Abstract
BackgroundAqueous extracts from leaves of well known species of the Lamiaceae family were examined for their potency to inhibit infection by human immunodeficiency virus type 1 (HIV-1).ResultsExtracts from lemon balm (Melissa officinalis L.), peppermint (Mentha × piperita L.), and sage (Salvia officinalis L.) exhibited a high and concentration-dependent activity against the infection of HIV-1 in T-cell lines, primary macrophages, and in ex vivo tonsil histocultures with 50% inhibitory concentrations as low as 0.004%. The aqueous Lamiaceae extracts did not or only at very high concentrations interfere with cell viability. Mechanistically, extract exposure of free virions potently and rapidly inhibited infection, while exposure of surface-bound virions or target cells alone had virtually no antiviral effect. In line with this observation, a virion-fusion assay demonstrated that HIV-1 entry was drastically impaired following treatment of particles with Lamiaceae extracts, and the magnitude of this effect at the early stage of infection correlated with the inhibitory potency on HIV-1 replication. Extracts were active against virions carrying diverse envelopes (X4 and R5 HIV-1, vesicular stomatitis virus, ecotropic murine leukemia virus), but not against a non-enveloped adenovirus. Following exposure to Lamiaceae extracts, the stability of virions as well as virion-associated levels of envelope glycoprotein and processed Gag protein were unaffected, while, surprisingly, sucrose-density equilibrium gradient analyses disclosed a marked increase of virion density.ConclusionAqueous extracts from Lamiaceae can drastically and rapidly reduce the infectivity of HIV-1 virions at non-cytotoxic concentrations. An extract-induced enhancement of the virion's density prior to its surface engagement appears to be the most likely mode of action. By harbouring also a strong activity against herpes simplex virus type 2, these extracts may provide a basis for the development of novel virucidal topical microbicides.
Highlights
Aqueous extracts from leaves of well known species of the Lamiaceae family were examined for their potency to inhibit infection by human immunodeficiency virus type 1 (HIV-1)
Potent anti-HIV activity of aqueous extracts from sage, peppermint, and lemon balm We systematically investigated the potency of aqueous extracts prepared from dried leaves of well known members of the Lamiaceae family, lemon balm, peppermint, and sage to inhibit HIV-1 infection in vitro and ex vivo
Stocks from the prototypic X4 HIV1NL4-3 strain were first incubated with concentrations of aqueous extracts ranging from 0.006 to 6% for 1 h at 37°C and subsequently, these suspensions were mixed with an equivalent volume of culture medium and added to the human T-lymphoblastoid cell line Sup-T1
Summary
Aqueous extracts from leaves of well known species of the Lamiaceae family were examined for their potency to inhibit infection by human immunodeficiency virus type 1 (HIV-1). Advances in HIV pharmacotherapy led to the current highly active antiretroviral therapy (HAART), which has had significant impact on HIV/acquired immunodeficiency syndrome (AIDS) in the developed world, and these drugs have acted to prolong survival and to alleviate suffering. The incidence of side effects and HIV drug resistance in patients under HAART is high [1] and HIV/AIDS persists as a major cause of morbidity in Western societies and continues to surge unabated in the developing word. The concept of topical microbicides to prevent transmission of HIV has emerged as an important strategy to control the HIV pandemic [2]. The increased incidence of HIV infection in women aged 15–49 years in resource-poor countries has emphasized the need to develop female-controlled, efficacious and safe microbicides for vaginal application [3,4]. Desirable basic characteristics of topical microbicides include a high in vitro activity against a wide range of HIV-1 strains, a broad activity against other sexually-transmitted pathogens, noto-low cytotoxicity in in vitro assays, stability under likely storage conditions, low cost, and good acceptance in the target population [3,4]
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