Maca (Lepidium meyenii Walp.) inhibits HIV-1 infection through the activity of thiadiazole alkaloids in viral integration.

ETHNOPHARMACOLOGY RELEVANCE: Lepidium meyenii Walp. (maca) has been traditionally used for centuries in the Central Andes region both as food and as medicine. In the last decades, its fertility enhancer properties have gained importance, with the majority of the scientific literature related to this topic. However, other traditional uses are less known as metabolic or infectious diseases. AIM OF THE STUDY: The main purpose of this study is to investigate the anti-infectious activity of L. meyenii, specifically in HIV-1 infection. There are previous reports of the transcriptional related activity of L. meyenii extracts in human T lymphocytes via transcription factors as NF-κB. Since T lymphocytes are the main target of HIV-1 infection and NF-κB is strongly involved in HIV-1 transcription, L. meyenii could display antiviral activity. MATERIAL AND METHODS: Chromatography and spectroscopy techniques were used to isolate and identify the compounds in the active extracts. An antiviral assay system based on recombinant viruses was used to evaluate the anti-HIV activity. Cell toxicity was tested for all the extracts and compounds. Viral entry was studied using VSV-HIV chimera viruses and reverse transcription and viral integration were studied by qPCR of viral DNA in infected cells. Finally, viral transcription was studied in primary lymphocytes transfected with HIV-1 or NF-κB luciferase reporter plasmids. RESULTS: n-Hexane extracts of purple maca displayed anti-HIV activity in an in vitro assay. A bioassay-guided fractionation led to the identification of three thiadiazole alkaloids with antiviral activity. All the compounds were able to inhibit HIV infection of MT-2 cell lines and primary lymphocytes (PBMCs) with IC50 values in the low micromolar range. The mechanism of action differs between the three compounds: one of them showed activity on viral entry, and all the three compounds inhibited viral integration at low concentrations. Remarkably, none of the compounds inhibited reverse transcription or viral transcription. CONCLUSIONS: n-Hexane extracts of the purple ecotype of L. meyenii inhibit HIV-1 infection in vitro and three active thiadiazole alkaloids were isolated acting mainly on viral integration and viral entry.

Dapivirine Bioadhesive Vaginal Tablets Based on Natural Polymers for the Prevention of Sexual Transmission of HIV.

Young sub-Saharan women are a group that is vulnerable to the sexual transmission of HIV. Pre-exposure prophylaxis through vaginal microbicides could provide them an option for self-protection. Dapivirine has been demonstrated to have topical inhibitory effects in HIV, and to provide protection against the sexual transmission of this virus. This paper reports on the studies into swelling behaviour, bioadhesion and release carried out on dapivirine tablets based on chitosan, locust bean gum and pectin, to select the most suitable formulation. The modified simulated vaginal fluid led to a high solubility of dapivirine and allowed the dapivirine release profiles to be characterized in sink conditions; this aqueous medium is an alternative to organic solvents, which are not a realistic option when evaluating systems whose behaviour varies in aqueous and organic media. Of the formulations evaluated, dapivirine/pectin tablets containing 290 mg of polymer and 30 mg of dapivirine present the most moderate swelling, making them the most comfortable dosage forms. Their high bioadhesive capacity would also allow the formulation to remain in the action zone and release the drug in a sustained manner, pointing to this formulation as the most promising candidate for future evaluations of vaginal microbicides for the prevention of HIV.

Chitosan and Kappa-Carrageenan Vaginal Acyclovir Formulations for Prevention of Genital Herpes. In Vitro and Ex Vivo Evaluation.

Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Polysaccharides, such as chitosan and carrageenan, which have good binding capacity with mucosal tissues, are now included in vaginal delivery systems. Marine polymer-based vaginal mucoadhesive solid formulations have been developed for the controlled release of acyclovir, which may prevent the sexual transmission of the herpes simplex virus. Drug release studies were carried out in two media: simulated vaginal fluid and simulated vaginal fluid/simulated seminal fluid mixture. The bioadhesive capacity and permanence time of the bioadhesion, the prepared compacts, and compacted granules were determined ex vivo using bovine vaginal mucosa as substrate. Swelling processes were quantified to confirm the release data. Biocompatibility was evaluated through in vitro cellular toxicity assays, and the results showed that acyclovir and the rest of the materials had no cytotoxicity at the maximum concentration tested. The mixture of hydroxyl-propyl-methyl-cellulose with chitosan- or kappa-carrageenan-originated mucoadhesive systems that presented a complete and sustained release of acyclovir for a period of 8-9 days in both media. Swelling data revealed the formation of optimal mixed chitosan/hydroxyl-propyl-methyl-cellulose gels which could be appropriated for the prevention of sexual transmission of HSV.

The artemisia L. Genus: a review of bioactive essential oils.

