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Comparative screening of plant essential oils: phenylpropanoid moiety as basic core for antiplatelet activity.

Essential oils extracted from different plants (Anthemis nobilis L., Artemisia dracunculus L., Cannabis sativa L., Cupressus sempervirens L., Cymbopogon citratus (DC.) Stapf., Curcuma longa L., Foeniculum vulgare L., Hypericum perforatum L., Hyssopus officinalis L., Mentha spicata L., Monarda didyma L., Ocimum basilicum L., Ocotea quixos Kosterm., Origanum vulgare L., Pinus nigra J.F. Arnold, Pinus silvestris L., Piper crassinervium Kunth., Rosmarinus officinalis L., Salvia officinalis L., Salvia sclarea L., Santolina chamaecyparissus L., Thymus vulgaris L., Zingiber officinaie L.) were screened in guinea pig and rat plasma in order to assess antiplatelet activity and inhibition of clot retraction. The oils were chemically analysed and a relationship between components and ability to affect hemostasis was evidenced. O. quixos, F. vulgaris, and A. dracunculus showed the highest antiplatelet activity against ADP, Arachidonic Acid and the Thromboxane A2 agonist U46619 (IC50, 4-132 microg ml(-1)), and a good ability to destabilize clot retraction (IC50, 19-180 microg ml(-1)). For these oils a significant correlation between antiplatelet potency and phenylpropanoids content (54-86%) was evidenced thus suggesting a key role for this moiety in the prevention of clot formation. These findings provide the rationale to take in account the antiplatelet activity in the pharmacological screening of natural products containing phenylpropanoids.

Animals↗

Screening the receptorome for plant-based psychoactive compounds.

Throughout time, humans have used psychoactive plants and plant-derived products for spiritual, therapeutic and recreational purposes. Furthermore, the investigation of psychoactive plants such as Cannabis sativa (marijuana), Nicotiana tabacum (tobacco) and analogues of psychoactive plant derivatives such as lysergic acid diethylamide (LSD) have provided insight into our understanding of neurochemical processes and diseases of the CNS. Currently, many of these compounds are being used to treat a variety of diseases, such as depression and anxiety in the case of Piper methysticum Kava Kava (Martin et al., 2002; Singh and Singh, 2002). G-protein coupled receptors (GPCRs) are the most common molecular target for both psychoactive drugs and pharmaceuticals. The "receptorome" (that portion of the genome encoding ligand reception) encompasses more than 8% of the human genome (Roth et al., 2004) and as such provides a large number of possible targets for psychoactive drug interactions. A systematic, comprehensive study is necessary to identify novel active psychoactive plant-based compounds and the molecular targets of known compounds. Herein we describe the development of a high throughput system (HTS) to screen psychoactive compounds against the receptorome and present two examples (Salvia divinorum, the "magic mint" hallucinogen and Banisteriopsis caapi, the main component of Ayahuasca, a psychoactive beverage) where HTS enabled the identification of the molecular target of each compound.

Animals↗

Natural rhythm: evidence for occult 40 Hz gamma oscillation in resting motor cortex.

Fast gamma oscillations, often at 40 Hz, have been demonstrated throughout the brain including the thalamus, auditory, visual and motor cortices. The function of gamma rhythms is elusive, but several authors have hypothesized that they contribute to the "binding" of diverse information into a single coherent percept, and to the synchronization of movement. In skeletal muscle a "Piper rhythm" around 40 Hz is commonly observed during maximal voluntary contraction, and has been shown to correlate with activity of similar frequency in a limited area of contralateral motor cortex. Gamma rhythms are detected primarily during complex cortical activity, and are seldom recorded at rest or coherently over wide areas. Here we use bihemispheric transcranial magnetic stimulation (TMS) to study time-dependent correlations between evoked motor potentials from non-homologous muscles in opposite limbs of normal volunteers. The results suggest the presence of an occult, synchronous 40 Hz rhythm across broad areas of resting motor cortex in both hemispheres.

Biological Clocks↗

Elevated expression of NF-kappaB in oral submucous fibrosis--evidence for NF-kappaB induction by safrole in human buccal mucosal fibroblasts.

