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Screening for antimicrobial activity of ten medicinal plants used in Colombian folkloric medicine: a possible alternative in the treatment of non-nosocomial infections.

BACKGROUND: The antimicrobial activity and Minimal Inhibitory Concentration (MIC) of the extracts of Bidens pilosa L., Bixa orellana L., Cecropia peltata L., Cinchona officinalis L., Gliricidia sepium H.B. & K, Jacaranda mimosifolia D.Don, Justicia secunda Vahl., Piper pulchrum C.DC, P. paniculata L. and Spilanthes americana Hieron were evaluated against five bacteria (Staphylococcus aureus, Streptococcus beta hemolític, Bacillus cereus, Pseudomonas aeruginosa, and Escherichia coli), and one yeast (Candida albicans). These plants are used in Colombian folk medicine to treat infections of microbial origin. METHODS: Plants were collected by farmers and traditional healers. The ethanol, hexane and water extracts were obtained by standard methods. The antimicrobial activity was found by using a modified agar well diffusion method. All microorganisms were obtained from the American Type Culture Collection (ATCC). MIC was determined in the plant extracts that showed some efficacy against the tested microorganisms. Gentamycin sulfate (1.0 microg/ml), clindamycin (0.3 microg/ml) and nystatin (1.0 microg/ml) were used as positive controls. RESULTS: The water extracts of Bidens pilosa L., Jacaranda mimosifolia D.Don, and Piper pulchrum C.DC showed a higher activity against Bacillus cereus and Escherichia coli than gentamycin sulfate. Similarly, the ethanol extracts of all species were active against Staphylococcus aureus except for Justicia secunda. Furthermore, Bixa orellana L, Justicia secunda Vahl. and Piper pulchrum C.DC presented the lowest MICs against Escherichia coli (0.8, 0.6 and 0.6 microg/ml, respectively) compared to gentamycin sulfate (0.9 8 g/ml). Likewise, Justicia secunda and Piper pulchrum C.DC showed an analogous MIC against Candida albicans (0.5 and 0.6 microg/ml, respectively) compared to nystatin (0.6 microg/ml). Bixa orellana L, exhibited a better MIC against Bacillus cereus (0.2 microg/ml) than gentamycin sulfate (0.5 microg/ml). CONCLUSION: This in vitro study corroborated the antimicrobial activity of the selected plants used in folkloric medicine. All these plants were effective against three or more of the pathogenic microorganisms. However, they were ineffective against Streptococcus beta hemolytic and Pseudomonas aeruginosa. Their medicinal use in infections associated with these two species is not recommended. This study also showed that Bixa orellana L, Justicia secunda Vahl. and Piper pulchrum C.DC could be potential sources of new antimicrobial agents.

Acanthaceae↗

Prospective study of fatigue in localized prostate cancer patients undergoing radiotherapy.

The objectives were to (1) prospectively evaluate fatigue utilizing validated instruments in patients with localized prostate cancer, and (2) examine the relationships between fatigue, depression, quality of life, and sleep disturbance. The instruments used included: Piper Fatigue Scale, Beck Depression Inventory, Epworth Sleepiness Scale, and Functional Assessment of Cancer Therapy for Prostate Scale. Data on cancer stage, prostate specific antigen levels, hematocrit, patient's body weight and radiation dosage were recorded. Patients were evaluated preradiotherapy, middle of radiotherapy, completion of radiotherapy, and at 4-5 weeks follow-up. Thirty-six veterans with localized prostate cancer were studied. Mean age was 66.9 years (range 55-79). Duration of treatment was 7-8 weeks. Univariate procedure and Wilcoxon Signed Rank-test were used to examine changes in pretreatment scores for each of the three subsequent study periods. To adjust for multiple comparisons Bonferroni test was used. Spearman Correlations were calculated among parameters. No significant changes were noted in mean scores of hematocrit and body weight during the study period. On the Piper Fatigue Scale, adjusted for multiple comparisons, the median scores were significantly higher at completion of radiotherapy as compared with preradiotherapy values. Three patients (8%) were experienced fatigue according to Piper Fatigue Scale before treatment as compared to nine patients (25%) at completion of radiotherapy. On Prostate Cancer Specific and Physical Well Being subscales of the Functional Assessment for Prostate Cancer Therapy, the scores were significantly lower at middle and completion of radiotherapy than at pretreatment. At preradiotherapy, middle of radiotherapy, completion of radiotherapy and follow-up evaluation, patients scoring higher on the Piper Fatigue Scale were more likely to report a poorer quality of Physical Well Being on Functional Assessment of Cancer Therapy for Prostates. No significant changes were noted in the Beck Depression Inventory and Epworth Sleepiness Scale scores during treatment. Eight patients scored 10 or more on the Beck Depression Inventory before starting radiotherapy, suggesting depressive symptomatology. Of these, only seven patients scored 10 or more at completion of treatment. The incidence of fatigue is lower in our study than in previously published data. A relationship exists between fatigue scores and physical well being subscale scores. Higher scores on the Piper Fatigue Scale at the completion of radiotherapy, as well as no changes on depression and sleepiness scales, suggest that fatigue may not be the result of depression or sleep disturbance. Based upon our previous work, we propose that the physical expression of fatigue may be secondary to a decline in neuromuscular efficiency and enhanced muscle fatigue.

