Anti-SARS-CoV and Anti-cancer Effects of Emodin

Document Type : Review Article

Authors

1 Department of Biology, Faculty of Basic Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.

2 Department of Nursing, Faculty of Nursing and Midwifery, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.

3 Department of Biology, Hamedan Branch, Islamic Azad University, Hamedan, Iran.

4 Department of Biology, Urmia Branch, Islamic Azad University, Urmia, Iran.

5 Department of Biology, Faculty of Basic Sciences, Ahar Branch, Islamic Azad University, Ahar, Iran.

Abstract

Background and aims: The SARS-CoV-2 disease 2019 (COVID-19), whose spread started in the late December in 2019 in China, is the main concern in the world today. Potential anti-coronavirus targets can be categorized into two classes depending on the target, one is operating on the host immune system or human cells, and the other is on coronavirus itself. Anthraquinones are generally extracted from the Polygonaceae family, and have many beneficiary characteristics such as being antibacterial, anti-cancer and anti-diabetes. Emodin anthraquinones represent an important role in human health and have golden healthful features making them a drug to cure many illnesses. The aim of this study was to review the inhibiting effect of emodin on cancer and SARS-CoV-2.
 
Methods: This comprehensive literature review was performed on papers that have been published from 1994 till 2020 in various data resources such as NCBI, Science direct, Springer and Web of science. The selected keywords were emodin, medicinal plant, anticancer plant and medicinal herbs, cancer and SARS-CoV-2.
 
Results: Different studies were found that emodin is known as an effective agent to obstruct the interaction of the S protein of SARS-CoV and the host ACE2 (Angiotensin converting enzyme 2) and the infection caused by the retrovirus. In addition, the outbreak of cancer in patients infected by SARS-CoV-2 (COVID-19) is more than it among the general population.
 
Conclusion: Therefore, the present research is going to outline and highlight the anti SARS-CoV-2 therapeutic strategies of emodin and the anti-cancer characteristics’ of this drug.

