ABSTRACT
The activities of 13 sesquiterpenes isolated from Tripterygium wilfordii Hook fil. var. regelii Makino were studied against herpes simplex virus type 1 (HSV-1) in vitro. Among these compounds, only triptofordin C-2 showed a selectivity index of more than 10. The compound, which could also inhibit the replication of human cytomegalovirus (HCMV), did not affect either adsorption or penetration of HSV-1 to host cells, but showed moderate virucidal activity against several enveloped viruses including HSV-1, HCMV, measles virus and influenza A virus. Triptofordin C-2 suppressed viral protein synthesis of infected cells when added at early steps of HSV-1 replication and exerted inhibition of translation of the transcripts of the immediate early genes. When acyclovir and triptofordin C-2 were evaluated in combination for antiviral activity against HSV-1 replication, additive antiviral effects were observed for this virus.
Subject(s)
Antiviral Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Sesquiterpenes/pharmacology , Simplexvirus/drug effects , Virus Replication/drug effects , Acyclovir/pharmacology , Adsorption/drug effects , Cell Division/drug effects , Cell Line , Drug Interactions , HeLa Cells/drug effects , HeLa Cells/virology , Humans , In Vitro Techniques , Sesquiterpenes/isolation & purification , Simplexvirus/physiologyABSTRACT
Dihydroagarofuran sesquiterpenes, which were isolated from Tripterygium wilfordii Hook fil. var. regelii Makino and Euonymus sieboldianus Blume, showed inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Triptogelin A-1, one of the active dihydroagarofuran sesquiterpenes, exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. Interestingly, triptogelin A-1 was more effective when applied after TPA-treatment (post-treatment) than before TPA-treatment (pretreatment). The findings indicate that these dihydroagarofuran sesquiterpenes might be valuable antitumor promoters.
Subject(s)
Bridged Bicyclo Compounds/pharmacology , Sesquiterpenes/pharmacology , Skin Neoplasms/prevention & control , Tetradecanoylphorbol Acetate , 9,10-Dimethyl-1,2-benzanthracene , Animals , Antigens, Viral/drug effects , Bridged Bicyclo Compounds/administration & dosage , Female , Herpesvirus 4, Human/immunology , Mice , Mice, Inbred ICR , Sesquiterpenes/administration & dosage , Skin Neoplasms/chemically induced , Tumor Cells, CulturedABSTRACT
To search for possible antitumor promoters, we carried out a primary screening of thirty-seven dihydroagarofuran sesquiterpenes from Tripterygium wilfordii Hook fil. var. regelii Makino and Euonymus sieboldianus Blume, using their possible inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation which is induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Some of these sesquiterpenes, triptofordin F-2 (Takaishi et al., 1988), 1,2,6,8,15-pentaacetoxy-9-benzoyloxy-4-hydroxy-beta-dihydroagarofuran and triptogelin A-1 (Takaishi et al., 1990) were observed to significantly inhibit the EBV-EA activation at low doses. Based on the results, the structural requirements for the activity of these compounds were discussed [corrected].
