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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2013

Open Access 01-12-2013 | Research article

Effects of cocktail of four local Malaysian medicinal plants (Phyllanthus spp.) against dengue virus 2

Authors: Sau Har Lee, Yin Quan Tang, Anusyah Rathkrishnan, Seok Mui Wang, Kien Chai Ong, Rishya Manikam, Bobby Joe Payne, Indu Bala Jaganath, Shamala Devi Sekaran

Published in: BMC Complementary Medicine and Therapies | Issue 1/2013

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Abstract

Background

The absence of commercialized vaccines and antiviral agents against dengue has made the disease a major health concern around the world. With the current dengue virus transmission rate and incidences, the development of antiviral drugs is of vital need. The aim of this project was to evaluate the possibility of developing a local medicinal plant, Phyllanthus as an anti-dengue agent.

Methods

Cocktail (aqueous and methanolic) extracts were prepared from four species of Phyllanthus (P.amarus, P.niruri, P.urinaria, and P.watsonii) and their polyphenolic compounds were identified via HPLC and LC-MS/MS analysis. MTS assay was then carried out to determine the maximal non-toxic dose (MNTD) of the extracts, followed by screening of the in vitro antiviral activity of aqueous cocktail extracts against DENV2 by means of time-of-addition (pre-, simultaneous and post-) using RT-qPCR. The differentially expressed proteins in the treated and infected cells were analysed with two dimensional gel electrophoresis experiments.

Results

Several active compounds including gallic acid, geraniin, syringin, and corilagen have been identified. The MNTD of both aqueous and methanolic extracts on Vero cells were 250.0 μg/ml and 15.63 μg/ml respectively. Phyllanthus showed strongest inhibitory activity against DENV2 with more than 90% of virus reduction in simultaneous treatment. Two-dimensional analysis revealed significantly altered levels of thirteen proteins, which were successfully identified by tandem MS (MS/MS). These altered proteins were involved in several biological processes, including viral entry, viral transcription and translation regulations, cytoskeletal assembly, and cellular metabolisms.

