Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 May;11(Suppl 1):S190-208.
doi: 10.4103/0973-1296.157734.

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

Affiliations

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

I E Cock et al. Pharmacogn Mag. 2015 May.

Abstract

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.

Keywords: Australian plants; Piceid; Proteus mirabilis; combretastatin; inflammation; resveratrol; rheumatoid arthritis; stilbene.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: None declared.

Figures

Figure 1
Figure 1
A proposed schematic representation of the main events in rheumatoid arthritis (RA) disease etiology and progression. Only major events are shown. Numbers refer to current and/or proposed targets for the prevention and treatment of RA
Figure 2
Figure 2
Antibacterial activity of plant water and methanolic extracts measured as zones of inhibition (mm) against Proteus mirabilis. Inhibition zones are represented as the means of at least triplicate experiments ± standard error of the mean. M and W refer to methanolic and water extracts respectively. (a) 1 = A. auriculiformis leaf; 2 = A. diasparima leaf; 3 = A. leptoloba leaf; 4 = A. moluccanus nut; 5 = A. excelsa leaf; 6 = A. caerulea fruit; 7 = A. caerulea leaf; 8 = B. citriodora leaf; 9 = B. myrtiflora leaf; 10 = Callistemon citrinus leaf; 11 = C. citrinus flower; 12 = C. formosus leaf; 13 = C. salignus leaf; 14 = C. salignus flower; 15 = C. oliveri leaf; 16 = Davidsonia pruriens leaf; 17 = D. pruriens fruit; 18 = D. leichhardtii leaf; 19 = Elaeocarpus angustifolius fruit; 20 = E. baileyana leaf; 21 = E. major leaf; 22 = Kunzea flavescens leaf; 23 = Leptospermum bracteata leaf; 24 = L. bracteata flower; 25 = L. juniperium leaf; 26 = L. juniperium flower; 27 = L. longifolium leaf; 28 = L. petersoni leaf; 29 = Macadamia integriflora nut; 30 = M. integriflora leaf; (b) 31 = M. alternifolia leaf; 32 = M. quinquenervia leaf; 33 = Petalostigma pubescens leaf; 34 = P. pubescens fruit; 35 = P. triloculorae leaf; 36 = P. triloculorae fruit; 37 = P. augustifolium leaf; 38 = Scaevola spinescens leaf; 39 = Syzygium anisatum leaf; 40 = S. australe leaf; 41 = S. australe fruit; 42 = S. forte leaf; 43 = S. francisii leaf; 44 = S. moorei leaf; 45 = S. puberculum leaf; 46 = S. wilsonii leaf; 47 = S. leuhmannii leaf; 48 = S. leuhmannii fruit; 49 = Tasmannia insipida leaf; 50 = T. lanceolata leaf; 51 = T. lanceolata fruit; 52 = T. lanceolata peppercorn; 53 = T. stipitata leaf; Amp = Ampicillin control (2 μg); Chl = Chloramphenicol control (10 μg)
Figure 3
Figure 3
The lethality of Australian plant extracts (2000 μg/ml) towards Artemia franciscana nauplii after 24 hours exposure. Results are expressed as mean ± SEM of at least triplicate determinations. M and W refer to methanolic and water extracts respectively. (a) 1 = Acacia auriculiformis leaf; 2 = A. diasparima leaf; 3 = A. leptoloba leaf; 4 = A. moluccanus nut; 5 = A. excelsa leaf; 6 = A. caerulea fruit; 7 = A. caerulea leaf; 8 = Backhousia citriodora leaf; 9 = B. myrtiflora leaf; 10 = C. citrinus leaf; 11 = Callistemon citrinus flower; 12 = C. formosus leaf; 13 = C. salignus leaf; 14 = C. salignus flower; 15 = C. oliveri leaf; 16 = Davidsonia pruriens leaf; 17 = D. pruriens fruit; 18 = D. leichhardtii leaf; 19 = Elaeocarpus angustifolius fruit; 20 = E. baileyana leaf; 21 = E. major leaf; 22 = Kunzea flavescens leaf; 23 = Leptospermum bracteata leaf; 24 = L. bracteata flower; 25 = L. juniperium leaf; 26 = L. juniperium flower; 27 = L. longifolium leaf; 28 = L. petersoni leaf; 29 = Macadamia integriflora nut; 30 = M. integriflora leaf; (b) 31 = M. alternifolia leaf; 32 = M. quinquenervia leaf; 33 = Petalostigma pubescens leaf; 34 = P. pubescens fruit; 35 = P. triloculorae leaf; 36 = P. triloculorae fruit; 37 = P. augustifolium leaf; 38 = Scaevola spinescens leaf; 39 = Syzygium anisatum leaf; 40 = S. australe leaf; 41 = S. australe fruit; 42 = S. forte leaf; 43 = S. francisii leaf; 44 = S. moorei leaf; 45 = S. puberculum leaf; 46 = S. wilsonii leaf; 47 = S. leuhmannii leaf; 48 = S. leuhmannii fruit; 49 = Tasmannia insipida leaf; 50 = T. lanceolata leaf; 51 = T. lanceolata fruit; 52 = T. lanceolata peppercorn; 53 = T. stipitata leaf. PC = Potassium dichromate positive control (1000 μg/ml); NC = seawater negative control
Figure 4
Figure 4
Reversed-phase high performance liquid chromatography total peak chromatogram of 10 μl injections of the methanolic extracts of Tasmannia lanceolata fruit (a) in positive ionisation mode and (b) in negative ionisation mode. Extracts were dried and resuspended in deionised water. Arrows indicate the stilbene peaks detected in each chromatogram. Chromatography conditions were as described in the methods section
Figure 5
Figure 5
Reversed-phase high performance liquid chromatography total peak chromatogram of 10 μl injections of the aqueous extracts of Tasmannia lanceolata fruit (a) in positive ionisation mode and (b) in negative ionisation mode. Extracts were dried and resuspended in deionised water. Arrows indicate the stilbene peaks detected in each chromatogram. Chromatography conditions were as described in the methods section
Figure 6
Figure 6
Chemical structures of (a) resveratrol and the stilbenes and stilbene glycosides identified in Tasmannia lanceolata extracts: (b) piceid, (c) combretastatin A-1, (d) combretastatin A-4. (b1-b5) represent the molecular weight fragments of piceid detected by ESI-MS in positive mode; (c1-c2) represent the molecular weight fragments of combretastatin A-1 detected by ESI-MS in positive mode; (d1-d2) represent the molecular weight fragments of combretastatin A-4 detected by ESI-MS in positive mode