Keywords

Main Subjects


1.Cui J, Li F, Shi Z-L. Origin and evolution of pathogenic coronaviruses. Nature reviews Microbiology. 2019;17(3):181-92.
2.Li X, Song Y, Wong G, Cui J. Bat origin of a new human coronavirus: there and back again. Science China Life Sciences. 2020;63(3):461-2.
3.Li W, Shi Z, Yu M, Ren W, Smith C, Epstein JH, et al. 2191341. Bats Are Natural Reservoirs of SARS-Like Coronaviruses. Science. 2005;310(5748):676-9.
4.Dominguez SR, O’Shea TJ, Oko LM, Holmes KV. Detection of group 1 coronaviruses in bats in North America. Emerging infectious diseases. 2007;13(9):1295.
5.Gralinski LE, Menachery VD. Return of the Coronavirus: 2019-nCoV. Viruses. 2020;12(2):135.
6.Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin. BioRxiv 2020.
7.Li X, Song Y, Wong G, Cui J. Bat origin of a new human coronavirus: there and back again. Science China Life Sciences2020;63(3):461-2.
8.Wei X, Li X, Cui J. Evolutionary perspectives on novel coronaviruses identified in pneumonia cases in China. National Science Review. 2020;7(2):239-42.
9.Wong MC, Cregeen SJJ, Ajami NJ, Petrosino JF. Evidence of recombination in coronaviruses implicating pangolin origins of nCoV-2019. Biorxiv. 2020.
10.Xiao K, Zhai J, Feng Y, Zhou N, Zhang X, Zou J-J, et al. Isolation and characterization of 2019-nCoV-like coronavirus from Malayan pangolins. BioRxiv. 2020.
11.Lam TT-Y, Shum MH-H, Zhu H-C, Tong Y-G, Ni X-B, Liao Y-S, et al. Identification of 2019-nCoV related coronaviruses in Malayan pangolins in southern China. BioRxiv. 2020.
12.Tang X, Wu C, Li X, Song Y, Yao X, Wu X, et al. On the origin and continuing evolution of SARS-CoV-2. National Science Review. 2020.
13.Bosch BJ, van der Zee R, de Haan CA, Rottier PJ. The coronavirus spike protein is a class I virus fusion protein: structural and functional characterization of the fusion core complex. Journal of virology. 2003;77(16):8801-11.
14.Cancarevic I, Tathineni P, Malik BH. Coronavirus Disease 2019 (COVID-19) in Cancer Patients. Cureus. 2020;12(4).
15.Liang W, Guan W, Chen R, Wang W, Li J, Xu K, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. The Lancet Oncology. 2020;21(3):335-7.
16.Wu C, Liu Y, Yang Y, Zhang P, Zhong W, Wang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B. 2020.
17.Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. The Lancet. 2020;395(10223):470-3.
18.Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. BioRxiv. 2020.
19.Sakai K, Ami Y, Tahara M, Kubota T, Anraku M, Abe M, et al. The host protease TMPRSS2 plays a major role in in vivo replication of emerging H7N9 and seasonal influenza viruses. Journal of virology. 2014;88(10):5608-16.
20.Tarnow C, Engels G, Arendt A, Schwalm F, Sediri H, Preuss A, et al. TMPRSS2 is a host factor that is essential for pneumotropism and pathogenicity of H7N9 influenza A virus in mice. Journal of virology. 2014;88(9):4744-51.
21.Matsuyama S, Nagata N, Shirato K, Kawase M, Takeda M, Taguchi F. Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2. Journal of virology. 2010;84(24):12658-64.
22.Shirato K, Kawase M, Matsuyama S. Middle East respiratory syndrome coronavirus infection mediated by the transmembrane serine protease TMPRSS2. Journal of virology. 2013;87(23):12552-61.
23.Böttcher-Friebertshäuser E, Klenk H-D, Garten W. Activation of influenza viruses by proteases from host cells and bacteria in the human airway epithelium. Pathogens diseases. 2013;69(2):87-100.
24.Momattin H, Mohammed K, Zumla A, Memish ZA, Al-Tawfiq JA. Therapeutic options for Middle East respiratory syndrome coronavirus (MERS-CoV)–possible lessons from a systematic review of SARS-CoV therapy. International Journal of Infectious Diseases. 2013;17(10):e792-e8.
