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Anti-inflammatory alkaloid cepharanthine inhibits HIV-1 replication in chronically infected cells.


Int Conf AIDS. 1998;12:1010 (abstract no. 60049). Unique Identifier :

OBJECTIVES: To determine whether cepharanthine, a clinically approved drug for the treatment of chronic inflammatory diseases in Japan, inhibits HIV-1 replication in chronically infected cells. DESIGN: Cepharanthine is a biscoclaurine alkaloid isolated from Stephania Cepharantha Hayata and has been shown to have anti-inflammatory, anti-allergic, and immunomodulatory activities in vivo. As several inflammatory cytokines and oxidative stresses are involved in the pathogenesis of HIV-1 infection, we investigated the inhibitory effects of cepharanthine on TNF-alpha- and phorbol myristate acetate (PMA)-induced HIV-1 expression in chronically infected cell lines. METHODS: Two HIV-1 chronically infected cell lines, U1 (monocytic) and ACH-2 (T-lymphocytic), were stimulated with TNF-alpha or PMA in the presence of various concentrations of the compound. After a 3-day incubation, the production of HIV-1 was determined by a p24 antigen ELISA. The inhibitory effects of cepharanthine on HIV-1 long terminal repeat (LTR)-driven gene expression and nuclear factor kappa B (NF-kappa B) activation were examined in HeLa and U1 cells, respectively. RESULTS: Cepharanthine dose-dependently inhibited HIV-1 expression in TNF-alpha- and PMA-stimulated U1 cells but not in ACH-2 cells. Its 50% effective and cytotoxic concentrations were 0.016 and 2.2 micrograms/ml in PMA-stimulated U1 cells, respectively. Cepharanthine was found to suppress the HIV-1 LTR-driven gene expression through the inhibition of NF-kappa B activation. CONCLUSIONS: Cepharanthine proved to be a highly potent inhibitor of HIV-1 expression in a monocytic cell line. As it is widely used for the treatment of patients with various inflammatory diseases in Japan, the compound should be further pursued for its chemotherapeutic potential in HIV-1-infected patients.

MEETING ABSTRACTS Alkaloids/*PHARMACOLOGY Anti-HIV Agents/*PHARMACOLOGY Anti-Inflammatory Agents, Non-Steroidal/*PHARMACOLOGY Cell Line Human HIV-1/*DRUG EFFECTS Monocytes/*VIROLOGY T-Lymphocytes/*VIROLOGY Virus Replication/*DRUG EFFECTS


Information in this article was accurate in December 30, 1998. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.