Nuclear factor-kappa B (NF-kappaB) is considered to be important in many inflammatory and immune responses. The aim of this study was to compare NF-kappaB expression in normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induction of NF-kappaB expression. Seventeen OSF and six normal buccal mucosa specimens were examined by immunohistochemistry. Primary human buccal mucosal fibroblasts (BMFs) were established and challenged with safrole, a major polyphenolic compound in the influorescence of Piper betel, by cytotoxicity and western blot assays. Furthermore, glutathione precursor N-acetyl-L-cysteine (NAC), extracellular signal-regulated protein kinase (ERK) inhibitor PD98059, cyclooxygenase-2 (COX-2) inhibitor NS-398, dexamethasone, and cyclosporin A were added to find the possible mechanism. NF-kappaB expression was significantly higher in OSF specimens and expressed mainly by fibroblasts, endothelial cells, and inflammatory cells. Safrole was cytotoxic to BMFs in a dose-dependent manner (p<0.05). Western blot demonstrated highly elevated NF-kappaB protein expression in BMFs stimulated by safrole (p<0.05). In addition, pretreatment with pharmacological agents markedly inhibited the safrole induced-NF-kappaB expression (p<0.05). The result suggests that chewing areca quid may activate NF-kappaB expression that may be involved in the pathogenesis of OSF. NF-kappaB expression induced by safrole in fibroblasts may be mediated by ERK activation and COX-2 signal transduction pathway.

Blotting, Western↗

Platelet-activating factor (PAF) receptor-binding antagonist activity of Malaysian medicinal plants.

Forty-nine methanol extracts of 37 species of Malaysian medicinal plants were investigated for their inhibitory effects on platelet-activating factor (PAF) binding to rabbit platelets, using 3H-PAF as a ligand. Among them, the extracts of six Zingiberaceae species (Alpinia galanga Swartz., Boesenbergia pandurata Roxb., Curcuma ochorrhiza Val., C. aeruginosa Roxb., Zingiber officinale Rosc. and Z. zerumbet Koenig.), two Cinnamomum species (C. altissimum Kosterm. and C. pubescens Kochummen.), Goniothalamus malayanus Hook. f. Momordica charantia Linn. and Piper aduncum L. are potential sources of new PAF antagonists, as they showed significant inhibitory effects with IC50 values ranging from 1.2 to 18.4 microg ml(-1).

Animals↗

CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants.

Thirty samples of Indonesian medicinal plants were analyzed for their capacity to inhibit in vitro metabolism by human cytochrome P450 3A4 (CYP3A4) and CYP2D6 with a radiometric assay. The MeOH-soluble fractions of 25 samples, prepared from water extracts, demonstrated inhibitory activity more than 50% on the metabolism mediated by CYP3A4, and 21 samples on the metabolism mediated by CYP2D6. Among the MeOH-soluble fractions, Piper nigrum leaf showed the highest inhibitory activity against CYP3A4 (91.7%), and Punica granatum against CYP2D6 (98.1%). The water extracts of which MeOH-soluble fraction showed inhibitory activity more than 70% were fractionated with EtOAc. From the EtOAc-soluble fractions, Curcuma heyneana (67.0%), Pi. cubeba (75.0%), Pi. nigrum fruit (84.0%), Pi. nigrum leaf (85.8%), and Zingiber aromaticum (75.3%) demonstrated inhibitory activity more than 50% on the metabolism mediated by CYP3A4, but only Pi. nigrum fruit (72.8%) and Pi. nigrum leaf (69.1%) showed strong inhibitory activity against CYP2D6. For samples that showed more than 70% inhibition, their IC(50) values were determined. The most potent inhibitory activity against CYP3A4 (IC(50) value of 25 microg/ml) was found for the extract of Pi. nigrum leaf, while that of Catharanthus roseus showed the most potent inhibitory effect against CYP2D6 (IC(50) value of 11 microg/ml). These results should indicate once more the possibility of potential medicinal plant-drug interactions.

Cytochrome P-450 CYP2D6↗

Kavalactones fail to inhibit alcohol dehydrogenase in vitro.

In recent years, Kava kava (Piper methysticum, Forst. f., Piperaceae), a folkloric beverage and popular herbal remedy, has been implicated in a number of liver failure cases. Many hypotheses as to the mechanism of its hepatotoxicity, for example interactions with other co-ingested medication, have been postulated. This present study investigated whether pharmacokinetic interactions between kava constituents and alcohol via alcohol dehydrogenase (ADH) inhibition by individual kavalactones might explain its claimed hepatotoxic effects. Four kavalactones, (+/-)-kavain, methysticin, yangonin and desmethoxyyangonin, fail to inhibit ADH in vitro at 1, 10 or 100 microM concentrations.

