In vitro activity of uva-ursi against cytochrome P450 isoenzymes and P-glycoproteinThis article is one of a selection of papers published in this special issue (part 2 of 2) on the Safety and Efficacy of Natural Health Products.

2007 ◽  
Vol 85 (11) ◽  
pp. 1099-1107 ◽  
Author(s):  
B. Chauhan ◽  
C. Yu ◽  
A. Krantis ◽  
I. Scott ◽  
J. T. Arnason ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Moderate Activity ◽  
Natural Health Products ◽  
Natural Health ◽  
Herbal Products ◽  
Safety And Efficacy ◽  
Methanol Extracts ◽  
Metabolism Enzymes ◽  
Health Products

Some natural health products (NHPs) affect drug metabolism enzymes and transport proteins, potentially affecting the safety and efficacy of the drug or other NHPs. This study was undertaken to characterize the effect of uva-ursi ( Arctostaphylos uva-ursi ) on cytochrome P450 isozyme (3A4, 3A5, 3A7, 2C19, and 19)-mediated metabolism and P-glycoprotein (P-gp) transport. Three bulk and 2 capsulated uva-ursi samples were obtained from commercial outlets. The capsules were batched, and herbal samples were ground to a common consistency. Aqueous and methanol extracts were freshly prepared. Cytochrome P450 isozyme-mediated metabolism was determined by using in vitro bioassays. P-gp transport function was determined by using a rhodamine 123 (Rh123) uptake test in human (THP-1) monocytes and human Caco-2 cells. All products were analyzed by HPLC for arbutin, gallic acid, myricitrin, and isoquercetin. A large variation was observed in the biomarkers found between the bulk and capsulated samples. Our data indicate that both the aqueous and methanol extracts of all 5 uva-ursi products showed high cytochrome P450 isozyme inhibition, with the exception of the methanol extracts against cytochromes P3A4 and P19, which had low to moderate activity. The aqueous extracts of uva-ursi showed an inhibitory effect on Rh123 efflux by P-gp at 1 h and an inductive effect at 18 h for both cell lines. Our results show that the uva-ursi herbal products tested here have pharmacological properties, including the potential capacity to affect drug safety and efficacy. Further studies are warranted against a wider range of cytochrome P450 isozymes and to determine whether these effects are clinically significant.

scholarly journals Inhibition of Human Cytochrome P450 Metabolism by Blended Herbal Products and Vitamins

2011 ◽  
Vol 14 (1) ◽  
pp. 1 ◽  
Author(s):  
Teresa W Tam ◽  
Humayoun Akhtar ◽  
John Thor Arnason ◽  
Kosta Cvijovic ◽  
Heather Boon ◽  
...  
Keyword(s):  
Adverse Event ◽  
Cytochrome P450 ◽  
Drug Metabolism ◽  
Drug Disposition ◽  
Natural Health Products ◽  
Carotene Content ◽  
Herbal Products ◽  
Cytochrome P450 Activity ◽  
Health Products

Purpose. The use of supplements as herbal and micronutrient natural health products with conventional health products has become increasingly popular. It has been reported that some herbal products can inhibit the activity of cytochrome P450-mediated metabolism and drug disposition. This study was designed to investigate a case report of a severe adverse event to determine the potential interactions of femMED, Thyrosense and vitamins on cytochrome P450-mediated drug metabolism. Methods. The effect of extracts from these commercially available herbal formulations, trans-ß-carotene, multivitamins, and vitamin D3 supplements on cytochrome P450-mediated drug metabolism of marker substrates was determined in vitro. Results. The blended herbal products femMED and Thyrosense had a high potential to affect the safety and efficacy of many health products. Some vitamin and trans-β-carotene containing products also have the potential to affect drug disposition. The ß-carotene content of various products was analyzed and significant discrepancies were found among them and between values indicated on product labels. Product extracts also exhibited a low to moderate capacity to inhibit cytochrome P450 2C9, 2C19 and 3A4-mediated metabolism. Conclusions. The findings of this study suggest that these herbal products and most vitamin products may have an inhibitory effect on cytochrome P450 activity that could contribute to development of an adverse event. Further work is warranted to determine how supplementation with these products may affect drug metabolism in an in vivo context.

scholarly journals Creation of a Natural Health Products Database for Assessing Safety for Patients with Chronic Kidney Disease or Renal Transplant

