NLRP3 inflammasome. Int Immunopharmacol 2018, 65: 448-457.
34.   Liang YD, Bai WJ, Li CG, et al. Piperine Suppresses Pyroptosis and Interleukin-1beta Release upon ATP Triggering and Bacterial Infection. Front Pharmacol 2016, 7: 390.
35.   Li CG, Yan L, Jing YY, et al. Berberine augments ATP-induced inflammasome activation in macrophages by enhancing AMPK signaling. Oncotarget 2017, 8: 95-109.
36.   Kang R, Zeng L, Zhu S, et al. Lipid Peroxidation Drives Gasdermin D-Mediated Pyroptosis in Lethal Polymicrobial Sepsis. Cell Host Microbe 2018, 24: 97-108.
37.   Ye B, Chen X, Dai S, et al. Emodin alleviates myocardial ischemia/reperfusion injury by inhibiting gasdermin D-mediated pyroptosis in cardiomyocytes. Drug Des Devel Ther 2019, 13: 975-990.
38.   Liu H, Sun Y, Zhang Y, et al. Role of Thymoquinone in Cardiac Damage Caused by Sepsis from BALB/c Mice. Inflammation 2019, 42: 516-525.
39.   Ahn H, Kim J, Kang SG, et al. Mercury and arsenic attenuate canonical and non-canonical NLRP3 inflammasome activation. Sci Rep 2018, 8: 13659.
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