Numerous members of the Anthemideae tribe 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 industry. Essential oils generally have a broad spectrum of bioactivity, owing to the presence of several active ingredients that work through various modes of action. Due to their mode of extraction, mostly by distillation from aromatic plants, they contain a variety of volatile molecules such as terpenes, phenol-derived aromatic and aliphatic components. The large genus Artemisia L., from the tribe Anthemideae, comprises important medicinal plants which are currently the subject of phytochemical attention due to their biological and chemical diversity. Artemisia species, widespread throughout the world, are one of the most popular plants in Chinese traditional preparations and are frequently used for the treatment of diseases such as malaria, hepatitis, cancer, inflammation and infections by fungi, bacteria and viruses. Extensive studies of the chemical components of Artemisia have led to the identification of many compounds as well as essentials oils. This review summarizes some of the main reports on the chemistry and anti-infective activities of Artemisia. Li. essential oils from the data in the recent literature (2000-2011).

Quinoline-based compounds as modulators of HIV transcription through NF-kappaB 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.

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.

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 world's 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.

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.

COX-2 and sPLA2 inhibitory activity of aqueous extract and polyphenols of Rhizophora mangle (red mangrove).

The aqueous extract of Rhizophora mangle bark and its polyphenolic fractions showed remarkable in vitro antiinflammatory activity in a preliminary study. The low molecular weight fraction exhibited cyclooxygenase-2 inhibitory activity while the total aqueous extract and the low molecular weight fraction showed secretory phospholipase A(2) inhibitory activity.

Phenylpropanoid glycosides from Scrophularia scorodonia: in vitro anti-inflammatory activity.

Five phenylpropanoid glycosides isolated from Scrophularia scorodonia L. (Scrophulariaceae), namely angoroside A (1), angoroside C (2), angoroside D (3), acteoside (4) and isoacteoside (5), had been evaluated as potential inhibitors of some macrophage functions involved in the inflammatory process. These compounds have been tested in two experimental systems: ionophore-stimulated mouse peritoneal macrophages and human platelets serve as source of COX-1 and 5-LOX, and mouse peritoneal macrophages stimulated with E. coli LPS are the means of testing for COX-2, NO and TNF-alpha activity. None of compounds assayed had a significant effect on LTC(4)-release from calcium ionophore-stimulated mouse peritoneal macrophages. However, the release of PGE(2) by mouse peritoneal macrophages stimulated with calcium ionophore was inhibited by most of these compounds. In the TXB(2)-release assay, acteoside (4), angoroside A (1) and angoroside C (2) showed a significant effect. These five compounds, except angoroside C (2) significantly inhibited LPS-induced PGE(2), NO and TNF-alpha in a concentration-dependent manner. In LPS-stimulated macrophages, the phenylpropanoid glycoside angoroside C (2) only had activity on NO. These results indicate that the pharmacology of these compounds may participate in the anti-inflammatory effect of Scrophularia scorodonia.

Flavonoids and a sesquiterpene lactone from Tanacetum microphyllum inhibit anti-inflammatory mediators in LPS-stimulated mouse peritoneal macrophages.

In our ongoing research into anti-inflammatory compounds from Tanacetum microphyllum, four naturally occurring flavonoids (santin, ermanin, centaureidin and 5,3'-dihydroxy-4'-methoxy-7-methoxycarbonylflavonol) and one sesquiterpene lactone (hydroxyachillin) isolated from this plant, were evaluated as potential inhibitors of some macrophage functions involved in the inflammatory process. These five compounds significantly inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E (2) (PGE (2)) in a concentration-dependent manner. In the tumour necrosis factor-alpha (TNF-alpha) assay, only centaureidin and hydroxyachillin significantly inhibited the accumulation of TNF-alpha. These results indicate that these compounds may contribute to the anti-inflammatory properties of T. microphyllum.

Screening of South American plants against human immunodeficiency virus: preliminary fractionation of aqueous extract from Baccharis trinervis.

Ethanolic and aqueous extracts of 14 South American medicinal plants were tested for inhibitory activity on human immunodeficiency virus (HIV). Both extracts were relatively non-toxic to human lymphocytic MT-2 cells, but only the aqueous extract of Baccharis trinervis exhibited potent anti-HIV activity in an in vitro MTT assay. To delineate the extract-sensitive phase, some studies of the antiviral properties of the active extract are described in this paper. Based on the results presented here, a separation scheme was devised, which permitted the preliminary fractionation of the extract, with the aim of finding an inhibitor of this virus.

Antiviral activity of seven iridoids, three saikosaponins and one phenylpropanoid glycoside extracted from Bupleurum rigidum and Scrophularia scorodonia.

As part of our screening of antiviral agents from medicinal plants, 11 compounds from plant origin (Bupleurum rigidum and Scrophularia scorodonia), three saikosaponins, seven iridoids and one phenylpropanoid glycoside were tested in vitro against herpes simplex type I (HSV-1), vesicular stomatitis virus (VSV) and poliovirus type 1. Five of these compounds showed antiviral activity against VSV. The percentages of cellular viability at the non-toxic limit concentrations of the active compounds were: verbascoside 53.6 % at 500 microg/ml, 8-acetylharpagide 32.1 % at 500 microg/ml, harpagoside 43.3 % at 450 microg/ml, scorodioside 47.8 % at 500 microg/ml and buddlejasaponin IV 56.9 % at 25 microg/ml. Although none of the saikosaponins were active against HSV-1, the iridoid scorodioside showed moderate in vitro anti-HSV-1 activity (30.6 % at 500 microg/ml). However, none of the compounds tested in this survey had any effect against poliovirus.