The potential of selected Australian medicinal plants with anti‑Proteus activity for the treatment and prevention of rheumatoid arthritis

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, Syzygium australe, 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.