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

Abstract

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.

Hydrolyzable Tannins (Chebulagic Acid and Punicalagin) Target Viral Glycoprotein-Glycosaminoglycan Interactions To Inhibit Herpes Simplex Virus 1 Entry and Cell-to-Cell Spread

“…We have previously identified several tannins of various plant sources that exhibit potent antiviral activities against HSV-1 and HSV-2. These include 1,3,4,6-tetra-O-galloyl-␤-D-glucose (77), casuarinin (10), ent-epiafzelechin-(4␣3R8)-epiafzelechin (17), excoecarianin (16), geraniin (77), hippomanin A (76), prodelphinidin B-2 3Ј-O-gallate (11), prodelphinidin B-2 3,3Ј-di-O-gallate (12), pterocarnin A (13), and putranjivain A (14). Studies from other laboratories have also reported a series of tannins and related compounds capable of inhibiting HSV infections (25,56,64,71,72).…”

“…The cytotoxic effects of CHLA, CHLI, PUG, and PUN on the different cell types used in the present study were measured by the calorimetric XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-5-phenylamino)-carbonyl]-2H-tetrazolium hydroxide) assay as described previously with some modifications (16). Briefly, cells were seeded in 96-well plates (10 4 cells per well) and incubated overnight to form a monolayer.…”

Castalagin: Some aspects of the mode of Anti-Herpes Virus Activity

“…Virucidal effects of excoecarianin, casuarinin, and geraniin have been established as well [28][29][30][31][32].…”

Phyllanthus Sp a Local Plant With Multiple Medicinal Properties

“…The only drawback of these limited anti-HSV drugs is the development of viral resistance against these treatments and drug toxicity (19)(20)(21). Drug-resistant viral strains were increasingly isolated from patients, in particular immunocompromised individuals (20).…”

“…This revealed that excoecarianin primarily inactivate HSV-2 virus particles to prevent viral infection. It was also able to act synergistically with acyclovir to exhibit antiviral effect against HSV-2 infection in Vero cells (21).…”