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Inhibitory effects of sudanese medicinal plant extracts on hepatitis C virus (HCV) protease.

One hundred fifty-two methanol and water extracts of different parts of 71 plants commonly used in Sudanese traditional medicine were screened for their inhibitory effects on hepatitis C virus (HCV) protease (PR) using in vitro assay methods. Thirty-four extracts showed significant inhibitory activity (>/=60% inhibition at 100 microg/mL). Of these, eight extracts, methanol extracts of Acacia nilotica, Boswellia carterii, Embelia schimperi, Quercus infectoria, Trachyspermum ammi and water extracts of Piper cubeba, Q. infectoria and Syzygium aromaticum, were the most active (>/=90% inhibition at 100 microg/mL). From the E. schimperi extract, two benzoquinones, embelin (I) and 5-O-methylembelin (II), were isolated and found as potent HCV-PR inhibitors with IC(50) values of 21 and 46 microM, respectively. Inhibitory activities of derivatives of I against HCV-PR as well as their effects on other serine proteases were also investigated.

Chromatography, High Pressure Liquid↗

Effect of black pepper and piperine on bile secretion and composition in rats.

The influence of black pepper (Piper nigrum L.) and its active principle, piperine on the secretion and composition of bile was investigated in the rat. They were administered by gavage (black pepper at 250 or 500 mg and piperine at 12.5 or 25 mg/kg body wt.) or fed in the diet for 4 weeks (black pepper at 0.2 and 0.4%, piperine at 0.01 and 0.02%). The lower dose by gavage of black pepper caused an increase in bile solids while with other treatments bile secretion or dry matter in bile was not changed. Dietary feeding of black pepper caused an increase in bile flow with a concomitant decrease in bile solids -- a hydrocholagoguic effect. Cholesterol and bile acid output were not affected by black pepper or piperine at either level irrespective of the mode of administration; in contrast, the secretion of uronic acids in bile was enhanced by both levels of pepper as also of piperine indicating possible excretion of some of the components of black pepper or of piperine as glucuronides.

Alkaloids↗

Saccade and cognitive impairment associated with kava intoxication.

Kava is an extract from the Piper methysticum Forst. f. plant that has social and spiritual importance in Pacific islands societies. Herbal remedies that contain kava are used for the psychiatric treatment of anxiety and insomnia. Laboratory studies have found only subtle, if any, changes on cognitive or motor functions from the acute effects of consuming small clinical doses of kava products. Intoxication from recreational doses of kava has not been studied. The performance of individuals intoxicated from drinking kava (n=11) was compared with a control group (n=17) using saccade and cognitive tests. On average, intoxicated individuals had consumed 205 g of kava powder each (approximately 150 times clinical doses) in a group session that went for 14.4 h and ended 8 h prior to testing. Intoxicated kava drinkers showed ataxia, tremors, sedation, blepharospasm and elevated liver enzymes (GGT and ALP), together with saccadic dysmetria, saccadic slowing and reduced accuracy performing a visual search task that only became evident as the task complexity increased. Kava intoxication is characterized by specific abnormalities of movement coordination and visual attention but normal performance of complex cognitive functions. Saccade abnormalities suggest disruption of cerebellar and GABAergic functions.

Adult↗

Improving the physical status and quality of life of women treated for breast cancer: a pilot study of a structured exercise intervention.

BACKGROUND AND OBJECTIVES: This pilot project assessed the acceptability of a mixed-type, moderate-intensity exercise programme following breast cancer treatment, and the impact on presence of lymphoedema, fitness, body composition, fatigue, mood and quality of life. METHODS: Ten women completed the programme and measures of fitness (sub-maximal ergometer test), body composition (bio-electrical impedance), lympoedema (bio-electrical impedance and arm circumferences), fatigue (revised Piper Fatigue Scale), mood (Hospital Anxiety and Depression Scale), quality of life (FACT-B) and general well-being, at baseline, completion of the programme, and 6-week and 3-month follow-up. RESULTS: Participation in the programme caused no adverse effect on the presence of lymphoedema. There was a trend towards reduction in fatigue and improved quality of life across the testing phases. Women rated the programme extremely favourably, citing benefits of the support of other women, trained guidance, and the opportunity to experience different types of exercise. CONCLUSIONS: A mixed-type, moderate-intensity exercise program in a group format is acceptable to women following breast cancer treatment, with the potential to reduce fatigue and improve quality of life, without exacerbating or precipitating lymphoedema. This pilot work needs to be confirmed in larger randomised studies.

