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Regulation of cell proliferation, gene expression, production of cytokines, and cell cycle progression in primary human T lymphocytes by piperlactam S isolated from Piper kadsura.

Effects of piperlactam S (C(17)H(13)NO(4); mol. wt. 295) isolated from Piper kadsura on phytohemagglutinin (PHA) stimulated cell proliferation were studied in primary culture of human T cells. The results showed that piperlactam S suppressed T cell proliferation at about 0 to 12 h after stimulation with PHA. Synthesis of total cellular proteins and RNA in activated cell cultures was also suppressed. The inhibitory action of piperlactam S was not through direct cytotoxicity. Cell cycle analysis indicated that piperlactam S arrested the cell cycle progression of activated T cells from the G(1) transition to the S phase. In an attempt to further localize the point in the cell cycle at which arrest occurred, a set of key regulatory events leading to the G(1)/S boundary, including gene expression of cytokines and c-Fos protein synthesis, was examined. Piperlactam S suppressed, in activated T lymphocytes, the production and mRNA expression of cytokines such as interleukin-2 (IL-2), IL-4, and interferon-gamma in a dose-dependent manner. In addition, Western blot analysis indicated that c-Fos protein expressed in activated T lymphocytes was decreased by piperlactam S. Results of kinetic study indicated that inhibitory effects of piperlactam S on IL-2 mRNA expressed in T cells might be related to blocking c-Fos protein synthesis. Thus, the suppressant effects of piperlactam S on proliferation of T cells activated by PHA seemed to be mediated, at least in part, through inhibition of early transcripts of T cells, especially those of important cytokines, IL-2, IL-4, and arresting cell cycle progression in the cells.

Adult↗

Selective effect of 2',6'-dihydroxy-4'-methoxychalcone isolated from Piper aduncum on Leishmania amazonensis.

2',6'-Dihydroxy-4'-methoxychalcone (DMC) was purified from the dichloromethane extract of Piper aduncum inflorescences. DMC showed significant activity in vitro against promastigotes and intracellular amastigotes of Leishmania amazonensis, with 50% effective doses of 0.5 and 24 micrograms/ml, respectively. Its inhibitory effect on amastigotes is apparently a direct effect on the parasites and is not due to activation of the nitrogen oxidative metabolism of macrophages, since the production of nitric oxide by both unstimulated and recombinant gamma interferon-stimulated macrophages was decreased rather than increased with DMC. The phagocytic activity of macrophages was functioning normally even with DMC concentrations as high as 80 micrograms/ml, as seen by electron microscopy and by the uptake of fluorescein isothiocyanate-labeled beads. Ultrastructural studies also showed that in the presence of DMC the mitochondria of promastigotes were enlarged and disorganized. Despite destruction of intracellular amastigotes, no disarrangement of macrophage organelles were observed, even at 80 micrograms of DMC/ml. These observations suggest that DMC is selectively toxic to the parasites. Its simple structure may well enable it to serve as a new lead compound for the synthesis of novel antileishmanial drugs.

Animals↗

Effects of oxazepam and an extract of kava roots (Piper methysticum) on event-related potentials in a word recognition task.

Twelve healthy volunteers were tested in a double-blind crossover study to assess the effects of oxazepam and an extract of kava roots (Piper methysticum) on behavior and event-related potentials (ERPs) in a recognition memory task. The subjects' task was to identify within a list of visually presented words those that were shown for the first time and those that were being repeated. The repeated words were associated with an increased positivity beginning approximately 250 ms poststimulus. Oxazepam led to a reduction of a negative component in the 250-500 ms range for both old and new words and to a reduction of the old/new difference in the ERP associated with a significantly worse recognition rate. Kava on the other hand showed a slightly increased recognition rate and a larger ERP difference between old and new words.

Adult↗

Carcinogenicity testing of black pepper (Piper nigrum) using the Egyptian toad (Bufo regularis) as a quick biological test animal.

Milled black pepper (Piper nigrum) force-fed to Egyptian toads as a suspension in amphibian saline or injected subcutaneously in the dorsal lymph sac as an ethanol extract, induced primary tumours in the liver and secondary tumours in other organs (kidney and spleen). When applied to the skin of experimental animals as an ethanol extract, black pepper induced primary tumours in the liver and secondary tumours in the ileum and stomach. Tumours of the liver were diagnosed as hepatocellular carcinomas and those of the other organs as metastases of the primary liver tumours. It is speculated that one or more constituents of black pepper may be responsible for tumour induction in the organs of the Egyptian toad Bufo regularis.

