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eCAM Advance Access published online on October 6, 2009
eCAM, doi:10.1093/ecam/nep157
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© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Excoecarianin, Isolated from Phyllanthus urinaria Linnea, Inhibits Herpes Simplex Virus Type 2 Infection through Inactivation of Viral Particles

Hua-Yew Cheng1, Chien-Min Yang2,3, Ta-Chen Lin4, Liang-Tzung Lin5, Lien-Chai Chiang6 and Chun-Ching Lin2

1Department of Cosmetic Applications & Management, Tung Fang Institute of Technology, 829 Kaohsiung County, 2School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, 807 Kaohsiung, 3Department of Cosmetology and Health Care, Min Hwei College of Health Care Management, 736 Tainan County, 4Department of Nursing, Central Taiwan University of Sciences and Technology, 406 Taichung, Taiwan, 5Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 1X5 and 6Department of Microbiology, College of Medicine, Kaohsiung Medical University, 807 Kaohsiung, Taiwan

Phyllanthus urinaria Linnea (Euphorbiaceae) is one of the traditional medicinal plants widely used by oriental people to treat various diseases. We have previously demonstrated that the acetone extract of P. urinaria inhibits herpes simplex virus type 2 (HSV-2) but not HSV-1 infection. In a continuing effort to clarify the antiviral mechanisms of P. urinaria, we isolated the pure compound excoecarianin from the whole plant of P. urinaria through acetone extraction, and investigated its anti-HSV-1 and HSV-2 activities. Our results indicated that excoecarianin protected Vero cells from HSV-2 but not HSV-1 infection, and its 50% inhibitory concentration (IC50) was 1.4 ± 0.1 µM. The antiviral effective concentration of excoecarianin did not affect the viability or the morphology of Vero cells. Although excoecarianin inhibited HSV-2 infection, the inhibitory effect, however, was most prominent when excoecarianin was concurrently added with the virus. Pretreatment of Vero cells with excoecarianin with removal of the drug prior to infection did not yield any antiviral effects, and the same observation was made for post viral entry treatment. Subsequent studies revealed that excoecarianin inactivated HSV-2 virus particles to prevent viral infection. A synergistic antiviral effect against HSV-2 was also observed when Vero cells were treated with a combination of acyclovir (ACV) and excoecarianin. These results suggested that excoecarianin merits to be further explored as an entry inhibitor against HSV-2 and could potentially be investigated for combinatorial drug treatment with nucleoside analogues such as ACV in therapeutic management of HSV-2 infection.

Keywords: antiviral activity – excoecarianin – herpes simplex virus type 2 – Phyllanthus urinaria – viral inactivation

For reprints and all correspondence: C.-C. Lin, No. 100, Shin-Chuan 1st Road, Kaohsiung Medical University, Kaohsiung City, Taiwan. Tel: +886-7-3121101 ext. 2122; Fax: +886-7-3135125; E-mail: aalin{at}kmu.edu.tw

Received March 26, 2009; accepted August 24, 2009


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