https://www.thelancet.com/pdfs/journals/lancet/PIIS0140673699064570.pdf

Herb-drug interactions

http://repositorium.sdum.uminho.pt/bitstream/1822/5522/1/Phytochemistry-Paterson%5b1%5d.pdf

Ganoderma - a therapeutic fungal biofactory.

Tea leaves produce organic compounds that may be involved in the defense of the plants against invading pathogens including insects, bacteria, fungi, and viruses. These metabolites include polyphenolic compounds, the six so-called catechins, and the methyl-xanthine alkaloids caffeine, theobromine, and theophylline. Postharvest inactivation of phenol oxidases in green tea leaves prevents oxidation of the catechins, whereas postharvest enzyme-catalyzed oxidation (fermentation) of catechins in tea leaves results in the formation of four theaflavins as well as polymeric thearubigins. These substances impart the black color to black teas. Black and partly fermented oolong teas contain both classes of phenolic compounds. A need exists to develop a better understanding of the roles of polyphenolic tea compounds in food and medical microbiology. This overview surveys and interprets our present knowledge of activities of tea flavonoids and teas against foodborne and other pathogenic bacteria, virulent protein toxins produced by some of the bacteria, virulent bacteriophages, pathogenic viruses and fungi. Also covered are synergistic, mechanistic, and bioavailability aspects of the antimicrobial effects. Further research is suggested for each of these categories. The herein described findings are not only of fundamental interest, but also have practical implications for nutrition, food safety, and animal and human health.

/pdf/overview-of-antibacterial-antitoxin-antiviral-and-antifungal-45wgb3gvm3.pdf

Overview of antibacterial, antitoxin, antiviral, and antifungal activities of tea flavonoids and teas

Herbs are often administered in combination with therapeutic drugs, raising the potential of herb-drug interactions. An extensive review of the literature identified reported herb-drug interactions with clinical significance, many of which are from case reports and limited clinical observations. Cases have been published reporting enhanced anticoagulation and bleeding when patients on long-term warfarin therapy also took Salvia miltiorrhiza (danshen). Allium sativum (garlic) decreased the area under the plasma concentration-time curve (AUC) and maximum plasma concentration of saquinavir, but not ritonavir and paracetamol (acetaminophen), in volunteers. A. sativum increased the clotting time and international normalised ratio of warfarin and caused hypoglycaemia when taken with chlorpropamide. Ginkgo biloba (ginkgo) caused bleeding when combined with warfarin or aspirin (acetylsalicylic acid), raised blood pressure when combined with a thiazide diuretic and even caused coma when combined with trazodone in patients. Panax ginseng (ginseng) reduced the blood concentrations of alcohol (ethanol) and warfarin, and induced mania when used concomitantly with phenelzine, but ginseng increased the efficacy of influenza vaccination. Scutellaria baicalensis (huangqin) ameliorated irinotecan-induced gastrointestinal toxicity in cancer patients. Piper methysticum (kava) increased the ‘off’ periods in patients with parkinsonism taking levodopa and induced a semicomatose state when given concomitantly with alprazolam. Kava enhanced the hypnotic effect of alcohol in mice, but this was not observed in humans. Silybum marianum (milk thistle) decreased the trough concentrations of indinavir in humans. Piperine from black (Piper nigrum Linn) and long (P. longum Linn) peppers increased the AUC of phenytoin, propranolol and theophylline in healthy volunteers and plasma concentrations of rifamipicin (rifampin) in patients with pulmonary tuberculosis. Eleutheroccus senticosus (Siberian ginseng) increased the serum concentration of digoxin, but did not alter the pharmacokinetics of dextromethorphan and alprazolam in humans. Hypericum perforatum (hypericum; St John’s wort) decreased the blood concentrations of ciclosporin (cyclosporin), midazolam, tacrolimus, amitriptyline, digoxin, indinavir, warfarin, phenprocoumon and theophylline, but did not alter the pharmacokinetics of carbamazepine, pravastatin, mycophenolate mofetil and dextromethorphan. Cases have been reported where decreased ciclosporin concentrations led to organ rejection. Hypericum also caused breakthrough bleeding and unplanned pregnancies when used concomitantly with oral contraceptives. It also caused serotonin syndrome when used in combination with selective serotonin reuptake inhibitors (e.g. sertraline and paroxetine). In conclusion, interactions between herbal medicines and prescribed drugs can occur and may lead to serious clinical consequences. There are other theoretical interactions indicated by preclinical data. Both pharmacokinetic and/or pharmacodynamic mechanisms have been considered to play a role in these interactions, although the underlying mechanisms for the altered drug effects and/or concentrations by concomitant herbal medicines are yet to be determined. The clinical importance of herb-drug interactions depends on many factors associated with the particular herb, drug and patient. Herbs should be appropriately labeled to alert consumers to potential interactions when concomitantly used with drugs, and to recommend a consultation with their general practitioners and other medical carers.

Herb-drug interactions: a literature review.

