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The importance of pharmacological synergy in psychoactive herbal medicines.

The therapeutic effects of many herbal medicines have been well established; however, definitive mechanisms of action remain to be elucidated for many psychoactive herbal medications. Although several mechanisms have been identified, they are often insufficient to account for the observed effects of the plant or its extracts. This review emphasizes that, in addition to searching for more potent mechanisms, one must consider the additive and supra-additive effects of a plant's multiple constituents. Synergy may occur through pharmacokinetic and/or pharmacodynamic interactions. Examples are given that illustrate synergistic actions in St. John's wort (Hypericum perforatum), kava kava (Piper methysticum), and valerian (Valeriana officinalis).

Drug Synergism↗

[Agricultural application of sludge dredged from landscape water bodies].

The feasibility and ecological effects of agricultural application of sludge dredged from the Grand Canal (Hangzhou Section) were studied. Applied too much dredged sludge to red soil and paddy soil affected the germination of alpine fescue [Fescuta ovina var. brachyphylla (Schult.) Piper] and colver (Trifolium repens. L) seeds, while there wasn't significantly affects in pot experiment. While the application rate was lower than 270 t.hm-2, the growth of pakchoi (Brassica chinensis L.) increased as application rate increasing. While the application rate was higher than 270 t.hm-2, the growth of pakchoi decreased. The flowers and grasses in garden were more suitable for the dredged sludge application, and there was significant increase of growth while the application rate was lower than 1080 t.hm-2. Contents of copper and zinc exceed hygiene standard, while the application rate was above 1350 t.hm-2. While the application rate was lower than 450 t.hm-2, the pollution of the groundwater had not been observed. The results showed that land application was an economical and feasible way for the disposal of sludge dredged from landscape water bodies, and horticultural application was more safe and economical than agricultural application.

Crops, Agricultural↗

Pexelizumab Alexion.

Alexion and Procter & Gamble (P&G) are developing pexelizumab (h5G1.1-SC), a short-acting, recombinant complement C5 inhibitor for the potential treatment of complications of cardiovascular surgery, such as complement activation during cardiopulmonary bypass (CPB) procedures, for which it has completed phase II trials [275707]. By November 2001, the companies were also conducting two phase II trials for the treatment of acute myocardial infarction (MI) and by March 2002, patient accrual in the first of these MI trials (COMPLY) had been completed [429171], [443067]. In April 2002, accrual in the second MI trial (COMMA) was also completed [446377]. Results from the MI trials had been expected in the first half of 2002 [435888]. By January 2002, pivotal phase III trials had been initiated in patients undergoing coronary artery bypass graft (CABG) with CPB [435058]. The compound may also have potential in the treatment of stroke [188595]. In September 2000, the US FDA granted Alexion Fast Track status for pexelizumab for CPB patients [381531]. The company is collaborating with P&G to develop and commercialize this inhibitor drug for patients undergoing CPB during CABG [313015]. In December 2001, the terms of the collaboration were altered and as a result Alexion was to play an increased role in the development and marketing of pexelizumab in the US [433296]. Alexion licensed the complement protein C5 technology from Enzon Inc, developed during Enzon's short chain antigen binding (SCA) proteins program, in May 1996 [352743]. Analysts at US Bancorp Piper Jaffray predicted in January 2002 that pexelizumab has potential peak sales of US $350 million. At this time, approval for the CPB indication was expected in the US in the second half of 2004, and sales in 2005 were expected to reach US $50 million, rising to US $227 million in 2008. In the rest of the world, CPB approvals were expected to begin in the second half of 2005. Sales in 2006 were expected to reach US $35 million, rising to US $110 million in 2008 [438051].

Animals↗

Densitometric analysis of kawain in kava-kava root extracts.

A thin layer chromatographic-densitometric method for the identification and determination of kawain in a mixture of kavalactones obtained from a methanol extract of kava-kava roots (Piper methysticum) was developed. The main compounds present in the extract were separated with good results using silica gel F 254 coated TLC plates as the stationary phase and hexane-dioxane-butyl acetate-ammonia 25% (7:2:3:0.5 v/v/v/v) as the mobile phase. The qualitative identification and quantitative measurement of kawain were obtained by UV measurements at lambda=250 nm. The described method demonstrates very high sensitivity with the limit of detection established at 20 ng. 99.38% of the kawain was recovered and the concentration range showed a linearity from 0.0005% to 0.004%. Under these conditions, the percent of kawain in the presence of other kavalactones in the prepared extracts (I-VII), was determined. Similar results were obtained for all extracts, with the kawain content ranging from 1.01% to 1.16%.