Adult↗

Superheated water chromatography-nuclear magnetic resonance spectroscopy of kava lactones.

Three kava lactone constituents of Piper methysticum, namely, kawain, methysticin and desmethoxyyangonin, have been separated and identified by reversed-phase HPLC using superheated deuterium oxide as the mobile phase and on-line 1H-NMR detection. The method avoids the use of organic solvents in the mobile phase and hence interferences in the NMR analysis are minimised.

Chromatography, High Pressure Liquid↗

Longitudinal course of depression, fatigue, and quality of life in patients with high risk melanoma receiving adjuvant interferon.

PURPOSE: Treatment of malignant melanoma with interferon-alpha has been associated with a variety of side effects ranging from fatigue to depression, and a concomitant impact on quality of life (QOL), in a variety of case reports and cross-sectional clinical trials. Few, if any, studies have been conducted with the express purpose of assessing the longitudinal course of depression, fatigue, and QOL before and during interferon therapy. DESCRIPTION OF STUDY: The current study reports on 16 patients who were assessed at 6 points in time: baseline, post high dose, and 1, 2, 3, and 6 months post high dose treatment with interferon-alpha with the Brief Symptom Inventory, Beck Depression Inventory, Revised Piper Fatigue Scale, and Functional Assessment of Cancer Therapy-Biological Response Modifiers. RESULTS: Results revealed consistent changes from baseline through 6 month assessment. Specifically, increased somatic complaints, depression, and fatigue were observed on the BSI, BDI, and RPFS, respectively. Additional reductions in QOL on the FACT-BRM were also identified. CLINICAL IMPLICATIONS: The findings suggest that IFN has a significant effect on QOL, but that it may be the somatic symptoms of fatigue that contribute to changes on measures of mood. Limiting the amount of fatigue and depression would appear to be significant if individuals are to successfully complete IFN therapy.

Angiogenesis Inhibitors↗

Antibacterial, antiprotozoal and antioxidant activity of five plants used in Izabal for infectious diseases.

Methanol and aqueous extracts from fi ve plant species, used in traditional medicine in Guatemala for the treatment of microbial infections, were tested in vitro for their ability to scavenge DPPH, OH(.) and O(2) (-) radicals and to inhibit lipoperoxidation (LPO) in order to establish a relationship between their antioxidant activities and their effects against infectious agents. Acalypha guatemalensis, Ocimum micranthum and Smilax spinosa possessed a significant activity against both the three free radicals assayed and LPO; Guazuma ulmifolia showed effects against DPPH and OH(.). Piper auritum showed no activity. These extracts were also evaluated for antibacterial and antiprotozoal activities. A. guatemalensis showed activity against Pseudomonas aeruginosa; S. spinosa was active against Salmonella typhi, and A. guatemalensis, and S. spinosa against Trypanosoma cruzi or Leishmania spp.

Animals↗

Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction.

Here we describe a liquid chromatography/mass spectrometry (LC/MS) method with automated online extraction (LC/LC/MS) to simultaneously determine the in vitro inhibitory potency of herbal extracts on six major human drug-metabolising cytochrome P450 enzymes. Substrates were incubated with a commercially available mixture of CYP1A2/2C8/2C9/2C19/2D6 and 3A4 from baculovirus-infected insect cells and the resulting metabolites were quantified with LC/LC/MS using electrospray ionisation in the selected ion monitoring mode. Consistent inhibitory activities were obtained for known inhibitors and plant extracts using the enzyme/substrate cocktail and the individual enzymes/substrates. Popular herbal remedies including devil's claw root (Harpagophytum procumbens), feverfew herb (Tanacetum parthenium), fo-ti root (Polygonum multiflorum), kava-kava root (Piper methysticum), peppermint oil (Mentha piperita), eucalyptus oil (Eucalyptus globulus), red clover blossom (Trifolium pratense) and grapefruit juice (GJ; Citrus paradisi) could be identified as inhibitors of the applied CYP enzymes with IC(50) values between 20 and 1000 microg/mL.

