Dietary flavonoids: effects on xenobiotic and carcinogen metabolism.

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.

Impact of plant products on innate and adaptive immune system of cultured finfish and shellfish

Background:

Nutritional status plays an important role in the incidence of postoperative complications and the prognosis of various tumours. The prognostic value of preoperative nutritional factors in patients with pancreatic cancer is not known.



Methods:

This retrospective study included 268 patients who underwent resection for adenocarcinoma of the pancreas. The predictive value of preoperative nutritional status for postoperative outcome (survival, complications) was assessed. Nutritional factors included the three constitutional indices, serum albumin and Onodera's prognostic nutrition index (PNI), calculated as 10 × serum albumin (g/dl) + 0·005× total lymphocyte count (per mm3).



Results:

In multivariable analysis preoperative low PNI (but not low albumin) was an independent prognostic factor for poor survival: hazard ratio (HR) 1·73 (95 per cent confidence interval (c.i.) 1·21 to 2·47). The accuracy of a PNI value of less than 45 as cut-off for clinically significant preoperative malnutrition in predicting 1- or 2-year survival after surgery was, however, limited (66·4 and 56·3 per cent respectively). Low preoperative albumin concentration and PNI were significantly associated with postoperative complications: odds ratio 1·98 (95 per cent c.i. 1·18 to 3·32) and 2·14 (1·23 to 3·73) respectively. Low PNI and low body mass index were independently associated with pancreatic fistula: HR 2·52 (1·37 to 4·63) and 0·40 (0·17 to 0·93) respectively.



Conclusion:

The PNI is associated with overall survival and postoperative complications, in particular pancreatic fistula, in patients with pancreatic cancer. The moderate accuracy of PNI as a predictor of survival limits its clinical use. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Nutritional predictors of postoperative outcome in pancreatic cancer

This article discusses the insect CYP genes and P450 enzymes. Cytochrome P450, or CYP genes, constitutes one of the largest family of genes, with representatives in virtually all living organisms, from bacteria to protists, plants, fungi, and animals. The multiple functions of insect P450 enzymes, their complex biochemistry, and their toxicological and physiological importance are presented. Physiological functions are not restricted to one branch of the P450 evolutionary tree, and the ramifications that seem typical of “environmental response genes” are found in both microsomal and mitochondrial P450 encoding genes. The CYP3 and CYP4 clans seem the most diverse, and the smaller CYP2 and mitochondrial CYP clans seem to have proportionally more genes found as orthologs across species. There are many physiological functions for P450s that just are not known or suspected. CYP4C7 was shown to be selectively expressed in the corpora allata and to metabolize JH and its precursors to new metabolites.

Insect CYP Genes and P450 Enzymes

A resurgence in the use of medical herbs in the Western world, and the co-use of modern and traditional therapies is becoming more common. Thus there is the potential for both pharmacokinetic and pharmacodynamic herb-drug interactions. For example, systems such as the cytochrome P450 (CYP) may be particularly vulnerable to modulation by the multiple active constituents of herbs, as it is well known that the CYPs are subject to induction and inhibition by exposure to a wide variety of xenobiotics. Using in vitro, in silico, and in vivo approaches, many herbs and natural compounds isolated from herbs have been identified as substrates, inhibitors, and/or inducers of various CYP enzymes. For example, St. John's wort is a potent inducer of CYP3A4, which is mediated by activating the orphan pregnane X receptor. It also contains ingredients that inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Many other common medicinal herbs also exhibited inducing or inhibiting effects on the CYP system, with the latter being competitive, noncompetitive, or mechanism-based. It appears that the regulation of CYPs by herbal products complex, depending on the herb type, their administration dose and route, the target organ and species. Due to the difficulties in identifying the active constituents responsible for the modulation of CYP enzymes, prediction of herb-drug metabolic interactions is difficult. However, herb-CYP interactions may have important clinical and toxicological consequences. For example, induction of CYP3A4 by St. John's wort may partly provide an explanation for the enhanced plasma clearance of a number of drugs, such as cyclosporine and innadivir, which are known substrates of CYP3A4, although other mechanisms including modulation of gastric absorption and drug transporters cannot be ruled out. In contrast, many organosulfur compounds, such as diallyl sulfide from garlic, are potent inhibitors of CYP2E1; this may provide an explanation for garlic's chemoproventive effects, as many mutagens require activation by CYP2E1. Therefore, known or potential herb-CYP interactions exist, and further studies on their clinical and toxicological roles are warranted. Given that increasing numbers of people are exposed to a number of herbal preparations that contain many constituents with potential of CYP modulation, high-throughput screening assays should be developed to explore herb-CYP interactions.

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Interactions of herbs with cytochrome P450.

Preclinical studies have established that the Ganoderma lucidum polysaccharide (GLPS) fractions have potent anti‐tumor activity, which has been associated with the immuno‐stimulating effects of GLP...

Effects of Ganopoly® (A Ganoderma lucidum Polysaccharide Extract) on the Immune Functions in Advanced‐Stage Cancer Patients

Preclinical studies have established that the Ganoderma lucidum polysaccharide (GLPS) fractions have potent anti-tumor activity, which has been associated with the immuno-stimulating effects of GLPS. However, it is unclear whether GLPS has immuno-modulating effects in humans in vivo. This study aimed to investigate the effects of Ganopoly 1

Wenqi Jiang

Papers

Interactions of herbs with cytochrome P450.

Effects of Ganopoly® (A Ganoderma lucidum Polysaccharide Extract) on the Immune Functions in Advanced‐Stage Cancer Patients

Polysaccharide Extract) on the Immune Functions in Advanced-Stage Cancer Patients