Anti-Anxiety Agents↗

Relationship between oscillations in the basal ganglia and synchronization of cortical activity.

The functions of oscillations within the basal ganglia are poorly understood. We discuss in the present paper, the possible physiological or pathological roles of oscillatory activities within the basal ganglia, and their relationship to cortical oscillations. Three aspects are presented: 1. What do we know from animal studies? 2. What do we know from neurophysiological studies in parkinsonian patients? 3. What is the effect of L-dopa treatment and electrical stimulation within basal ganglia circuits on cortical oscillations? Animal studies suggest that neuronal oscillations are spontaneously generated within the basal ganglia system, especially from the GPE and the subthalamic nucleus (STN), but are mainly synchronized by cortical activity via the striatal inputs. Dopamine depletion results in a global increase of oscillations within the whole basal ganglia system, particularly in the GP-NST network. Oscillations within the basal ganglia may, in part, be related to tremor since they are enhanced, especially in the globus pallidus internus (GPI) and the STN, in human and animal dopaminergic depletion. However, they also play a role in the physiology of movement as revealed by coherence analysis between cortex, muscles and GPI/STN in parkinsonian patients undergoing deep brain stimulation. It is known that the basal ganglia may influence cortico-muscular oscillations such as the Piper rhythm and other rhythms in the beta band. In off-drug parkinsonian patients, low frequency oscillations (4-10 Hz) are favoured, presumably resulting in bradykinesia and low force. When medically (Ldopa) or surgically (deep brain stimulation) treated, these low frequency oscillations are replaced by high frequency (70 Hz) oscillations that are important for motor programs to be correctly executed. Studies of cortical reactivity related to planning of voluntary movement in parkinsonian patients provide evidence that it is possible to influence cortical reactivity through the basal ganglia system.

Animals↗

Hepatic toxicity possibly associated with kava-containing products--United States, Germany, and Switzerland, 1999-2002.

Since 1999, health-care professionals in Germany, Switzerland, and the United States have reported the occurrence of severe hepatic toxicity possibly associated with the consumption of products containing kava (i.e., kava kava or Piper methysticum). A total of 11 patients who used kava products had liver failure and underwent subsequent liver transplantation. On March 25, 2002, in response to five such case reports (four in Europe and one in the United States), the Food and Drug Administration (FDA) issued a consumer advisory and subsequently completed an investigation already underway of a similar U.S. case. This report presents the investigation of the two U.S. cases of liver failure associated with kava-containing dietary supplement products and summarizes the European cases. FDA continues to advise consumers and health-care providers about the potential risk associated with the use of kava-containing products.

Adolescent↗

Effect of co-administration of piperine on pharmacokinetics of beta-lactam antibiotics in rats.

Co-administration of piperine, an alkaloid isolated from Piper nigrum L. enhanced bioavailability of beta lactam antibiotics, amoxycillin trihydrate and cefotaxime sodium significantly in rats. The improved bioavailability is reflected in various pharmacokinetic parameters viz. tmax, Cmax, t(1/2) and AUC, of these antibiotics. The increased bioavailability could be attributed to the effect of piperine on microsomal metabolising enzymes or enzymes system.

Alkaloids↗

[Neurological syndromes associated with the ingestion of plants and fungi with a toxic component (II). Hallucinogenic fungi and plants, mycotoxins and medicinal herbs].