Conclusions

Phyllanthus could be potentially developed as an anti-DENV agent.
Appendix
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Literature
1.
Beatty ME, Stone A, Fitzsimons DW, Hanna JN, Lam SK, Vong S, Guzman MG, Mendez-Galvan JF, Halstead SB, Letson GW: Best practices in dengue surveillance: a report from the Asia-Pacific and Americas Dengue Prevention Boards. PLoS Negl Trop Dis. 2010, 4 (11): e890-10.1371/journal.pntd.0000890.CrossRefPubMedPubMedCentral
2.
Murrell S, Wu SC, Butler M: Review of dengue virus and the development of a vaccine. Biotechnol Adv. 2011, 29 (2): 239-247. 10.1016/j.biotechadv.2010.11.008.CrossRefPubMed
3.
Noble CG, Chen YL, Dong H, Gu F, Lim SP, Schul W, Wang QY, Shi PY: Strategies for development of Dengue virus inhibitors. Antiviral Res. 2010, 85 (3): 450-462. 10.1016/j.antiviral.2009.12.011.CrossRefPubMed
4.
Steuer C, Gege C, Fischl W, Heinonen KH, Bartenschlager R, Klein CD: Synthesis and biological evaluation of alpha-ketoamides as inhibitors of the Dengue virus protease with antiviral activity in cell-culture. Bioorg Med Chem. 2011, 19 (13): 4067-4074. 10.1016/j.bmc.2011.05.015.CrossRefPubMed
5.
Gutsche I, Coulibaly F, Voss JE, Salmon J, d’Alayer J, Ermonval M, Larquet E, Charneau P, Krey T, Megret F: Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein. Proc Natl Acad Sci U S A. 2011, 108 (19): 8003-8008. 10.1073/pnas.1017338108.CrossRefPubMedPubMedCentral
6.
TDR/WHO: Dengue: guidelines for diagnosis, treatment, prevention and control. 2009, Geneva: World Health Organization
7.
Halstead SB, Porterfield JS, O’Rourke EJ: Enhancement of dengue virus infection in monocytes by flavivirus antisera. AmJTrop Med Hyg. 1980, 29 (4): 638-642.
8.
Appanna R, Huat TL, See LL, Tan PL, Vadivelu J, Devi S: Cross-reactive T-cell responses to the nonstructural regions of dengue viruses among dengue fever and dengue hemorrhagic fever patients in Malaysia. Clin Vaccine Immunol. 2007, 14 (8): 969-977. 10.1128/CVI.00069-07.CrossRefPubMedPubMedCentral
9.
Chang J, Schul W, Yip A, Xu X, Guo JT, Block TM: Competitive inhibitor of cellular alpha-glucosidases protects mice from lethal dengue virus infection. Antiviral Res. 2011, 92 (2): 369-371. 10.1016/j.antiviral.2011.08.003.CrossRefPubMedPubMedCentral
10.
Kato D, Era S, Watanabe I, Arihara M, Sugiura N, Kimata K, Suzuki Y, Morita K, Hidari KI, Suzuki T: Antiviral activity of chondroitin sulphate E targeting dengue virus envelope protein. Antiviral Res. 2010, 88 (2): 236-243. 10.1016/j.antiviral.2010.09.002.CrossRefPubMed
11.
Jacobs M: Dengue. Medicine. 2005, 33 (7): 18-20. 10.1383/medc.2005.33.7.18.CrossRef
12.
Piraino F, Brandt CR: Isolation and partial characterization of an antiviral, RC-183, from the edible mushroom Rozites caperata. Antiviral Res. 1999, 43 (2): 67-78. 10.1016/S0166-3542(99)00035-2.CrossRefPubMed
13.
Herrmann EC, Kucera LS: Antiviral substances in plants of the mint family (labiatae). 3. Peppermint (Mentha piperita) and other mint plants. Proc Soc Exp Biol Med. 1967, 124 (3): 874-878. 10.3181/00379727-124-31874.CrossRefPubMed
14.
Aswal BS, Goel AK, Kulshrestha DK, Mehrotra BN, Patnaik GK: Screening of Indian plants for biological activity: Part XV. Indian J Exp Biol. 1996, 34 (5): 444-467.PubMed
15.
Lee-Huang S, Zhang L, Huang PL, Chang YT: Anti-HIV activity of olive leaf extract (OLE) and modulation of host cell gene expression by HIV-1 infection and OLE treatment. Biochem Biophys Res Commun. 2003, 307 (4): 1029-1037. 10.1016/S0006-291X(03)01292-0.CrossRefPubMed
