La Fundación Medina analiza la interacción medicamentosa de los extractos de hongos

El objetivo del estudio desarrollado por la Fundación Medina, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, es evaluar el potencial inhibitorio de los extractos fúngicos incluidos en las formulaciones de la línea Micosalud sobre las principales isoformas del CYP450 (CYP3A4, CYP2D6 y CYP2C9).

Las conclusiones de este estudio demostraron una baja posibilidad de interacciones medicamentosas in vivo por inhibición del CYP450.

Assessment CYP450 Inhibition by Fungi Dietary Supplements


Due in part to the increased consumption of herbal products on a global scale, a sharp rise in the reported number of both in vitro and in vivo interactions of dietary supplements with prescription drugs that are metabolized by cytochrome P450 (CYP) enzymes has been observed. Popular products such as ginseng, saw palmetto and St. John’s wort have demonstrated potent in vitro inhibition or induction of CYP activity. While reports of in vivo interactions are not as numerous, natural products such as garlic, goldenseal and grapefruit juice have shown the potential to affect CYP activity in vivo. As the wide-spread use of herbal and alternative medicines continues, an increased awareness on the part of the research and medical communities should afford safer use of these products in the future.


The aim of this study was to evaluate the in vitro inhibitory potential of 8 different commonly used fungi preparations on the main CYP450 isoforms (CYP3A4, CYP2D6 and CYP2C9). These products: Coriolus versicolor, Ganoderma Lucidum, Lentinula Edodes, Grifola Frondosa, Agaricus Blazei, Cordyces Sinensis and Polyporus Umbellatus are all registered in Spain as dietary supplement products by the Spanish Medicine Agency.

Methods and Materials

Preparation of herbal extracts

The dry commercial herbal products (pills or capsules) were grounded in a mortar, if needed, and dissolved in water and DMSO 80/20 for extraction. The recommended daily dosage of each fungi preparation was taken as basis for all extractions1 for further details. These in vitro concentrations are expected to cover the range of concentrations occurring in the small intestine and blood in vivo. All fungi stock solutions were kept at 4°C, avoiding light.

Enzyme assay

Human liver microsomes (0.25 mg/ml) were incubated in separate 96 well plates for 15 min. at 37° C in a 0.1 mM potassium phosphate buffer (pH 7.4) containing each respective probe substrate Testosterone at 50 μM for CYP3A4, dextromethorphan at 10 μM for CYP2D6, and diclofenac at 20 μM for CYP2C9) and a NADPH-regenerating system (1.25 mM NADP +, 3.3 mM glucose-6-phosphate, 3.3 mM MgCl 2 and 0.4 U/ml glucose-6-phosphate dehydrogenase). Fungi extracts were dissolved in DMSO/water (20/80) and were added in volumes of 2 μl. The positive control inhibitor (ketoconazole for CYP3A4, quinidine for CYP2D6 and sulphafenazole for CYP2C9 ) were dissolved in DMSO/water (20/80) and were added in volumes of 2 μl. All incubations were performed in 0.2% DMSO. The total incubation volume was 200μl. The reaction was terminated by the addition of 90 μl acetonitrile. The formation of specific reaction products (6-beta-hydroxy-testosterone, dextrorphan and 4’-hydroxy-diclofenac) was monitored by liquid chromatography coupled to mass spectrometry as previously described2.


Summary of IC50 values for fungi dietary supplements in main CYP450 isoforms

Interaccion medicamentosa fundacion medina


As previously demonstrated from a crude comparison of in vitro inhibition potency and magnitude of drug interactions, in almost all cases, if the inhibitory potency was ≤1 μM, an in vivo drug-drug interaction would be observed; however, if the inhibitory potency was ≥10 μM, there still is low possibility that the drug could cause an interaction3. Therefore the fungi dietary supplements assessed in this work present low possibility of displaying in vivo drug interactions by inhibition of CYP450.


  • Hellum, B. H.; Hu, Z.; Nilsen, O. G. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes Basic Clin Pharmacol Toxicol 2007, 100: 23-30.
  • Pérez, J.; Díaz, C.; Salado, I. G.; Pérez, D. I.; Peláez, F.; Genilloud, O.; Vicente, F. Evaluation of the effect of compound aqueous solubility in cytochrome P450 inhibition assays Advances in Bioscience and Biotechnology 2013, 4: 12.
  • Obach, R. S.; Walsky, R. L.; Venkatakrishnan, K.; Gaman, E. A.; Houston, J. B.; Tremaine, L. M. The utility of in vitro cytochrome P450 inhibition data in the prediction of drug-drug interactions J Pharmacol Exp Ther 2006, 316: 336-348.


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