Alcohol Dehydrogenase↗

Herbal remedies for anxiety - a systematic review of controlled clinical trials.

Anxiety is a prominent indication for herbal medicine. This systematic review was therefore aimed at summarising the evidence for or against the anxiolytic efficacy of such treatments. Six databases were searched for all randomised clinical trials testing herbal monopreparations in the alleviation of anxiety. Seven such studies and one systematic review were located. Eight different herbals were studied. The herbal medicines, which, according to these data are associated with anxiolytic activity in humans, are Piper methysticum and Bacopa monniera. Only for kava were independent replications available. It was concluded that there is a lack of rigorous studies in this area and that only kava has been shown beyond reasonable doubt to have anxiolytic effects in humans.

Anti-Anxiety Agents↗

Safety of ethanolic kava extract: Results of a study of chronic toxicity in rats.

BACKGROUND: Recently, potential liver toxicity was discussed with the intake of kava extract preparations (Piper methysticum) as anxiolytic drugs. The aim of this study was to test chronic toxicity in rats by oral application of an ethanolic kava full extract. METHODS: Wistar rats of both sexes were fed 7.3 or 73 mg/kg body weight of ethanolic kava extract for 3 and 6 months. The animals were examined for changes in body weight, hematological and liver parameters, and macroscopical and microscopical histological changes in the major organs. RESULTS: No signs of toxicity could be found. CONCLUSIONS: The results are in accordance with the medical experience regarding the use of kava preparations and the long tradition of kava drinking in the South Pacific island states. Specifically, the results do not back the suspicion of potential liver toxicity.

Animals↗

Kava kava: examining new reports of toxicity.

Before 1998, extracts of kava kava, Piper methysticum, were considered to be very safe alternatives to anxiolytic drugs and to possibly exert a wide range of other benefits. Major reviews published through the end of 2002 continued to confirm kava's safety and efficacy. Nevertheless, by January 2003 kava extracts had been banned in the entire European Union and Canada, and were subject to cautions and advisories by the US FDA as a result of 11 cases of hepatic failure leading to liver transplants, including four deaths. A total of 78 cases of hepatotoxicity reputedly linked to kava ingestion are available for review from various databases. Of these adverse events, four probably are linked to kavalactones taken alone and another 23 are potentially linked to kava intake, but also involve the concomitant ingestion of other compounds with potential hepatotoxicity. Three possible mechanisms for kavalactone hepatotoxicity are known: inhibition of cytochrome P450, reduction in liver glutathione content and, more remotely, inhibition of cyclooxygenase enzyme activity. The direct toxicity of kava extracts is quite small under any analysis, yet the potential for drug interactions and/or the potentiation of the toxicity of other compounds is large. Presently, kava toxicity appears to be "idiosyncratic." The risk-to-benefit ratio of kava extracts, nevertheless, remains good in comparison with that of other drugs used to treat anxiety.

Animals↗

Nutritional aspects of cancer-related fatigue.

Fatigue, which may well be the most common experience of patients with cancer, remains underappreciated by health care professionals. Perhaps one reason is that because of its complexity and many components, fatigue is not completely understood. Knowledge of fatigue models, such as the integrated Fatigue Model of Piper, can help dietitians identify potential causes of fatigue such as activity-rest patterns, and identification can lead dietitians to early intervention. Understanding cancer treatment factors, such as nausea and decreased participation in activities of daily living, that are believed to play a part in fatigue form another level on which dietitians can provide intervention. Through intervention, dietitians, working with patients and other members of the multidisciplinary team, may increase the understanding and appreciation of fatigue as well as provide relief from it. Efforts to maintain nutritional status can decrease or prevent some of the fatigue associated with cancer and its treatment. Therefore, the goal of clinical dietitians who work with a fatigued patient with cancer is to use nutrition management to minimize therapeutic side effects and maximize the patient's nutritional parameters.

Fatigue↗

Neuromuscular fatigue in prostate cancer patients undergoing radiation therapy.