Chemical Fractionation↗

Widespread tannin intake via stimulants and masticatories, especially guarana, kola nut, betel vine, and accessories.

Tannins are increasingly recognized as dietary carcinogens and as antinutrients interfering with the system's full use of protein. Nevertheless, certain tannin-rich beverages, masticatories, and folk remedies, long utilized in African, Asiatic, Pacific, and Latin American countries, are now appearing in North American sundry shops and grocery stores. These include guarana (Paullinia cupana HBK.) from Brazil, kola nut (Cola nitida Schott & Endl. and C. acuminata Schott & Endl.) from West Africa, and betel nut (Areca catechu L.) from Malaya. The betel nut, or arecanut, has long been associated with oral and esophageal cancer because of its tannin content and the tannin contributed by the highly astringent cutch from Acacia catechu L. and Uncaria gambir Roxb. and the aromatic, astringent 'pan' (leaves of Piper betel L.) chewed with it. In addition to the constant recreational/social ingestion of these plant materials, they are much consumed as aphrodisiacs and medications. Guarana and kola nut enjoy great popularity in their native lands because they are also rich in caffeine, which serves as a stimulant. Research and popular education on the deleterious effects of excessive tannin intake could do much to reduce the heavy burden of early mortality and health care, especially in developing countries.

Animals↗

Effects of methysticin on three different models of seizure like events studied in rat hippocampal and entorhinal cortex slices.

Methysticin is one of the constituents of Piper methysticum which possesses anticonvulsant and neuroprotective properties. Its effects on different in vitro seizure models were tested using extracellular recordings in rat temporal cortex slices containing the hippocampus and the entorhinal cortex. Elevating [K+]0 induced seizure-like events with tonic and clonic electrographic phases in area CA1. Lowering [Ca2+]0 caused recurrent seizure like episodes with large negative field potential shifts. Lowering Mg2+ induced short recurrent discharges in area CA3 and CA1 while ictaform events lasting for many seconds were induced in the subiculum, entorhinal and temporal neocortex. In the hippocampus the activity stayed stable over a number of hours. In contrast, the ictaform events in the subiculum, entorhinal and temporal cortex changed their characteristics after one to two hours to late recurrent discharges. In a concentration-range from 10 to 100 microM methysticin reversibly blocked all these types of epileptiform activity. Decreases in [Ca2+]0 and associated slow field potentials evoked by repetitive stimulation of the stratum radiatum or the alveus remained almost unaffected by methysticin. A paired pulse stimulus paradigm used to test for effects of methysticin on synaptically evoked transient field potentials in normal medium revealed interference with mechanisms involved in frequency potentiation. While responses to alvear stimulation were largely unaffected, the responses to a paired pulse stimulus to stratum radiatum were depressed over the whole range of tested stimulus intervals. The findings suggest that methysticin has effects on different patterns of epileptiform activity possibly by interfering with processes responsible for frequency potentiation.

Animals↗

High incidence of Aspergillus flavus and aflatoxins in stored groundnut in Ghana and the use of a microbial assay to assess the inhibitory effects of plant extracts on aflatoxin synthesis.

