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St. John's wort extract induces CYP3A and CYP2E1 in the Swiss Webster mouse.

This investigation was designed to determine the ability of St. John's wort (SJW), a readily available antidepressant, to induce various hepatic drug metabolizing enzymes. SJW (140 or 280 mg/kg/day) was administered to male Swiss Webster mice for 1, 2, or 3 weeks. Enzymatic activity was analyzed in hepatic microsomes for all of the following drug metabolizing enzymes: CYP3A, CYP1A, CYP2E1, and UDP-glucuronosyltransferase (UDPGT). The catalytic activity of CYP1A was unchanged from control following any dose or duration of SJW, while both CYP3A and CYP2E1 catalytic activities were increased 2-fold by both SJW concentrations but only following 3 weeks of administration. Results from Western immunoblotting studies supported the changes in catalytic activity, as protein levels for CYP2E1 and CYP3A were increased (2.5-fold and 6-fold, respectively) following 3 weeks of SJW administration. Additionally, the catalytic activity of the conjugation enzyme UDPGT was unchanged from control following all SJW treatments. These results indicate that in the mouse moderate doses of SJW cause an increase in the catalytic activity and polypeptide levels of CYP2E1 and CYP3A but only following 21 days of administration, while the catalytic activity of CYP1A and UDPGT activity remain unaffected.

Animals↗

What you need to know about dietary supplements.

Herbs and botanicals are used by a large number of people in the United States and have been used therapeutically in Europe for decades. Consumers are becoming more interested and subsequently better informed on the use of herbs to self-treat minor illness. Unfortunately, because of conflicting and anecdotal information, variable potency, and the widespread availability of herbs, many home care patients are left vulnerable to potentially life-threatening situations. A neutral discussion of alternative medical treatment should occur with all home care patients. Carefully worded questions should be asked and documented in the medical record. Finally, science-based teaching tools outlining the risks and benefits of botanicals must be available. A registered dietitian or pharmacist should be able to help nurses and agencies locate appropriate teaching tools on dietary supplements, including commonly used herbs and meal replacements.

Aloe↗

Know the benefits and risks of using common herbal therapies.

Although Americans are increasingly using herbal products for a variety of health conditions, they may not be aware of the demonstrated risks and benefits of these products. This study found public knowledge of 5 commonly used herbal products to be quite low, even among users of the investigated herbs.

Adult↗

St. John's wort and the treatment of mild to moderate depression: a systematic review.

A systematic review of randomized controlled trials was conducted to determine the efficacy of St. John's Wort (SJW) in the treatment of mild to moderate depression. The Boyak and Lookinland Methodological Quality Index was used to evaluate the studies. Despite methodological concerns, all studies demonstrated a significant drop in the Hamilton Depression Rating Scale scores for clients taking SJW compared with placebo or pharmaceutical antidepressants. Practitioners may find SJW a viable complementary treatment alternative to traditional medical treatment. The results should encourage further research to validate these findings and seek the most appropriate preparations and dosing for this popular herb.

Antidepressive Agents↗

Herbal interactions with cardiovascular drugs.

The prevalence of herb-drug interactions has been exaggerated. Nonetheless, some herbs, including garlic, ginkgo, ginseng, and St John's wort, can have a significant influence on concurrently administered drugs. Herbal medicines may mimic, decrease, or increase the action of prescribed drugs. This can be especially important for drugs with narrow therapeutic windows and in sensitive patient populations such as older adults, the chronically ill, and those with compromised immune systems.

Anticoagulants↗

Drug-herb interaction among commonly used conventional medicines: a compendium for health care professionals.

The objective of the review was to consolidate the clinical and pharmacologic aspects of drug-herb interactions to develop a compendium of information to provide prescribers with a measure of the risk of interactions, a description of the clinical consequences, and an assessment of the quality (ie, validity) of evidence. A variety of electronic databases and hand-searched references were used to identify documentation of interactions between herbal products and drugs from the most commonly used therapeutic classes. MEDLINE, Allied and Complementary Medicine Database, CINHAL, HealthSTAR, and EMBASE were searched from 1966 to the present. One hundred sixty-two citations were identified. Only 22 citations met the inclusion criteria. Using a matrix of 165 possible drug-herb interaction pairs (15 therapeutic drug classes by 11 herbal products), we identified 51 (31%) interactions discussed in the literature. Twenty-two of these 51 drug-herb pairs (43%) were supported by randomized clinical trials, case-control studies, cohort studies, case series, or case studies. The remaining interaction pairs reflected theoretic reasoning in the absence of clinical data. Most interactions were pharmacokinetic, with most actually or theoretically affecting the metabolism of the affected product by way of the cytochrome p450 enzymes. In this review, warfarin was the most common drug and St. John's wort was the most common herbal product reported in drug-herb interactions. To create a comprehensive and valid list of herb-drug interactions would require a substantial increase in research activities in this area. Improvements in the quality of methodology used are also necessary.