16.
Yamada K, Ogawa H, Hara A, Yoshida Y, Yonezawa Y, Karibe K, Nghia VB, Yoshimura H, Yamamoto Y, Yamada M: Mechanism of the antiviral effect of hydroxytyrosol on influenza virus appears to involve morphological change of the virus. Antiviral Res. 2009, 83 (1): 35-44. 10.1016/j.antiviral.2009.03.002.CrossRefPubMed
17.
Zhu W, Chiu LC, Ooi VE, Chan PK, Ang PO: Antiviral property and mechanisms of a sulphated polysaccharide from the brown alga Sargassum patens against Herpes simplex virus type 1. Phytomedicine. 2006, 13 (9–10): 695-701.CrossRefPubMed
18.
Cui X, Wang Y, Kokudo N, Fang D, Tang W: Traditional Chinese medicine and related active compounds against hepatitis B virus infection. Biosci Trends. 2010, 4 (2): 39-47.PubMed
19.
Cacciotti P, Libener R, Betta P, Martini F, Porta C, Procopio A, Strizzi L, Penengo L, Tognon M, Mutti L: SV40 replication in human mesothelial cells induces HGF/Met receptor activation: a model for viral-related carcinogenesis of human malignant mesothelioma. Proc Natl Acad Sci U S A. 2001, 98 (21): 12032-12037. 10.1073/pnas.211026798.CrossRefPubMedPubMedCentral
20.
Eldeen I, Seow E, Abdullah R, Sulaiman S: In vitro antibacterial, antioxidant, total phenolic contents and anti-HIV-1 reverse transcriptase activities of extracts of seven Phyllanthus sp. S Afr J Bot. 2010, 77 (1): 75-79.CrossRef
21.
Schmelzer GH: Plant resources of tropical Africa: medicinal plants. Prota. 2008, 11: 270-271.
22.
Tang YQ, Jaganath IB, Sekaran SD: Phyllanthus spp. induces selective growth inhibition of PC-3 and MeWo human cancer cells through modulation of cell cycle and induction of apoptosis. PLoS One. 2010, 5 (9): e12644-10.1371/journal.pone.0012644.CrossRefPubMedPubMedCentral
23.
Lee SH, Jaganath IB, Wang SM, Sekaran SD: Antimetastatic effects of Phyllanthus on human lung (A549) and breast (MCF-7) cancer cell lines. PLoS One. 2011, 6 (6): e20994-10.1371/journal.pone.0020994.CrossRefPubMedPubMedCentral
24.
Yong YK, Thayan R, Chong HT, Tan CT, Sekaran SD: Rapid detection and serotyping of dengue virus by multiplex RT-PCR and real-time SYBR green RT-PCR. Singapore Med J. 2007, 48 (7): 662-668.PubMed
25.
Venkateswaran PS, Millman I, Blumberg BS: Effects of an extract from Phyllanthus niruri on hepatitis B and woodchuck hepatitis viruses: in vitro and in vivo studies. Proc Natl Acad Sci U S A. 1987, 84 (1): 274-278. 10.1073/pnas.84.1.274.CrossRefPubMedPubMedCentral
26.
Zhou S, Xu C, Zhou N, Huang Y, Huang L, Chen X, Hu Y, Liao Y: Mechanism of protective action of Phyllanthus urinaria L. against injuries of liver cells]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica. 1997, 22 (2): 109-PubMed
27.
Rajeshkumar NV, Kuttan R: Phyllanthus amarus extract administration increases the life span of rats with hepatocellular carcinoma. J Ethnopharmacol. 2000, 73 (1–2): 215-219.CrossRefPubMed
28.
Ott M, Thyagarajan SP, Gupta S: Phyllanthus amarus suppresses hepatitis B virus by interrupting interactions between HBV enhancer I and cellular transcription factors. Eur J Clin Invest. 1997, 27 (11): 908-915. 10.1046/j.1365-2362.1997.2020749.x.CrossRefPubMed
29.
Mazumder A, Mahato A, Mazumder R: Antimicrobial potentiality of Phyllanthus amarus against drug resistant pathogens. Nat Prod Res. 2006, 20 (4): 323-326. 10.1080/14786410600650404.CrossRefPubMed
