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The poisoning of 'awa: the non-traditional use of an ancient remedy.

In the traditional practice of Native Hawaiians, 'awa (Piper methysticum) has long been revered as a medicine, a sacred plant central to religious ceremony, and a social drink. In the late 1990s, 'awa attracted global attention as an herbal alternative to existing pharmaceuticals for reducing stress, anxiety, pain and assorted ailments. Marketed since 1994 as a dietary supplement, within seven years 'awa had earned the title of a "superstar" and quickly became one of the top eight herbal remedies in an expanding $18 billion-plus herbal remedy industry. In one study, the plant was even argued to possess chemopreventive properties, when cancer incidence and kava consumption in Pacific island communities were correlated. In 2002, however, the remedy was banned in several European countries, after case reports of liver toxicity allegedly associated with its nontraditional use surfaced. In the United States (US), the Food and Drug Administration issued a consumer advisory leading several retailers to voluntarily withdraw products containing 'awa from their shelves. These actions have sent shock waves throughout Pacific Island communities seeking to derive economic benefit from a relatively new and little-regulated industry. Moreover, they threaten the vitality of centuries of Native Hawaiian cultural practice. Clinical studies advocating both sides of the safety debate have been published, as producers, marketers and users attempt to influence government action. At the same time, issues of cultural exploitation, religious freedom, traditional practice, and native intellectual property rights are absent from the debate, leaving the future of native practice hanging in the balance. Whether or not the herb's status is restored, the situation raises critical questions: Is 'awa toxic? Or, does the poison derive from its use outside of traditional practice?

Chemical and Drug Induced Liver Injury↗

Adulticidal activity of some Malaysian plant extracts against Aedes aegypti Linnaeus.

The adulticidal activity of methanol extracts from three Malaysian plants namely Acorus calamus Linn., Litsea elliptica Blume and Piper aduncum Linn. against adult of Aedes aegypti (L.) were studied. Standard WHO bioassay tests were used to evaluate the effectiveness of these plant extracts. The hexane fraction from methanol extract of Acorus calamus rhizome was the most effective, exhibiting LC50 and LC90 values of 0.04 mgcm(-2) and 0.09 mgcm(-2) respectively. For L. elliptica, the methanol fraction also displayed good adulticidal property with the LC50 and LC90 values of 0.11 mgcm(-2) and 6.08 mgcm(-2) respectively. It is found that hexane fraction of the P. aduncum crude extract was the least effective among the three plants showing LC50 and LC90 values of 0.20 mgcm(-2) and 5.32 mgcm(-2), respectively. However, although A. calamus showed lowest LC values, the LT50 results indicated that the methanol fraction of L. elliptica was most potent extract among the extracts tested.

Journal Article↗

Interaction of potassium phosphonate fungicide in laterite soil.

Potassium phosphonate is a fungicide widely used to control Phytophthora fungi species in many crops all over the world. In this paper, an attempt has been made to study the interaction of potassium phosphonate with soil under varying pH and calcium level. Several reports available in literature indicate that the phosphonate in organic form adsorb strongly on almost all mineral surfaces and natural materials like soil and sediments. The present study conducted on laterite soil of Kerala using 2 mm sieved sample indicated that phosphonate obeys Freundlich adsorption isotherm. Though at lower concentrations, Langmuir model equally fits well, deviation was observed at higher concentrations. pH and calcium content of the soil had striking influence on the interaction of the chemical with the soil. The calcium source also appeared to influence the adsorption phenomenon. Since potassium phosphonate is extensively used to control Phytophthora fungi species in black pepper (Piper nigrum) plantations in India and liming is a standard practice followed as soil amendment in acid soils to increase the soil pH, this study may help to maintain good soil quality.

Computer Simulation↗

Correlates of fatigue in people with breast or lung cancer.

