G.H.N. Towers

Biological activities of sesquiterpene lactones

Abstract Sesquiterpene lactones are characteristic constituents of the Compositae but also occur sporadically in other angiosperm families and even in some liverworts. These bitter substances often contain as a major structural feature an α,β-unsaturated-γ-lactone, which in recent studies has been shown to be associated with anti-tumor, cytotoxic, anti-microbial and phytotoxic activity. They are known to poison livestock, to act as insect feeding deterrents and to cause allergic contact dermatitis in humans. This review highlights the present state of knowledge on the biological activities and mechanism of action of some sesquiterpene lactones.

Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca

Ayahuasca is a hallucinogenic beverage derived by boiling the bark of the Malpighiaceous liana Banisteriopsis caapi together with the leaves of various admixture plants, viz. Psychotria viridis, Psychotria carthagenensis , or Diplopterys cabrerana . B. caapi contains harmine, harmaline, and tetrahydroharmine while the admixtures contain N,N-dimethyltryptamine (DMT). DMT, a potent hallucinogen, is inactive orally due to degradation by visceral monoamine oxidase (MAO). The beta-carbolines, however, are highly active reversible inhibitors of MAO and may protect the DMT from deamination by MAO and render it orally active. This mechanism has been proposed to underlie the oral activity of ayahuasca but has not been experimentally confirmed. In the present study the constituents of the admixture plants and the alkaloids of eight ayahuasca samples from Peru were qualitatively and quantitatively analyzed using two-dimensional thin-layer chromatography (TLC), high pressure liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). Several B. caapi cultivars were quantitatively compared for variations in alkaloid content. Three admixture plants used rarely in the manufacture of ayahuasca were also screened for alkaloids. A selected sample of beta-carbolines were screened for activity as MAO inhibitors using an in vitro assay system, and structure/activity relationships were compared. Inhibition observed with single compounds was compared with the activity of selected samples of ayahuasca which were screened in the system and also with the activity of mixtures of beta-carbolines. The levels of DMT and beta-carbolines found in the ayahuasca samples examined in the present study were an order of magnitude greater than the levels reported in a previous study. Ayahuasca was found to be an extremely effective inhibitor of MAO in vitro and the degree of inhibition was directly correlated with the concentration of MAO-inhibiting beta-carbolines. Inhibition experiments using mixtures of beta-carbolines indicated that their effects in combination are additive, rather than synergistic or antagonistic. Implications of the results in understanding the pharmacology of ayahuasca are discussed.

HYPOCRELLIN, FROM HYPOCRELLA BAMBUASE, IS PHOTOTOXIC TO HUMAN-IMMUNODEFICIENCY-VIRUS

Abstract Hypocrellin, a photodynamic perylene quinonoid isolated from the Chinese medicinal fungus Hypocrella bambuase, was evaluated for antiviral activity against the human immunodeficiency virus (HIV‐1). Hypocrellin was phototoxic to HIV‐1, almost as good as the structurally similar plant pigment hypericin, and like hypericin its activity required visible light. In contrast peroxyhypocrellin had little or no effect on the virus.

Screening of selected medicinal plants of Nepal for antimicrobial activities

In an ethnopharmacological screening of selected medicinal plants used in Nepal, methanol extracts from 21 plant species were assayed for activity against 8 strains of bacteria and 5 strains of fungi. Duplicate assays were conducted with and without exposure to UV-A radiation to test for light-activated or light-enhanced activity. All 21 of the extracts showed activity against at least 2 bacterial strains, and 20 showed activity against at least 2 fungi. Six extracts were active only when exposed to UV-A light, and the antibiotic or antifungal effect of 14 extracts was enhanced upon exposure to light.