25.Zumla A, Chan JF, Azhar EI, Hui DS, Yuen K-Y. Coronaviruses—drug discovery and therapeutic options. Nature reviews Drug discovery. 2016;15(5):327.
26.Yamaya M, Shimotai Y, Hatachi Y, Homma M, Nishimura H. Serine Proteases and their Inhibitors in Human Airway Epithelial. 2016.
27.Cheng Z, Zhou J, To KK-W, Chu H, Li C, Wang D, et al. Identification of TMPRSS2 as a susceptibility gene for severe 2009 pandemic A (H1N1) influenza and A (H7N9) influenza. The Journal of infectious diseases. 2015;212(8):1214-21.
28.Harcourt BH, Jukneliene D, Kanjanahaluethai A, Bechill J, Severson KM, Smith CM, et al. Identification of severe acute respiratory syndrome coronavirus replicase products and characterization of papain-like protease activity. Journal of virology. 2004;78(24):13600-12.
29.Chen X, Yang X, Zheng Y, Yang Y, Xing Y, Chen ZJP. SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex. Protein cell. 2014;5(5):369-81.
30.Yuan L, Chen Z, Song S, Wang S, Tian C, Xing G, et al. p53 degradation by a coronavirus papain-like protease suppresses type I interferon signaling. Journal of Biological Chemistry. 2015;290(5):3172-82.
31.Li S-W, Wang C-Y, Jou Y-J, Huang S-H, Hsiao L-H, Wan L, et al. SARS coronavirus papain-like protease inhibits the TLR7 signaling pathway through removing Lys63-linked polyubiquitination of TRAF3 and TRAF6. International journal of molecular sciences. 2016;17(5):678.
32.Yang H, Xie W, Xue X, Yang K, Ma J, Liang W, et al. Design of wide-spectrum inhibitors targeting coronavirus main proteases. PLoS biology. 2005;3(10).
33.Subissi L, Imbert I, Ferron F, Collet A, Coutard B, Decroly E, et al. SARS-CoV ORF1b-encoded nonstructural proteins 12–16: replicative enzymes as antiviral targets. Antiviral research. 2014;101:122-30.
34.Imbert I, Guillemot JC, Bourhis JM, Bussetta C, Coutard B, Egloff MP, et al. A second, non‐canonical RNA‐dependent RNA polymerase in SARS Coronavirus. The EMBO journal. 2006;25(20):4933-42.
35.Ivanov KA, Ziebuhr J. Human coronavirus 229E nonstructural protein 13: characterization of duplex-unwinding, nucleoside triphosphatase, and RNA 5′-triphosphatase activities. Journal of virology. 2004;78(14):7833-8.
36.Millet JK, Whittaker GR. Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis. Virus research. 2015;202:120-34.
37.Xia S, Liu Q, Wang Q, Sun Z, Su S, Du L, et al. Middle East respiratory syndrome coronavirus (MERS-CoV) entry inhibitors targeting spike protein. Virus research. 2014;194:200-10.
38.Kamitani W, Narayanan K, Huang C, Lokugamage K, Ikegami T, Ito N, et al. Severe acute respiratory syndrome coronavirus nsp1 protein suppresses host gene expression by promoting host mRNA degradation. Proceedings of the National Academy of Sciences. 2006;103(34):12885-90.
39.Narayanan K, Huang C, Lokugamage K, Kamitani W, Ikegami T, Tseng C-TK, et al. Severe acute respiratory syndrome coronavirus nsp1 suppresses host gene expression, including that of type I interferon, in infected cells. Journal of virology. 2008;82(9):4471-9.
40.Forni D, Cagliani R, Mozzi A, Pozzoli U, Al-Daghri N, Clerici M, et al. Extensive positive selection drives the evolution of nonstructural proteins in lineage C betacoronaviruses. Journal of virology. 2016;90(7):3627-39.
41.Goto T, Kennel SJ, Abe M, Takishita M, Kosaka M, Solomon A, et al. A novel membrane antigen selectively expressed on terminally differentiated human B cells. 1994.
42.Ishikawa J, Kaisho T, Tomizawa H, Lee BO, Kobune Y, Inazawa J, et al. Molecular cloning and chromosomal mapping of a bone marrow stromal cell surface gene, BST2, that may be involved in pre-B-cell growth. Genomics. 1995;26(3):527-34.
