Hydrophobic π-π stacking interactions and hydrogen bonds drive self-aggregation of luteolin in water.

Luteolin is a flavonoid obtained from different plant species. It is known for its versatile biological activities. However, the beneficial effects of luteolin have been limited to small concentrations as a result of poor water solubility. This study aimed at investigating the hydrophobic interaction and hydration of luteolin towards the improvement of its solubility when used as a drug. We report the aggregation properties of luteolin in water by varying the number of monomers using atomistic molecular dynamics simulation. Results show that the equilibrium structure of luteolin occurs in an aggregated state with different structural arrangements. As the monomers size increase, the antiparallel flipped conformation dominates over T-shaped antiparallel, T-shaped parallel, and antiparallel conformations. The formation of intramolecular hydrogen bonding of 0.19 nm between the keto-enol groups results in hydrophobic characteristics. A larger cluster exhibits slow hydrogen bond dynamics for luteolin-luteolin than luteolin-water interaction. Water structure at large cluster size exhibited slow dynamics and low self-diffusion of luteolin. The existence of hydrophobic π-π and hydrogen bonds between luteolin molecules drives strong self-aggregation resulting in poor water solubility. Breakage of these established interactions would result in increased solubility of luteolin in water.

Anti-respiratory syncytial virus and anti-herpes simplex virus activity of six Tanzanian medicinal plants with extended studies of Erythrina abyssinica stem bark.

ETHNOPHARMACOLOGICAL RELEVANCE: Except for few highly pathogenic viruses, no antiviral drug has been approved for treatment of viral infections in humans. Plant extracts, selected based on their ethno-medical use, represent an important source of compounds for the development of novel candidate antiviral drugs. This especially concerns plants with ethnomedical records on their use in treatment of viral infections. AIM OF THE STUDY: To identify and document medicinal plants used by traditional health practitioners (THPs) for treatment of respiratory infections and muco-cutaneous lesions in order to study their antiviral activity including identification of active components and elucidation of mode of antiviral activity. MATERIALS AND METHODS: The ethno-medical survey was performed in the Kagera region of Tanzania. The THPs were asked for plants used for treatment of signs and symptoms of respiratory infections and watery muco-cutaneous blisters in oral and genital regions. The plants identified were successively extracted with n-hexane, ethyl acetate and water, and the extracts assayed for anti-respiratory syncytial virus (RSV), anti-herpes simplex virus 2 (HSV-2), and anti-human parainfluenza virus 2 (HPIV-2) activity in cultured cells. Antiviral components were separated by ethanol precipitation and CL-6B chromatography, and the mode of antiviral activity elucidated by the time-of-addition assay and selection for the virus variants resistant to antiviral plant extract. RESULTS: THPs identified fifteen plants used for treatment of respiratory infections and muco-cutaneous blisters. The water extract, but not n-hexane or ethyl acetate extracts, of six of these plants including Erythrina abyssinica stem bark, inhibited infectivity of two glycosaminoglycan-binding viruses i.e., RSV and HSV-2 but not the sialic acid binding HPIV-2. An activity-guided separation revealed that antiviral component(s) of water extract of E. abyssinica could be precipitated with ethanol. This sample potently and selectively inhibited RSV and HSV-2 infectivity in cultured cells with IC50 values of 2.1 µg/ml (selectivity index >476) and 0.14 µg/ml (selectivity index >7143) respectively. The sample exhibited inhibitory effect on the virus attachment to and entry into the cells by directly targeting the viral particles. Indeed, 10 consecutive virus passages in HEp-2 cells in the presence of this extract selected for a resistant RSV variant lacking the attachment, viral membrane-associated, G protein due to a stop codon at amino acid residue 33 (Leu33stop). Fractionation of the E. abyssinica extract on a CL-6B column revealed that anti-RSV and HSV-2 activity correlated with carbohydrate content. The most pronounced antiviral activity was associated with a carbohydrate containing ingredient of molecular mass of <5 kDa, which may polymerize to antiviral composites of up to 410 kDa. CONCLUSIONS: Altogether, the water extract of six medicinal plants showed anti-RSV and anti-HSV-2 activities. Extended studies of the stem bark of E. abyssinica identified antiviral components that potently and selectively inhibited infectivity of free RSV and HSV-2 particles, a feature of importance in topical treatment of these infections. This observation confirms ethno-medical information concerning the use of E. abyssinica extract for treatment of respiratory infections and herpetic lesions.

Indigenous to Tanzania.

The objective of this study was to evaluate free radical scavenging capacity of crude extracts from forest basidiomycetous fungi, domestic zygomycetous fungi and marine ascomycetous fungi. Lethal concentration values that kill 50% of the brine shrimps (LC50) were determined from 19 fungal extracts using brine shrimp test (BST). The LC50 values of fungal extract ranged between 0.28-40 µg/ml. The basidiomycetous (Lactarius volemoides) was the most toxic fungi with LC50 of 0.28 µg/ml while ascomycete Pichia guilliermondii showed the least toxicity with LC50 of 40 µg/ml. The concentrations of eleven fungal extracts were further evaluated on their ability to scavenge free radical using 1-diphenyl-2-picrylhydrazyl (α,α-diphenyl-ß-picrylhydrazyl) (DPPH) as a dye reagent for spectrophotometric assay at 517 nm. The extract concentrations that decreased the initial DPPH radical by 50% (EC50) were determined. The EC50 values ranged from 19-60.4 µg/ml ascorbic acid equivalents. Extracts from an edible but undomesticated basidiomycetous fungus isolated from Miombo forest and identified as Termitomyces microcarpus showed the highest scavenging effect with EC50 at 19 µg/ml while that from ascomycete Candida tropicalis showed the least EC50 at 60.4 µg/ml. These results draw attention to wild undomesticated Miombo fungi as potential source of nutritional supplements worth further investigation.

Free Radical Scavenging Activity of Some Fungi Indigenous to Tanzania

Abstract:The objective of this study was to evaluate free radical scavenging capacity of crude extracts from forest basidiomycetous fungi; domestic zygomycetous fungi and marine ascomycetous fungi. Lethal concentration values that kill 50 of the brine shrimps (LC50) were determined from 19 fungal extracts using brine shrimp test (BST). The LC50 values of fungal extract ranged between 0.28- 40?g/ml. The basidiomycetous ( Lactarius volemoides check for this species in other resources ) was the most toxic fungi with LC50 of 0.28?g/ml while ascomycete Pichia guilliermondii check for this species in other resources showed the least toxicity with LC50 of 40?g/ml. The concentrations of eleven fungal extracts were further evaluated on their ability to scavenge free radical using 1-diphenyl-2-picrylhydrazyl (?;?-diphenyl-?-picrylhydrazyl) (DPPH) as a dye reagent for spectrophotometric assay at 517nm. The extract concentrations that decreased the initial DPPH radical by 50 (EC50) were determined. The EC50 values ranged from 19-60.4?g/ml ascorbic acid equivalents. Extracts from an edible but undomesticated basidiomycetous fungus isolated from Miombo forest and identified as Termitomyces microcarpus check for this species in other resources showed the highest scavenging effect with EC50 at 19?g/ml while that from ascomycete Candida tropicalis check for this species in other resources showed the least EC50 at 60.4?g/ml. These results draw attention to wild undomesticated Miombo fungi as potential source of nutritional supplements worth further investigation