References

    1. Lawrence RC, Helmick CG, Arnett FC, Deyo RA, Felson DT, Giannini EH, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum. 1998;41:778–99. - PubMed
    1. Aletaha D, Kapral T, Smolen JS. Toxicity profiles of traditional disease modifying antirheumatic drugs for rheumatoid arthritis. Ann Rheum Dis. 2003;62:482–6. - PMC - PubMed
    1. Nepom GT, Byers P, Seyfried C, Healey LA, Wilske KR, Stage D, et al. HLA genes associated with rheumatoid arthritis. Identification of susceptibility alleles using specific oligonucleotide probes. Arthritis Rheum. 1989;32:15–21. - PubMed
    1. Rashid T, Darlington G, Kjeldsen-Kragh J, Forre O, Collado A, Ebringer A. Proteus IgG antibodies and C-reactive protein in English, Norwegian and Spanish patients with rheumatoid arthritis. Clin Rheumatol. 1999;18:190–5. - PubMed
    1. Blankenberg-Sprenkels SH, Fielder M, Feltkamp TE, Tiwana H, Wilson C, Ebringer A. Antibodies to Klebsiella pneumoniae in Dutch patients with ankylosing spondylitis and acute anterior uveitis and to Proteus mirabilis in rheumatoid arthritis. J Rheumatol. 1998;25:743–7. - PubMed

LinkOut - more resources