Adenocarcinoma↗

Muscle sounds in Parkinson's disease.

BACKGROUND: A sound with a frequency of around 40 Hz can be heard, with a stethoscope, in the muscles of the hand and forearm during tonic contraction or movement. This sound is the acoustic correlate of the Piper rhythm seen in electromyographic records of muscle activity. The way in which motor activity is organised at the cortical level may determine the frequency of the sound heard. METHODS: The wrist extensor muscles in the forearm of seven patients with idiopathic Parkinson's disease, studied with and without antiparkinsonian treatment, and a control group of seven healthy men were auscultated during very strong extension of the wrist and during repeated slow flexion and extension of this joint. FINDINGS: In healthy people, the Piper-band sound made by muscle activity is 40-50 Hz. In all seven parkinsonian patients, when off medication, the normal Piper-band sound was replaced by a pulsatile muscle activity of 10 Hz during strong wrist extension, and in four patients during repeated flexion and extension of the wrist. After treatment with dopaminergic drugs, the Piper mode of muscle discharge was restored and motor performance was improved. INTERPRETATION: The Piper mode of muscle discharge is dependent on the normal functioning of pallidal projections to the motor areas of the cortex. In abnormal function a muscle discharge of 10 Hz dominates, which is suboptimal when fast or powerful contractions are necessary.

Adult↗

The relationship between ligand aggregation and G-quadruplex DNA selectivity in a series of 3,4,9,10-perylenetetracarboxylic acid diimides.

Human telomeres are comprised of d(TTAGGG) repeats that are capable of forming G-quadruplex DNA structures. Ligands that bind to and stabilize these G-quadruplex DNA structures are potential inhibitors of the cancer cell-associated enzyme telomerase. Other potential biological uses of G-quadruplex targeting ligands have been proposed. One particularly challenging aspect of the contemplated uses of G-quadruplex targeting ligands is their selectivity for G-quadruplex DNA versus double-stranded DNA structures. We have previously reported the observation that two structurally related 3,4,9,10-perylenetetracarboxylic acid diimide-based G-quadruplex DNA ligands, PIPER [N,N'-bis(2-(1-piperidino)ethyl)-3,4,9,10-perylenetetracarboxylic acid diimide] and Tel01 [N,N'-bis(3-(4-morpholino)propyl)-3,4,9,10-perylenetetracarboxylic acid diimide], have different levels of G-quadruplex DNA binding selectivity at pH 7 as determined by absorbance changes in the presence of different DNA structures [Kerwin, S. M., Chen, G., Kern, J. T., and Thomas, P. W. (2002) Bioorg. Med. Chem. Lett. 12, 447-450]. Here we report that the less G-quadruplex DNA selective ligand PIPER can unwind double-stranded, closed circular plasmid DNA, as determined by a topoisomerase I assay. A model for the interaction of Tel01 with the G-quadruplex DNA structure formed by d(TAGGGTTA) was determined from NMR experiments. This model is similar to the previously published model for PIPER bound to the same G-quadruplex DNA and failed to provide a structural basis for the observed increased selectivity of Tel01 interaction with G-quadruplex DNA. In contrast, investigation into the aggregation state of Tel01 and PIPER as well as other 3,4,9,10-perylenetetracarboxylic acid diimide analogues bearing basic side chains demonstrates that ligand aggregation is correlated with G-quadruplex DNA binding selectivity. For all six analogues examined, those ligands that were aggregated at pH 7 in 70 mM potassium phosphate, 100 mM KCl, 1 mM EDTA buffer also demonstrated G-quadruplex DNA binding selectivity under these buffer conditions. Ligands that were not aggregated under these conditions display much lower levels of G-quadruplex DNA selectivity. The aggregation state of these ligands is extremely sensitive to the buffer pH. Tel01, which is aggregated at pH 7, is not aggregated at pH 6.4, where it demonstrates only modest G-quadruplex DNA binding selectivity, and PIPER in pH 8.5 buffer is both aggregated and highly G-quadruplex DNA-selective. To our knowledge, these studies demonstrate the first DNA structure selectivity as achieved through pH-mediated ligand aggregation. The potential impact of these findings on the selectivity of other classes of G-quadruplex DNA ligands is discussed.