Administration, Cutaneous↗

Survivors of the Piper Alpha oil platform disaster: long-term follow-up study.

BACKGROUND: The long-term psychological effects of surviving a major disaster are poorly understood. We undertook a survey of survivors of the Piper Alpha oil platform disaster (1988). AIMS: To examine the role of factors relating to the trauma, the survivors and the survivors' circumstances. METHOD: Ten years after the disaster, 78% (46/59) of the survivors were located, of whom 72% (33/46) agreed to be interviewed. A further three individuals completed postal measures. RESULTS: The most stringent diagnostic criteria for post-traumatic stress disorder (PTSD) were met by 21% (7/33) of the survivors over 10 years after the disaster. Features such as physical injury, personal experience and survivor guilt were associated with significantly higher levels of post-traumatic symptoms. CONCLUSIONS: A narrow definition of factors affecting outcome will limit the potential for improving survivor well-being in the long-term after major disasters. Specific symptoms that are not included in the criteria for the diagnosis of PTSD, together with issues such as re-employment, need to be addressed.

Accidents, Occupational↗

Synthesis of gibbilimbols A-D, cytotoxic and antibacterial alkenylphenols isolated from Piper gibbilimbum.

Gibbilimbols A [(E)-4-(4-decenyl)phenol, 1], B [(E)-4-(3-decenyl)phenol, 2], C [(E)-4-(4-octenyl)phenol, 3] and D [(E)-4-(3-octenyl)phenol, 4] were synthesized by coupling the phenolic parts with the alkyne parts and then reducing the triple bond of the resulting alkynylphenols. These alkenylphenols (1-4) are the cytotoxic and antibacterial constituents of the leaves of a medicinal plant (Piper gibbilimbum) that is used as a traditional medicine in Papua New Guinea.

Anti-Infective Agents↗

Effect of leaf essential oil from Piper solmsianum C.DC. in mice behaviour.

The essential oil from Piper solmsianum leaves and its major compound (sarisan) were tested to verify their influences upon mice behaviour. The essential oil was obtained by hydrodistillation in a modified Clevenger extractor and analysed by GC/ MS. This analysis revealed in the oil the presence of monoterpenes, sesquiterpenes and of arylpropanoids. The compound sarisan, a myristicin analogue, was isolated from the oil to perform the pharmacological tests. Emulsions of the oil and of sarisan (5.0 and 10.0% v/v) were used in the tests. Pentobarbital (30 mg/ kg s.c.) or diazepam (2.5 mg/ kg s.c.) were tested as standard drugs to verify depressant or anxiolytic effects, respectively. Both essential oil and sarisan showed to have exciting and depressant effects in the tested animals.

Akathisia, Drug-Induced↗

Antibacterial activity of extracts and neolignans from Piper regnellii (Miq.) C. DC. var. pallescens (C. DC.) Yunck.

The evaluation of the activity of the aqueous and ethyl acetate extracts of the leaves of Piper regnellii was tested against gram-positive and gram-negative bacteria. The aqueous extract displayed a weak activity against Staphylococcus aureus and Bacillus subtilis with minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of 1000 micrograms/ml. The ethyl acetate extract presented a good activity against S. aureus and B. subtilis with MIC and MBC at 15.62 micrograms/ml. In contrast to the relative low MICs for gram-positive bacteria, gram-negative bacteria were not inhibited by the extracts at concentrations < or = 1000 mg/ml. The ethyl acetate extract was fractionated on silica gel into nine fractions. The hexane and chloroform fractions were active against S. aureus (MIC at 3.9 micrograms/ml) and B. subtilis (MIC at 3.9 and 7.8 micrograms/ml, respectively). Using bioactivity-directed fractionation, the hexane fraction was rechromatographed to yield the antimicrobial compounds 1, 2, 5, and 6 identified as eupomatenoid-6, eupomatenoid-5, eupomatenoid-3, and conocarpan, respectively. The pure compounds 1 and 2 showed a good activity against S. aureus with MIC of 1.56 micrograms/ml and 3.12 micrograms/ml, respectively. Both compounds presented MIC of 3.12 micrograms/ml against B. subtilis. The pure compound 6 named as conocarpan was quite active against S. aureus and B. subtilis with MIC of 6.25 micrograms/ml. The antibacterial properties of P. regnellii justify its use in traditional medicine for the treatment of wounds, contaminated through bacteria infections.

