Luis Miguel Bedoya

Anti-HIV activity of medicinal plant extracts

As part of our screening of anti-AIDS agents from natural sources, ethanolic and aqueous extracts of 15 medicinal plants widely used in the folk medicine of the Iberian Peninsula were evaluated in vitro. Most of the extracts tested were relatively nontoxic to human lymphocytic MT-2 cells, but only the extracts of Tuberaria lignosa and Sanguisorba minor magnolii exhibited anti-HIV activity in an in vitro MTT assay. The aqueous extracts of these plants showed inhibitory effects against HIV-1 induced infections in MT-2 cells at concentrations ranging from 12.5 to 50 microg/ml and 50 microg/ml, respectively. Both extracts showed no appreciable cytotoxicity at these concentrations.

Natural Marine Anti-inflammatory Products

The marine environment has been shown to be the source of a great diversity of chemical structures with promising biological activities. The isolation, biological evaluation, chemical properties and synthetic elaborations of the products of marine organisms and microorganisms have attracted the attention of organic chemists, medicinal chemists, biologists and pharmacists. Marine organisms and microorganisms have provided a large proportion of the natural anti-inflammatory products over the last years. Marine organisms include green algae, brown algae, red algae, sponges, coelenterates, bryozoans, molluscs, tunicates, echinoderms, miscellaneous marine organisms and marine microorganisms and phytoplankton. This review describes current progress in the development of a selection of new anti-inflammatory agents from marine sources. The chemistry and biological evaluation are discussed.

An update on drug interactions with the herbal medicine Ginkgo biloba.

Medicinal plants are gaining in popularity due to the various advantages they offer, such as fewer side-effects, better patient compliance, relatively low cost and high accessibility as well as their high acceptability due to a long history of use. There is a widespread belief among the general public that herbal preparations are good for humans as they are all natural. However, the increasing use of herbal medicinal products in the community where people are also receiving prescription medicines suggests that adverse herb-drug interactions may be have significant public health consequences. There is little understanding or appreciation of the fact that these all natural preparations are actually a combination of potentially biologically active compounds already existing in marketed products in unknown quantities. Among the most popular herbal products used worldwide is Ginkgo biloba, used for the treatment of cerebral insufficiency, peripheral vascular diseases, and frequently taken for the enhancement of memory function. Although the safety of Ginkgo biloba is promising, accumulated data show evidence of significant interactions with medications, which can place individual patients at great risk. In this review, we examined the literature from 2000 to 2008 and focused on the importance of the risk of drug interactions and potential side effects when Ginkgo biloba is involved. The aim of this systematic review is to assess the clinical evidence on interactions between Ginkgo biloba and drugs.

Quinoline-based compounds as modulators of HIV transcription through NF-κB and Sp1 inhibition

18 quinoline-based compounds were tested for antiviral properties against human immunodeficiency syndrome (HIV). The compounds tested here contain quinoline or tetrahydroquinoline rings and can be divided into two main groups: group 1 includes 4-(2-oxopyrrolidinyl-1)-1,2,3,4-tetrahydroquinolines with 2-(3-nitrophenyl) substituent (N-series) or 2-(3-aminophenyl) moiety (H-series), and group 2 includes 2-(3-nitrophenyl)- or 2-(3-aminophenyl)-substituted quinolines (S-series). Two different antiviral assays were performed in order to test the anti-HIV activity of compounds: 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and recombinant virus assay (RVA). Results showed that the most active compounds were 2-aryl quinolines, particularly those containing methoxy substituents or no substituents in the quinoline skeleton. HIV transcription inhibition appears to be their target in both resting and phorbol myristate acetate (PMA) activated primary lymphocytes, and nuclear factor-kappaB (NF-kappaB) and specificity protein-1 (SP1) seems to be the most important transcription factors involved in their action.

Ellagitannins from Tuberaria lignosa as entry inhibitors of HIV

Screening of plants from the Iberian Peninsula for anti-human immunodeficiency virus (-HIV) activity revealed that aqueous extract of Tuberaria lignosa gave positive results. Following an activity-guided procedure, the crude extract was counterextracted, and the subsequent fractions obtained tested for their anti-HIV activity in vitro. The bioassay-guided fractionation of the extract afforded an ellagitannin enriched fraction (EEF) isolated for the first time from this species. This EEF exhibited antiviral activity against HIV in MT-2 infected cells, with an IC(50) value of 2.33mug/ml (selectivity index greater than 21). Inhibition of HIV infection by EEF appears to be mediated by CD4 down-regulation, the main receptor for HIV entry. CXCR4 and CCR5 receptors were not affected by EEF, explaining why EEF is able to inhibit R5 and X4 infections.

Anti-Infectious Activity in the Cistaceae Family in the Iberian Peninsula

Infectious diseases caused by bacteria, fungi, viruses and parasites are still a major threat to public health, despite the tremendous progress in human medicine. New antimicrobials are needed in medicine due to the rapid emergence of new resistant and opportunistic microbes and the increasing number of patients suffering from immunosuppressive situations, e.g., acquired immunodeficiency syndrome, transplantation, cancer, etc Research on new antimicrobial substances must therefore be continued and all possible strategies should be explored. Plants have been a source of therapeutic agents from more than 5000 years. Approximately 25% of modern medications are developed from plants. In the area of infectious diseases, 75% of new drugs originated from natural sources between 1981 and 2002. As less than 10% of the worlds biodiversity has been tested for biological activity, many more useful natural lead compounds are awaiting discovery. The Cistaceae family comprises a large number of species, growing in the warm temperate regions of the Mediterranean area, that have been and are still used as medicinal plants, particularly in folk medicine. In the present review, we analyse the past, present and future of medicinal plants of the Cistaceae family present in the Iberian Peninsula, both as potential antimicrobial crude drugs as well as a source of natural compounds that act as new anti-infectious agents.

