Abstract

Introduction: Duboisia leichhardtii F.Muell. is a medium to large tree which is native to subtropical regions of eastern Australia. Duboisia spp. contain a number of psychoactive tropane and pyrrolidine alkaloids with reported antibacterial activity. Despite this, D. leichhardtii leaf extracts have not been rigorously examined for growth inhibitory properties against many bacteria, including the bacterial triggers of autoimmune inflammatory diseases. Methods: The antimicrobial activity of D. leichhardtii leaf solvent extracts was investigated by disc diffusion and growth time course assays against a panel of bacterial triggers of autoimmune diseases. The growth inhibitory activity was further quantified by MIC determination and growth time course assays. Toxicity was determined using the Artemia franciscana nauplii bioassay. Results: Methanolic and aqueous D. leichhardtii leaf solvent extracts were potent inhibitors of the bacterial triggers of rheumatoid arthritis and ankylosing spondylitis. The methanolic extract displayed the most potent bacterial growth inhibitory activity. It was particularly potent against P. mirabilis (MICs of 85 and 116 μg/mL against reference and clinical strains respectively) and P. vulgaris (MIC of 187 μg/mL). The methanolic extract was also a good inhibitor of K. pneumoniae growth (MICs of 143 and 118 μg/mL against reference and clinical strains respectively). The aqueous and ethyl acetate extracts were also potent bacterial growth inhibitors, albeit with higher MIC values. The antibacterial activity of the methanolic and aqueous D. leichhardtii leaf extracts were further investigated by growth time course assays which showed significant growth inhibition in cultures of P. mirabilis and K. pneumoniae within 1 h of exposure. All extracts were determined to be nontoxic in the Artemia franciscana nauplii bioassay, indicating their safety for use in preventing these autoimmune inflammatory diseases. Conclusions: The lack of toxicity of the D. leichhardtii leaf extracts and their growth inhibitory bioactivity against the bacterial triggers of rheumatoid arthritis and ankylosing spondylitis indicate their potential in the development of new therapies targeting the onset of these diseases.

Highlights

  • Duboisia leichhardtii F.Muell. is a medium to large tree which is native to subtropical regions of eastern Australia

  • As Proteus spp. ( P. mirabilis) have been identified as a microbial trigger of rheumatoid arthritis,[2,3,4] our results indicate the potential of the D. leichhardtii leaf extracts in preventing and treating that disease

  • As K. pneumoniae has been shown to initiate ankylosing spondylitis,[2,5,6,7] our results indicate the potential of the D. leichhardtii leaf extracts in the prevention and treatment of that disease

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Summary

Introduction

Duboisia leichhardtii F.Muell. is a medium to large tree which is native to subtropical regions of eastern Australia. Results: Methanolic and aqueous D. leichhardtii leaf solvent extracts were potent inhibitors of the bacterial triggers of rheumatoid arthritis and ankylosing spondylitis. Conclusions: The lack of toxicity of the D. leichhardtii leaf extracts and their growth inhibitory bioactivity against the bacterial triggers of rheumatoid arthritis and ankylosing spondylitis indicate their potential in the development of new therapies targeting the onset of these diseases. Current treatment strategies aim to alleviate the symptoms ( pain, swelling and inflammation) with analgesics and antiinflammatory agents, and/or to modify the disease process through the use of disease modifying drugs None of these treatments is ideal as prolonged drug therapy is often accompanied by unwanted side effects and toxicity.[1] There is a need to develop safer, more effective treatments for these conditions which alleviate the symptoms, but may cure or prevent the disease. A greater understanding of the onset and progression of these disorders should greatly assist in more relevant drug discovery and development

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