Case-Control Studies↗

Herbal-drug therapy interactions: a focus on dementia.

Older people with dementia are often prescribed numerous medications. Use of herbal therapies in addition to these conventional drug therapies may lead to interactions that result in an adverse drug event. We have conducted a systematic review to identify all studies that examined interactions between herbal and conventional drug therapies (i.e. prescription or over-the-counter). Using a MEDLINE search of English-language studies published between 1980 and 2000, we limited our search to those herbal therapies most likely to be used for the treatment of dementia (memory loss and decreased concentration) and related symptoms. We identified 28 articles that describe interactions between these herbal (i.e. St. John's wort, ginkgo biloba, kava, valerian, and ginseng) and conventional drug therapies. Of these articles, 11 examined St. John's wort, four examined ginkgo biloba, five examined kava, one examined valerian, and seven examined ginseng. We identified a series of potential interactions between herbal and conventional drug therapy that place older people at risk for an adverse drug event. Health care professionals need to be aware of these potential interactions.

Aged↗

St. John's wort and its constituent hyperforin concordantly regulate expression of genes encoding enzymes involved in basic cellular pathways.

OBJECTIVES AND METHODS: The effects of St. John's wort and hyperforin on gene expression were analysed in HepG2 cells by Affymetrix microarray hybridization and real time reverse transcription-PCR. RESULTS: Both compounds increased mRNAs of the drug metabolizing enzymes CYP3A4, CYP1A1, CYP1A2 and the flavin containing monooxygenase FMO5, and of the multidrug resistance protein MRP2. CYP4F2 and the reduced nicotinamide adenine dinucleotide dehydrogenase NQO1 were downregulated. Expression of genes mediating cholesterol biosynthesis was decreased, while facilitated glucose transporters and glycolysis genes were induced, indicating increased glucose metabolism. Changes of a considerable number of additional transcripts corresponded to reports on gene regulation by hypoxia. Endoplasmic reticulum stress-regulated genes involved in unfolded protein response and in protection of cells from apoptosis were downregulated. Other calcium binding proteins were affected by both treatments, suggesting an increase in intracellular calcium. CONCLUSIONS: St. John's wort and hyperforin concordantly affected expression of genes not only mediating metabolism and transport of exogenous and endogenous compounds, but also involved in energy metabolism, intracellular calcium regulation, cell proliferation and apoptosis.

Base Sequence↗

Natural health product-drug interactions: a systematic review of clinical trials.

Interactions between natural health products (NHP) and prescription medications are of increasing concern. This paper aims to identify all clinical trials of NHP-drug interactions. To determine the prevalence and outcomes of clinical investigations of NHP-drug pharmacokinetic interactions, electronic databases were searched from inception through March 2004, as well as reference lists from published reports and experts in the field for unpublished studies. Eligible studies were clinical investigations of the interaction between a NHP and the metabolism of a regulated medication in humans. Studies were excluded that only investigated the metabolism of an NHP or examined food-drug or NHP-NHP interactions. Two reviewers selected studies for inclusion and independently extracted data. Forty-seven trials were identified, studying an average of 14 participants/study (95% confidence interval [CI] 11-18), examined drug interactions with 19 different herbal preparations. All trials were pharmacokinetic studies, 41 of healthy volunteers and 6 of patients. Ten different herbal medicines as well as 5 different traditional herbal concoctions were studied. Potentially clinically significant drug interactions were observed with St. John wort (16/24 studies), garlic (2/5 studies), and American ginseng (1 study). Research on NHP-drug interactions is limited in number and scope. With the exception of St. John wort, clinicians and the public do not have information that permits strong inferences about interactions between NHPs and conventional medications.

Clinical Trials as Topic↗