OBJECTIVE: To determine the etiology of fatigue in prostate cancer patients undergoing radiation therapy (RT). METHODS: Thirteen prescreened men (60 to 76 years in age, 58 to 130 kg in body weight) were evaluated for neuromuscular fatigue (NMF) of the tibialis anterior (TA) muscle, cardiopulmonary fatigue (CPF), and psychological-subjective fatigue (PSF) at 1 to 2 weeks before RT (Pre), at the end of 8 weeks of RT (RT), and at 5 to 6 weeks after completion of RT (Post). OUTCOME MEASURES: For NMF, the TA muscle was fatigued by sustained isometric contraction at 80% of maximum voluntary contraction for 60 seconds on a force dynamometer. Neuromuscular efficiency (NME) expressed as a ratio of isometric force (in Newtons) and respective integrated electromyograms were measured. For CPF, stress testing was performed on a treadmill using the modified Bruce protocol. Piper Fatigue Scale, Beck Depression Inventory, and Epworth Sleepiness Scale were administered to evaluate PSF. DATA ANALYSIS: Paired t tests, single factor analysis of variance, and nonparametric analysis. RESULTS: At RT, there was a significant decline in NME of TA at the beginning (18.4%, p < .01) and the end (29.2%, p < .001) of sustained muscle contraction for 60 seconds. Post values were lower but nonsignificant in comparison with Pre values. NME recovered within 5 to 6 weeks after RT. No abnormalities were detected in CPF or PSF. No correlation was found between the decline in NME and psychological status of the patients. CONCLUSION: Results provide definitive evidence of transient decline in NME in prostate cancer patients at the completion of RT. The effect seems to be specific for neuromuscular performance alone and is independent of the cardiovascular or psychological status of the patients.

Adenocarcinoma↗

Post-insult exposure to (+/-) kavain potentiates N-methyl-D-aspartate toxicity in the developing hippocampus.

Kavapyrone extracts of the pepper plant Piper methysticum Forst. have been reported to be pharmacologically active in the brain by modulating the function of several ionotropic receptor systems and voltage-sensitive ion channels. While kavapyrones have previously demonstrated neuroprotective effects against several forms of neurotoxicity, the possibility remains that perturbed function of neuronal ion transport may prove to be neurotoxic in some instances. The present studies were designed to examine the effects of the kavapyrone, (+/-) kavain, on viability of organotypic hippocampal explants exposed to the excitotoxin N-methyl-D-aspartate (NMDA). Exposure to (+/-) kavain (1-600 microM) for 24 h did not alter neuronal viability in the CA1, CA3, or dentate gyrus regions of hippocampal explants. However, higher concentrations of (+/-) kavain (> or =300 microM) produced marked neurotoxicity in the lacunosum moleculare layer of the hippocampus. One hour of exposure to NMDA (20 microM) produced significant neuronal death in both the CA3 and CA1 pyramidal cell regions, effects prevented by co-exposure to MK-801 (30 microM). Co-exposure of explants to (+/-) kavain (1-100 microM) with NMDA did not alter the severity of NMDA-induced neurotoxicity. However, exposure of NMDA-treated explants to (+/-) kavain (> or =10 microM) for 24 h after insult produced significant increases in neurotoxicity in the CA1 and dentate gyrus regions of explants. In conclusion, while the kavapyrone (+/-) kavain is neurotoxic only at high concentrations when exposed alone to the developing hippocampus, it appears to adversely affect neuronal recovery following excitotoxic insults.

Animals↗

[Preliminary reports from a psychometric fixation-regression study using the McGill Object Relations Scale].

