Hypericum in Infection: Identification of Anti-viral and Anti-inflammatory Constituents

Authors: BIRT, DIANE - IOWA STATE UNIVERSITY; Widrlechner, Mark; HAMMER, KIMBERLY - IOWA STATE UNIVERSITY; HILLWIG, MATTHEW - IOWA STATE UNIVERSITY; WEI, JINGQIANG - IOWA STATE UNIVERSITY; KRAUS, GEORGE - IOWA STATE UNIVERSITY; MURPHY, PATRICIA - IOWA STATE UNIVERSITY; McCoy, Joe Ann; WURTELE, EVE - IOWA STATE UNIVERSITY; NEIGHBORS, JEFFREY - UNIVERSITY OF IOWA; WIEMER, DAVID - UNIVERSITY OF IOWA; MAURY, WENDY - UNIVERSITY OF IOWA; PRICE, JASON - UNIVERSITY OF IOWA

Submitted to: Pharmaceutical Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/7/2009
Publication Date: 8/30/2009
Citation: Birt, D.F., Widrlechner, M.P., Hammer, K., Hillwig, M.L., Wei, J., Kraus, G.A., Murphy, P.A., Mccoy, J.H., Wurtele, E.S., Neighbors, J.D., Wiemer, D.F., Maury, W.J., Price, J.P. 2009. Hypericum in Infection: Identification of Anti-viral and Anti-inflammatory Constituents. Pharmaceutical Biology. 47(8):774-782.

Interpretive Summary: This paper reports on ongoing anti-viral and anti-inflammatory research on St. John's wort (Hypericum) conducted by the Iowa Center for Research on Botanical Dietary Supplements. These projects use genetically diverse, well-documented plant populations conserved by the USDA-ARS North Central Regional Plant Introduction Station (NCRPIS) along with strength in synthetic chemistry research at Iowa State University to efficiently tap the natural diversity of these plants and help discover key constituents and interactions among them that influence human health benefit and toxicity. The NCRPIS conserves a diverse array of Hypericum populations, focusing on the species most widely used as a botanical dietary supplement. Center chemists have developed novel synthetic pathways for key compounds from Hypericum, which are then used as standards and for bioactivity studies. Both light-dependent and independent anti-viral activity has been identified through a fractionation process guided by bioactivity and an HIV-1 infection screen. We focus on light-independent activity, since it is likely to be due to novel chemicals, and fractions with this activity are undergoing further analysis. Anti-inflammatory activity has largely been found to be light-independent. Fractionation of a flavonoid-rich extract revealed four compounds that together inhibit an inflammatory response in mouse cells. We continue to explore novel populations of Hypericum to identify constituents and interactions that contribute to potential health benefits related to infection. These findings should be useful for other researchers studying dietary supplements, the development of anti-viral therapies, and inflammatory responses, as well as for health practictioners.

Technical Abstract: The Iowa Center for Research on Botanical Dietary Supplements seeks to optimize Echinacea, Hypericum and Prunella supplements for human-health benefit, focusing on anti-viral, anti-inflammatory and anti-pain effects. This paper reports on ongoing anti-viral and anti-inflammatory studies on Hypericum, using genetically diverse, well-documented populations of these genera conserved by the USDA-ARS North Central Regional Plant Introduction Station (NCRPIS) and the strength of synthetic chemistry research at Iowa State University to efficiently tap natural diversity and help discover key constituents and interactions among them that impact bioactivity and toxicity. The NCRPIS conserves more than 180 populations of Hypericum, focusing on H. perforatum and representing about 13% of recognized taxa. Center chemists have developed novel synthetic pathways for key flavones, acyl phloroglucinols, hyperolactones and a tetralin from Hypericum, which are used as standards and for bioactivity studies. Both light-dependent and independent anti-viral activities have been identified through bioactivity-guided fractionation of H. perforatum and an HIV-1 infection screen. Our Center focuses on light-independent activity, since it is likely to be due to novel chemicals, and polar fractions with this activity are undergoing further analysis. Anti-inflammatory activity has largely been found to be light-independent. Fractionation of a flavonoid-rich extract revealed four compounds (amentoflavone, chlorogenic acid, pseudohypericin and quercetin) that together inhibit lipopolysaccharide-induced prostaglandin E2 activity. We continue to explore novel populations of Hypericum to identify constituents and interactions that contribute to potential health benefits related to infection.