INTRODUCTION: A wide range of fungi and medicinal herbs, rich in hallucinogenic substances and widely used for mystic and medicinal purposes, can give rise to neurotoxic symptoms. DEVELOPMENT: We review the toxic syndromes that can arise from the ingestion of hallucinogenic fungi, cacti and plants, together with descriptions of cases of acute poisoning resulting from the use of medicinal herbs and from foodstuffs that are contaminated by mycotoxins. A series of different psychedelic fungi belonging to the Psilocybe, Panaeolus and Stropharia genera contain hallucinogenic alkaloids such as psilocybin. Some of the most notable plants displaying hallucinogenic and sedative properties are Papaver somniferum, Erytroxylum sp. and Cannabis sativa. Infusions of ayahuasca are obtained from the lianas and roots of different plants with psychoactive properties, such as Banisteriopsis caapi and Psychotria viridis, which contain alkaloids derived from tryptamine and from the beta carboline harmala. Peyote, a cactus rich in mescaline, and Claviceps purpurea (a fungus rich in LSD) are strong hallucinogens. We also examine ergotism and mycotoxicosis from Arthrinium sp. Poisoning from mycotoxin containing moulds on sugar cane can give rise to encephalopathy and late dystonia. Some of the more noteworthy medicinal plants for which neurological toxicity has been reported are Hypericum perforatum, kava kava (Piper methysticum), Aconitum sp. and Callilepis laureola. CONCLUSIONS: Because of the increasingly more widespread consumption of herbs and fungi and their potentially neurotoxic effects, in clinical practice there is a need to be aware of the neurological syndromes deriving from their use.

Administration, Oral↗

DuP 734 [1-(cyclopropylmethyl)-4-(2'(4''-fluorophenyl)-2'- oxoethyl)piperidine HBr], a potential antipsychotic agent: preclinical behavioral effects.

It has been suggested that sigma receptors may be involved in the etiology of psychosis and that 5-hydroxytryptamine2 (5-HT2) antagonists may have utility in treating the negative symptoms of psychosis as well as reducing the side effects associated with the typical antipsychotic haloperidol. We have evaluated the potential antipsychotic effects of 1-(cyclopropylmethyl)-4-(2'(4''-fluorophenyl)-2'-oxoethyl)piper i din e HBr (DuP 734), a selective and potent sigma and 5-HT2 receptor ligand with weak affinity for D2 receptors, in behavioral animal models that are not necessarily dependent on dopamine antagonism. DuP 734 potently blocked mescaline-induced scratching (ED50 = 0.35 mg/kg, p.o.) and aggressive activity (ED50 = 1.9 mg/kg, p.o.) and was relatively much weaker as an apomorphine antagonist (ED50 = 12 mg/kg, p.o.). This was in contrast to the typical antipsychotic agents such as haloperidol and chlorpromazine, which were very potent in all three tests. In rats, DuP 734 did not antagonize avoidance behavior or induce catalepsy, and, therefore, differed from the potent dopamine receptor antagonist antipsychotics. It did, however, reduce lever response rates in a random interval 60-sec food reward schedule of reinforcement (ED50 = 6.0 mg/kg, p.o.) in rats. The results suggest that DuP 734 may have antipsychotic activity without the liability of motor side effects typical of neuroleptics. Although DuP 734 itself did not antagonize avoidance activity, it significantly enhanced the potency of haloperidol in blocking avoidance behavior by 3-fold (by shifting the ED50 from 0.94 to 0.36 mg/kg, p.o.), whereas the ED50 of haloperidol for blockade of escape behavior and induction of catalepsy was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗

Bioassay screening of Amazonian plants.

OBJECTIVE: The purpose of this study was to evaluate several biological activities of thirty plant extracts collected in the North West Amazon (Ecuador). Some of these plants are being used for their reputed medicinal properties by the natives of this region. METHODS: Five in vitro bioassays were used to screen the plant material. 1. The brine shrimp lethality examination (BSLT) in microplate is a general test that seems capable of detecting a broad spectrum of bioactivity present in crude plant extracts. 2. Free radical scavenging properties were studied in a colorimetric assay using 2,2-diphenyl-1-picrylhydrazyl (DPPH). 3. The beta-glucosidase inhibition test is thought to be a method for the evaluation of anti-AIDS, anti-diabetic or anti-obesity compounds. 4. The xanthine oxidase inhibition assay is used to identify potential anti-gout agents. 5. The antibacterial activity that is being used to isolate and identify antibiotic drugs. RESULTS: In the BSLT, we found that Piscidia carthagenensis demonstrated very good activity with a LC50: 21.81 micrograms/mL. It is considered that plant extracts with low LC50 values may contain metabolites with cytotoxic, antifungal, insecticidal or pesticide activities. In the antioxidant activity bioassay, several plant extracts were confirmed to have excellent free radical scavenging properties. Rhus juglandifolia and Clusia venusta leaves exhibited an ED50: 3.12 micrograms/mL and 3.61 micrograms/mL, respectively. Piper reticulatum (84%), Inga heteroptera (77%), Clusia venusta (70.9%), and Rhus juglandifolia (70.5%) showed fairly good inhibition activity for beta-glucosidase. On the other hand, none of the plant extracts was capable of inhibiting xanthine oxidase. Finally, the Gram-positive microorganisms Staphylococcus aureus and Corynebacterium diphteriae were found to be sensitive to the majority of the plant extracts, whereas the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, and Salmonella typhi were proved to be resistant toward the plant extracts. CONCLUSIONS: It is important to continue investigating our plant kingdom, especially the world tropical reserves as an alternative for finding new or better drugs. It should be essential to follow-up this type of investigation to isolate and elucidate the active principles of the bio-positive plants.

