Arch Pharm Res
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As the uses of herbal medicines from traditional natural products are increased, the need for pharmacokinetic studies and relevant data are also increased for safe pharmacotherapy. The market entry for the traditional herbal medicine is easier compared with that for synthetic drugs because of a lower regulatory barrier. Thus, the exact mechanisms for the absorption, distribution, metabolism and excretion of active components in herbal medicines and the potential herb-drug interactions are not always fully understood. ⋯ In this review, the effects of nine botanicals (ginkgo, green tea, grapes, licorice, saw palmetto, garlic milk thistle, ginseng and St. John's wort) on metabolic enzymes and transporters affecting absorption and disposition of herbal products are summarized. The source of samples (extracts and individual components), the species (human and animal) and in vivo and in vitro systems were separately reviewed for a better understanding of herb-drug interactions.
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Myocardial ischemia is a condition in which lack of blood flow to the cardiac muscle occurs resulting in deficient oxygen and nutrient supply to the heart. The restoration of blood flow to an organ or tissue is termed reperfusion. ⋯ However, numerous experimental studies reveal that the cardioprotective effects of postconditioning are suppressed in various pathological states. This review critically discusses the mechanisms involved in the cardioprotective effects of postconditioning and factors affecting the cardioprotective potential of myocardial postconditioning.
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Sevoflurane, one of the most commonly used inhalation anesthetics, induces apoptosis and oxidative stress in lymphocytes. Propofol, an intravenous anesthetic, exhibits antiapoptotic and antioxidative activities. Therefore, the present study aimed to investigate whether propofol attenuates sevoflurane-induced cellular injury in human peripheral lymphocytes. ⋯ Five and ten μg/mL propofol attenuated the impact of sevoflurane on cell viability, apoptosis and ΔΦm, and 5, 10 and 25 μg/mL propofol inhibited the production of intracellular reactive oxygen species stimulated by sevoflurane. However, a combination of 50 μg/mL propofol and 8% sevoflurane led to more severe cellular injury than sevoflurane alone. The results suggest that propofol can attenuate sevoflurane-induced cellular injury of human peripheral lymphocytes in a concentration-dependent manner, providing a rational for the clinical use of sevoflurane combined with appropriate doses of propofol.
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Ischemic preconditioning can provide protection to neurons from subsequent lethal ischemia. The molecular mechanisms of neuronal ischemic tolerance, however, are still not well-known. The present study, therefore, examined the role of MAPK and PI3K/Akt pathways in ischemic tolerance induced by preconditioning with sublethal oxygen-glucose deprivation (OGD) in cultured rat cortical neurons. ⋯ Finally, treatment with an inhibitor of PI3K, wortmannin, applied from 15 min before and during lethal OGD abolished not only the preconditioning-induced neuroprotection but also the Akt activation. Concomitant with blockade of the Akt activation, PI3K inhibition also resulted in activation of Bad and GSK-3β. The results suggest that ischemic tolerance induced by sublethal OGD preconditioning is primarily mediated through activation of the PI3K/Akt pathway, but not the MAPK pathway, in rat cortical neurons.
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Melanoma has the capacity to spread via the blood stream to the brain, and has been notoriously resistant to drug therapy. An activating mutation in the gene encoding BRAF is known to be responsible for half of melanomas. This article provides a review of GSK2118436 and PLX4032 as potential therapeutics for the treatment of melanomas by inhibiting oncogenic BRAF.