Anthracenes↗

Toxicological deterioration of some plant extracts on Fannia canicularis (Diptera: Muscidae).

The early third instar larvae of Fannia canicularis were treated with various concentrations of Rumex dentatus, Protulaca deracea and Piper cubebae extracts. The Rumex dentatus was more toxic than Protulaca deracea and Piper cubebae. The extract mixture of Rumex dentatus and Piper cubebae induced a high synergistic action against the treated larvae, but the mixture of Protulaca deracea and Piper cubebae indicated an antagonistic effect. The reproductive potential of treated insects together with the biochemistry of their ovaries and testes were determined. The results indicated that the tested mixtures had delayed effects represented by the decreased the ovarian and testicular protein and the disturbance of their amino acid contents. This might be due in part to the interference of these mixtures with gonadal development, which affected negatively the fecundity and fertility of adults.

Animals↗

Frequent measurement of chronic pain: an electronic diary and empirical findings.

The PIPER (Prompting Intensity of Pain Electronic Recorder) is a compact data-logging device, easily worn by a subject. It emits audible beeps at pre-programmed times, prompting the subject to enter a pain rating by button press. Ratings are stored, for later down-loading. We report two studies suggesting that PIPER pain ratings have good reliability, and good validity assessed against the VAS. In a third study, the PIPER was found practical for use by elderly subjects, and for periods of more than 2 months. In addition, PIPER pain ratings taken 4 times per day were found to have different properties than 4 other measures of chronic pain, suggesting that very frequent measures should be taken if a full understanding of chronic pain is to be obtained.

Aged↗

Antioxidant activity of a salt-spice-herbal mixture against free radical induction.

A combination of spices (Piper nigrum, Piper longum and Zingiber officinale), herbs (Cyperus rotundus and Plumbago zeylanica) and salts make up Amrita Bindu. The study was focused to evaluate the antioxidant property of individual ingredients in Amrita Bindu against the free radical 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). The analysis revealed the antioxidant potential of the ingredients in the following order: Piper nigrum>Piper longum>Cyperus rotundus>Plumbago zeylanca>Zingiber officinale. Two different experiments were designed. In experiment I, rats were fed with normal diet whereas in experiment II rats were given feed mixed with Amrita Bindu for 3 weeks (4 g/kg of feed). Rats from both experimental groups were challenged against a single intraperitonial injection of phenylhydrazine (PHZ) (7.5 mg/kg body weight). At the end of 24 and 72 h, blood was analysed for free radicals and antioxidant levels. It was interesting to note that rats with Amrita Bindu pretreatment showed significantly lower levels of free radicals, lipid peroxidation and protein carbonyls along with significantly higher levels of antioxidants when compared with rats without Amrita Bindu pretreatment on PHZ administration. These results reveal that Amrita Bindu, a salt-spice-herbal mixture exerts a promising antioxidant potential against free radical induced oxidative damage.

Animals↗

Inhibition of unwinding of G-quadruplex structures by Sgs1 helicase in the presence of N,N'-bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide, a G-quadruplex-interactive ligand.

