Ashley Dowell

Kava in the treatment of generalized anxiety disorder: a double-blind, randomized, placebo-controlled study

Abstract Kava (Piper methysticum) is a plant-based medicine, which has been previously shown to reduce anxiety. To date, however, no placebo-controlled trial assessing kava in the treatment of generalized anxiety disorder (GAD) has been completed. A total of 75 participants with GAD and no comorbid mood disorder were enrolled in a 6-week double-blind trial of an aqueous extract of kava (120/240 mg of kavalactones per day depending on response) versus placebo. &ggr;-Aminobutyric acid (GABA) and noradrenaline transporter polymorphisms were also analyzed as potential pharmacogenetic markers of response. Reduction in anxiety was measured using the Hamilton Anxiety Rating Scale (HAMA) as the primary outcome. Intention-to-treat analysis was performed on 58 participants who met inclusion criteria after an initial 1 week placebo run-in phase. Results revealed a significant reduction in anxiety for the kava group compared with the placebo group with a moderate effect size (P = 0.046, Cohen d = 0.62). Among participants with moderate to severe Diagnostic and Statistical Manual of Mental Disorders–diagnosed GAD, this effect was larger (P = 0.02; d = 0.82). At conclusion of the controlled phase, 26% of the kava group were classified as remitted (HAMA ⩽ 7) compared with 6% of the placebo group (P = 0.04). Within the kava group, GABA transporter polymorphisms rs2601126 (P = 0.021) and rs2697153 (P = 0.046) were associated with HAMA reduction. Kava was well tolerated, and aside from more headaches reported in the kava group (P = 0.05), no other significant differences between groups occurred for any other adverse effects, nor for liver function tests. Standardized kava may be a moderately effective short-term option for the treatment of GAD. Furthermore, specific GABA transporter polymorphisms appear to potentially modify anxiolytic response to kava.

Adulteration of Ginkgo biloba products and a simple method to improve its detection

Extracts of ginkgo (Ginkgo biloba) leaf are widely available worldwide in herbal medicinal products, dietary supplements, botanicals and complementary medicines, and several pharmacopoeias contain monographs for ginkgo leaf, leaf extract and finished products. Being a high-value botanical commodity, ginkgo extracts may be the subject of economically motivated adulteration. We analysed eight ginkgo leaf retail products purchased in Australia and Denmark and found compelling evidence of adulteration with flavonol aglycones in three of these. The same three products also contained genistein, an isoflavone that does not occur in ginkgo leaf. Although the United States Pharmacopeia - National Formulary (USP-NF) and the British and European Pharmacopoeias stipulate a required range for flavonol glycosides in ginkgo extract, the prescribed assays quantify flavonol aglycones. This means that these pharmacopoeial methods are not capable of detecting adulteration of ginkgo extract with free flavonol aglycones. We propose a simple modification of the USP-NF method that addresses this problem: by assaying for flavonol aglycones pre and post hydrolysis the content of flavonol glycosides can be accurately estimated via a simple calculation. We also recommend a maximum limit be set for free flavonol aglycones in ginkgo extract.

Ocean warming and CO2-induced acidification impact the lipid content of a marine predatory gastropod

Ocean warming and acidification are current global environmental challenges impacting aquatic organisms. A shift in conditions outside the optimal environmental range for marine species is likely to generate stress that could impact metabolic activity, with consequences for the biosynthesis of marine lipids. The aim of this study was to investigate differences in the lipid content of Dicathais orbita exposed to current and predicted future climate change scenarios. The whelks were exposed to a combination of temperature and CO2-induced acidification treatments in controlled flowthrough seawater mesocosms for 35 days. Under current conditions, D. orbita foot tissue has an average of 6 mg lipid/g tissue, but at predicted future ocean temperatures, the total lipid content dropped significantly, to almost half. The fatty acid composition is dominated by polyunsaturated fatty acids (PUFA 52%) with an n-3:6 fatty acid ratio of almost 2, which remains unchanged under future ocean conditions. However, we detected an interactive effect of temperature and pCO2 on the % PUFAs and n-3 and n-6 fatty acids were significantly reduced by elevated water temperature, while both the saturated and monounsaturated fatty acids were significantly reduced under increased pCO2 acidifying conditions. The present study indicates the potential for relatively small predicted changes in ocean conditions to reduce lipid reserves and alter the fatty acid composition of a predatory marine mollusc. This has potential implications for the growth and survivorship of whelks under future conditions, but only minimal implications for human consumption of D. orbita as nutritional seafood are predicted.