2017 ◽  
Vol 70 (5) ◽  
Author(s):  
Sharon Leung ◽  
Karen Shalansky ◽  
Puneet Vashisht ◽  
Marianna Leung ◽  
Judith G Marin
Keyword(s):  
Renal Transplant ◽  
Safety Information ◽  
Natural Health Products ◽  
Immunomodulatory Effects ◽  
Natural Health ◽  
Transplant Patients ◽  
Health Products ◽  
Site Web ◽  
Natural Medicines

<p><strong>ABSTRACT</strong></p><p><strong>Introduction:</strong> There is a lack of published safety information on the use of natural health products (NHPs) for patients with chronic kidney disease (CKD) or renal transplant.</p><p><strong>Objective:</strong> To create an online database to provide evidence-based safety recommendations for commonly used NHPs, specific to patients with CKD or renal transplant.</p><p><strong>Methods:</strong> NHPs used by CKD and transplant patients in British Columbia were identified from the records of the BC Provincial Renal Agency. For each NHP, several databases (MEDLINE, Embase, Lexi-Natural Products, PubMed Dietary Supplement Subset, and Natural Medicines) were searched for any information pertaining to dosage, adverse drug reactions, drug interactions, immunomodulatory effects, and pharmacokinetics in patients with renal disease. Each NHP was given 1 of 4 safety ratings: likely safe, possibly safe, possibly unsafe, and likely unsafe. An NHP was classified as “possibly unsafe” for patients with renal transplant if it had demonstrated in vitro immunomodulatory effects and/or significant interactions with transplant medications due to effects on the cytochrome P450 3A4 isozyme.</p><p><strong>Results:</strong> Of the 19 627 BC-registered patients with renal disease (as of August 2014), 4122 (21%) were using one or more NHPs. The Herbal-CKD website (www.herbalckd.com) was created in 2015 to provide information about 47 commonly used NHPs and 2 known nephrotoxins (aristolochic acid and silver). This website provides a systematic evaluation of safety information for selected NHPs for patients with CKD (both nondialysis and dialysis-dependent) and kidney transplant. The most common NHP safety classification was “possibly safe”, reflecting the paucity of studies in renal populations and the availability of safety data for the general population. Limitations of the website include difficulty in interpreting and generalizing the safety literature because most NHP formulations are not standardized, and others are combination products.</p><p><strong>Conclusion:</strong> The website www.herbalckd.com provides an easy-to-use, evidence-based tool for health care professionals to assess the safety of NHPs for CKD and transplant patients.</p><p><strong>RÉSUMÉ</strong></p><p><strong>Contexte :</strong> On observe qu’il n’existe que très peu d’information publiée sur l’innocuité des produits de santé naturels (PSN) pour les patients souffrant d’insuffisance rénale chronique ou ayant subi une greffe rénale.<strong> </strong></p><p><strong>Objectif :</strong> Créer une base de données en ligne qui sert à fournir des recommandations de sécurité fondées sur des données probantes au sujet des PSN les plus employés spécifiquement à l’intention des patients atteints d’insuffisance rénale chronique ou ayant subi une greffe rénale.</p><p><strong>Méthodes :</strong> Les PSN utilisés par les patients souffrant d’insuffisance rénale chronique ou ayant subi une greffe rénale ont été répertoriés d’après les dossiers de la BC Provincial Renal Agency. Pour chaque PSN, plusieurs bases de données (MEDLINE, Embase, Lexi-Natural Products, PubMed Dietary Supplement Subset et Natural Medicines) ont été interrogées afin d’y chercher des informations sur la posologie, les réactions indésirables aux médicaments, les interactions médicamenteuses, les effets immunomodulateurs et la pharmacocinétique chez les patients atteints d’insuffisance rénale. Chaque PSN s’est vu attribuer l’un de quatre degrés de sécurité : probablement sécuritaire, possiblement sécuritaire, possiblement nocif et probablement nocif. Un PSN était classé « possiblement nocif » pour les patients ayant subi une greffe rénale s’il a manifesté in vitro des effets immunomodulateurs ou des interactions importantes avec les médicaments antirejet à cause de l’isozyme 3A4 du cytochrome P450.</p><p><strong>Résultats :</strong> Parmi les 19 627 patients insuffisants rénaux inscrits en Colombie-Britannique, 4 122 (21 %) utilisaient au moins un PSN (en date d’août 2014). Le site Web HerbalCKD (www.herbalckd.com) a été créé en 2015 afin de fournir de l’information sur 47 des PSN les plus utilisés et sur deux néphrotoxines connues (l’acide aristolochique et l’argent). Ce site Web offre une évaluation systématique des informations sur l’innocuité de PSN choisis qui pourraient être utilisés par les patients souffrant d’insuffisance rénale chronique (dialysés ou non) ou ayant subi une greffe rénale. Les PSN étaient le plus souvent classés sous « possiblement sécuritaire », ce qui souligne le peu d’études auprès des populations souffrant de troubles rénaux et la disponibilité de données sur l’innocuité dans la population générale. Parmi les limites du site Web, on compte la difficulté à interpréter et à généraliser la littérature sur l’innocuité parce que la plupart des formules de PSN ne sont pas normalisées et que certains PSN sont un mélange de substances.</p><p><strong>Conclusion :</strong> Le site Web www.herbalckd.com représente pour les professionnels de la santé un outil simple et fondé sur des données probantes leur permettant d’évaluer l’innocuité de PSN pour les patients atteints d’insuffisance rénale chronique ou ayant subi une greffe rénale.</p>

