Antiviral activity of the marine alga Symphyocladia latiuscula against herpes simplex virus (HSV-1) in vitro and its therapeutic efficacy against HSV-1 infection in mice.
The antiviral activities of extracts from 5 species of marine algae collected at Haeundae (Pusan, Korea), were examined using plaque reduction assays. Although the activity of a methanol (MeOH) extract of Sargassum ringoldianum (Sargassaceae) was the most potent against several types of viruses, it was also cytotoxic. A MeOH extract of Symphyocladia latiuscula (Rhodomelaceae) and its fractions exhibited antiviral activities against acyclovir (ACV) and phosphonoacetic acid (PAA)-resistant (AP(r)) herpes simplex type 1 (HSV-1), thymidine kinase (TK(-)) deficient HSV-1 and wild type HSV-1 in vitro without cytotoxicity. The major component, 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (TDB) of a CH(2)Cl(2)-soluble fraction was active against wild type HSV-1, as well as AP(r) HSV-1 and TK(-) HSV-1 (IC(50) values of 5.48, 4.81 and 23.3 microg/ml, respectively). The therapeutic effectiveness of the MeOH extract and TDB from S. latiuscula was further examined in BALB/c mice that were cutaneously infected with HSV-1 strain 7401H. Three daily oral administrations of the MeOH extract and TDB significantly delayed the appearance of score 2 skin lesions (local vesicles) and limited the development of further score 6 (mild zosteriform) lesions in infected mice without toxicity compared with controls. In addition, TDB suppressed virus yields in the brain and skin. Therefore TDB should be a promising anti HSV agent.
Park
Hye-Jin
HJ
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Pusan 608-737, Korea.
Kurokawa
Masahiko
M
Shiraki
Kimiyasu
K
Nakamura
Norio
N
Choi
Jae-Sue
JS
Hattori
Masao
M
D000212:Acyclovir / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000821:virology; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral; D004987:Ethers / Q000302:isolation & purification / Q000494:pharmacology*; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy* / Q000503:physiopathology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D000461:Rhodophyta / Q000737:chemistry / Q000302:isolation & purification; D012867:Skin / Q000187:drug effects / Q000821:virology; D013937:Thymidine Kinase / Q000172:deficiency; D014709:Vero Cells; D010948:Viral Plaque Assay
C439224:2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether; D000998:Antiviral Agents; D004987:Ethers; D013937:Thymidine Kinase; D010746:Phosphonoacetic Acid; D000212:Acyclovir