Anti-Bacterial Agents↗

Efficacy of botanical insecticides from Piper species (Piperaceae) extracts for control of Ruropean chafer (Coleoptera: Scarabaeidae).

Biopesticides, including botanicals, can offer a safe and effective alternative to conventional insecticides for controlling major insect pests within an integrated pest management program. The current study highlights the practical application of a botanical insecticide for controlling a major insect pest of turfgrass: European chafer, Rhizotrogus majalis (Razoumowsky). Greenhouse and field trials were conducted to test the efficacy of a botanical formulation based on black pepper, Piper nigrum L. (Piperaceae), seed extracts to R. majalis larvae. The 7-d P. nigrum extract LC50 for R. majalis third instars was 2.5%. Successful treatment in the field was accomplished with the application of a 2% P. nigrum formulation to turfgrass infested with R. majalis second and third instars, whereas 4% extract was required in a second field trial with older third instars. The 2% pepper extract activity was comparable with the conventional insecticide diazinon in the first field trial. However, the 4% pepper extracts significantly affected the earthworm populations in treated plots compared with diazinon in the second field trail. The analysis of soil residues for piperamides in the P. nigrum extract determined a half-life of 1 - 2.6 d in the first and second field trials, respectively. This confirmed the expectation that under field conditions the residual activity would be less than conventional insecticides, thereby reducing the environmental risk associated with pesticide use. We recommend the pepper formulation for spot treatment applications when population densities reveal an epicenter of infestation rather than broadcasting over large areas, thus helping to minimize cost and negative affects on nontarget invertebrates.

Animals↗

The antimicrobial efficiency of Piper betle Linn leaf (stalk) against human pathogenic bacteria and phytopathogenic fungi.

The in vitro antimicrobial activity of different varieties of Piper betle Linn, leaf stalk extracts were studied against human pathogenic bacteria and phytopathogenic fungi by comparing the results with standard microbial susceptibility testing biodiscs. The ethyl acetate and ethanol extracts of all the four varieties have shown significant activity against bacteria Vibrio cholerae ogawa, Staphylococcus aureus, Diplococcus pneumoniae and Klebsiella aerogenes. The hexane and benzene extracts have shown moderate activity, while other extracts have shown poor or no activity. In the same way ethyl acetate and ethanol extracts of all the varieties have shown moderate to significant activity against most of the fungi tested, while other extracts showed poor or moderate activity.

Anti-Bacterial Agents↗

Mosquito larvicidal activity of pipernonaline, a piperidine alkaloid derived from long pepper, Piper longum.

A methanol extract of Piper longum fruit was found to be active against mosquito larvae of Culex pipiens pallens at 10 microg/ml after 24 h. A piperidine alkaloid, pipernonaline, was found to be responsible for this activity, with the 24-h median lethal dose (LD50) value for this compound being 0.21 mg/liter. The LD50 value of pipernonaline was not much higher than those for the 3 organophosphorous insecticides malathion, chlorpyrifos-methyl, and pirimiphos-methyl, used for comparative purpose in this study. Structural elucidation of pipernonaline was by means of mass spectrometry (1H and 13C nuclear magnetic resonance imaging).

Alkaloids↗

Determination of 1,3-benzodioxanes in Piper mullesua by high-performance thin-layer chromatography.

A new, simple, precise, and rapid high-performance thin-layer chromatographic method was developed for the determination of 6 benzodioxanes in Piper mullesua extract: 1',3'-benzodioxole-5'-(2,4,8-triene-isobutyl nonanoate), 1',3'-benzodioxole-5'-(2,4,12-triene-isobutyl tridecanoate), fargesin, sesamin, asarinin, 1',3'-benzodioxole-5'-(2,4,8-triene-methyl nonanoate). The ingredients were separated on a precoated Silica Gel 60 F254 plate with a solvent system of toluene-acetone (92 + 8). The 6 benzodioxanes were well separated and easily identified in this chromatographic system. The separated benzodioxanes were visualized by color development with a spray reagent consisting of 1 g vanillin dissolved in 100 mL H2SO4-ethanol (5 + 95, v/v). Quantitation was performed by scanning the spots and comparing the integrated areas of compounds in samples with those of standards. Recoveries from samples spiked with known amounts of the benzodioxanes were excellent. The results were comparable with those estimated by liquid chromatography.

Chromatography, Liquid↗

GC/MS investigations of the minor constituents of Piper guineense stem.