Adjuvant activities of saponins from the root of Polygala senega L.This article is one of a selection of papers published in this special issue (part 2 of 2) on the Safety and Efficacy of Natural Health Products.

2007 ◽  
Vol 85 (11) ◽  
pp. 1184-1194 ◽  
Author(s):  
Georgios S. Katselis ◽  
Alberto Estrada ◽  
Dennis K.J. Gorecki ◽  
Branka Barl
Keyword(s):  
Haemolytic Activity ◽  
Triterpenoid Saponin ◽  
Natural Health Products ◽  
Vaccine Adjuvants ◽  
Natural Health ◽  
Canadian Prairies ◽  
Quillaja Saponaria ◽  
Polygala Senega ◽  
Health Products

Eight pure triterpenoid saponin compounds isolated from the root of Polygala senega L., a plant indigenous to the Canadian prairies, were evaluated for their immunological activity in mouse models. The specific antibody responses of the IgG2a subclass increased significantly when isolated P. senega saponins were used as adjuvants in the immunization of mice with OVA antigen. In addition, increased IL-2 levels were observed in spleen cell cultures from P. senega saponin-immunized mice after in vitro secondary antigen stimulation. The saponins were tested for their toxicity in mice by using a haemolytic activity assay and found to be less toxic than Quillaja saponaria saponins that have long been used as adjuvants in vaccine formulations. This study has shown the potential of P. senega saponins to be considered as a natural source of vaccine adjuvants with biological activity equivalent to the current commercially available saponin adjuvants.

XP-828L (Dermylex), a new whey protein extract with potential benefit for mild to moderate psoriasisThis article is one of a selection of papers published in this special issue (part 1 of 2) on the Safety and Efficacy of Natural Health Products.

2007 ◽  
Vol 85 (9) ◽  
pp. 943-951 ◽  
Author(s):  
Réjean Drouin ◽  
Éric Lamiot ◽  
Kim Cantin ◽  
Sylvie F. Gauthier ◽  
Yves Pouliot ◽  
...  
Keyword(s):  
Whey Protein ◽  
Mechanism Of Action ◽  
Natural Health Products ◽  
Concomitant Treatment ◽  
Natural Health ◽  
Protein Extract ◽  
Murine Splenocytes ◽  
Health Products

Natural health products (NHPs) or complementary and alternative medicine (CAM) are commonly used to prevent disorders or support the usual treatments of many diseases. XP-828L, a whey protein extract, has demonstrated potential benefits for the treatment of mild to moderate psoriasis. The aim of this study was to analyze further clinical data that demonstrated the clinical benefits and safety of the XP-828L in patients with psoriasis and the potential mechanism of action of this product in vitro. Oral administration (2.5 g, twice a day, over 112 days) of XP-828L in 42 human subjects with mild to moderate psoriasis improved their PGA scores (physician’s global assessment). Moreover, no significant changes in haematology or hepatic and renal parameters were observed throughout the study period, indicating the safety of the product. In vitro experiments showed that XP-828L decreased the proliferation of concanavalin A (ConA)-stimulated murine splenocytes and their production of interleukin (IL)-2 and interferon (IFN)-γ. Although the in vivo mechanism of action of XP-828L remains unknown, XP-828L represents an NHP to be used as an alternative or concomitant treatment for mild to moderate psoriasis and potentially for other immune-mediated diseases.