INTRODUCTION: Psychosexual development is generally assessed clinically, that is to say, in a qualitative manner (Piper and Duncan, 1999). Dymetryszyn, Bouchard, Bienvenu, De Carufel, and Gaston (1997) recently proposed a more quantitative approach based on the overall maturity of the subject's object relations. BACKGROUND: Object-relation maturity is quantified using a profile that defines a score for each stage of an individual's psychosexual development: oral-narcissistic, oral-objectal, anal, phallic pre-oedipal, oedipal, and genital. The McGill Object Relations Scale (MORS) (Dymetryszyn et al., 1997) was adapted (Combalbert, Vautier, Bourdet-Loubère, Favard, & Bouchard, 2002) and then used to obtain the quantitative scores. The relationship between overall object-relation maturity and psychosexual development is complex. Psychosexual development is considered here to be a constant latent dimension. Accordingly, the higher the level of development, the greater the individual's possibility of establishing the object relations that correspond to more evolved stages. Inversely, the lower the level of development, the more the individual is forced to rely on object relations corresponding to earlier stages of development. However, the connection between the object-relation maturity profile and psychosexual development is made even more complex by the existence of the well-known phenomenon of fixation-regression. OBJECTIVES: This article attempts to determine how fixation-regression is reflected in the structure of the profiles of a sample of individuals whose clinical diagnosis suggests probable regression to the anal stage. METHODS: The subjects chosen had borderline personality disorder coupled with either perversion or psychopathy. The data were modelled using an unfolding model. MORS was used on 60 criminal subjects who had been charged with, or convicted of, crimes against persons. The nosographic diagnosis was based on the psychiatric assessment of the prisoners. DSM IV diagnostic criteria were used as a reference to confirm or refute the pronounced diagnosis. Only subjects who met at least five criteria for borderline personality disorder were included in the sample. To assess the reliability of the individual scores, two expert judges blindly scored the 60 protocols. RESULTS: The results obtained with an unfolding model support the hypothesis that the observed ordinates for the oral-narcissistic, oral-objectal, phallic pre-oedipal, oedipal, and genital stages obey a law of synchrony that complies with the postulate of a continuum in psychosexual development. The second main result was the fact that the observed ordinates for the level corresponding to the anal stage could not be described by the model. Furthermore, this finding did not come from a possible scoring error, since inter-judge reliability was 0.93 for that level. DISCUSSION: These results are encouraging for the utilization of MORS as a technique for quantifying object relations. This study on a sample of individuals with a high probability of anal stage fixation-regression suggests that this type of phenomenon can be objectified by means of MORS profiles. However, the present study has some limitations of its own. The main methodological drawback pertains to the subjective aspect of the protocol scoring. The two judges had a great deal of joint experience in scoring other protocols on the MORS grid. This could explain the particularly high inter-judge correlations, compared to the within-class correlations published by Dymetryszyn et al. (1997). CONCLUSION: One cannot rule out the possibility that our analyses would have had different outcomes had other independent judges scored the 60 protocols. Moreover, our results cannot be generalized without replication. A critical test would be to replicate our analyses on similar data, and to examine the unfolding model's behavior on data from a sample of ordinary adults diagnosed as not having strong fixation-regression tendencies. If the synchrony laws defined by the unfolding model are correct, the anal stage should be included in the arc formed by projecting the six stages on the factorial plane of the principal component analysis. Fundamental research based on the psychosexual theory of the libido and supported by statistical data can objectify the vicissitudes of psychosexual development (such as fixation-regression) or developmental differences across groups of individuals. This makes a strong case for pursuing MORS-based investigations.

Adult↗

Anticonvulsive action of (+/-)-kavain estimated from its properties on stimulated synaptosomes and Na+ channel receptor sites.

Kava pyrones are constituents of the intoxicating pepper (Piper methysticum Forst), which has been shown to be anticonvulsive. The question of how the excitability of neurons is affected was investigated by determining the interaction of (+/-)-kavain with epitopes (site 1, site 2) of voltage-dependent Na+ channels and the action of (+/-)-kavain on 4-aminopyridine-stimulated synaptosomes as model of repetitive firing neurons. [3H]Saxitoxin and [3H]batrachotoxin were used for radioligand-binding assays performed with synaptosomal membranes. Gultamate released from 4-aminopyridine-stimulated cerebrocortical synaptosomes and the cytosolic concentrations of Na+ and Ca2+ ([Na+]i, [Ca+]i) were detected fluorometrically by using an enzyme-linked assay, sodium-binding benzofuranisophthalate (SBFI) and Fura-2, respectively. (+/-)-Kavain failed to compete with [3H]saxitoxin up to 400 mumol/l but dose-dependently suppressed binding of [3H]batrachotoxin with an IC50 value of 88 mumol/l (Ki = 72 mumol/l) although displacement of [3H]batrachotoxin was restricted to 33% of control at 400 mumol/l (+/-)-kavain. In stimulated synaptosomes, 5 mmol/l 4-aminopyridine provoked an increase in [Na+]i and [Ca2+]i by 9 mmol/l Na+ and 235 nmol/l Ca2+. Comparable to the reduction in [3H]batrachotoxin binding, 400 mumol/l (+/-)-kavain suppressed the increase in [Na+]i and [Ca2+]i to 38 and 29% of control, respectively. Consistent with the increase in [Na+]i and [Ca2+]i, 5 mmol/l 4-aminopyridine provoked glutamate release (rate: 38 pmol/s*mg protein) which was dose-dependently diminished to 60% of control by 400 mumol/l (+/-)-kavain. KCl depolarization (40 mmol/l) provoked an increase in [Ca2+]i and glutamate release almost identical to the responses elicited by 4-aminopyridine but 400 mumol/l (+/-)-kavain suppressed only the rate of glutamate release by 9% of control. The data suggest an interaction of (+/-)-kavain with voltage-dependent Na+ and Ca2+ channels, thereby suppressing the 4-aminopyridine-induced increase in [Na+]i, [Ca2+]i and the release of endogenous glutamate.

