Cytochrome P450 2D6 (CYP2D6), an important CYP isoform with regard to drug-drug interactions, accounts for the metabolism of ∼30% of all medications. To date, few studies have assessed the effects of botanical supplementation on human CYP2D6 activity in vivo. Six botanical extracts were evaluated in three separate studies (2 extracts per study), each incorporating 18 healthy volunteers (9 females). Subjects were randomized to receive a standardized botanical extract for 14 days on separate occasions. A 30-day washout period was interposed between each supplementation phase. In study 1, subjects received milk thistle (Silybum marianum) and black cohosh (Cimicifuga racemosa). In study 2, kava kava (Piper methysticum), and goldenseal (Hydrastis canadensis) extracts were administered, and in study 3 subjects received St. John's wort (Hypericum perforatum) and Echinacea (Echinacea purpurea). The CYP2D6 substrate, debrisoquine (5 mg), was administered before and at the end of supplementation. Pre-and post-supplementation phenotypic trait measurements were determined for CYP2D6 using 8-hour debrisoquine urinary recovery ratios (DURR). Comparisons of pre-and post-supplementation DURR revealed significant inhibition (∼50%) of CYP2D6 activity for goldenseal, but not for the other extracts. Accordingly, adverse herb-drug interactions may result with concomitant ingestion of goldenseal supplements and drugs that are CYP2D6 substrates.

Phytochemical-mediated modulation of cytochrome P450 enzymes (CYPs) may underlie many herbdrug interactions. This study's purpose was to assess the effects of milk thistle and black cohosh supplementation on CYP3A activity and compare them to a clinically recognized inducer, rifampin, and inhibitor, clarithromycin. Healthy volunteers were randomly assigned to receive a standardized milk thistle (900 mg) or black cohosh (80 mg) supplement for 14 days. Subjects also received rifampin (600 mg) and clarithromycin (1000 mg) for 7 days as positive controls for CYP3A induction and inhibition, respectively. Midazolam was administered orally before and after each supplementation and control period. The effects of milk thistle, black cohosh, rifampin, and clarithromycin on midazolam pharmacokinetics were determined using noncompartmental techniques. Unlike those observed for rifampin and clarithromycin, midazolam pharmacokinetics were unaffected by milk thistle or black cohosh. Milk thistle and black cohosh appear to have no clinically relevant effect on CYP3A activity in vivo. KeywordsCytochrome P450s; botanical supplements; pharmacokinetics; drug interactions Concomitant self-administration of botanical supplements with conventional medications is a growing trend in the United States. Approximately 20% of adults take prescription medications concurrently with botanical dietary supplements. 1,2 This upsurge in botanical supplement usage has sparked an increased concern regarding herb-drug interactions. 3,4 Supplementderived phytochemicals appear to modulate various cytochrome P450 enzymes (i.e., CYP3A4) and drug transporters (i.e., P-glycoprotein [P-gp,) in vitro, and such activities may underlie many herb-drug interactions. Of the hundreds of botanical supplements sold in the United States, St. John's wort (Hypericum perforatum) is the most noteworthy for producing clinically

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Herbal medicine is used worldwide either as a sole treatment method or as part of a comprehensive treatment plan alongside orthodox methods of diagnosis and treatment. A survey reported that, in the USA, nearly one-sixth of women took at least one herbal product in 2000. Despite their widespread use, numerous reports show that the herbal products available to consumers are of variable quality. This disparity in quality of herbal preparations can be attributed to the fact that their production is complicated. To produce high-quality herbal products, attention must be paid to, among others, phytochemical variations due to plant breed, organ specificity, stages of growth, cultivation parameters, contamination by microbial and chemical agents, substitution, adulteration with synthetic drugs, heavy metal contamination, storage and extraction. This review focuses on organ specificity, seasonal variations, the effect of drying and storage, and the extraction of phytochemical constituents. Special emphasis is placed on the four most frequently used herbal products in the USA: echinacea, Ginkgo biloba, ginseng and St John's Wort.

Hemicellulose in lignocellulosic biomass can be depolymerized into fermentable sugars using dilute acid pretreatment. However, this pretreatment results in the production of degradation compounds that inhibit subsequent hydrolysis and fermentations steps. Understanding the effect of pretreatment processing parameters on hemicellulose depolymerization could possibly result in minimization of degradation compounds. We report on depolymerization studies of in-house-purified birchwood xylan oligomers, namely, xylobiose, xylotriose, and xylotetraose, and on commercially available xylose, furfural, and formic acid. On the basis of the current study, the optimum hydrolysis conditions were at temperatures between 120 and 130 °C and acid concentrations between 0.6 and 1.0 v/v%, where carbohydrate monomers were maximized, and degradation products were minimized. These results indicate that it is possible to improve hemicellulose-to-xylose conversion efficiency while minimizing degradation product generation, reducing detoxification requirements.

Seeds of milk thistle (Silybum marianum L. Gaertner) contain silymarins and ca. 25% (w/w) of oil. A pre-treatment step involving refluxing with petroleum ether is usually performed before extraction of the silymarins using organic solvents. This paper compares the extraction of whole and defatted milk thistle seeds in various solvents as a function of temperature. The extraction of whole seeds of milk thistle with water at 50, 70 and 85 degrees C was also examined: the yield of silymarin increased with increasing water temperature. In most cases, ethanol at 60 degrees C recovered the largest quantities of silymarins. However, boiling water proved to be an efficient extraction solvent for the more polar silymarins such as taxifolin and silychristin, even when using whole seeds. Extractions of defatted seed meal with boiling ethanol returned maximum yields of 0.62, 3.89, 4.04, and 6.86 mg/g defatted seed of taxifolin, silychristin, silybinin A and silybinin B, respectively. When extracting defatted seed meal with ethanol, yields of taxifolin, silybinin A and silybinin B were, respectively, 6.8-, 0.95-, 1.7- and 1.6-fold higher than when extracting whole seeds. When extracting with boiling water, the yields of silychristin, silybinin A, and silybinin B were 380, 47 and 50% higher for whole seeds compared with defatted seeds.

Biomass pretreatment often leads to the formation of compounds that are inhibitory to enzymatic hydrolysis. To remove inhibitory compounds prior to enzymatic hydrolysis, pretreated biomass is washed with at least 3 volumes of water. However, this washing step would be difficult to manage in commercial operations because of the unsustainable water consumption. This study reports on the effects of formic acid and furfural on Accellerase 1500 with cellulose powder and dilute acid-pretreated poplar as substrates. Using cellulose powder as the substrate for enzymatic hydrolysis with the addition of 5 or 10 mg/mL formic acid, glucose recovery was reduced by 34% and 81%, respectively, in comparison to the control. The addition of furfural, at 2 or 5 mg/mL, to the enzymatic system reduced glucose recovery by 5% and 9%, respectively. When 5 mg/mL of formic acid was combined with 5 mg/mL of furfural, glucose recovery in the cellulose powder enzymatic system was reduced by 59%. Inhibition of sugar recovery was more pronounced when dilute acid-pretreated poplar was used as a substrate for enzymatic hydrolysis. At 24 h incubation, recovery reductions were 94%, 97%, and 93% in the presence of 5 or 10 mg/mL formic acid or the 5 mg/mL combination.