title: Houttuynia cordata targets the beginning stage of herpes simplex virus infection.
abstract: Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti-HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovir-resistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV.
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors: Pei-Yun
authors: PY
authors: Hung
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine, National Taiwan University, Taipei 100, Taiwan; NTU Center for Genomic Medicine, National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors: Bing-Ching
authors: BC
authors: Ho
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors: Szu-Yuan
authors: SY
authors: Lee
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
authors: Sui-Yuan
authors: SY
authors: Chang
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
authors: Chuan-Liang
authors: CL
authors: Kao
authors: School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors: Shoei-Sheng
authors: SS
authors: Lee
authors: Department of Clinical Laboratory Sciences and Medical Biotechnology College of Medicine, National Taiwan University, Taipei 100, Taiwan; Department of Laboratory Medicine, National Taiwan University Hospital, Taipei 100, Taiwan.
authors: Chun-Nan
authors: CN
authors: Lee
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D024882:Drug Resistance, Viral / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006358:Hot Temperature; D052859:Houttuynia / Q000737:chemistry*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D014759:Viral Envelope Proteins / Q000378:metabolism; D014771:Virion / Q000187:drug effects / Q000502:physiology; D053586:Virus Internalization / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects; D014867:Water / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D016328:NF-kappa B; D010936:Plant Extracts; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; D014867:Water; D000212:Acyclovir
references: J Nat Prod. 2003 Jul;66(7):1022-37
references: 12880330
references: Arch Pharm Res. 2009 Feb;32(2):275-82
references: 19280159
references: Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12408-13
references: 14530405
references: Clin Infect Dis. 2003 Dec 1;37(11):1527-33
references: 14614676
references: J Nutr Sci Vitaminol (Tokyo). 2003 Oct;49(5):327-33
references: 14703307
references: Cell Microbiol. 2004 May;6(5):401-10
references: 15056211
references: J Virol. 2004 May;78(10):5147-56
references: 15113897
references: Eur J Pharmacol. 2004 Aug 2;496(1-3):41-8
references: 15288573
references: N Engl J Med. 1974 Oct 17;291(16):828-30
references: 4371760
references: Lloydia. 1975 Mar-Apr;38(2):92-6
references: 1134217
references: Ann Intern Med. 1983 Mar;98(3):404-6
references: 6299155
references: EMBO J. 1984 Dec 20;3(13):3135-41
references: 6098466
references: Proc Natl Acad Sci U S A. 1985 Aug;82(16):5265-9
references: 2991915
references: Nature. 1985 Sep 12-18;317(6033):179-82
references: 2993923
references: Antimicrob Agents Chemother. 1985 Dec;28(6):740-4
references: 3002245
references: J Virol. 1987 Mar;61(3):829-39
references: 3027408
references: J Virol. 1988 Dec;62(12):4605-12
references: 2846873
references: N Engl J Med. 1989 Feb 2;320(5):293-6
references: 2536136
references: J Virol. 1990 Jun;64(6):2569-76
references: 2159532
references: J Virol. 1991 Mar;65(3):1090-8
references: 1847438
references: J Acquir Immune Defic Syndr. 1991;4(10):967-9
references: 1832460
references: Oral Surg Oral Med Oral Pathol. 1991 Jul;72(1):47-50
references: 1653925
references: J Virol. 1992 Aug;66(8):5002-12
references: 1321283
references: J Nat Prod. 1992 Oct;55(10):1525-7
references: 1333516
references: Acta Virol. 2000 Oct;44(5):289-307
references: 11252674
references: Antiviral Res. 2002 Nov;56(2):153-66
references: 12367721
references: J Virol. 1993 Sep;67(9):5088-97
references: 8394437
references: Planta Med. 1995 Jun;61(3):237-41
references: 7617766
references: Cell. 1996 Nov 1;87(3):427-36
references: 8898196
references: J Rheumatol. 1997 Sep;24(9):1680-4
references: 9292787
references: Virology. 1998 Jun 20;246(1):179-89
references: 9657005
references: Intervirology. 1997;40(5-6):343-56
references: 9675639
references: Cell. 1999 Oct 1;99(1):13-22
references: 10520990
references: Chem Pharm Bull (Tokyo). 2005 Dec;53(12):1604-9
references: 16327201
references: Arch Pharm Res. 2005 Nov;28(11):1293-301
references: 16350858
references: Neurology. 2006 Jan 10;66(1):75-80
references: 16401850
references: Virology. 2006 Feb 20;345(2):468-81
references: 16297954
references: J Biol Chem. 2006 Mar 17;281(11):7110-7
references: 16407234
references: Exp Toxicol Pathol. 2006 Aug;58(1):59-64
references: 16793246
references: JAMA. 2006 Aug 23;296(8):964-73
references: 16926356
references: Zhongguo Zhong Yao Za Zhi. 2006 Aug;31(16):1335-7
references: 17061554
references: Antiviral Res. 2006 Dec;72(3):242-51
references: 16876885
references: Zhongguo Zhong Yao Za Zhi. 2006 Nov;31(21):1753-8
references: 17260784
references: Cardiovasc Toxicol. 2006;6(2):111-30
references: 17303919
references: Antiviral Res. 2007 Sep;75(3):227-33
references: 17459492
references: Am J Chin Med. 2007;35(3):465-75
references: 17597505
references: J Neurovirol. 2007 Oct;13(5):416-25
references: 17994426
references: Virol J. 2007;4:120
references: 17996071
references: Antiviral Res. 2008 Jul;79(1):62-70
references: 18353452
references: J Ethnopharmacol. 2008 Jun 19;118(1):79-85
references: 18479853
references: Eur J Pharm Sci. 2009 Jun 28;37(3-4):329-33
references: 19491023
references: Antiviral Res. 2009 Nov;84(2):131-41
references: 19665486
references: Br J Dermatol. 2010 Jan;162(1):176-84
references: 19709100
references: Antimicrob Agents Chemother. 2011 Feb;55(2):459-72
references: 21078929
references: Antiviral Res. 2011 Nov;92(2):341-5
references: 21951655
references: Biotechnol Lett. 2012 May;34(5):831-8
references: 22350287
references: Surv Ophthalmol. 2012 Sep;57(5):448-62
references: 22542912
references: J Ethnopharmacol. 2006 Mar 8;104(1-2):245-9
references: 16213118
references: Mol Biol (Mosk). 2008 May-Jun;42(3):470-7
references: 18702305
references: J Vet Sci. 2008 Sep;9(3):267-72
references: 18716446
references: J Clin Invest. 2008 Oct;118(10):3470-7
references: 18769632
references: J Nutr. 2008 Dec;138(12):2309-15
references: 19022950
references: Am J Chin Med. 2003;31(3):355-62
references: 12943167