N,N'-Bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide (PIPER), a perylene derivative, is a very potent and selective G-quadruplex DNA-interactive agent. It has been shown to inhibit DNA polymerase and telomerase by stacking externally to the G-tetrads in the G-quadruplex structures. Recently, we have demonstrated that this small molecule greatly accelerates the assembly of G-quadruplex structures in a cell-free system. In this report, we present data demonstrating that PIPER prevents the unwinding of G-quadruplex structures by yeast Sgs1 helicase. Sgs1 belongs to the RecQ DNA helicase family whose members include other G-quadruplex DNA unwinding helicases, such as human Bloom's syndrome and human Werner's syndrome helicases. PIPER specifically prevents the unwinding of G-quadruplex DNA but not duplex DNA by Sgs1. Competition experiments indicate that this inhibitory activity is due to the interaction of PIPER with G-quadruplex structures rather than the helicase itself. These results combined with previous studies suggest a possible mechanism of action for these G-quadruplex-interactive agents inside cells: they might induce G-quadruplex formation in G-rich regions on genomic DNA, stabilize these structures, and prevent them from being cleared by enzymes such as helicases. The G-quadruplex structures may, in turn, disrupt some critical cellular events such as DNA replication, transcription regulation, and telomere maintenance.

Anthracenes↗

Accelerated assembly of G-quadruplex structures by a small molecule.

In the presence of alkali cations, notably potassium and sodium, DNA oligomers that possess two G-rich repeats associate into either a tetrameric parallel G-quadruplex or a variety of dimeric antiparallel G-quadruplexes. The formation of such structures is normally a very slow process. Some proteins, such as the beta-subunit of the Oxytricha telomere-binding protein, promote the formation of G-quadruplex structures in a chaperone-like manner. In this report, we present data concerning the role of a perylene derivative, PIPER, in the assembly of G-quadruplex structures as the first example of a small ligand behaving as a driver in the assembly of polynucleotide secondary structures. Gel-shift experiments demonstrate that PIPER can dramatically accelerate the association of a DNA oligomer containing two tandem repeats of the human telomeric sequence (TTAGGG) into di- and tetrameric G-quadruplexes. In so doing, PIPER alters the oligomer dimerization kinetics from second to first order. The presence of 10 microM PIPER accelerates the assembly of varied dimeric G-quadruplexes an estimated 100-fold from 2 microM oligomer. These results imply that some biological effects elicited by G-quadruplex-interactive agents, such as the induction of anaphase bridges, may stem from the propensity such compounds have for assembling G-quadruplexes.

Anthracenes↗

Early responses of resistant and susceptible potato roots during invasion by the potato cyst nematode Globodera rostochiensis.

Signals from roots of resistant (cv. Maris Piper) and susceptible (cv. Désirée) potato cultivars during invasion by second stage juveniles (J2s) of the potato cyst nematode, Globodera rostochiensis, were investigated. Novel experimental chambers enabled the recording of electrophysiological responses from roots during nematode invasion. The root cell membrane potentials were maintained throughout the 3 d required to assess invasion and feeding site development. The steady-state resting membrane potentials of Désirée were more negative than those of Maris Piper on day 1, but the reverse on day 3. After 5 d there was no difference between the two cultivars. Intracellular microelectrodes detected marked spike activity in roots after the application of J2s and there were distinct and reproducible differences between the two cultivars, with the response from Désirée being much greater than that from Maris Piper. The responses to mechanical stimulation of roots by blunt micropipettes and sharp electrodes were consistent and similar in both cultivars to the responses in Maris Piper obtained after nematode invasion, but could not account for the marked response found in Désirée. Exogenous application of exoenzymes, used to mimic nematode chemical secretions, resulted in a distinct depolarization pattern that, although similar in both cultivars, was different from patterns obtained during nematode invasion or mechanical stimulation. The pH of homogenates prepared from roots of both cultivars was measured and a Ca2+ channel blocker was used to assess the role of Ca2+ in nematode invasion. The results indicated a role for Ca2+ in the signalling events that occur during nematode invasion.

Animals↗

The comparative analgesic efficacy of transcutaneous electrical nerve stimulation and a non-steroidal anti-inflammatory drug for painful osteoarthritis.

Thirty-six non-hospitalized subjects with chronic pain from OA of the knee participated in an evaluation of transcutaneous electrical nerve stimulation (TENS) and naproxen, an NSAID. All pre-experiment treatment was withdrawn. Each subject experienced in some order three 3-week treatment phases: NSAID plus placebo TENS; TENS plus placebo drug; and double placebo. A broad range of pain measures was used, including daily diary ratings, and four-times-per-day ratings entered into a small electronic data logger (the PIPER) worn by the subject. A substantial placebo response occurred across all conditions, which may have masked treatment differences. Broad comparisons across subjects, combining the four main measures of pain, found no significant differences among the three experimental treatments. Analysis of diary and PIPER data for individuals suggested that, in a small minority of subjects, the NSAID plus placebo TENS combination may be more effective than double placebo. The PIPER ratings seemed to tap aspects of the pain experience different from those captured by conventional measures, suggesting the value of very frequent pain assessments, such as those entered by a subject into the PIPER, in the study of chronic pain.

