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Background There is a need to develop potential new therapies for the management of diabetes and hypertension. Australian medicinal plants collected from the Kuuku I’yu (Northern Kaanju) homelands, Cape York Peninsula, Queensland, Australia were investigated to determine their therapeutic potential. Extracts were tested for inhibition of protein glycation and key enzymes relevant to the management of hyperglycaemia and hypertension. The inhibitory activities were further correlated with the antioxidant activities. Methods Extracts of five selected plant species were investigated: Petalostigma pubescens, Petalostigma banksii, Memecylon pauciflorum, Millettia pinnata and Grewia mesomischa. Enzyme inhibitory activity of the plant extracts was assessed against α-amylase, α-glucosidase and angiotensin converting enzyme (ACE). Antiglycation activity was determined using glucose-induced protein glycation models and formation of protein-bound fluorescent advanced glycation endproducts (AGEs). Antioxidant activity was determined by measuring the scavenging effect of plant extracts against 1, 1-diphenyl-2-picryl hydrazyl (DPPH) and using the ferric reducing anti-oxidant potential assay (FRAP). Total phenolic and flavonoid contents were also determined. Results Extracts of the leaves of Petalostigma banksii and P. pubescens showed the strongest inhibition of α-amylase with IC50 values of 166.50 ± 5.50 μg/mL and 160.20 ± 27.92 μg/mL, respectively. The P. pubescens leaf extract was also the strongest inhibitor of α-glucosidase with an IC50 of 167.83 ± 23.82 μg/mL. Testing for the antiglycation potential of the extracts, measured as inhibition of formation of protein-bound fluorescent AGEs, showed that P. banksii root and fruit extracts had IC50 values of 34.49 ± 4.31 μg/mL and 47.72 ± 1.65 μg/mL, respectively, which were significantly lower (p

1. The metabolism of the anti-inflammatory diterpenoid polyandric acid A (PAA), a constituent of the Australian Aboriginal medicinal plant Dodonaea polyandra, and its de-esterified alcohol metabolite, hydrolysed polyandric acid A (PAAH) was studied in vitro using human liver microsomes (HLM) and recombinant UDP-glucuronosyltransferase (UGT) and cytochrome P450 (CYP) enzymes.2. Hydrolysis of PAA to yield PAAH occurred upon incubation with HLM. Further incubations of PAAH with HLM in the presence of UGT and CYP cofactors resulted in significant depletion, with UGT-mediated depletion as the major pathway.3. Reaction phenotyping utilising selective enzyme inhibitors and recombinant human UGT and CYP enzymes revealed UGT2B7 and UGT1A1, and CYP2C9 and CYP3A4 as the major enzymes involved in the metabolism of PAAH.4. Analysis of incubations of PAAH with UDP-glucuronic acid-supplemented HLM and recombinant enzymes by UPLC/MS/MS identified three glucuronide metabolites. The metabolites were further characterised by β-glucuronidase and mild alkaline hydrolysis. The acyl glucuronide of PAAH was shown to be the major metabolite.5. This study demonstrates the in vitro metabolism of PAA and PAAH and represents the first systematic study of the metabolism of an active constituent of an Australian Aboriginal medicinal plant. Refereed/Peer-reviewed

Aim: To provide an estimate of the numbers of medication errors and adverse drug reactions that occur along a person's journey through their hospital stay in Australia. Methods: A search of databases and online resources was undertaken to identify published literature on medication safety in the acute care setting in Australia from 2008 to 2013. Data on the rates of adverse drug reactions and medication errors associated with hospitalization was extracted from the published studies. This evidence was synthesized with evidence from previous reviews of medication safety in the acute care setting in Australia conducted in 2002 and 2008. Results: Findings from the Australian literature across the two previous reviews of medication safety and the present review indicate the proportion of all hospital admissions that are medication-related is between 2 and 3%. Studies assessing medication errors on admission to hospital suggest there may be an overall rate of two errors for every three patients at the time of admission to hospital. Large studies examining the rates of prescribing errors in major Australian teaching hospitals give insight into the rates of prescription error and suggest that prescription error rates of up to one error per patient occur in the hospital system. The best available evidence from more recent research suggests that errors (excluding errors of timing) occur in around 9% of medication administrations in hospital. At hospital discharge, errors in medication documentation in discharge summaries may occur at a rate of up to two errors per patient. Conclusions: Medication safety in the various stages of the patient journey through acute care in Australia continues to be a significant problem. However, the extent of medication-related problems in acute care needs to be interpreted within the context of increasingly complex health care. There are an estimated 230 000 medication-related hospital admissions occurring per year. This suggests an annual cost of medication-related admissions of AU$1.2 billion. Refereed/Peer-reviewed

