Abstract
Global HIV-1 treatment would benefit greatly from safe herbal medicines with scientifically validated novel anti-HIV-1 activities. The root extract from the medicinal plant Pelargonium sidoides (PS) is licensed in Germany as the herbal medicine EPs®7630, with numerous clinical trials supporting its safety in humans. Here we provide evidence from multiple cell culture experiments that PS extract displays potent anti-HIV-1 activity. We show that PS extract protects peripheral blood mononuclear cells and macrophages from infection with various X4 and R5 tropic HIV-1 strains, including clinical isolates. Functional studies revealed that the extract from PS has a novel mode-of-action. It interferes directly with viral infectivity and blocks the attachment of HIV-1 particles to target cells, protecting them from virus entry. Analysis of the chemical footprint of anti-HIV activity indicates that HIV-1 inhibition is mediated by multiple polyphenolic compounds with low cytotoxicity and can be separated from other extract components with higher cytotoxicity. Based on our data and its excellent safety profile, we propose that PS extract represents a lead candidate for the development of a scientifically validated herbal medicine for anti-HIV-1 therapy with a mode-of-action different from and complementary to current single-molecule drugs.
Highlights
As of August 2012, 23 single-molecule drugs were approved for anti-HIV-1 therapy in the USA by the FDA [1]
To determine anti-HIV activity of Pelargonium sidoides (PS) extract with primary HIV-1 target cells, we used ex vivo cultures of human peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (MDM)
Inhibition of infection of PBMCs by PS extract was determined by measuring infectious virus titers of supernatants of cultures exposed to HIV-1LAI and different concentrations of PS extract (EC50 = 5.7062.7 mg/ml; n = 4)
Summary
As of August 2012, 23 single-molecule drugs were approved for anti-HIV-1 therapy in the USA by the FDA [1]. The continuous need for the development of new therapeutic anti-HIV-1 agents arises from the rapid emergence of viruses resistant to these drugs (reviewed in [2], [3]), the necessity for continuous life-long treatment [4], the challenges of providing antiretroviral treatment in resource-limited settings [5] and the need for novel drugs with fewer adverse effects [6]. While medicinal plants have been reported to display antiHIV-1 activity (reviewed in [8,9]), herbal preparations are currently not part of conventional therapeutic regimens. Antiviral potencies and modes-of-actions of medicinal plants are poorly understood. They have been considered mainly as sources for the isolation of single anti-HIV-1 hit molecules by conventional drug-discovery approaches [9,10]. Herbal preparations have many potential benefits for anti-HIV therapy, including the complementation of existing drug therapies, improvement of anti-HIV treatment in resource-limited settings and reduction of the risk of emergence of viral resistance
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