Parvifloranines A and B, Two 11-Carbon Alkaloids from Geijera parviflora

Two novel alkaloids (parvifloranines A and B), possessing an unusual 11-carbon skeleton linked with amino acids, were isolated from Geijera parviflora, an endemic Australian Rutaceae. Their structures were elucidated by extensive spectroscopic measurements including 2D NMR analyses. Parvifloranine A was found to be a mixture of two enantiomers, (S)-1 and (R)-1, in a ratio of 1:4, based on their separation using a chiral column. Parvifloranine B is also believed to be a mixture of enantiomers. Proposed biosynthetic pathways are discussed. Parvifloranine A inhibited the synthesis of nitric oxide in LPS-stimulated RAW 264.7 macrophages with an IC50 value of 23.4 μM.

Investigation of nutritional properties of three species of marine turban snails for human consumption

Abstract Turban snails (family Turbinidae) are gastropod molluscs that are harvested for human consumption yet little is known about the nutritional properties of these snails, particularly from Australian waters. This study compares the proximate composition (ash, moisture, protein, and lipid content), fatty acid profiles, mineral, and trace element content of three species of turbinid snails; Turbo militaris, Lunella undulata, and Lunella torquata from northern New South Wales, Australia. They were all found to have relatively high protein in their flesh (16.0% to 18.5% of the fresh weight). L. torquata had a significantly higher lipid content (8.5% w/w) than L. undulata (5.2% w/w), whereas T. militaris (5.6% w/w) was not significantly different to either. Analysis with gas chromatography showed there was no significant difference in monounsaturated fatty acid (MUFA) content, with an average of approximately 14% of the total fatty acids in all three species. However, saturated fatty acids (SFA) were significantly higher in T. militaris (41%), whereas polyunsaturated fatty acids (PUFA) were significantly higher in L. undulata (46%). The ratio of n−3/n−6 fatty acids ranged from 1.1 in T. militaris to 1.4 in L. torquata, which is good for human health and comparable to other high value gastropods. The results indicate that T. militaris, L. undulata, and L. torquata provide a good source of essential elements such as zinc, selenium, and iron. At the location studied, toxic metals and metalloids were below safe recommended standards for human consumption. Overall, this study confirms the suitability of turban snails as a nutritional food for human consumption.

Temporal variation in condition index and meat quality of Lunella undulata (Turbinidae), in relation to the reproductive cycle

ABSTRACT Lunella undulata is a subtropical-temperate marine gastropod which is harvested commercially from temperate reefs in Australia. This paper aimed to evaluate monthly variation in the condition index (CI) and biochemical composition of the foot tissue of L. undulata in relation to the spawning cycle. The gonadosomatic index (GSI) varied significantly between males and females and across months (P = 0.0001), ranging from 43% to 70% in males and 41% to 71% for females. The highest GSI, as well as the highest CI for both sexes was recorded in December and April, whilst meat yield peaked in January, September and October. Protein, lipid, fatty acid and heavy metals in the foot tissue also significantly varied between months (P < 0.05). Throughout all 14 months of sampling, the foot tissue of L. undulata showed good nutritional quality, with high levels of protein and the polyunsaturated fatty acids, docosapentaenoic acid, eicosapentaenoic acid and arachidonic acid. Overall, despite some temporal variability in the biochemical composition, L. undulata could be harvested at any time of the year for human consumption, although it may be best to avoid peak spawning times, which occur around January in northern NSW.