Fatigue is regarded as a universal and unavoidable side effect of cancer therapy, yet its epidemiology and prevalence in populations of people with cancer have not been well-documented. Using the conceptual framework of Piper, et al., this study examined and described the perception and manifestations of fatigue and its physiological, biochemical, and behavioral correlates. A convenience sample (N = 77) of people with lung (n = 33) or breast cancer (n = 44) completed several instruments: a brief questionnaire, the Rhoten Fatigue Scale, a visual analogue scale (VAS), the Rhoten Fatigue Checklist, and the shortened version of the Profile of Mood States (POMS). Data on other factors thought to influence fatigue were collected via medical record audit. Seventy-five of 76 people (99%) completing the VAS experienced some level of fatigue. Significant correlates of fatigue included level of pain and POMS scores. Preliminary findings suggest that fatigue is a common problem with a complex etiology and that nurses must consider potential contributing factors when assessing fatigue and its impact on the individual.

Adult↗

Effect of piperine on pentobarbitone induced hypnosis in rats.

Piperine (1-peperoyl piperidine), a major alkaloid isolated from Piper nigrum Linn, potentiated pentobarbitone sleeping time in dose dependant manner, with peak effect at 30 min. Blood and brain pentobarbitone levels were higher in piperine treated animals. Piperine treatment in rats, treated chronically with phenobarbitone, significantly potentiated pentobarbitone sleeping time, as compared to the controls. There was no alteration in barbital sodium sleeping time. It is possible that, piperine inhibits liver microsomal enzyme system and thereby potentiates the pentobarbitone sleeping time.

Alkaloids↗

Activation of sodium channels and inhibition of [3H]batrachotoxinin A-20-alpha-benzoate binding by an N-alkylamide neurotoxin.

BTG 502 [(2E,4E)-N-(1,2-dimethyl)-propyl-6-(5-bromonaphth-2-yl)-hexa -2,4- dienamide], a synthetic analog of insecticidal amides isolated from Piper species, stimulated 22Na+ uptake into mouse brain synaptoneurosomes in the presence of saturating concentrations of Leiurus quinquestriatus venom but had no effect on sodium uptake in the absence of venom. In the presence of Leiurus venom, half-maximal stimulation was achieved at a BTG 502 concentration of 1.7 microM, whereas maximal stimulation (2.3-fold greater than nonspecific uptake) was observed at 50 microM. In the absence of other modifiers, BTG 502 inhibited batrachotoxin (BTX)-dependent sodium uptake, producing 50% inhibition at 2 microM. In the presence of Leiurus venom, BTG 502 was a partial inhibitor of BTX-dependent 22Na+ uptake, producing half-maximal inhibition at 1.5 microM. The levels of residual BTX-dependent sodium uptake and maximal BTG 502-dependent sodium uptake measured in the presence of Leiurus venom were identical. BTG 502 inhibited the specific binding of [3H]batrachotoxinin A-20-alpha-benzoate (BTX-B) to the activator recognition site (site 2) of sodium channels in these preparations, producing half-maximal inhibition at 2 microM and maximal inhibition at 30 microM. Equilibrium analysis showed that BTG 502 was an apparent competitive inhibitor of [3H]BTX-B binding, producing a concentration-dependent decrease in the affinity of sodium channels for this ligand without affecting binding capacity. Kinetic analysis demonstrated that BTG 502 slowed the rate of formation of the ligand-receptor complex but did not alter the rate of dissociation of this complex. The effects of BTG 502 on 22Na+ uptake and [3H]BTX-B binding are consistent with the action of this compound as an antagonist at the activator recognition site of the voltage-sensitive sodium channel in the absence of Leiurus venom and as a partial agonist at this site in the presence of Leiurus venom. These results suggest that the N-alkylamides represent a novel chemical class of neurotoxins that act at site 2 of the sodium channel.

Animals↗

Alpha-2A and alpha-2B adrenergic receptor subtypes: attenuation of cyclic AMP production in cell lines containing only one receptor subtype.