Groundnut samples from 21 selected markets in the 10 regions of Ghana yielded high levels of the aflatoxigenic fungus Aspergillus flavus on half-strength potato dextrose agar. The fungus was associated with 31.7 and 12.8%, respectively, of all damaged and undamaged kernels assayed. Only 0.24% of total kernels assayed yielded A. parasiticus. Other fungi detected from total kernels assayed were A. niger (34%), A. candidus (1.45%), A. tamarii (3.93%), A. ochraceous (5.26%), Fusarium spp. (1.7%) Penicillium spp. (5.19%), a Mucor sp. (2.3%), a Trichoderma sp. (0.2%), Rhizopus stolonifer (12%) and certain unidentifiable fungi (11.72%). Total aflatoxin levels ranging from 5.7 to 22, 168 ppb were identified with damaged kernel samples. The mycotoxin was not detected in 50% of undamaged kernel samples tested and very low levels mostly ranging from 0.1 to 12.2 ppb were associated with the undamaged samples that tested positive for aflatoxins. In a novel in vitro microbial assay to determine the effectiveness of certain plant extracts against aflatoxin synthesis, extracts from Xylopia aethiopica, Monodera myristica, Cinnamomum verum and Piper nigrum permitted fungal growth in 1.5% potato-dextrose broth while completely suppressing NOR formation. These extracts, however, could not suppress NOR formation in a yeast extract sucrose medium.

Aflatoxins↗

Common Indian spices: nutrient composition, consumption and contribution to dietary value.

Nutrient composition of eight commonly consumed spices of South India was analysed. Spices analysed were red chillies (Capsicum annum), black pepper (Piper nigrum), coriander seeds (Coriandrum sativum), cumin seeds (Cuminum cyminum), garlic (Allium sativum), asafoetida (Ferula foetida), dry ginger (Zingiber officinale) and ajowan (Carum copticum). The nutrients analysed were proximate principles, minerals, starch, sugars, dietary fibre components, tannins, phytic acid, enzyme inhibitors and amino acids. Dry ginger, ajowan and asafoetida had high calcium (1.0-1.5%) and iron (54-62 mg/100 g) levels. The tannin content of spices was also high (0.9-1.3% DM). Dietary fibre ranged from 14-53%. Spices had appreciable amounts of essential amino acids like lysine and threonine. A survey revealed the average per capita consumption of spices to be 9.54 g and at that level, the nutrient contribution from spices ranged from 1.2 to 7.9% of an average adult Indian male's requirement for different nutrients.

Amino Acids↗

Influence of spices on protein utilisation of winged bean (Psophocarpus tetragonolobus) and horsegram (Dolichos biflorus).

The influence of a mixture of eleven spices commonly consumed in India on the utilisation of protein from boiled winged bean (Psophocarpus tetragonolobus) and horsegram (Dolichos biflorus) was studied at 10 and 20 percent level of protein intake in experimental rats. Spices used in the mixture include red chillies (Capsicum annum), black pepper (Piper nigrum), coriander (Coriandrum sativum), cumin (Cuminum cyminum), garlic (Allium sativum), ajowan (Carum copticum), turmeric (Curcuma longa), caraway seeds (Carum carui) and fennel seeds (Foeniculum vulgare). Addition of this spice mixture at 1.5% level of the diet decreased the TD of both legumes, significantly only in the case of horsegram. A significant increase was observed in the BV of both the legumes at both levels of protein tested.

Analysis of Variance↗

Influence of spices on utilization of sorghum and chickpea protein.

Influence of eight common Indian spices on the protein quality of sorghum and chickpea was studied. Spices used include red chillies (Capsicum annum), black pepper (piper nigrum), coriander seeds (Coriandrum sativum) cumin seeds (Cuminum cyminum), garlic (Allium sativum), asafoetida (Ferula foetida), dry ginger (Zingiber officinale) and ajowan (Carum copticum). Addition of spices did not affect protein digestibility (TD) of sorghum. The BV of all sorghum diets with spices was higher than that of control diet. However, it was significant only in case of diets combined with red chilli + coriander (1:1) mix, black pepper + cumin (1:1) mix, coriander and cumin. Addition of spices did not have any effect on TD or BV of chickpea diets.

Animals↗

Effects of Betel chewing on the central and autonomic nervous systems.

