| Summary: | <p>Abstract</p> <p>Background</p> <p>Light-dependent activities against enveloped viruses in St. John's Wort (<it>Hypericum perforatum</it>) extracts have been extensively studied. In contrast, light-independent antiviral activity from this species has not been investigated.</p> <p>Results</p> <p>Here, we identify the light-independent inhibition of human immunodeficiency virus-1 (HIV-1) by highly purified fractions of chloroform extracts of <it>H. perforatum</it>. 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, <it>H. perforatum </it>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.</p> <p>Conclusion</p> <p>Through bioguided fractionation, we have identified that 3-hydroxy lauric acid found in field grown <it>Hypericum perforatum </it>has anti-HIV activity. This novel anti-HIV activity can be potentially developed into inexpensive therapies, expanding the current arsenal of anti-retroviral agents.</p>
|
|---|