Animals↗

Mast cell stabilization, lipoxygenase inhibition, hyaluronidase inhibition, antihistaminic and antispasmodic activities of Aller-7, a novel botanical formulation for allergic rhinitis.

Allergic rhinitis, also known as hay fever, rose fever or summer catarrh, is a major challenge to health professionals. A large number of the world's population, including approximately 40 million Americans, suffers from allergic rhinitis. A novel, botanical formulation (Aller-7) has been developed for the treatment of allergic rhinitis using a combination of extracts from seven medicinal plants, including Phyllanthus emblica, Terminalia chebula, T. bellerica, Albizia lebbeck, Piper nigrum, Zingiber officinale and P. longum, which have a proven history of efficacy and health benefits. The clinical manifestations of allergy are due to a number of mediators that are released from mast cells. The effect of Aller-7 on rat mesenteric mast cell degranulation was studied by incubating different concentrations of Aller-7 and challenging them with a degranulating agent, compound 48/80. The inhibitory activity of Aller-7 was determined against lipoxygenase and hyaluronidase, the key enzymes involved in the initiation and maintenance of inflammatory responses. Furthermore, most of these manifestations are due to histamine, which causes vasodilatation, increasing capillary permeability and leading to bronchoconstriction. Hence, the antihistaminic activity of Aller-7 was determined is isolated guinea pig ileum substrate using cetirizine as a positive control. The antispasmodic effect of Aller-7 on contractions of guinea pig tracheal chain was determined using papaverine and cetirizine as controls. Aller-7 exhibited potent activity in all these in vitro models tested, thus demonstrating the novel anti-allergic potential of Aller-7.

Animals↗

Major ion correlation in groundwater of Kancheepuram Region, South India.

Groundwater samples were collected from both dugwells and borewells in an intensively irrigated area of Kancheepuram Taluk, Tamil Nadu. pH, EC and TDS of groundwater samples were measured in the site. The collected samples were analysed in the laboratory for Ca, Mg, Na, K, Cl, HCO3, CO3, SO4, NO3, P-PO4 and Si-SiO2. The results are used for inter elemental correlation analysis which indicates that most of the elements having good correlation. Piper Trilinear diagram is used to find out the hydrochemical type of groundwater which shows that most of them are CaHCO3 and the remaining are CaMgCl type. Hydrochemical characteristics of groundwater indicate that silicate weathering reaction is a probable source for high concentration of major ions.

Environmental Monitoring↗

Spectrophotometric method for estimation of alkaloids precipitable with Dragendorff's reagent in plant materials.

A rapid, easy, and simple spectrophotometric method was developed for the estimation of total alkaloids precipitated by Dragendorff's reagent (DR) in plant materials. It is based on the formation of yellow bismuth complex in nitric acid medium with thiourea. The yellow-colored complex formed obeys Lambert-Beer's law in the concentration range of 0.06-50 microg/mL with lambdamax at 435 nm. Using this method, the alkaloidal percentage of certain alkaloids (ajamalicine, papaverine, cinchonine, piperine, berberine) and some plant materials containing alkaloids (Berberis aristata, Solanum nigrum, and Piper longum) were determined. The method was compared with other methods. It can be used for routine analysis of commercial samples by industries dealing with herbal drugs for standardization of plant materials containing alkaloids and for alkaloid-containing pharmaceutical products.

Alkaloids↗

Epidemiology of betel quid usage.