Bioavailable inhibitors of HIV-1 RNA biogenesis identified through a Rev-based screen

New antiretroviral agents with alternative mechanisms are needed to complement the combination therapies used to treat HIV-1 infections. Here we report the identification of bioavailable molecules that interfere with the gene expression processes of HIV-1. The compounds were detected by screening a small library of FDA-approved drugs with an assay based on measuring the displacement of Rev, and essential virus-encoded protein, from its high-affinity RNA binding site. The antiretroviral activity of two hits was based on interference with post-integration steps of the HIV-1 cycle. Both hits inhibited RRE-Rev complex formation in vitro, and blocked LTR-dependent gene expression and viral transcription in cellular assays. The best compound altered the splicing pattern of HIV-1 transcripts in a manner consistent with Rev inhibition. This mechanism of action is different from those used by current antiretroviral agents. The screening hits recognized the Rev binding site in the viral RNA, and the best compound did so with substantial selectivity, allowing the identification of a new RNA-binding scaffold. These results may be used for developing novel antiretroviral drugs.

Essential Oils from the Asteraceae Family Active against Multidrug-Resistant Bacteria

Abstract Natural products have played a pivotal role in antibiotic drug discovery, with most anti-infective drugs being derived from natural products or natural product leads. However, the rapid onset of resistance to most anti-infective drugs considerably diminishes their effectiveness and requires a constant supply of new drugs for the effective treatment of infections. Infectious diseases account for a third of all deaths worldwide. The spread of multidrug-resistant strains of bacteria makes it necessary to identify new classes of antibacterials and compounds that inhibit these resistance mechanisms. Numerous members of the Asteraceae family are important as cut flowers and ornamental crops, as well as being medicinal and aromatic plants, many of which produce essential oils used in folk and modern medicine and in the cosmetics and pharmaceutical industries. Essential oils generally have a broad spectrum of bioactivity, owing to the presence of several active ingredients (e.g., terpenes and phenol-derived aromatic and aliphatic components) that have various modes of action. Extensive studies of the chemical components of Asteraceae species have led to the identification of many substances, including essentials oils, with interesting antibacterial activity. This review summarizes some of the main reports on the chemistry and antibacterial activity of Asteraceae essential oils in the recent literature (2005 to May 2012).

Freeze-dried bioadhesive vaginal bigels for controlled release of Tenofovir

Abstract Nowadays, million women live with the human immunodeficiency virus (HIV) worldwide and many of them are dying per year, particularly in Sub‐Saharan Africa. The development of systems that can be accessed by this population group to prevent the sexual transmission of the virus is therefore necessary. The aim of this work was the formulation of freeze‐dried bioadhesive vaginal bigels releasing Tenofovir in a controlled manner. Systems containing three different proportions of guar gum hydrogel and sesame oil were prepared, adding Span®60 or Span®60 and Tween®60 as surfactants. Drug and excipients were evaluated by cytotoxicity assays, showing no toxicity at the concentrations tested neither for the drug nor any of the excipients. Fresh formulations were characterised through texture analyses and confocal laser microcopy. The system with the lowest guar gum hydrogel/sesame oil proportion and containing Span®60 and Tween®60 (batch ST1) had the highest consistency and adhesion capacity according to texture analyses. Furthermore, a genuine bigel microstructure was observed. After freeze‐drying, swelling, bioadhesion and drug release tests were performed on the resulting systems. ST1 showed the longest bioadhesion time and the most controlled release, as well as a low swelling grade, becoming an interesting option for preventing HIV sexual transmission in women. Graphical abstract Figure. No Caption available.

Promiscuous, Multi-Target Lupane-Type Triterpenoids Inhibits Wild Type and Drug Resistant HIV-1 Replication Through the Interference With Several Targets

Current research on antiretroviral therapy is mainly focused in the development of new formulations or combinations of drugs belonging to already known targets. However, HIV-1 infection is not cured by current therapy and thus, new approaches are needed. Bevirimat was developed by chemical modification of betulinic acid, a lupane-type pentacyclic triterpenoid (LPT), as a first-in-class HIV-1 maturation inhibitor. However, in clinical trials, bevirimat showed less activity than expected because of the presence of a natural mutation in Gag protein that conferred resistance to a high proportion of HIV-1 strains. In this work, three HIV-1 inhibitors selected from a set of previously screened LPTs were investigated for their targets in the HIV-1 replication cycle, including their maturation inhibitor effect. LPTs were found to inhibit HIV-1 infection acting as promiscuous compounds with several targets in the HIV-1 replication cycle. LPT12 inhibited HIV-1 infection mainly through reverse transcription, integration, viral transcription, viral proteins (Gag) production and maturation inhibition. LPT38 did it through integration, viral transcription or Gag production inhibition and finally, LPT42 inhibited reverse transcription, viral transcription or Gag production. The three LPTs inhibited HIV-1 infection of human primary lymphocytes and infections with protease inhibitors and bevirimat resistant HIV-1 variants with similar values of IC50. Therefore, we show that the LPTs tested inhibited HIV-1 infection through acting on different targets depending on their chemical structure and the activities of the different LPTs vary with slight structural alterations. For example, of the three LPTs under study, we found that only LPT12 inhibited infectivity of newly-formed viral particles, suggesting a direct action on the maturation process. Thus, the multi-target behavior gives a potential advantage to these compounds since HIV-1 resistance can be overcome by modulating more than one target.