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). (+info)
Valerian is a traditional herbal sleep remedy that has been studied with a variety of methodologic designs using multiple dosages and preparations. Research has focused on subjective evaluations of sleep patterns, particularly sleep latency, and study populations have primarily consisted of self-described poor sleepers. Valerian improves subjective experiences of sleep when taken nightly over one- to two-week periods, and it appears to be a safe sedative/hypnotic choice in patients with mild to moderate insomnia. The evidence for single-dose effect is contradictory. Valerian is also used in patients with mild anxiety, but the data supporting this indication are limited. Although the adverse effect profile and tolerability of this herb are excellent, long-term safety studies are lacking. (+info)
(3/38) Incorporation of isobutyrate and valerate into cellular plasmalogen by Bacteroides succinogenes.
Wegner, G. H. (University of Wisconsin, Madison) and E. M. Foster. Incorporation of isobutyrate and valerate into cellular plasmalogen by Bacteroides succinogenes. J. Bacteriol. 85:53-61. 1963.-Bacteroides succinogenes was found to require both a branched-chain volatile fatty acid (e.g., isobutyric) and a straight-chain acid (e.g., valeric) for growth. The organism used the acids as precursors for the synthesis of long-chain fatty acids and fatty aldehydes, which in turn were employed in the synthesis of phospholipid, mainly ethanolamine plasmalogen. Isobutyric acid was incorporated primarily into branched-chain C(14) and C(16) acids (tentatively identified as 12-methyl tridecanoic and 14-methyl pentadecanoic acids, respectively), and into fatty aldehydes. Valeric acid was used mainly for the synthesis of n-C(13) and n-C(15) fatty acids and fatty aldehydes. Apparently the two short-chain fatty acids were built up by the addition of two-carbon units to form the long-chain acids and aldehydes of the plasmalogen. (+info)
(4/38) Effect of supplemental tryptophan, vitamin E, and a herbal product on responses by pigs to vibration.
Economic losses related to increased stress during the transport of pigs are well documented. The effects of supplementing of tryptophan (Trp), vitamin E, or a herbal product via feed or drinking water were investigated in terms of effects on stress response in pigs during transport simulation. The study consisted of three analogous experiments. For the testing in each experiment, the pigs (23.5+/-3.2 kg) were allocated to one of two treatments, with and without supplementation of a product. The applied doses were Trp (5 g/L drinking water for 3 d), vitamin E (additional amount of 300 mg/kg feed for 21 d, as-fed basis), and Sedafit (2.5 g/L drinking water for 2 d). Sedafit is a commercial herbal product containing Valeriana officinalis L. and Passiflora incarnata L. as active components. In each experiment of the study, at least 47 pigs were involved, which were treated in groups of 3. The day before transport simulation, a Holter device was attached to the pigs to produce an electrocardiogram during the night (rest values), as well as during vibration in the transport simulator (1.2 Hz, 1 m/s2), where the behavior of the pigs (standing-sitting-lying) was also observed. Samples of saliva (taken before, during, and after [3x] vibration) and blood (taken before and after vibration) were analyzed for cortisol and intermediate metabolites (glucose, lactate, creatine kinase, and nonesterified fatty acids), respectively. Pigs supplemented with Trp tended to spend more time lying down during the second hour of vibration (P < 0.05). Vitamin E decreased the peak heart rate (P < 0.05), ventricular ectopic beats (P < 0.01), and ST elevation (P < 0.10). The supplementation of Sedafit resulted in smaller increases of the investigated heart variables (minimum heart rate, P < 0.05; ventricular ectopic beats, P < 0.05; ST elevation, P < 0.01) during and after stress evocation compared with the control group. None of the tested products influenced the intermediate metabolites; one possible explanation for this finding may be that peak values were reached before the time of bleeding. In conclusion, Trp had a positive behavioral effect in this experiment, and vitamin E and Sedafit mediated an increase in some heart variables, suggesting sedative and antianxiety effects. (+info)
(5/38) Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers.
Valerian (Valeriana officinalis) is a popular dietary supplement. The objective of this study was to assess the influence of a valerian extract on the activity of the drug-metabolizing enzymes cytochrome P450 2D6 (CYP2D6) and 3A4. Probe drugs dextromethorphan (30 mg; CYP2D6 activity) and alprazolam (2 mg; CYP3A4 activity) were administered orally to healthy volunteers (n = 12) at baseline and again after exposure to two 500-mg valerian tablets (1000 mg) nightly for 14 days. The valerian supplement contained a total valerenic acid content of 5.51 mg/tablet. Dextromethorphan to dextorphan metabolic ratios (DMRs) and alprazolam pharmacokinetics were determined at baseline and after valerian treatment. The DMR was 0.214 +/- 0.025 at baseline and 0.254 +/- 0.026 after valerian supplementation (p > 0.05). For alprazolam, the maximum concentration in plasma was significantly increased after treatment with valerian (25 +/- 7 ng/ml versus 31 +/- 8 ng/ml; p < 0.05). There were no significant differences in other pharmacokinetic parameters at baseline and after valerian exposure (all p values > or = 0.05; time to reach maximum concentration in plasma, 3.0 +/- 3.2 versus 3.1 +/- 2.1 h; area under the plasma concentration versus time curve, 471 +/- 183 versus 539 +/- 240 hx ng x ml(-1); half-life of elimination, 13.5 +/- 4.3 versus 12.2 +/- 5.6 h). Our results indicate that although a modest increase was observed in the alprazolam Cmax, typical doses of valerian are unlikely to produce clinically significant effects on the disposition of medications dependent on the CYP2D6 or CYP3A4 pathways of metabolism. (+info)
(6/38) In vitro activity of commercial valerian root extracts against human cytochrome P450 3A4.