The purpose of this study was to assess the biofilm-removing efficacy and inflammatory activity of a serrulatane diterpenoid, 8-hydroxyserrulat-14-en-19-oic acid (1), isolated from the Australian medicinal plant Eremophila neglecta. Biofilm breakup activity of compound 1 on established Staphylococcus epidermidis and Staphylococcus aureus biofilms was compared to the antiseptic chlorhexidine and antibiotic levofloxacin. In a time-course study, 1 was deposited onto polypropylene mesh to mimic a wound dressing and tested for biofilm removal. The ex-vivo cytotoxicity and effect on lipopolysaccharide-induced pro-inflammatory cytokine release were studied in mouse primary bone-marrow-derived macrophage (BMDM) cells. Compound 1 was effective in dispersing 12 h pre-established biofilms with a 7 log10 reduction of viable bacterial cell counts, but was less active against 24 h biofilms (approximately 2 log10 reduction). Compound-loaded mesh showed dosage-dependent biofilm-removing capability. In addition, compound 1 displayed a significant inhibitory effect on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secretion from BMDM cells, but interleukin-1 beta (IL-1β) secretion was not significant. The compound was not cytotoxic to BMDM cells at concentrations effective in removing biofilm and lowering cytokine release. These findings highlight the potential of this serrulatane diterpenoid to be further developed for applications in wound management. Refereed/Peer-reviewed

Purpose : We have previously reported that the Australian Northern Kaanju (Kuuku I’yu) medicinal plant Dodonaea polyandra has anti-inflammatory activity. This is attributed largely to the presence of clerodane diterpenoids contained within the leaf resin. We envisaged developing a topical preparation to treat indications relating to skin inflammation. However, it was unknown whether the resin could be incorporated into a suitable dosage form while retaining the therapeutic value demonstrated in previous work. Therefore, the following study was undertaken to assess parameters of safety and efficacy for a prototype formulation containing the leaf resin extracted from D. polyandra . Methods: Using the assessment criteria of optimum appearance, tactile feeling, spreadability and odour, 78 different formulations were developed. Formulation stability was assessed using a centrifugal test with preparations displaying phase separation further modified or re-formulated. A prototype formulation containing 5% w/w plant resin was selected and subjected to in vitro release studies. This was quantified through HPLC analysis using two major bioactive diterpenoids as reference. The prototype formulation was tested for efficacy in a TPA-induced acute murine skin inflammation model as well as a 3D human skin model for irritancy/toxicity (Epiderm™). Results: The prototype resin cream was a chartreuse-coloured homogenous semisolid preparation that was readily spreadable upon contact with skin with no sensation of tackiness, residual greasiness, or irritation. The optimized cream showed no phase separation after 30 min centrifugation at 825 g . In the TPA-induced inflammation model, the resin formulation significantly reduced ear thickness and interleukin-1 beta levels in mouse ear tissue. The 5% w/w resin cream formulation showed no irritancy in a 3D human skin model. Conclusions: Our results demonstrate that bioactive resin from D. polyandra can be formulated into a stable and non-irritant semi-solid dosage form and reduce parameters of acute skin inflammation in vivo . This article is open to POST-PUBLICATION REVIEW . Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Plants have historically and still remain an important source of medication for many Indigenous populations around the world. Culturally, there appears to be a link between people and plants, regardless of origin, with different methods of medicine preparation having been empirically designed and adopted depending on the intended use. This chapter examines the use of plants in Indigenous medicine systems, in particular the medicinal use of plants by the Australian Aboriginal peoples. It explores phytotherapies used by Australian Indigenous peoples. Key aspects of traditional Australian Aboriginal medicine philosophy, medicine preparation, genera of plants that are particularly prized in Australian Indigenous medicine, efficacy, and safety are highlighted. In Australia, suggested changes to the regulatory framework, in which oral history relating to plant use is more clearly defined and recognized, may facilitate novel medicinal products appearing on the market that are based on Australian Aboriginal traditional medicines usc Refereed/Peer-reviewed