The interactions of metal ions with quinolone antibacterial agents

The absorption characteristics and oral bioavailability of three tea catechins, namely (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), and (-)-epigallocatechin gallate (EGCG), were assessed in this study. Male Sprague Dawley rats (210-230 g) received either an intravenous (i.v. 50 mg/kg) or oral (5000 mg/kg) dose of decaffeinated catechin-fraction containing EC (5%), EGCG (50%), and ECG (13%). Concentrations of the compounds in plasma, urine, and feces were measured using HPLC. A non-compartmental approach was employed for pharmacokinetic analysis. Results indicated that maximum plasma concentrations for the catechins (15-112 micrograms/ml) were achieved at 2 h post-oral dosing and the apparent volume of distribution (Vd/F) ranged from 30 to 63 l/kg. Absolute bioavailability (F) of EC, EGCG, and ECG was assessed to be 0.39, 0.14, and 0.06, respectively. Estimates of terminal elimination half-life (t1/2, lambda z) of the catechins after oral dosing were 451-479 min and were 1.4-10 fold longer than those observed for the i.v. dosing. The discrepancy in terminal elimination and low rate and extent of absorption indicated the possibility of flip-flop kinetics. Respective urinary recoveries were 0.17-4.72% and 2.11-14.2% after oral and i.v. dosing. In conclusion, the low systemic availability of tea catechins observed could be a result of slow absorption, high first pass effect, and wide tissue distribution.

Oral absorption and bioavailability of tea catechins.

Ganoderma lucidum was studied for its antioxidative activity by bioassay guided isolation in conjunction with in vitro tests. The powdered crude drug was treated with boiling water and the aqueous extract (Ex1) was further separated to obtain terpene and polysaccharide fractions. The two fractions and Ex1 were screened for their antioxidative effect against pyrogallol induced erythrocyte membrane oxidation and Fe (II)-ascorbic acid induced lipid peroxidation. All tested samples showed antioxidative activities in a dose dependent manner and the terpene fraction was found to possess the highest effect compared with the others. Chemical isolation of the terpene fraction resulted in the detection of ganoderic acids A, B, C and D, lucidenic acid B and ganodermanontriol as major ingredients.

Triterpene antioxidants from ganoderma lucidum.

We evaluated the significance of a reported clinical case of drug-drug interaction between ginseng and warfarin using a robust pharmacokinetic/pharmacodynamic approach in a rat model. The influence of ginseng on the pharmacokinetics and pharmacodynamics of oral warfarin after a single dose (2 mg kg(-1)) and at steady state (0.2 mg kg(-1) daily x 6 days) was studied in male Sprague-Dawley rats. Prothrombin time was employed as a pharmacodynamic index. Warfarin plasma concentration and vitamin K content in the ginseng extract were assessed by validated HPLC assays. The pharmacokinetics of warfarin after a single dose were not altered in the presence of ginseng; peak plasma concentration (control 7.8+/-0.5; ginseng 7.3+/-2.5 microg mL(-1)), time to peak (control 2.6+/-1.0; ginseng 3.1+/-1.1 h), elimination half-life (control 14.3+/-5.8; ginseng 10.6+/-3.1 h), and oral clearance (control 17.5+/-3.3; ginseng 20.2+/-5.5 mL h(-1)) were not significantly different (P>0.05). Similarly, alterations in the pharmacokinetics of warfarin were not detected under the multiple dosing paradigm. Under both dosing conditions, ginseng also showed no significant impact on the pharmacodynamics of warfarin as assessed by the area under the prothrombin time vs time curve (multiple dosing; control 3776+/-619, ginseng 3830+/-362 sh) and maximum prothrombin time (control 57.2+/-11.8, ginseng 63.3+/-9.1 s). Furthermore, the content of vitamin K was undetectable in the ginseng decoction. In conclusion, current data obtained in the rat showed no significant impact of ginseng on the pharmacokinetics/pharmacodynamics of warfarin when they are concomitantly administered.

Possible influences of ginseng on the pharmacokinetics and pharmacodynamics of warfarin in rats.

Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl4 intoxication model.

Over the past few decades, the importance of applying pharmacokinetic principles to the design of drug regimens has been increasingly recognised by clinicians From the perspective of antimicrobial chemotherapy, an improvement in clinical outcome and/or a reduction in toxicity are of primary interest Before application of these pharmacokinetic theories can be effective, the interrelationships between antimicrobial, pathogen and host factors must be clearly defined Information regarding the pharmacokinetics of the antimicrobial and the quantification of pathogen susceptibility is required

Ronald C. Li

Papers

Oral absorption and bioavailability of tea catechins.

Triterpene antioxidants from ganoderma lucidum.

Possible influences of ginseng on the pharmacokinetics and pharmacodynamics of warfarin in rats.

Evaluation of the protective effects of Schisandra chinensis on Phase I drug metabolism using a CCl4 intoxication model.

Achieving an Optimal Outcome in the Treatment of Infections The Role of Clinical Pharmacokinetics and Pharmacodynamics of Antimicrobials