30.
Kloucek P, Polesny Z, Svobodova B, Vlkova E, Kokoska L: Antibacterial screening of some Peruvian medicinal plants used in Calleria District. J Ethnopharmacol. 2005, 99 (2): 309-312. 10.1016/j.jep.2005.01.062.CrossRefPubMed
31.
Mazunder UK, Gupta M, Rajeshwar Y: Antihyperglycemic effect and antioxidant potential of Phyllanthus niruri (Euphorbiaceae) in streptozotocin induced diabetic rats. Eur Bull Drug Res. 2005, 13 (1): 15-23.
32.
Raphael KR, Sabu MC, Kuttan R: Hypoglycemic effect of methanol extract of Phyllanthus amarus Schum & Thonn on alloxan induced diabetes mellitus in rats and its relation with antioxidant potential. Indian J Exp Biol. 2002, 40 (8): 905-909.PubMed
33.
Yang CM, Cheng HY, Lin TC, Chiang LC, Lin CC: The in vitro activity of geraniin and 1,3,4,6-tetra-O-galloyl-beta-D-glucose isolated from Phyllanthus urinaria against herpes simplex virus type 1 and type 2 infection. J Ethnopharmacol. 2007, 110 (3): 555-558. 10.1016/j.jep.2006.09.039.CrossRefPubMed
34.
Yang Y, Zhang L, Fan X, Qin C, Liu J: Antiviral effect of geraniin on human enterovirus 71 in vitro and in vivo. Bioorg Med Chem Lett. 2012, 22 (6): 2209-2211. 10.1016/j.bmcl.2012.01.102.CrossRefPubMed
35.
Kwon H-J, Kim H-H, Yoon S, Ryu Y, Chang J, Cho K-O, Rho M-C, Park S-J, Lee W: In Vitro inhibitory activity of Alpinia katsumadai extracts against influenza virus infection and hemagglutination. Virol J. 2010, 7 (1): 307-10.1186/1743-422X-7-307.CrossRefPubMedPubMedCentral
36.
Sepulveda CS, Garcia CC, Fascio ML, D’Accorso NB, Docampo Palacios ML, Pellon RF, Damonte EB: Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative. Antiviral Res. 2012, 93 (1): 16-22. 10.1016/j.antiviral.2011.10.007.CrossRefPubMed
37.
Alvarez AL, del Barrio G, Kouri V, Martinez PA, Suarez B, Parra F: In vitro anti-herpetic activity of an aqueous extract from the plant Phyllanthus orbicularis. Phytomedicine. 2009, 16 (10): 960-966. 10.1016/j.phymed.2009.03.023.CrossRefPubMed
38.
Jindadamrongwech S, Thepparit C, Smith D: Identification of GRP 78 (BiP) as a liver cell expressed receptor element for dengue virus serotype 2. Arch Virol. 2004, 149 (5): 915-927. 10.1007/s00705-003-0263-x.CrossRefPubMed
39.
Chavez-Salinas S, Ceballos-Olvera I, Reyes-del Valle J, Medina F, del Angel RM: Heat shock effect upon dengue virus replication into U937 cells. Virus Res. 2008, 138 (1–2): 111-118.CrossRefPubMed
40.
Delneste Y, Magistrelli G, Gauchat J-F, Haeuw J-F, Aubry J-P, Nakamura K, Kawakami-Honda N, Goetsch L, Sawamura T, Bonnefoy J-Y: Involvement of LOX-1 in dendritic cell-mediated antigen cross-presentation. Immunity. 2002, 17 (3): 353-362. 10.1016/S1074-7613(02)00388-6.CrossRefPubMed
41.
Suksanpaisan L, Cabrera-Hernandez A, Smith DR: Infection of human primary hepatocytes with dengue virus serotype 2. J Med Virol. 2007, 79 (3): 300-307. 10.1002/jmv.20798.CrossRefPubMed
42.
Ishiki Y, Ohnishi H, Muto Y, Matsumoto K, Nakamura T: Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and has a potent antihepatitis effect in vivo. Hepatology. 1992, 16 (5): 1227-1235.PubMed
43.
Kashiwakura Y, Tamayose K, Iwabuchi K, Hirai Y, Shimada T, Matsumoto K, Nakamura T, Watanabe M, Oshimi K, Daida H: Hepatocyte growth factor receptor is a coreceptor for adeno-associated virus type 2 infection. J Virol. 2005, 79 (1): 609-614. 10.1128/JVI.79.1.609-614.2005.CrossRefPubMedPubMedCentral