Detection of delta-9-tetrahydrocannabinol (THC) in oral fluid, blood and urine following oral consumption of low-content THC hemp oil.

Hemp-derivative (Cannabis sativa L.) food products containing trace levels of Δ-9-tetrahydrocannabinol (THC) are proposed for consumption in Australia and New Zealand; however, it is unclear whether use of these products will negatively affect existing drug screening protocols. This double-blind, within-subjects, cross-over trial assessed 35 adults (17 male; 18 female), aged 22-52 years [Mean=30.7, Standard Deviation (S.D)±7.6]. Low dose THC oil [5mL bearer sesame oil containing 10mg/kg THC (0.046mg THC per 5mL dose)]; high dose THC oil [5mL bearer sesame oil containing 20mg/kg THC (0.092mg THC per 5mL dose)]; and a placebo oil (THC negative) was consumed during a three-week protocol. The Securetec Drugwipe® II Twin device assessed THC presence (cut-off 20ng/mL) in oral fluid at baseline, at 5, 30, 60, 120 and 240min post-treatment. Blood was drawn at baseline, 30, 120 and 240min post-treatment, and urine at baseline and 240min post-treatment. No THC was detected in oral fluid, blood or urine samples at any time-point following consumption of the low or high THC dose. Trace concentrations of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THCa) were detected in blood 4-h after consumption of the high THC treatment (M=0.0001mg/L) and in urine at 4-h post consumption of both low and high THC treatments (M=0.0001mg/L and 0.0004mg/L, respectively). Consumption of low-content THC oil does not result in positive biological assessments. It is therefore highly unlikely that ingestion of products containing these levels of THC will negatively impact existing region-specific drug driving enforcement protocols.

Ecotype Variation of Methyl Eugenol Content in Tea Tree (Melaleuca alternifolia and Melaleuca linariifolia)

Methyl eugenol is a natural phenylpropanoid compound found in a wide range of plants used for food, flavouring, cosmetics, and health‐care. As a suspected rodent carcinogen, methyl eugenol may also be harmful to humans when present in significant concentrations. Consequently, its level has been restricted in some foodstuffs and cosmetics for some markets. In order to assess the potential to breed uniformly low methyl eugenol cultivars for an essential oil crop, tea tree, the source of ‘Oil of Melaleuca, terpinene‐4‐ol type’, we examine levels in individual trees (n = 30) from two geographic regions and six terpene chemotypes. Overall, methyl eugenol levels were low in this species (Mean [SD] 354 [239] ppm, n = 30), much lower than levels predicted to be of toxicological concern. Within each chemotype, there was a lack of evidence for correlations between terpenoid constituents and methyl eugenol levels. Further support for the independence of methyl eugenol and terpene biosynthesis was evident from similar mean levels in selected (Mean [SD] 586 [339] ppm, n = 12) and undomesticated Melaleuca alternifolia trees (Mean [SD] 480 [299] ppm, n = 5) with terpinen‐4‐ol type oils. By contrast, methyl eugenol level varied by geographic origin and chemotype. Trees from the upland region, where there is a prevalence of terpinolene type trees, had lower average methyl eugenol levels than trees from the coastal region, where there is a prevalence of terpinen‐4‐ol and 1,8‐cineole type trees.

A simple HPLC method for detecting adulteration of ginkgo extracts with flavonol glycosides

We have shown that current USP and EP/BP methods for quantifying ginkgo flavonoids cannot detect adulteration with free flavonol aglycones. We propose a simple modification of these methods, based on the measurement of aglycones preand post-hydrolysis, to allow for the accurate estimation of the amounts of both glycosides and free aglycones in ginkgo leaf extracts. The presence of genistein in products with high levels of free aglycones is consistent with adulteration with Sophora japonica L., which contains genistein, quercetin and kaempferol glycosides [5], and has previously been reported as a suspected adulterant of ginkgo extracts [4]. Pharmacopoeial tests for ginkgo extracts should be improved in order that they might effectively ensure the authenticity, efficacy and safety of this important phytomedicine.