Abstract
BackgroundLight-dependent activities against enveloped viruses in St. John's Wort (Hypericum perforatum) extracts have been extensively studied. In contrast, light-independent antiviral activity from this species has not been investigated.ResultsHere, we identify the light-independent inhibition of human immunodeficiency virus-1 (HIV-1) by highly purified fractions of chloroform extracts of H. perforatum. Both cytotoxicity and antiviral activity were evident in initial chloroform extracts, but bioassay-guided fractionation produced fractions that inhibited HIV-1 with little to no cytotoxicity. Separation of these two biological activities has not been reported for constituents responsible for the light-dependent antiviral activities. Antiviral activity was associated with more polar subfractions. GC/MS analysis of the two most active subfractions identified 3-hydroxy lauric acid as predominant in one fraction and 3-hydroxy myristic acid as predominant in the other. Synthetic 3-hydroxy lauric acid inhibited HIV infectivity without cytotoxicity, suggesting that this modified fatty acid is likely responsible for observed antiviral activity present in that fraction. As production of 3-hydroxy fatty acids by plants remains controversial, H. perforatum seedlings were grown sterilely and evaluated for presence of 3-hydroxy fatty acids by GC/MS. Small quantities of some 3-hydroxy fatty acids were detected in sterile plants, whereas different 3-hydroxy fatty acids were detected in our chloroform extracts or field-grown material.ConclusionThrough bioguided fractionation, we have identified that 3-hydroxy lauric acid found in field grown Hypericum perforatum has anti-HIV activity. This novel anti-HIV activity can be potentially developed into inexpensive therapies, expanding the current arsenal of anti-retroviral agents.
Highlights
Light-dependent activities against enveloped viruses in St
Inhibition of human immunodeficiency virus-1 (HIV) infection by chloroform extracts Inhibition of human immunodeficiency virus-1 (HIV-1) infectivity by light-dependent constituents found in H. perforatum is well established, but these same compounds have extensive cellular cytotoxicity and require a light source for activation, thereby reducing their potential value as clinical antiviral therapeutics [16,2022]
To determine if light-independent anti-HIV activity is present in H. perforatum extracts, we began by extracting dried aerial material with chloroform
Summary
Light-dependent activities against enveloped viruses in St. John's Wort (Hypericum perforatum) extracts have been extensively studied. The constituents hypericin and pseudohypericin effectively inhibit infection by a number of enveloped viruses of medical importance, including human immunodeficiency virus-1 (HIV), herpes simplex virus (HSV) and influenza A virus [12,13,14,15]. These inhibitory activities are light-dependent, which has lead to innovative strategies for delivering these compounds with bursts of light in vivo [16]; the need for light to activate hypericin remains problematic for many practical applications. Photocytotoxicity was responsible for the premature termination of a clinical trial that tested the efficacy of hypericin against HIV in AIDS patients [19]
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