4-Aminopyridine↗

Acupressure and fatigue in patients with end-stage renal disease-a randomized controlled trial.

The purpose of the study is to investigate the effectiveness of acupressure on fatigue in patients with end-stage renal-disease (ESRD). The study was a randomized control trial; qualified patients were randomly assigned into acupressure group, sham group or control group. A total of 106 participants were included in the study. The measures included the revised Piper Fatigue Scale (PFS), VAS of Fatigue, the Pittsburgh Sleep Quality Index and the Beck Depression Inventory. Data of fatigue measures were collected at pretreatment and a week following treatment. Sleep quality and depression were collected during post-test only. The statistical methods included the descriptive statistics, one-way ANOVA, ANCOVA, and repeated-measures ANOVA. ANCOVA that adjusted for differences in baseline fatigue scores (PFS), post-test of depression and sleep quality, result was significant, F(2,100)=3.99, p=0.02. Post-hoc tests revealed that patients in the acupressure group were significantly having lower scores of fatigue than patients in the control group. ANCOVA results also significant for VAS of Fatigue among groups, F(2,100)=5.63, p=0.003. Comparisons indicated that there were significant differences between the acupressure group and the control group (p=0.01) and between the sham group and control group (p=0.003). Predialysis fatigue was assessed routinely by using a rating of 0-10. Repeated-measures ANOVA results demonstrate the group main effect was significant in the perceived fatigue (F(2,88)=19.46, p<0.001). Follow-up tests indicated there were significant differences between the acupressure group and the control group (p<0.001) and between the sham group and control group (p<0.001). The study provided an alternative method for health care providers to managing ESRD patients with fatigue.

Acupressure↗

Comparison of subcritical water and organic solvents for extracting kava lactones from kava root.

Subcritical water extraction of lactones from a kava (Piper metlhysticum) root was compared to a Soxhlet extraction with water, to boiling in water, and to a sonication in acetone. For ground kava (250-500 microm), 2 h of subcritical water extraction were required for a complete extraction at 100 degrees C, while at 175 degrees C, 20 min were sufficient. For a complete extraction of the unground (shredded) kava, the time of extraction was extended to 40 min at 175 degrees C. Boiling for 2 h and extraction with Soxhlet apparatus for 6 h, both of which employed water at atmospheric pressure, produced yields 40-60% lower than those obtained with subcritical water. With unground kava, 40 min of subcritical water extraction yielded essentially the same recoveries of lactones as 18 h of sonication with acetone, methylene chloride, or methanol.

Kava↗

Identification of some human urinary metabolites of the intoxicating beverage kava.

Methane chemical ionization (CI) gas chromatography-mass spectrometry (GC-MS) has been used to identify some of the human urinary metabolites of the kava lactones following ingestion of kava prepared by the traditional method of aqueous extraction of Piper methysticum. All seven major, and several minor, kava lactones were identified in human urine. Observed metabolic transformations include the reduction of the 3,4-double bond and/or demethylation of the 4-methoxyl group of the alpha-pyrone ring system. Demethylation of the 12-methoxy substituent in yangonin (or alternatively hydroxylation at C-12 of desmethoxyyangonin) was also recognised. This product was isolated by high-performance liquid chromatographic analysis of crude urine extracts and characterised by methane CI GC-MS. In contrast to the situation prevailing in the rat no dihydroxylated metabolites of the kava lactones, or products from ring opening of the 2-pyrone ring system, were identified in human urine. GC-MS analysis of urine can be readily utilised to determine whether donors have recently consumed kava.

Beverages↗