44.
Voraphani N, Theamboonlers A, Khongphatthanayothin A, Srisai C, Poovorawan Y: Increased level of hepatocyte growth factor in children with dengue virus infection. Ann Trop Paediatr. 2010, 30 (3): 213-218. 10.1179/146532810X12786388978607.CrossRefPubMed
45.
McNiven MA, Thompson HM: Vesicle formation at the plasma membrane and trans-Golgi network: the same but different. Science. 2006, 313 (5793): 1591-1594. 10.1126/science.1118133.CrossRefPubMed
46.
El-Bacha T, Menezes MM, Azevedo e Silva MC, Sola-Penna M, Da Poian AT: Mayaro virus infection alters glucose metabolism in cultured cells through activation of the enzyme 6-phosphofructo 1-kinase. Mol Cell Biochem. 2004, 266 (1–2): 191-198.CrossRefPubMed
47.
Ranji A, Boris-Lawrie K: RNA helicases: emerging roles in viral replication and the host innate response. RNA Biol. 2010, 7 (6): 775-787. 10.4161/rna.7.6.14249.CrossRefPubMedPubMedCentral
48.
Yang SH, Liu ML, Tien CF, Chou SJ, Chang RY: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interaction with 3′ ends of Japanese encephalitis virus RNA and colocalization with the viral NS5 protein. J Biomed Sci. 2009, 16: 40-10.1186/1423-0127-16-40.CrossRefPubMedPubMedCentral
49.
Nisole S, Stoye JP, Saib A: TRIM family proteins: retroviral restriction and antiviral defence. Nat Rev Microbiol. 2005, 3 (10): 799-808. 10.1038/nrmicro1248.CrossRefPubMed
50.
Yap MW, Nisole S, Lynch C, Stoye JP: Trim5α protein restricts both HIV-1 and murine leukemia virus. Proc Natl Acad Sci U S A. 2004, 101 (29): 10786-10.1073/pnas.0402876101.CrossRefPubMedPubMedCentral
51.
Nitsche C, Behnam MA, Steuer C, Klein CD: Retro peptide-hybrids as selective inhibitors of the Dengue virus NS2B-NS3 protease. Antiviral Res. 2012, 94 (1): 72-79. 10.1016/j.antiviral.2012.02.008.CrossRefPubMed
52.
Limjindaporn T, Wongwiwat W, Noisakran S, Srisawat C, Netsawang J, Puttikhunt C, Kasinrerk W, Avirutnan P, Thiemmeca S, Sriburi R: Interaction of dengue virus envelope protein with endoplasmic reticulum-resident chaperones facilitates dengue virus production. Biochem Biophys Res Comm. 2009, 379 (2): 196-200. 10.1016/j.bbrc.2008.12.070.CrossRefPubMed
53.
Daikoku T, Kudoh A, Sugaya Y, Iwahori S, Shirata N, Isomura H, Tsurumi T: Postreplicative mismatch repair factors Are recruited to Epstein-Barr virus replication compartments. J Biol Chem. 2006, 281 (16): 11422-11430. 10.1074/jbc.M510314200.CrossRefPubMed
54.
Mohni KN, Mastrocola AS, Bai P, Weller SK, Heinen CD: DNA mismatch repair proteins Are required for efficient herpes simplex virus 1 replication. J Virol. 2011, 85 (23): 12241-12253. 10.1128/JVI.05487-11.CrossRefPubMedPubMedCentral
55.
Kanlaya R, Pattanakitsakul S-n, Sinchaikul S, Chen S-T, Thongboonkerd V: Vimentin interacts with heterogeneous nuclear ribonucleoproteins and dengue nonstructural protein 1 and is important for viral replication and release. Mol BioSys. 2010, 6 (5): 795-806. 10.1039/b923864f.CrossRef
Metadata
Title
Effects of cocktail of four local Malaysian medicinal plants (Phyllanthus spp.) against dengue virus 2
Authors
Sau Har Lee
Yin Quan Tang
Anusyah Rathkrishnan
Seok Mui Wang
Kien Chai Ong
Rishya Manikam
Bobby Joe Payne
Indu Bala Jaganath
Shamala Devi Sekaran
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2013
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/1472-6882-13-192

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