Chemical investigations by GC/MS-analysis of stem extracts of Piper guineense resulted in the detection and identification of thirty-nine new constituents of the stem, apart from previously isolated constituents. These are isobutyl, pyrrolidyl and piperidyl amide alkaloids. Fifteen new natural products have been identified. Four of these natural products have been designated iyeremide A and B (these are pyrrolidine and piperidine analogues of pellitorine) and cycloguineense A and B, which are also piperidine analogues of cyclostachine A and B. There is a need to confirm the structures of some of these new constituents by synthesis. Apart from these amide alkaloids, many volatile oil components-monoterpenes, sesquiterpenes, terpenoids, lignans and sterols--were detected.

Alkaloids↗

Constituents of West African medicinal plants. XIV. Constituents of Piper guineense Schum, and Thonn.

Piper guineense Schum, and Thonn. (Piperaceae), a woodsy climber of Ghana and other parts of West Africa, has been used as a condiment and a native medicinal. Chromatography of an extract of the fruits afforded the amides piperine, N-isobutyloctadeca-trans-2-trans-4-dienamide, sylvatine, delta alpha beta-dihydropiperine, trichostachine and delta alpha beta-dihydropiperlonguminine, the last of which is a new naturally occurring amide. In a similar manner, chromatography of an acetone extract of the roots afforded piperine, trichostachine and delta alpha beta-dihydropiperine while an acetone extract of the leaves yielded dihydrocubebin, a new naturally occurring lignan.

1-Propanol↗

Determination of six kavalactones in dietary supplements and selected functional foods containing Piper methysticum by isocratic liquid chromatography with internal standard.

Kava (Piper methysticum) dietary products have been sold worldwide for treatment of nervous anxiety, tension, and restlessness. Recent reports showed potential association of kava usage and liver injuries. This study was conducted to develop simple and reliable methodologies for the extraction and determination of 6 major kavalactones: (+)-methysticin, (+)-dihydromethysticin, (+)-kavain, (+)-dihydrokavain, yangonin, and desmethoxyyangonin. Ultrasonic extraction techniques and isocratic reversed-phase liquid chromatography (LC) were optimized for different types of samples, including capsules containing kava root extract or root powder, raw root material, tea bags, and snack bar. A suitable internal standard, 5,7-dihydroxyflavone, was used for LC calibration. Kavalactones were completely separated in 30 min using a Luna C18-2 column at 60 degrees C with an isocratic mobile phase consisting of 2-propanol-acetonitrile-water-acetic acid (16 + 16 + 68 + 0.1, v/v/v/v). Within-laboratory, intraday, and interday method variation (% relative standard deviation) for most samples extracted by methanol or methanol-water mixture were <5%. Lower levels of kavalactone contents and higher variations were observed for tea bags from water extraction or infusion as compared to methanol extraction. Labeling information of tea bags based on methanol extraction could be misleading to consumers. Analytical recoveries of snack bar fortified at 10 and 20 microg/g were >84% with RSD values <8%. Methods developed in this study offer a simple and reproducible means for analysis of kavalactones in various matrixes of dietary products.

Calibration↗

[Neolignans from Piper polysyphorum C.DC].

Piper polysyphorum C.DC (Piperaceae) is indigenous to the southern part of China. In the course of screening for inhibitors of platelet activating factor (PAF), the nonpolar fraction was found to exhibit PAF inhibitory activity. One new neclignan named polysyphorin and three new enantiomeric forms of (+)-virolongin, (+)-grandisin and (+)-lancifolin D were isolated. Two known neolignans, wallichinine and hancinone D were also obtained from the same sources. The structure determination was based upon spectroscopic analysis (UV, IR, CD, MS, 1HNMR, 13CNMR, COSY) and derivative preparation. The structure for polysyphorin was established as threo-delta 7'-7-hydroxy-3,4,5,3',5'-pentamethoxy-8-O-4' -neolignan. It is a racemic enantiomer. The PAF inhibitory activities were reported.

Drugs, Chinese Herbal↗

[Psychopharmacologic profile of an aqueous extract of Piper umbellatum].

Piper umbellatum is a plant currently utilized in traditional medicine as a sedative. Administered to rats by intraperitoneal injection, an aqueous extract of this plant brings about an ataxia with a decrease in the animal's watchfulness which lasts about 48 hours. Are also concomitant to this decrease in watchfulness, a fall of the rectal temperature, a decrease of spontaneous motor activity as well as an increase of analgesic activity.

Analgesics↗