PURPOSE: Valerian root ( Valeriana officinalis L.) has been used since antiquity as a medicinal herb. Recent studies have found that certain herbal products used concomitantly with conventional therapeutic products can markedly affect drug disposition. METHODS: The in vitro effect of aliquots from 14 commercially available single-entity and blended products containing valerian root on cytochrome P450 CYP3A4-mediated metabolism and P-glycoprotein transport has been determined with aqueous, ethanol and acetonitrile extracts. RESULTS: Hydroxyvalerenic acid, acetoxyvalerenic acid and valerenic acid content was analyzed and wide variation was found between samples and compared to the concentrations noted on the product labels. Valerian extracts from the products tested also exhibited a marked capacity to inhibit cytochrome P450 3A4-mediated metabolism and P-glycoprotein transport based upon the ATPase assay. CONCLUSIONS: There is wide variation between commercially available samples of valerian root. The findings from this study suggest that valerian root may have an initial inhibitory effect when taken with therapeutic products. Further work is warranted to determine whether valerian root can affect other CYP450 isozymes and how the results of this in vitro investigation can be extrapolated to in vivo situations. (+info)
(7/38) In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes.
OBJECTIVES: Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of goldenseal ( Hydrastis canadensis ), black cohosh ( Cimicifuga racemosa ), kava kava ( Piper methysticum ), or valerian ( Valeriana officinalis ) extracts affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4/5 activity. METHODS: Twelve healthy volunteers (6 women) were randomly assigned to receive goldenseal, black cohosh, kava kava, or valerian for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe drug cocktails of midazolam and caffeine, followed 24 hours later by chlorzoxazone and debrisoquin (INN, debrisoquine), were administered before (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4/5, CYP1A2, CYP2E1, and CYP2D6 by use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. The content of purported "active" phytochemicals was determined for each supplement. RESULTS: Comparisons of presupplementation and postsupplementation phenotypic ratio means revealed significant inhibition (approximately 40%) of CYP2D6 (difference, -0.228; 95% confidence interval [CI], -0.268 to -0.188) and CYP3A4/5 (difference, -1.501; 95% CI, -1.840 to -1.163) activity for goldenseal. Kava produced significant reductions (approximately 40%) in CYP2E1 only (difference, -0.192; 95% CI, -0.325 to -0.060). Black cohosh also exhibited statistically significant inhibition of CYP2D6 (difference, -0.046; 95% CI, -0.085 to -0.007), but the magnitude of the effect (approximately 7%) did not appear to be clinically relevant. No significant changes in phenotypic ratios were observed for valerian. CONCLUSIONS: Botanical supplements containing goldenseal strongly inhibited CYP2D6 and CYP3A4/5 activity in vivo, whereas kava inhibited CYP2E1 and black cohosh weakly inhibited CYP2D6. Accordingly, serious adverse interactions may result from the concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 and CYP3A4/5 substrates. Kava kava and black cohosh may interact with CYP2E1 and CYP2D6 substrates, respectively. Valerian appears to be less likely to produce CYP-mediated herb-drug interactions. (+info)
(8/38) Exposure to airborne microorganisms, dust and endotoxin during processing of valerian roots on farms.
The aim of this study was to determine the levels of microorganisms, dust and endotoxin in the air during various stages of valerian (Valeriana officinalis) roots processing by herb farmers and to examine the species composition of airborne microflora. Air samples were collected on glass fibre filters by use of personal samplers on 15 farms owned by valerian cultivating farmers, located in Lublin province (eastern Poland). The concentrations of total viable microorganisms (bacteria + fungi) in the air showed a marked variability and were within a range of 0.95-7,966.6 x 10(3) cfu/m (3). Though median was relatively low (10.75 x 10(3) cfu/m (3)), on 4 farms the concentrations exceeded the level of 10(5) cfu/m (3) and on 1 farm the level of 10(6) cfu/m (3). During the processing of valerian roots, distinct changes could be observed in the composition of airborne microflora. In the first stages of processing, the freshly dug and washed roots until shaking in the drying room, the most numerous were Gram-negative bacteria of the family Pseudomonadaceae (mostly Stenotrophomonas maltophilia, Pseudomonas chlororaphis and Pseudomonas fluorescens). After drying, the dominant organisms were thermo-resistant endospore-forming bacilli (Bacillus spp.) and fungi, among which prevailed Aspergillus fumigatus. Altogether, 29 species or genera of bacteria and 19 species or genera of fungi were identified in the farm air during valerian processing, of these, 10 and 12 species or genera respectively were reported as having allergenic and/or immunotoxic properties. The concentrations of airborne dust and endotoxin on the examined farms were very large and ranged from 10.0-776.7 mg/m (3), and from 0.15-24,448.2 microg/m (3), respectively (medians 198.3 mg/m (3) and 40.48 microg/m (3)). In conclusion, farmers cultivating valerian could be exposed during processing of valerian roots to large concentrations of airborne microorganisms, dust and endotoxin posing a risk of work-related respiratory disease. (+info)