43.Blasius AL, Giurisato E, Cella M, Schreiber RD, Shaw AS, Colonna M. Bone marrow stromal cell antigen 2 is a specific marker of type I IFN-producing cells in the naive mouse, but a promiscuous cell surface antigen following IFN stimulation. The Journal of Immunology. 2006;177(5):3260-5.
44.Taylor JK, Coleman CM, Postel S, Sisk JM, Bernbaum JG, Venkataraman T, et al. Severe acute respiratory syndrome coronavirus ORF7a inhibits bone marrow stromal antigen 2 virion tethering through a novel mechanism of glycosylation interference. Journal of virology. 2015;89(23):11820-33.
45.Taylor JK, Coleman CM, Postel S, Sisk JM, Bernbaum JG, Venkataraman T, et al. Severe acute respiratory syndrome coronavirus ORF7a inhibits bone marrow stromal antigen 2 virion tethering through a novel mechanism of glycosylation interference. Journal of virology. 2015;89(23):11820-33.
46.Zeng R, Yang R-F, Shi M-D, Jiang M-R, Xie Y-H, Ruan H-Q, et al. Characterization of the 3a protein of SARS-associated coronavirus in infected vero E6 cells and SARS patients. Journal of molecular biology. 2004;341(1):271-9.
47.Wang K, Xie S, Sun BJBeBA-B. Viral proteins function as ion channels. 2011;1808(2):510-5.
48.Lu W, Zheng B-J, Xu K, Schwarz W, Du L, Wong CK, et al. Severe acute respiratory syndrome-associated coronavirus 3a protein forms an ion channel and modulates virus release. Proceedings of the National Academy of Sciences. 2006;103(33):12540-5.
49.Peng W, Qin R, Li X, Zhou H. Botany, phytochemistry, pharmacology, and potential application of Polygonum cuspidatum Sieb. et Zucc.: a review. Journal of ethnopharmacology. 2013;148(3):729-45.
50.Shan B, Cai Y-Z, Brooks JD, Corke HJFC. Antibacterial properties of Polygonum cuspidatum roots and their major bioactive constituents. 2008;109(3):530-7.
51.Dong X, Fu J, Yin X, Cao S, Li X, Lin L, et al. Emodin: a review of its pharmacology, toxicity and pharmacokinetics. Phytotherapy Research. 2016;30(8):1207-18.
52.Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P. Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Medicinal research reviews. 2007;27(5):591-608.
53.Zhang H-Q, Zhou C-H, Wu Y-Q. Effect of emodin on small intestinal peristalsis of mice and relevant mechanism. World Journal of Gastroenterology: WJG. 2005;11(20):3147.
54.Ali S, Watson M, Osborne R. The stimulant cathartic, emodin, contracts the rat isolated ileum by triggering release of endogenous acetylcholine. Autonomic Autacoid Pharmacology. 2004;24(4):103-5.
55.Hsu S-C, Chung J-G. Anticancer potential of emodin. BioMedicine. 2012;2(3):108-16.
56.Teng Z-h, Zhou S-y, Ran Y-h, Liu X-y, Yang R-t, Yang X, et al. Cellular absorption of anthraquinones emodin and chrysophanol in human intestinal Caco-2 cells. Bioscience, biotechnology, biochemistry. 2007;71(7):1636-43.
57.Lee H-Z, Hsu S-L, Liu M-C, Wu C-H. Effects and mechanisms of aloe-emodin on cell death in human lung squamous cell carcinoma. European journal of pharmacology. 2001;431(3):287-95.
58.Koyama J, Morita I, Tagahara K, Nobukuni Y, Mukainaka T, Kuchide M, et al. Chemopreventive effects of emodin and cassiamin B in mouse skin carcinogenesis. Cancer letters. 2002;182(2):135-9.
59.Chen Y-C, Shen S-C, Lee W-R, Hsu F-L, Lin H-Y, Ko C-H, et al. Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of caspase 3 cascade but independent of reactive oxygen species production. Biochemical pharmacology. 2002;64(12):1713-24.
60.Srinivas G, Anto RJ, Srinivas P, Vidhyalakshmi S, Senan VP, Karunagaran D. Emodin induces apoptosis of human cervical cancer cells through poly (ADP-ribose) polymerase cleavage and activation of caspase-9. European journal of pharmacology. 2003;473(2-3):117-25.