Betel chewing has been claimed to produce a sense of well-being, euphoria, heightened alertness, sweating, salivation, a hot sensation in the body and increased capacity to work. Betel chewing also leads to habituation, addiction and withdrawal. However, the mechanisms underlying these effects remain poorly understood. Arecoline, the major alkaloid of Areca nut, has been extensively studied, and several effects of betel chewing are thought to be related to the actions of this parasympathomimetic constituent. However, betel chewing may produce complex reactions and interactions. In the presence of lime, arecoline and guvacoline in Areca nut are hydrolyzed into arecaidine and guvacine, respectively, which are strong inhibitors of GABA uptake. Piper betle flower or leaf contains aromatic phenolic compounds which have been found to stimulate the release of catecholamines in vitro. Thus, betel chewing may affect parasympathetic, GABAnergic and sympathetic functions. Betel chewing produces an increase in heart rate, blood pressure, sweating and body temperature. In addition, EEG shows widespread cortical desynchronization indicating a state of arousal. In autonomic function tests, both the sympathetic skin response and RR interval variation are affected. Betel chewing also increases plasma concentrations of norepinephrine and epinephrine. These results suggest that betel chewing mainly affects the central and autonomic nervous systems. Future studies should investigate both the acute and chronic effects of betel chewing. Such studies may further elucidate the psychoactive mechanisms responsible for the undiminished popularity of betel chewing since antiquity.

Animals↗

The effect of area on the critical flicker threshold.

The relation between the luminance required to discriminate flicker of constant rate (critical flicker threshold) and the size of theretinal area stimulated was determined under photopic conditions. At small stimulus fields (diameter less than 44 min of arc) the slope of the critical flicker threshold vs. area approximated to Riccò's law [log (I-A) = constant]; with larger fields (diameter up to 116 min of arc) the slope approximated to Piper's law [log (I-square root A) - constant].

Adult↗

Current status of fertility control methods in India.

Approximately 48.2% of couples of 15 to 49 years of age practice family planning methods in India. Female sterilization accounts for 34.2%, with male sterilization declining from 3.4% in 1992-93 to 1.9% in 1998-99. Use of the condom increased to 3.1% from 2.4%. There is an urgent need for research to develop new contraceptive modalities especially for men and also for women and to make existing methods more safe, affordable and acceptable. Current efforts in India to develop a male contraceptive are mainly directed towards (i) development of antispermatogenic agents to suppress sperm production, (ii) prevention of sperm maturation, (iii) prevention of sperm transport through vas deferens or rendering these sperm infertile and (iv) prevention of sperm deposition. Research work in the field of prevention of sperm transport through vas deferens has made significant advances. Styrene maleic anhydride (SMA) disturbed the electrical charge of spermatozoa leading to acrosome rupture and consequent loss in fertilizing ability of sperm. A multicentre phase-III clinical trial using SMA is continuing and it is hoped that the SMA approach would be available in the near future as an indigenously developed injectable intra-vasal male contraceptive. The safety and efficacy of available oral contraceptives were evaluated. An indigenously developed oral contraceptive 'Centchorman', which is a nonsteroidal, weakly estrogenic but potently antiestrogenic, was found to be safe and effective and is now being marketed in India since 1991 as a 'once a week' pill. Cyclofem and Mesigyna have been recommended as injectable contraceptives with proper counselling and service delivery by Indian studies. It has been recommended that these injectable contraceptives be added to the existing range of contraceptive methods available in the National Family Planning Programme. Based on the Indian studies CuT 200 was also recommended. Studies have indicated the advantage of intrauterine devices (IUD); they are long acting, relatively easily removed and fertility returns rapidly after their removal. Recent studies have recommended CuT 200 for use up to 5 years. The combination of some plant products i.e. Embelia ribes, Borax and Piper longum has been found to be safe and effective as a female contraceptive and the results of phase-I clinical trials are encouraging. Research work is going on in the country in various areas with special reference to hormonal contraceptive - a three monthly injectable contraceptive, immuno-contraceptives, antiprogestins, etc.

Animals↗