Identification of light-independent inhibition of human immunodeficiency virus-1 infection through bioguided fractionation of Hypericum perforatum.
BACKGROUND
Light-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.


RESULTS
Here, 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.


CONCLUSIONS
Through 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.
Maury
Wendy
W
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA. wendy-maury@uiowa.edu
Price
Jason P
JP
Brindley
Melinda A
MA
Oh
ChoonSeok
C
Neighbors
Jeffrey D
JD
Wiemer
David F
DF
Wills
Nickolas
N
Carpenter
Susan
S
Hauck
Cathy
C
Murphy
Patricia
P
Widrlechner
Mark P
MP
Delate
Kathleen
K
Kumar
Ganesh
G
Kraus
George A
GA
Rizshsky
Ludmila
L
Nikolau
Basil
B
D019380:Anti-HIV Agents / Q000302:isolation & purification* / Q000494:pharmacology* / Q000633:toxicity; D008401:Gas Chromatography-Mass Spectrometry; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D020902:Hypericum / Q000737:chemistry*; D007850:Lauric Acids / Q000302:isolation & purification* / Q000494:pharmacology* / Q000633:toxicity; D009227:Myristic Acids / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D010936:Plant Extracts / Q000737:chemistry*
C453840:3-hydroxy-lauric acid; D019380:Anti-HIV Agents; D007850:Lauric Acids; D009227:Myristic Acids; D010936:Plant Extracts; C009893:beta-hydroxymyristic acid