61.Shieh D-E, Chen Y-Y, Yen M-H, Chiang L-C, Lin C-C. Emodin-induced apoptosis through p53-dependent pathway in human hepatoma cells. Life sciences. 2004;74(18):2279-90.
62.Yi J, Yang J, He R, Gao F, Sang H, Tang X, et al. Emodin enhances arsenic trioxide-induced apoptosis via generation of reactive oxygen species and inhibition of survival signaling. Cancer Research. 2004;64(1):108-16.
63.Cha T-L, Qiu L, Chen C-T, Wen Y, Hung M-C. Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth. Cancer research. 2005;65(6):2287-95.
64.Huang Q, Shen H-M, Shui G, Wenk MR, Ong C-N. Emodin inhibits tumor cell adhesion through disruption of the membrane lipid Raft-associated integrin signaling pathway. Cancer research. 2006;66(11):5807-15.
65.Muto A, Hori M, Sasaki Y, Saitoh A, Yasuda I, Maekawa T, et al. Emodin has a cytotoxic activity against human multiple myeloma as a Janus-activated kinase 2 inhibitor. Molecular cancer therapeutics. 2007;6(3):987-94.
66.Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. The Lancet. 2020;395(10224):565-74.
67.Schwarz S, Wang K, Yu W, Sun B, Schwarz W. Emodin inhibits current through SARS-associated coronavirus 3a protein. Antiviral research. 2011;90(1):64-9.
68.Luo W, Su X, Gong S, Qin Y, Liu W, Li J, et al. Anti-SARS coronavirus 3C-like protease effects of Rheum palmatum L. extracts. Bioscience trends. 2009;3(4).
69.Pillaiyar T, Manickam M, Namasivayam V, Hayashi Y, Jung S-H. An Overview of Severe Acute Respiratory Syndrome–Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy. Journal of medicinal chemistry. 2016;59(14):6595-628.
70.Luo W, Su X, Gong S, Qin Y, Liu W, Li J, et al. Anti-SARS coronavirus 3C-like protease effects of Rheum palmatum L. extracts. Bioscience trends. 2009;3(4).
71.Yang H, Yang M, Ding Y, Liu Y, Lou Z, Zhou Z, et al. The crystal structures of severe acute respiratory syndrome virus main protease and its complex with an inhibitor. Proceedings of the National Academy of Sciences. 2003;100(23):13190-5.
72.Lin C-W, Tsai F-J, Tsai C-H, Lai C-C, Wan L, Ho T-Y, et al. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. 2005;68(1):36-42.
73.Masjedi A, Hashemi V, Hojjat-Farsangi M, Ghalamfarsa G, Azizi G, Yousefi M, et al. The significant role of interleukin-6 and its signaling pathway in the immunopathogenesis and treatment of breast cancer. Biomedicine Pharmacotherapy. 2018;108:1415-24.
74.Masjedi A, Hashemi V, Hojjat-Farsangi M, Ghalamfarsa G, Azizi G, Yousefi M, et al. The significant role of interleukin-6 and its signaling pathway in the immunopathogenesis and treatment of breast cancer. Biomedicine Pharmacotherapy. 2018;108:1415-24.
75.Liang Z, Chen H, Yu Z, Zhao Z. Comparison of raw and processed Radix Polygoni Multiflori (Heshouwu) by high performance liquid chromatography and mass spectrometry. Chinese Medicine. 2010;5(1):29.
76.Stark A, Townsend J, Wogan G, Demain A, Manmade A, Ghosh A. Mutagenicity and antibacterial activity of mycotoxins produced by Penicillium islandicum Sopp and Penicillium rugulosum. Journal of environmental pathology toxicology letters. 1978;2(2):313-24.
77.Van der Hoeven J, editor Occurrence and detection of natural mutagens and modifying factors in food products. Princess Takamatsu symposia; 1985.
78.Bruggeman I, Van der Hoeven J. Lack of activity of the bacterial mutagen emodin in HGPRT and SCE assay with V79 Chinese hamster cells. Mutation Research/Genetic Toxicology. 1984;138(2-3):219-24.
79.Mengs U, Krumbiegel G, Völkner W. Lack of emodin genotoxicity in the mouse micronucleus assay. Mutation Research/Genetic Toxicology Environmental Mutagenesis. 1997;393(3):289-93.
80.Brusick D, Mengs U. Assessment of the genotoxic risk from laxative senna products. Environmental molecular mutagenesis. 1997;29(1):1-9.