At least two subtypes of alpha-2 adrenergic receptors have been identified on the basis of antagonist affinities as determined mainly by radioligand binding assays. The human platelet and the HT29 human colonic adenocarcinoma cell contain alpha-2A adrenergic receptors, whereas the neonatal rat lung and the NG108 neuroblastoma X glioma hybrid cell contain the alpha-2B adrenergic receptor. Using the attenuation of the cyclic AMP accumulation as a functional assay, the affinities of various antagonists for the alpha-2 adrenergic receptor were determined in HT29 and NG108 cell lines. Dose-response curves to 5-bromo-6-(2-imidazoline-2-yl-amino)quinoxaline (UK 14,304) an alpha-2 adrenergic agonist, were generated in the absence and presence of three concentrations of various antagonists. Schild regressions were used to determine pA2 values and then dissociation constants (KB value) were calculated. Whereas phentolamine and yohimbine were equipotent at the receptor in the two cell lines, 2-(2,4-(O-methoxyphenyl)-piper-azin-1-yl)ethyl-4,4-dimethyl-1,3-(2 H,4H)- isoquinolindione (ARC-239) and prazosin were 100- and 30-fold more potent in the NG108 cell line than in the HT29 cell. These potency ratios determined from functional experiments are the same as those obtained from radioligand binding experiments. These functional data are consistent with the previous and more extensive binding data, and thus support the existence and definition of alpha-2A and alpha-2B adrenergic receptor subtypes.

Animals↗

Effect of ayurvedic medicines on beta-glucuronidase activity of Brunner's glands during recovery from cysteamine induced duodenal ulcers in rats.

Biochemical and histochemical studies revealed decreased beta-glucuronidase activity in the Brunner's glands of duodenal ulcerated rats. The enzyme activity showed gradual increase during recovery. Rats treated with a mixture of Ayurvedic medicines (Glycyrrhiza glabra, Terminalia chebula, Piper longum and Shanka Bhasma) recovered faster with concomitant increase in beta-glucuronidase activity in the Brunner's glands. It can be concluded that Ayurvedic medicines used do not act as antacid but improve the secretory status of Brunner's glands involved in the protection against duodenal ulcer.

Animals↗

Effect of aqueous and lipid-soluble extracts of kava on the conditioned avoidance response in rats.

The aqueous, pyrone-free extract from kava (Piper methysticum) and the lipid-soluble extract (kava resin) were tested for their effect on amphetamine-induced hypermotility in mice and on conditioned avoidance response behavior in rats in a shelf-jump apparatus. Both kava extracts reduced amphetamine-induced hypermotility. Aqueous kava extract in i.p. doses of 30 mg/kg to 500 mg/kg had no effect on conditioned avoidance responses. At or below 100 mg/kg i.p. kava resin also failed to modify the number of conditioned avoidance responses obtained. However, 125 mg/kg of resin significantly reduced the number of conditioned avoidance responses by 18%. Increasing the dose of kava to 150 mg/kg caused ataxia and sedation which was so marked that a modified protocol was necessary. Only a marginally greater effect on conditioned avoidance response was obtained under these conditions. The effect of kava extract was slight compared to that of the standard antipsychotic drugs chlorpromazine and haloperidol in our procedure.

Amphetamine↗

Chronic disease in goats orally infected with two isolates of the caprine arthritis-encephalitis lentivirus.

Newborn Saanen goats were orally infected with two distinct biologically cloned isolates of the caprine arthritis-encephalitis lentivirus (CAEV), designated CAEV(63) (Crawford TB, Adams DS, Cheevers WP, Cork LC: Science 207:997, 1980) and CAEV (Co) (Cork LC, Hadlow WJ, Crawford TB, Gorham JR, Piper RC: J Infect Dis 129:134, 1974; Narayan O, Clements JE, Strandberg JD, Cork LC, Griffin DE: J Gen Virol 50:69, 1980). All infected goats seroconverted for antibodies to CAEV, and there were no serologic reversions. Histologic lesions consisted of chronic inflammation of variable incidence and severity in joints and mammary gland. Clinical arthritis, estimated by enlargement of carpi, correlated with severe inflammation of radiocarpal synovium. Statistical evaluations of clinical and histologic parameters indicated that chronic joint disease was significantly more frequent and more severe in the group of goats infected with CAEV(63) than in the group infected with CAEV (Co). Thus, the severity of chronic arthritis is determined in part by the relative pathogenicity of individual CAEV isolates. Analysis of the temporal development of carpal arthritis during the first 3 years of infection indicated that (a) the extent of eventual chronic disease in individual joints was apparent relatively early after infection, (b) joints with severe chronic lesions were clinically enlarged at irregular intervals and (c) the pattern of recurrent arthritis was unique for each joint. Thus, chronic arthritis develops with a progressive course which may be promoted by recrudescent inflammation. Infectious virus was recovered 3 years after infection from selected tissues of 12 of 17 CAEV(63)-infected goats and 11 of 18 CAEV(Co)-infected goats. Virus recovery was independent of the virus isolate used for experimental infection and did not correlate with the severity of lesions.