Australian Aboriginal people have a long history of relying on plants for the treatment of various ailments and illnesses. Our ongoing collaborative research project initiated by Chuulangun Aboriginal Corporation (Cape York, Australia) has recently focussed on revealing whether Kuuku I’yu plant medicines possess anticancer-related activities and the chemistry responsible for this. Here, we present results from a study of the plant Litsea glutinosa, used traditionally for the treatment of gastrointestinal disorders. Four known aporphine alkaloids N-methylactinodaphnine (1), boldine (2), N-methyllaurotetanine (3), and isoboldine (4) were isolated by activity-guided fractionation and tested for cytotoxicity against HT29, SKMEL28, and primary human keratinocytes. Compound 1 was the most cytotoxic and this observation may be explained by the presence of a 1,2-methylenedioxy group. In silico docking revealed that a plausible mechanism for the observed cytotoxicity is the stabilization of a topoisomerase II (β) DNA–enzyme complex. The ethnopharmacological relevance of this study is discussed in the context of researching and using traditional knowledge in biomolecular discovery. Refereed/Peer-reviewed

Dodonaea polyandra is a medicinal plant used traditionally by the Kuuku I'yu (Northern Kaanju) indigenous people of Cape York Peninsula, Australia. The most potent of the diterpenoids previously identified from this plant, polyandric acid A (1), has been examined for inhibition of pro-inflammatory cytokine production and other inflammatory mediators using well-established acute and chronic mouse ear edema models and in vitro cellular models. Topical application of 1 significantly inhibited interleukin-1β production in mouse ear tissue in an acute model. In a chronic skin inflammation model, a marked reduction in ear thickness, associated with significant reduction in myeloperoxidase accumulation, was observed. Treatment of primary neonatal human keratinocytes with 1 followed by activation with phorbol ester/ionomycin showed a significant reduction in IL-6 secretion. The present study provides evidence that the anti-inflammatory properties of 1 are due to inhibition of pro-inflammatory cytokines associated with skin inflammation and may be useful in applications for skin inflammatory conditions including psoriasis and dermatitis.

New clerodane compounds isolated from plant material from Dodonaea polyandra are disclosed. The compounds have anti-inflammatory activity. Pharmaceutical and cosmetic compositions containing the compounds, as well as methods of treating inflammation using the compounds, are also disclosed

New clerodane compounds isolated from plant material from Dodonaea polyandra are disclosed. The compounds have anti-inflammatory activity. Pharmaceutical and cosmetic compositions containing the compounds, as well as methods of treating inflammation using the compounds, are also disclosed.

Four new benzoyl ester clerodane diterpenoids, 15,16-epoxy-8a-(benzoyloxy)methylcleroda-3,13(16),14-trien-18-oic acid (1), 15,16-epoxy-8a-(benzoyloxy)methyl-2a-hydroxycleroda-3,13(16),14-trien-18-oic acid (2), 15,16-epoxy-8a-(benzoyloxy)methyl-2-oxocleroda-3,13(16),14-trien-18-oic acid (3), and 15,16-epoxy-2a-benzoyloxycleroda-3,13(16),14-trien-18-oic acid (4), have been isolated from the leaves and stems of Dodonaea polyandra. The anti-inflammatory activities of compounds 1, 2, and 4 were evaluated by means of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. Compounds 2 and 4 exhibited maximum inhibition of inflammation (70-76%) at doses of 0.22 and 0.9 μmol/ear, respectively. Modest activity (45% inhibition) was maintained at nanomole/ear doses. Refereed/Peer-reviewed

New clerodane compounds isolated from plant material from Dodonaea polyandra are disclosed. The compounds have anti-inflammatory activity. Pharmaceutical and cosmetic compositions containing the compounds, as well as methods of treating inflammation using the compounds, are also disclosed.

