ABSTRACT
Alzheimer's disease (AD), a progressive neurodegenerative disorder, is characterized by the accumulation of neurotoxic ß-amyloid (Aß) peptides, which consequently affects cognitive decline and memory impairment. Current research on AD treatment is actively focusing on the prevention of neurotoxic Aß peptide accumulation. Monsonia angustifolia is reported to be consumed as an indigenous vegetable in Tanzania. In this study, we investigated the effect of the ethanol (EtOH) extract of M. angustifolia dried ground material on Aß production and spatial learning ability as protection against AD. The formation of Aß peptides was significantly reduced in HeLa cells stably transfected with the Swedish mutant form of ß-amyloid precursor protein (APPsw) after treatment with a 60% EtOH extract of M. angustifolia. We next examined the cognitive-improving effects of the EtOH extract in vivo. Tg2576 mice were treated with extract for 6 months and subjected to Morris water maze and novel object recognition tests. The results showed that the 60% EtOH extract of M. angustifolia significantly ameliorated behavioral deficits of the AD transgenic mice and reduced the level of insoluble Aß42 in the cerebral cortex and hippocampus. We further found that the 60% EtOH extract was effective for memory function recovery after shorter treatment (4 months). In addition, we isolated and identified several single compounds, justicidin A, 5-methoxyjusticidin A, chinensinaphthol, retrochinensinaphthol methyl ether, and suchilactone, from M. angustifolia and tested these compounds. Among them, justicidin A potently decreased the formation of Aß in APPsw-transfected cells. These data suggest that the 60% EtOH extract of M. angustifolia has the potential to be developed as a treatment of AD. Furthermore, justicidin A may contribute, at least partially, to the Aß alteration observed with the extract treatment.
Subject(s)
Alzheimer Disease/prevention & control , Geraniaceae/chemistry , Plant Extracts/administration & dosage , Alzheimer Disease/metabolism , Alzheimer Disease/psychology , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Animals , Cognition/drug effects , Disease Models, Animal , Humans , Male , Memory/drug effects , Mice , Mice, Transgenic , Plant Extracts/chemistryABSTRACT
AIM OF THE STUDY: Asthma is a chronic inflammatory disease of the lungs, characterized by increased sensitivity to bronchoconstriction associated with infiltration of immune cells, mucus hypersecretion and structural remodelling of the airways. In South Africa, the indigenous plant Siphonochilus aethiopicus, is used by traditional health practitioners to treat colds, wheezing of the chest, coughs, influenza, sinus problems and mild asthma. In this study we aimed to investigate the potential anti-inflammatory and anti-allergic properties of S. aethiopicus in vitro and its efficacy in a mouse model of allergic asthma. MATERIALS AND METHODS: The dried and powdered S. aethiopicus plant material was extracted separately with organic solvents (diethyl ether, ethanol) and water. Dried extracts as well as a purified furanoterpenoid compound present in the extracts were screened in vitro in a glucocorticoid and histamine H(1) receptor binding assay and a phosphodiesterase IV enzyme inhibition assay. Extracts were also evaluated for efficacy against ovalbumin (OVA)-induced allergic airway disease in mice. RESULTS: Biological assaying of extracts of the plant and the isolated furanoterpenoid showed significant in vitro inhibition of glucocorticoid and histamine H(1) receptor binding and phosphodiesterase IV activity, supporting a possible anti-inflammatory, anti-allergic and bronchodilatory effect. Administration of S. aethiopicus extracts to OVA-sensitized and challenged mice significantly reduced lung inflammation and the percentage of eosinophils in bronchoalveolar lavage fluid but did not influence airway hyperreactivity. CONCLUSION: This study provides evidence that S. aethiopicus has anti-inflammatory and anti-allergic properties in vitro and in vivo. These findings may support anecdotal accounts of its effectiveness against asthma, sinusitis, colds and flu.
Subject(s)
Anti-Asthmatic Agents/pharmacology , Asthma/drug therapy , Phytotherapy , Zingiberaceae , Animals , Anti-Asthmatic Agents/chemistry , Asthma/immunology , Asthma/pathology , Bronchial Hyperreactivity/drug therapy , Disease Models, Animal , Ethnopharmacology , Humans , In Vitro Techniques , Lung/drug effects , Lung/immunology , Lung/pathology , Medicine, African Traditional , Mice , Mice, Inbred BALB C , Ovalbumin/immunology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , South Africa , Zingiberaceae/chemistryABSTRACT
A selective analytical method based on high-performance liquid chromatography, combined with atmospheric pressure ionisation mass spectrometry, was developed for the detection of atractyloside. The analysis was performed on an Xterra Phenyl column utilising a gradient elution profile and a mobile phase consisting of 10 mM aqueous ammonium acetate buffer-methanol-acetonitrile. The calibration curve of the method (1 ng/ml-160 microg/ml) was best described by a second order polynomial function (r2 = 0.998) but displayed good linearity in the range of 100 ng/ml-1 microg/ml (r2 = 0.999). The limit of detection for the atractyloside standard was determined and found to be 100 pg/ml and the limit of quantification of atractyloside in tuber matrix was found to be 250 pg/ml. The relative standard deviation of the method was on average below 5% (n = 8). The method was successfully applied to the analysis of Callilepis laureola tubers and unknown powdered samples for the presence of atractyloside.