Administration, Oral↗

Piperine-mediated inhibition of glucuronidation activity in isolated epithelial cells of the guinea-pig small intestine: evidence that piperine lowers the endogeneous UDP-glucuronic acid content.

Piperine (1-peperoyl piperidine), a major component of the Piper species was reported recently by us to inhibit the activities of rat hepatic monooxygenases and UDP-glucuronyltransferase. This study explores further the basis of inhibition of glucuronidation. The effect of piperine on the rate of glucuronidation of 3-hydroxybenzo(a) pyrene and UDP-glucuronic acid content in the intact isolated epithelial cells of the guinea-pig small intestine was studied. The cells offered a fairly good system to study the modulation of glucuronidation activity. Glucuronidation of 3-hydroxybenzo(a) pyrene was dependent on the time of incubation, cellular protein and substrate concentration. From the kinetics of glucuronidation of 3-hydroxybenzo(a)pyrene in the isolated cell preparation the Vmax of 0.5 nmol of BP-3-glucuronide formed per min/mg of protein and Km of 25 microM were observed. The endogeneous concentration of UDP-glucuronic acid observed was 1.6 to 2.3 nmol/mg of cellular protein. Piperine caused a concentration-related decrease in UDP-glucuronic acid content and the rate of glucuronidation in the cells. It required much lower concentrations of piperine than D-galactosamine to diminish the endogeneous level of UDP-glucuronic acid. Rate of glucuronidation of 3-hydroxybenzo (a) pyrene was dependent on the endogeneous level of UDP-glucuronic acid. At 50 microM piperine, the rate of glucuronidation was reduced to about 50% of the basal rate. Piperine caused noncompetitive inhibition of hepatic microsomal UDP-glucuronyltransferase with Ki of 70 microM. The studies demonstrate that piperine modifies the rate of glucuronidation by lowering the endogeneous UDP-glucuronic acid content and also by inhibiting the transferase activity.

Alkaloids↗

Nonmutagenicity of betel leaf and its antimutagenic action against environmental mutagens.

Betel leaf (Piper betel) water and acetone extract are nonmutagenic in S. typhimurium strains with and without S9 mix. Both the extracts suppress the mutagenicity of betel quid mutagens in a dose dependent manner. Moreover both the extracts of betel leaf reduce the mutagenicity of benzo(a)pyrene and dimethylbenzanthracene. Acetone extract is more potent than water extract in inhibiting mutagenicity of environmental mutagens.

9,10-Dimethyl-1,2-benzanthracene↗

[Biotransformation of meclozine in the human body].

After oral administration of 1-[(4-chlorophenyl)-phenylmethyl]-4-[3-methylphenyl)-methyl]-piperazine (1, Meclozine) eleven compounds were isolated from human urine and faeces. The structural elucidation of the metabolites was accomplished by comparison of their spectral data with those of the synthetic reference compounds. The metabolites were identified as: Meclozine (1), N-[(4-chlorophenyl)-phenylmethyl]-piperazine (2), 3-(4-[(4-chlorophenyl)-phenylmethyl]-piperazino)-methyl-benzoic acid (3), 3-(4-[(4-chlorophenyl)-phenylmethyl]-piperazino)-methyl-benzamide] (4), 2-[3-(4-[(4-chlorophenyl)-phenylmethyl]-piperazino)-methyl-benzoyl ]-amino- ethanesulphonic acid (5), 3-(4-[(4-chlorophenyl)-3'-hydroxy-4'-methoxyphenylmethyl]-piper azino)- methyl-benzoic acid (6), 1-[(4-chlorophenyl)-phenylmethyl]-4-[(3-methylphenyl)-methyl]- piperazine-N4-oxide (7), 1-[(4-chlorophenyl)-phenylmethyl]-4-[(3-methylphenyl)-methyl]- piperazine-N,N'-dioxide (8), 3-methyl-benzoic acid (9), 3-methyl-hippuric acid (10) and 3-methyl-benzoic acid-glucuronide (11). The structure of compound 11 was confirmed after enzymatic cleavage and identification of the aglycon. A further metabolite was detected, but not identified.