Adult↗

[In vitro activity of beta-lactam antibiotics in combination with sulbactam against enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter. Results of a multicenter study].

The in vitro antimicrobial activity of ticarcillin (TICAR), mezlocillin (MEZLO), piperacillin (PIPER), cefoperazone (CPZ), cefotaxime (CTX) and ceftazidime (CAZ), alone and in combination with 8 micrograms/ml of sulbactam (SULB), was studied by agar dilution against TICAR resistant strains isolated in 8 hospitals over a period of 3 months in 1989 (747 enterobacteria, 110 Ps. aeruginosa and 48 Acinetobacter sp.). SULB did not modify the activity of beta-lactam antibiotics against Ps. aeruginosa. The 6 beta-lactam antibiotics SULB combinations were only active for 27% of Acinetobacter SULB sensitive. SULB restored the activity of: MEZLO, PIPER, CPZ in Enterobacteria producing a penicillinase; PIPER, CTX and CAZ in Enterobacteria producing a broad-spectrum beta-lactamase; MEZLO, PIPER, CTX and CAZ in M. morganii producing a derepressed cephalosporinase.

Acinetobacter↗

Comparison of vegetative anatomy of piperales. I. Juvenile xylem of twigs.

Medullary bundles of Piperaceae resemble those of Ranunculaceae. The nature of tracheary elements of primary xylem suggests that Houttuynia cordata (Saururaceae), Piper cubeba (Piperaceae) and Chloranthus officinalis (Chloranthaceae) are of lower evolutionary status than others. Among these three, P. cubeba shows stratification of secondary xylem, a specialized character. Lateral wall of metaxylem tracheary elements and distribution of bundles of Peperomia, suggest their primitive status and distinctness, supporting separation of "Peperomiacea:" (of NOVAK). Piper cubeba, Houttuynia and Chloranthus bear one important Ranunculaceous character: scalariform perforation in primary vessels. Primitive species of Peperomia carry probably another Ranunculaceous character, i.e., many circles of medullary bundles. Shape and pattern of vascular bundles of Piper cubeba, Houttuynia and Chloranthus are similar. Other species of Piper show modifications. Peperomia represents another distinct pattern.

Plants↗

Botanical insecticides for controlling agricultural pests: piperamides and the Colorado Potato Beetle Leptinotarsa decemlineata say (Coleoptera: Chrysomelidae).

The efficacy of extracts from two Piperaceae species, Piper nigrum L. and P. tuberculatum Jacq. were evaluated using larvae and adults of the Colorado Potato Beetle Leptinotarsa decemlineata (Say). Young larvae and neonates were the most susceptible; a 24-h LD(50) of 0.064% extract of P. tuberculatum was determined for 4-day-old larvae, while 0.05% extract of P. nigrum reduced larval survival up to 70% within one week after treatment of potato Solanum tuberosum L. (Solanaceae) plants. When an insecticide resistant strain of L. decemlineata larvae was tested with the P. tuberculatum extract, there was less than a 2-fold tolerance ratio compared to the 22-fold tolerance ratio to cypermethrin, a pyrethroid. Older larvae, pre-pupal stage and adults, were less sensitive to the P. nigrum extracts; the 24-h LD(50) was 0.5% (95% C.I. = 0.36, 0.65). However, the same concentration was equally effective under field conditions. In the greenhouse, P. nigrum at 0.5% was as effective at reducing adult L. decemlineata feeding as combinations with 2 separate botanical mixtures, garlic and lemon grass oil. Under field conditions, the residual activity of the P. nigrum extracts was less than 3 h. When adult L. decemlineata were placed on treated plants exposed to full sunlight for 0, 1.5, and 3 h, leaf damage progressively increased as the main active compound, piperine, was found to degrade by 80% after 3 h. An in vitro polysubstrate monoxygenase (PSMO) enzyme assay, using the substrate methoxyresorufin O-demethylation (MROD), determined that the principal P. nigrum active compound, piperine, is responsible for inhibition of that specific enzyme. The results suggest that Piper extracts could be used effectively as contact botanical insect control agents to protect potato plants from developing L. decemlineata larvae at concentrations less than 0.1%. There is also potential for Piper extracts to control insecticide resistant populations in conjunction with other integrated pest management (IPM) strategies used in conventional and organic agriculture.

