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Introduction:Multiple sclerosis is an autoimmune disease which can be triggered in genetic susceptible individuals by Acinetobacter spp. and Pseudomonas aeruginosa infections. Terminalia ferdinandiana (Kakadu plum) fruit has documented therapeutic properties as a general antiseptic agent. Extracts prepared from the leaves have also been shown to block several microbial triggers of autoimmune inflammatory diseases. This study examines the ability of Kakadu plum fruit extracts to inhibit some microbial triggers of multiple sclerosis. Methods: T. ferdinandiana fruit solvent extracts were investigated by disc diffusion assay against reference and clinical strains of A.baylyi and P. aeruginosa. Their MIC values were determined to quantify and compare their efficacies. Toxicity was determined using the Artemia franciscana nauplii bioassay. Active extracts were analysed by non-targeted HPLC-QTOF mass spectroscopy (with screening against 3 compound databases) and by GC-MS (with screening against 1 compound databases) for the identification and characterisation of individual components in crude plant extracts. Results: Methanolic, aqueous and ethyl acetate T. ferdinandiana leaf extracts displayed potent antibacterial activity in the disc diffusion assay against the bacterial triggers of multiple sclerosis (A.baylyi and P. aeruginosa). The methanol and ethyl acetate extracts had the most potent growth inhibitory activity, with MIC values less than 1000 µg/ ml against A. baylyi and P. aeruginosa (both reference and clinical strains). In comparison, the water extract was substantially less potent. Neither the chloroform nor hexane extracts inhibited the growth of any of the bacterial strains tested. All T. ferdinandiana fruit extracts were nontoxic in the Artemia fransiscana bioassay. Non-biased phytochemical analysis of the ethyl acetate extract revealed only low levels of the tannins gallic acid and chebulic acid and no other tannins. Conclusion: The low toxicity of the T. ferdinandiana fruit extracts and their potent inhibitory bioactivity against the bacterial triggers of multiple sclerosis indicates their potential as medicinal agents in the treatment and prevention of this disease. Phytochemical studies indicate that this activity is likely to be due to phytochemicals other than tannins.

Introduction: Autoimmune inflammatory diseases can be triggered by specific bacteria in susceptible individuals. Terminalia ferdinandiana (Kakadu plum) has documented therapeutic properties as a general antiseptic agent. However, the high ascorbic acid levels in Kakadu plum fruit may interfere with this activity. Methods: T. ferdinandiana leaf solvent extracts were investigated by disc diffusion assay against a panel of bacteria known to trigger autoimmune inflammatory diseases.Their MIC values were determined to quantify and compare their efficacies.Toxicity was determined using the Artemia franciscana nauplii bioassay. Non-targeted HPLC separation of crude extracts coupled to high resolution time-of-flight (TOF) mass spectroscopy with screening against 3 compound databases was used for the identification and characterisation of individual components in crude plant extracts. Results: Methanolic, aqueous and ethyl acetate T. Ferdinandiana leaf extracts displayed potent antibacterial activity in the disc diffusion assay against the bacterial triggers of rheumatoid arthritis, ankylosing spondylitis and multiple sclerosis. The ethyl acetate extract had the most potent inhibitory activity, with MIC values less than 120 µg/ml against P. mirabilis and A. baylyi (both reference and clinical strains). The ethyl acetate extract had similar potency against K. pneumonia (both reference and clinical strains), but had higher MIC values (2733 µg/ml) against P. aeruginosa. The methanolic extract was also a potent inhibitor of bacterial growth, with MIC values generally < 1000 µg/ml. In comparison, the water, chloroform and hexane leaf extracts were all substantially less potent antibacterial agents, with MICs values generally well over 1000 µg/ml. All T. ferdinandiana leaf extracts were either nontoxic or of low toxicity in the Artemia fransiscana bioassay.Non-biased phytochemical analysis of the ethyl acetate extract revealed the presence of high levels of tannins (exifone (4-galloylpyrogallol), ellagic acid dehydrate, trimethylellagic acid, chebulic acid, corilagin, punicalin, castalagin and chebulagic acid). Conclusion: The low toxicity of the T. ferdinandiana leaf extracts and their potent inhibitory bioactivity against the bacterial triggers of autoimmune inflammatory disorders indicates their potential as medicinal agents in the treatment and prevention of these diseases.

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Background:A wide variety of herbal medicines are used in indigenous Australian traditional medicinal systems to treat rheumatoid arthritis (RA) and inflammation. The current study was undertaken to test the ability of a panel of Australian plants with a history of the ethnobotanical usage in the treatment of inflammation for the ability to block the microbial trigger of RA.Materials and Methods:One hundred and six extracts from 40 plant species were investigated for the ability to inhibit the growth of the bacterial trigger of RA (Proteus mirabilis). The extracts were tested for toxicity in the Artemia nauplii bioassay. The most potent inhibitor of P. mirabilis growth was further analyzed by reversed-phase high performance liquid chromatography (RP-HPLC) coupled to high accuracy time-of-flight (TOF) mass spectroscopy.Results:Sixty-five of the 106 extracts tested (61.3%) inhibited the growth of P. The Aleurites moluccanus, Datura leichardtii, Eucalyptus major, Leptospermum bracteata, L. juniperium, Macadamia integriflora nut, Melaleuca alternifolia, Melaleuca quinquenervia, Petalostigma pubescens, P. triloculorae, P. augustifolium, Scaevola spinescens, Syzygiumaustrale, and Tasmannia lanceolata extracts were determined to be the most effective inhibitors of P. mirabilis growth, with minimum inhibitory concentration (MIC) values generally significantly below 1000 μg/ml. T. lanceolata fruit extracts were the most effective P. mirabilis growth inhibitors, with a MIC values of 11 and 126 μg/ml for the methanolic and aqueous extracts, respectively. Subsequent analysis of the T. lanceolata fruit extracts by RP-HPLC coupled to high-resolution TOF mass spectroscopy failed to detect resveratrol in either T. lanceolata fruit extract. However, the resveratrol glycoside piceid and 2 combretastatin stilbenes (A-1 and A-4) were detected in both T. lanceolata fruit extracts. With the exception of the Eucalyptus and Syzygium extracts, all extracts exhibiting Proteus inhibitory activity were also shown to be nontoxic, or of low toxicity in the Artemia nauplii bioassay.Conclusions:The low toxicity of these extracts and their inhibitory bioactivity against Proteus spp. indicate their potential in blocking the onset of rheumatoid arthritis.