Betel quid chewing is an ancient practice common in many countries of Asia and among migrated communities in Africa, Europe and North America. It enjoys complete social acceptance in many societies and is also popular among women. In its most basic form, betel quid consists of betel leaf (Piper betel), areca nut, the main psychoactive ingredient, and slaked lime (calcium hydroxide). Areca nut is said to be the fourth most commonly used psychoactive substance in the world, after caffeine, nicotine and alcohol. There are a great variety of ingredients and ways of preparing betel quid in different countries. In some, particularly in India, tobacco is added to the quid. In recent years, commercially-manufactured non-perishable forms of betel quid (pan masala or betel quid mixtures and gutka), not containing betel leaf, have been marketed. Within a short period of about 2 decades, this industry has risen in value to several hundred US million dollars. Use of areca nut in any form is not safe for oral health; the use of commercially manufactured forms seems even riskier.

Areca↗

Prevalence of fatigue among cancer patients undergoing external radiotherapy.

Between July 1999 to November 2000, 115 patients undergoing radiotherapy were evaluated for the development of treatment-related fatigue, using a modified Piper's fatigue scale. The above scale determines 4 dimensions of fatigue ie behavioral severity (6 items), affective meaning (5 items), sensory (5 items), and cognitive mood (6 items). Radiotherapy was delivered to the head and neck, breast, pelvis, and miscellaneous sub-sites. The area of the radiation field ranged from 25 to 480 cm2 (median 156 cm2). Forty-three percent of patients experienced significant fatigue, which altered their work environment. The individual components of fatigue were behavioral severity 25%, affective meaning 21%, sensory 18%, and cognitive mood 16%. Significant radiotherapy-related fatigue was higher in patients treated with advanced-stage disease, large radiotherapy field area, and low pre-radiotherapy hemoglobin level.

Adolescent↗

Breech presentation: evolution of management.

From the historical perspective, vaginal delivery of the persistent breech presentation had been the tradition since the 1st century A.D. The external cephalic version was perfected and popularized in the mid-16th century. A variety of instruments and maneuvers had been used in the 19th century, with successful application of forceps to the after-coming head, and in 1924, Edmund Piper developed forceps for application only to the after-coming head. Vaginal delivery of breech cases had been performed primarily for the safety of the mother. As blood banking, antibiotics and safe anesthesia became available and legal and the ethical and social milieu was changing, cesarean breech deliveries were performed more liberally to reduce the increased perinatal morbidity and mortality of infants born of vaginal breech deliveries. Liberalization of cesarean delivery resulted in increased maternal mortality, and increased maternal morbidity created potential hazards in subsequent pregnancies. Renewed interest in revival of the practice of external cephalic version created successful reduction in term breech presentation. Several retrospective, prospective and randomized studies of vaginal deliveries of some types of breech cases were conducted under strict, selective protocols, with results of outcome comparable to those of cesarean sections. The International Term Breech Collaborative Group, after study of a large number of frank and complete breech cases, concluded that planned cesarean delivery is a "substantially better method of delivery for the fetus" and that a policy of planned vaginal birth for term, singleton, breech fetuses should no longer be encouraged.

Adolescent↗

Cumulative trauma disorders in betel pepper leaf-cullers visiting a rehabilitation clinic: experience in Taitung.

BACKGROUND: Betel pepper (Piper betle L.) cultivation is an important agricultural industry in Taitung, Taiwan, and culling leaves is very labor-intensive. This case study compares the proportion of cumulative trauma disorders (CTDs) between cullers and those with other occupations. METHODS: Patients with musculoskeletal disorders in the rehabilitation clinic of a local hospital in Taitung were enrolled. This all female cohort was divided into a culler group (betel pepper cullers, n = 20), and a non-culler group (other occupations, n = 47). Three cullers were interviewed, and were also recorded to elucidate the related ergonomics. Patients were diagnosed using plain radiography and ultrasonography. RESULTS: The act of culling involves an overhead internal rotation of both shoulders with extended elbows while standing, followed by wrist flexion and forearm pronation. Flexing of the fingers is also required by the tools, 'iron nails' fitted onto both thumbs. The proportions of patients with shoulder impingement syndrome (SIS) and carpal tunnel syndrome (CTS) were significantly higher among cullers than non-cullers (0.45 vs. 0.15, p = 0.011 and 0.40 vs. 0.06, p = 0.002, respectively). Furthermore, the total frequency of CTDs displayed a positive linear correlation with employment duration (r = 0.618, p = 0.004). CONCLUSIONS: Proportions of occupational SIS and CTS were higher among betel pepper cullers than those with other occupations. These CTDs may have resulted from a prolonged static posture and repetitive motions during culling.

Adult↗