Agriculture↗

Effect of some medicinal plants on plasma antioxidant system and lipid levels in rats.

Several inflammatory diseases are thought to be related to oxidative injury and free oxygen radicals have been proposed as important causative agents of heart disease and aging. To investigate the effects of daily intake of medicinal plants on antioxidant enzymes, lipid peroxidation and lipid profiles in rat, 28 rats were randomly divided into four groups and administered with three plant extracts (0.2 g/kg body weight): Piper cubeba (fruit), Physalis angulata (flower), Rosa hybrida (flower) and with saline as a control. After 3 weeks, superoxide dismutase (SOD), catalase, thiobarbituric acid reactive substance (TBARS), triglyceride (TG) and cholesterol levels in plasma were measured. The SOD activity of the Piper cubeba group and the catalase activity of the Piper cubeba and Rosa hybrida groups were significantly increased compared with the control group, while the SOD and catalase activities of the Physalis angulata group were not significantly changed (p<0.05). TBARS, a marker of lipid peroxidation, was significantly lower in all experimental groups compeered with the control group. No significant changes occurred in the TG, total- and LDL-cholesterol of all groups, but the HDL-cholesterol of the Physalis angulata group was significantly increased. This study showed that the intake of medicinal plants in rats results in an increase in antioxidant enzyme activity and HDL-cholesterol, and a decrease in malondialdehyde, which may reduce the risk of inflammatory and heart disease.

Animals↗

Worker piping in honey bee swarms and its role in preparing for liftoff.

Worker piping, previously reported only in hives, was observed in swarms as they prepared to liftoff to fly to a new home. Pipers are excited bees which scramble through the swarm cluster, pausing every second or so to emit a pipe. Each pipe consists of a sound pulse which lasts 0.82 +/- 0.43 s and rises in fundamental frequency from 100-200 Hz to 200-250 Hz. Many. if not all, of the pipers are nest-site scouts. The scouts pipe when it is time to stimulate the non-scouts to warm themselves to a flight-ready temperature (35 degrees C) in preparation for liftoff. The time-course of worker piping matches that of swarm warming, both start at a low level, about an hour before liftoff, and both build to a climax at liftoff. When we excluded pipers from bees hanging in the cool, outermost layer of a swarm cluster, we found that these bees did not warm up. The form of worker piping that we have studied in swarms differs from the form of worker piping that others have studied in hives. We call the two forms "wings-together piping" (in swarms) and "wings-apart piping" (in hives).

Animals↗

Screening in mice of some medicinal plants used for analgesic purposes in the state of São Paulo. Part II.

Seventeen medicinal plants used popularly in Brazil for their reputed analgesic properties were tested in mice by the writhing and tail flick methods. All extractions were made in 50% aqueous ethanol at low temperatures. The oral dose administered was always 1 g extract/kg. Significant effects in both tests were produced by Lippia alba, Piper abutiloides, Piper cincinnatoris, Piper lindbergii and Tillandsia usneoides.

Analgesics↗

Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants.

Thirty samples of Indonesian medicinal plants were tested for their mechanism-based inhibition on cytochrome P450 3A4 (CYP3A4) and CYP2D6 via erythromycin N-demethylation and dextromethorphan O-demethylation activities in human liver microsomes. From screening with 0 and 20min preincubation at 0.5mg/ml of methanol extracts, five plants (Cinnamomum burmani bark, Foeniculum vulgare seed, Strychnos ligustrina wood, Tinospora crispa stem, and Zingiber cassumunar rhizome) showed more than 30% increase of CYP3A4 inhibition, while three (Alpinia galanga rhizome, Melaleuca leucadendron leaf, and Piper nigrum fruit) showed more than 30% increase of CYP2D6 inhibition. In these eight plants, Foeniculum vulgare seed, Cinnamomum burmani bark, and Strychnos ligustrina wood showed time-dependent inhibition on CYP3A4 and Piper nigrum fruit and Melaleuca leucadendron leaf on CYP2D6. Among these, four plants other than Melaleuca leucadendron revealed NADPH-dependent inhibition. Thus, Foeniculum vulgare, Cinnamomum burmani, and Strychnos ligustrina should contain mechanism-based inhibitors on CYP3A4 and Piper nigrum contain that on CYP2D6.

Cytochrome P-450 CYP2D6 Inhibitors↗