Arch Pharm Res
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Mesenchymal stem cells (MSCs) are adult stem cells that can be isolated from most adult tissues, including bone marrow, adipose, liver, amniotic fluid, lung, skeletal muscle and kidney. The term MSC is currently being used to represent both mesenchymal stem cells and multipotent mesenchymal stromal cells. Numerous reports on systemic administration of MSCs leading to functional improvements based on the paradigm of engraftment and differentiation have been published. ⋯ These include suppression of T cell proliferation, influencing dendritic cell maturation and function, suppression of B cell proliferation and terminal differentiation, and immune modulation of other immune cells such as NK cells and macrophages. In terms of the clinical applications of MSCs, they are being tested in four main areas: tissue regeneration for cartilage, bone, muscle, tendon and neuronal cells; as cell vehicles for gene therapy; enhancement of hematopoietic stem cell engraftment; and treatment of immune diseases such as graft-versus-host disease, rheumatoid arthritis, experimental autoimmune encephalomyelitis, sepsis, acute pancreatitis and multiple sclerosis. In this review, the mechanisms of immunomodulatory effects of MSCs and examples of animal and clinical uses of their immunomodulatory effects are described.
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The study of cytochrome P450 pharmacogenomics is of particular interest because of its promise in the development of rational means to optimize drug therapy with respect to patient's genotype to ensure maximum efficacy with minimal adverse effects. Drug metabolizing P450 enzymes are polymorphic and are the main phase I enzymes responsible for the metabolism of clinical drugs. ⋯ Predictive genotyping for P450 enzymes for a more effective therapy will be routine for specific drugs in the future. In this review, we discuss the current knowledge of polymorphic metabolism by functional alterations in nonsynonymous SNPs of P450 1A2, 2A6, 2C8, 2C9, 2C19, 2D6, and 3A4 enzymes.
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Interindividual variability in oral drug efficacy and toxicity is commonly observed in all therapeutic areas. Importantly, interindividual variability in drug uptake and metabolism can result in poor drug response, adverse drug reactions, or unfavorable drug-drug interaction. One of the common causes of individual variations in drug response is genetic variation of drug transporters and metabolizing enzymes. ⋯ Knowledge of the genotype-phenotype correlation and frequency distribution of functional single nucleotide polymorphisms may be a valuable tool for individualizing drug therapy. This information can also be useful for explaining inter-individual and inter-ethnic variations in drug response and/or adverse effects. In this review, we focus on the interplay between efflux transporter (ATP-binding cassette, sub-family B (MDR/TAP), member 1/ABCB1) and cytochrome P450s according to genetic polymorphism.
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As the use of herbal medicines increases, the public health consequences of drug-herb interactions are becoming more significant. Herbal medicines share the same drug metabolizing enzymes and drug transporters, including cytochrome P450 enzymes (CYPs), glucuronosyltransferases (UGTs), and P-glycoprotein, with several clinically important drugs. Interactions of several commonly used herbal medicines, such as Ginko biloba, milk thistle, and St. ⋯ This review describes major factors affecting the metabolism of herbal medicines, mechanisms of herb-drug interactions mediated by CYPs and UGTs, and several in vitro methods to assess the herb-drug interactions. Finally, drug interactions of Ginkgo biloba and St. John's wort, as representative herbal medicines, are described.
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Over the past few decades, a tremendous amount of work has been done on the molecular characterization of transport proteins in animals and humans, leading to a better understanding of the physiological roles of a number of transport proteins. Furthermore, there is increasing preclinical and clinical evidence to support the importance of transport proteins in the pharmacokinetics and toxicokinetics of a wide variety of structurally diverse drugs. As a consequence, the degree of expression and functionality of transport proteins may directly affect the therapeutic effectiveness, safety and target specificity of drugs. ⋯ However, increasing evidence suggests that some drug interactions result from changes in the activity and/or expression of drug transporters. Accordingly, assessment of the clinical relevance of transporter-mediated drug interactions has become a regulatory issue during the drug approval process and also the evaluation of drug interaction potential has become an integral part of risk assessment during drug development processes. Therefore, this review will highlight the role of some selected drug transporters in drug interactions, as well as their clinical implication.