Antiviral and antimicrobial activities of Colombian medicinal plants

Strong antiviral and antimicrobial activities were detected in methanolic extracts of 24 plants used medicinally in the treatment of skin infections in four different regions of Colombia. Thirteen extracts displayed activity against herpes simplex virus (HSV) whereas none was active against poliovirus. The antiviral activity was indicated by a total inhibition of viral cytopathic effects (CPE) at a non-cytotoxic concentration of the extract. The most potent extract was obtained from Byrsonima verbascifolia (L.) HBK. which showed anti-HSV activity at a concentration as low as 2.5 microg/ml. Antimicrobial screening was conducted using the disc diffusion assay against Klebsiella pneumoniae, Escherichia coli, Streptococcus faecalis, Mycobacterium phlei, Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella typhimurium and the human pathogenic yeast, Candida albicans. Anti-Candida activity was observed for Piper lanceaefolium HBK. and Juglans neotropica Diels. Twenty-two extracts displayed activity against Gram-positive bacteria whereas none was active against the Gram-negative species. We concluded that these Colombian medicinal plants represent an untapped source of potentially useful antivirals and are worthy of further study.

Antimicrobial activities of southern Nepalese medicinal plants.

In an ethnopharmacological screening of selected medicinal plants used in Nepal, methanol extracts from 20 plant species were assayed for activity against eleven strains of bacteria and four strains of fungi. Duplicate assays were conducted with and without exposure to ultraviolet (UV)-A radiation to test for light-activated or light-enhanced activity. Fifteen of the extracts showed activity against bacteria and fourteen showed activity against fungi. Five extracts were active only when exposed to UV-A light, and the antibiotic or antifungal effect of five extracts was enhanced upon exposure to light. Two of the most active extracts were from plants used to treat diarrhoea and dysentery. Bark from both Terminalia alata (Combretaceae) and Mallotus phillppensis (Euphorbiaceae) was active against Gram-positive and Gram-negative bacteria.

Antiviral activities of Nepalese medicinal plants

In a screening of plants used traditionally in Nepal to treat diseases that could be caused by viruses, methanol extracts from 21 species were assayed for activity against three mammalian viruses: herpes simplex virus, Sindbis virus and poliovirus. Assays were performed in UV-A or visible light, as well as dark. Individual species of Hypericum, Lygodium, and Maesa exhibited impressive antiviral activities, although their selective effects on the three viruses suggested that the antiviral ingredients were different in each extract. In addition, many of the other extracts showed partial inactivation of one or more test viruses.

Antimicrobial constituents of Rhus glabra

The antimicrobial activity of the methanol extract and isolated constituents of Rhus glabra (Anacardiaceae), a species used in folk medicine by North American native people, was evaluated against 11 microorganisms, including gram-positive and gram-negative bacteria. The extract was subsequently fractionated and monitored by bioassays leading to the isolation of three antibacterial compounds, the methyl ester of 3,4,5-trihydroxybenzoic acid (methyl gallate) (minimal inhibition concentration (MIC) 12.5 micrograms/ml), 4-methoxy-3,5-dihydroxybenzoic acid (MIC 25 micrograms/ml) and gallic acid (MIC > 1000 micrograms/ml). The first two compounds are reported here for the first time from Rhus glabra. Their structures were established using spectroscopic and chemical methods.

ANTIVIRAL ACTIVITY OF THE PHOTOACTIVE PLANT PIGMENT HYPERICIN

The polycyclic compound hypericin, a known photodynamic agent, was investigated for antiviral activity in the presence and absence of light. The three viruses tested: murine cytomegalovirus; Sindbis virus; and human immunodeficiency virus type 1, were all susceptible to hypericin; but these antiviral activities were considerably enhanced, in a dose‐dependent manner, by exposure to light.

Thiarubrine A, a bioactive constituent of Aspilia (Asteraceae) consumed by wild chimpanzees

Two African species ofAspilia (Asteraceae), which are used medicinally by man and which are eaten by wild chimpanzees in an unusual manner, were found to contain the potent antibiotic thiarubrine A as a major leaf phytochemical. Its presence in leaf material strengthens the view that the feeding behavior of wild chimpanzees is related to special physiological or pharmacological effects on the animals.