Biotransformation↗

Labelling of proteins with [35S]methionine in monolayer cultures of rat hepatocytes.

Optimal conditions for the labelling of proteins with [35S]methionine in monolayers of rat hepatocytes have been established. The ability to incorporate the radioactive amino acid was constant for at least 26 h and independent of whether the medium was buffered with CO2/HCO3 or with 4-(2-hydroxyethyl)-1-piper-azineethanesulphonic acid (Hepes). Preincubation in methionine-free medium for up to 30 min yielded increasing, and from 60 to 180 min decreasing, rates of incorporation. An apparent Km value of 0.06 mM was obtained for the incorporation reaction in cells preincubated for 40 min.

Animals↗

[Quid of betel].

After clarifying some necessary terminology to understand what quid of betel is, the authors, in the first part of this article, expose its location around the world. Then, they report on the three main basic components: Piper betle L. leaf, Areca catechu nut, and slaked lime. They add too some other ingredients which modify the taste of the quid to a certain extent. In the third part, the authors expose the role given to betel in the traditional medicine according to bibliographical sources available in different countries. Its appears that Areca nut is still the most commonly used. Then, they review the therapeutic qualities of the quid utilized by western medicine according to the different part of the organism, and finally they end by indicating the true importance to be given to this customary habit.

Adult↗

Gastric-acid output, pepsin output, and lean body mass in normal and duodenal-ulcer subjects.

Gastric-acid output bears a significant relationship to parietal cell mass and to lean body mass. The relationships of pepsin output to gastric-acid output and to lean body mass have been investigated in 13 normal subjects and 40 duodenal-ulcer patients. Peak pepsin output (P.P.O[I]) was stimulated by insulin-induced hypoglycaemia and the enzyme was assayed by Piper's method. Peak acid output to pentagastrin (P.A.O.[Pg] was obtained at a separate test. P.P.O.(I) correlated significantly with P.A.O.(Pg) in normal subjects (r equals 0-889, P less than 0-0001). P.P.O.(I) also showed good correlation with lean body mass (L.B.M.) (r equals 0-714, P less than 0-01), suggesting that P.P.O.(I) reflects peptic cell mass in normal subjects. In 40 duodenal-ulcer subjects there was no significant overall correlation of P.P.O.(I) with P.A.O(Pg) or with L.B.M. However, expressing the results as output of pepsin per milliequivalent of acid per kilogramme of lean body mass allowed separation of the ulcer patients into two groups whose ratios appeared to correlate with their symptomatic state at the time of testing: thus mean P.P.O(I) per meq. acid per kg. L.B.M. for duodenal-ulcer patients in relapse was significantly greater than the ratios for the patients in remission and for the normal group (P less than 0-001), suggesting either the presence of an increased sensitivity to insulin stimulation or a lack of pepsin inhibitor substance during a relapse of ulcer symptoms.

Body Height↗

Comparison of vegetative anatomy of Piperales. II. Leaf.

Many characters of leaf (hair, hypodermal cells, palisade layers, intercellular space, distinction between spongy and palisade parenchyma, "palisade ratio", distribution of collenchyma and sclerenchyma, presence or absence of starch grains, calcium oxalate crystals, number, shape and arrangement of bundles of petiole) are useful distinguishing characters. Reduction of palisade layers seems to be the trend of evolution in Piper and Peperomia.

Plants↗

Incidence of aflatoxin-potential contamination in Spanish sausages.

525 strains of moulds were isolated from 8 samples of red pepper (Capsicum annuum) and from 3 samples of black pepper (Piper nigrum). These spices were commonly added to the various kinds of spanish sausages, specially to the spanish "chorizo". Of these 525 isolated moulds, 100 belonged to the Aspergillus flavus group. 69 were isolated from red pepper and 31 from black pepper. Of these strains, 28 strains isolated from red pepper were found positive in producing aflatoxin B1 while only 8 of the strains isolated from black pepper produced aflatoxin B1. 16 of the strains isolated from red pepper also produced aflatoxin G1. After experimental contamination by these aflatoxicogenic strains of moulds of various kinds of spanish sausages, and after drying them under similar storage conditions used in the sausage industry, the presence of aflatoxin were detected only on the skin but not in the meat of the sausage.

Aflatoxins↗