NATURAL HEALTH PRODUCTS AND DRUG DISPOSITION

2005 ◽  
Vol 45 (1) ◽  
pp. 203-226 ◽  
Author(s):  
Brian C. Foster ◽  
J. Thor Arnason ◽  
Colin J. Briggs
Keyword(s):  
Health Care Professionals ◽  
Adverse Drug Events ◽  
Drug Disposition ◽  
Natural Health Products ◽  
Confounding Factors ◽  
Natural Health ◽  
Herbal Products ◽  
Health Products ◽  
History Of ◽  
Human Use

Botanicals such as herbal products (HPs) and nutraceuticals (NCs) are often regarded as low risk because of their long history of human use. Anecdotal and literature reports of adverse drug events (ADEs) and clinical studies with HPs are increasing, but many of the reports are incomplete and contradictory. These reports need to identify confounding factors and explain contradictory findings if they are to help health care professionals or patients understand what risks are involved. HPs are complex botanicals, not single-active ingredient (SAI) products. Studies can be confounded by different manufacturing processes and formulations, including cosmetics and food supplements; environment; chemotypes; misidentification or adulteration; and factors associated with the patient or user population such as use, total drug load, and genetics. Future studies need to be conducted with characterized product that includes all commercially available related products. Clinical trials should be relevant to the user population and take into account the confounding factors that may influence the interpretation of the findings.

scholarly journals The Effect of Natural Health Products and Traditional Medicines on the Activity of Human Hepatic Microsomal-Mediated Metabolism of Oseltamivir

2010 ◽  
Vol 13 (1) ◽  
pp. 43 ◽  
Author(s):  
Rui Liu ◽  
Teresa W Tam ◽  
Jingqin Mao ◽  
Ammar Saleem ◽  
Anthony Krantis ◽  
...  
Keyword(s):  
Liver Microsomes ◽  
Drug Efficacy ◽  
Metabolic Activation ◽  
Natural Health Products ◽  
Natural Health ◽  
Oseltamivir Carboxylate ◽  
Traditional Medicines ◽  
Health Products ◽  
Clinically Significant

Purpose. Oseltamivir is a prodrug that requires metabolic activation but there is little information on whether natural health products interact to prevent the biotransformation by the carboxylesterase. Methods. HPLC-DAD-ESI-MSD and fluorometric assays were used to determine if 50-pooled mixed gender human liver microsomes can mediate the formation of the active carboxylate metabolite and then if this reaction is affected by natural health products. Results. Extracts from 6 traditional Cree botanicals, a commercially available Echinacea product, Goldenseal and a traditional Chinese medicine reduced the formation of the active drug. In addition to oseltamivir carboxylate we report the detection of two new metabolites which are derivatives of oseltamivir carboxylate, one of which is a metabonate formed as a result of methanol. Conclusions. In vitro studies would suggest that there is the potential for some natural health products used by patients in response to pandemic A/H1N1 to reduce drug efficacy. Further studies are required to determine if these potential interactions could be clinically significant.

scholarly journals Melatonin Interaction Resulting in Severe Sedation

2015 ◽  
Vol 18 (2) ◽  
pp. 124 ◽  
Author(s):  
Brian C Foster ◽  
Kosta Cvijovic ◽  
Heather S Boon ◽  
Teresa W Tam ◽  
Rui Liu ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Active Surveillance ◽  
Cytochrome P450 Enzyme ◽  
Natural Health Products ◽  
Pharmacodynamic Interaction ◽  
Health Products ◽  
Vitro Analysis ◽  
Pharmacologically Active ◽  
In Vitro Analysis

Purpose. Natural health products (NHPs), including melatonin, are widely used products. Despite the widespread assumption that all NHPs are safe, they contain pharmacologically active substances and can therefore have adverse effects and/or interact with pharmaceuticals. Objective: To investigate the mechanism underlying NHP interactions identified through the Pharmacy SONAR active surveillance study. Methods: Active surveillance was undertaken in community pharmacies to identify adverse events in patients who had recently taken NHPs together with conventional pharmaceuticals. For suspected NHP-pharmaceutical interactions, the possible mechanism of action was explored by in vitro analysis of samples of different products to identify cytochrome P450 enzyme (CYP) inhibition potential. Results: Active surveillance identified a 19-year-old male taking citalopram, nortriptyline and oxycodone concomitantly and who experienced severe sedation when melatonin was added to this regimen. In vitro analysis involving several melatonin products showed product-dependent inhibition of CYP1A2, CYP2C19 and CYP3A7. Conclusion: The adverse event was likely due to a primary pharmacokinetic interaction between melatonin and citalopram; although mechanistically, interactions affecting cytochrome P450-mediated metabolism may have occurred with all of these health products. A pharmacodynamic interaction may also be possible, but beyond the capacity of this study to establish.Key words: Melatonin, citalopram, nortriptyline, oxycodone, drug interaction. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

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