Three prenylated flavonoids 5,7,4'-trihydroxy-3'(3-methylbut-2-enyl)-3-methoxy flavone, 5,7-dihydroxy-3'(3-methylbut-2-enyl)-3,4'-dimethoxy flavone and 5,7,4'-trihydroxy-3',5'(3-methylbuyt-2-enyl)-3-methoxy flavone together with three other known flavonoids were isolated from the medicinal plant Dodonaea polyandra. The plant is used in the traditional medicine system of Northern Kaanju people of Cape York Peninsula, Queensland, Australia. The extracts studied have previously been found to possess anti-inflammatory activity. Successive fractionation of leaf and stem extracts by column and high performance liquid chromatography led to the isolation of these compounds. Their structures were determined using a number of spectroscopic techniques including 1D and 2D NMR and high resolution mass spectroscopy. The structural elucidation is reported herein accompanied by full 1H and 13C NMR spectroscopic data. Spectroscopic data of known compounds was in agreement with that previously reported in literature. Refereed/Peer-reviewed

Refereed/Peer-reviewed

Thesis (PhD) -- University of South Australia, 1999

Background A number of surveys have examined use of complementary and alternative medicines (CAM) in Australia. However, there are limited Australian data on use of CAM and over-the-counter (OTC) medicines in the elderly population. The main aims of this study were to examine self-medication practices with CAM and OTC medicines among older Australians and variables associated with their use. Methods The Australian Longitudinal Study of Ageing (ALSA) is an ongoing multidisciplinary prospective study of the older population which commenced in 1992 in South Australia. Data collected in 4 waves of ALSA between 1992 and 2004 were used in this study with a baseline sample of 2087 adults aged 65 years and over, living in the community or residential aged care. OTC medicines were classified according to the World Health Organization Anatomical Therapeutic Chemical (ATC) classification. CAM were classified according a modified version of the classification adopted by the Therapeutics Goods Administration (TGA) in Australia. Results The prevalence of CAM or OTC use ranged from 17.7% in 2000-2001 to 35.5% in 2003-2004. The top classes of CAM and OTC medicines used remained relatively constant over the study period. The most frequent classes of CAM used were vitamins and minerals, herbal medicines and nutritional supplements while the most commonly used OTC were analgesics, laxatives and low dose aspirin. Females and those of younger age were more likely to be CAM users but no variable was associated with OTC use. Conclusion Participants seemed to self-medicate in accordance with approved indications, suggesting they were informed consumers, actively looking after their own health. However, use of analgesics and aspirin are associated with an increased risk of adverse drug events in the elderly. Future work should examine how self-medication contributes to polypharmacy and increases the risk of adverse drug reactions.

Background: This paper presents Part 1 of a two-part literature review examining medication safety in the Australian acute care setting. This review was undertaken for the Australian Commission on Safety and Quality in Health Care to update a previous national report on medication safety conducted in 2002. This first part of the review examines the extent and causes of medication incidents and adverse drug events in acute care. Methods: A literature search was conducted to identify Australian studies, published from 2002 to 2008, on the extent and causes of medication incidents and adverse drug events in acute care. Results: Studies published since 2002 continue to suggest approximately 2%-3% of Australian hospital admissions are medication-related. Results of incident reporting from hospitals show that incidents associated with medication remain the second most common type of incident after falls. Omission or overdose of medication is the most frequent type of medication incident reported. Studies conducted on prescribing of renally excreted medications suggest that there are high rates of prescribing errors in patients requiring monitoring and medication dose adjustment. Research published since 2002 provides a much stronger Australian research base about the factors contributing to medication errors. Team, task, environmental, individual and patient factors have all been found to contribute to error. Conclusion: Medication-related hospital admissions remain a significant problem in the Australian healthcare system. It can be estimated that 190,000 medication-related hospital admissions occur per year in Australia, with estimated costs of $660 million. Medication incidents remain the second most common type of incident reported in Australian hospitals. A number of different systems factors contribute to the occurrence of medication errors in the Australian setting. Refereed/Peer-reviewed