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      Cytochrome P450 and P-Glycoprotein-Mediated Interactions Involving African Herbs Indicated for Common Noncommunicable Diseases

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          Abstract

          Herbal remedies are regularly used to complement conventional therapies in the treatment of various illnesses in Africa. This may be because they are relatively cheap and easily accessible and are believed by many to be safe, cause fewer side effects, and are less likely to cause dependency. On the contrary, many herbs have been shown to alter the pharmacokinetics of coadministered allopathic medicines and can either synergize or antagonize therapeutic effects as well as altering the toxicity profiles of these drugs. Current disease burden data point towards epidemiological transitions characterised by increasing urbanization and changing lifestyles, risk factors for chronic diseases like hypertension, diabetes, and cancer which often present as multimorbidities. As a result, we highlight African herb-drug interactions (HDIs) modulated via cytochrome P450 enzyme family (CYP) and P-glycoprotein (P-gp) and the consequences thereof in relation to antihypertensive, antidiabetic, and anticancer drugs. CYPs are enzymes which account for to up to 70% of drug metabolism while P-gp is an efflux pump that extrudes drug substrates out of cells. Consequently, regulation of the relative activity of both CYP and P-gp by African herbs influences the effective drug concentration at the site of action and modifies therapeutic outcomes.

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          Global estimates of cancer prevalence for 27 sites in the adult population in 2008.

          Recent estimates of global cancer incidence and survival were used to update previous figures of limited duration prevalence to the year 2008. The number of patients with cancer diagnosed between 2004 and 2008 who were still alive at the end of 2008 in the adult population is described by world region, country and the human development index. The 5-year global cancer prevalence is estimated to be 28.8 million in 2008. Close to half of the prevalence burden is in areas of very high human development that comprise only one-sixth of the world's population. Breast cancer continues to be the most prevalent cancer in the vast majority of countries globally; cervix cancer is the most prevalent cancer in much of Sub-Saharan Africa and Southern Asia and prostate cancer dominates in North America, Oceania and Northern and Western Europe. Stomach cancer is the most prevalent cancer in Eastern Asia (including China); oral cancer ranks as the most prevalent cancer in Indian men and Kaposi sarcoma has the highest 5-year prevalence among men in 11 countries in Sub-Saharan Africa. The methods used to estimate point prevalence appears to give reasonable results at the global level. The figures highlight the need for long-term care targeted at managing patients with certain very frequently diagnosed cancer forms. To be of greater relevance to cancer planning, the estimation of other time-based measures of global prevalence is warranted. Copyright © 2012 UICC.
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            Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview.

            Active drug efflux transporters of the ATP binding cassette (ABC)-containing family of proteins have a major impact on the pharmacological behavior of most of the drugs in use today. Pharmacological properties affected by ABC transporters include the oral bioavailability, hepatobiliary, direct intestinal, and urinary excretion of drugs and drug-metabolites and -conjugates. Moreover, the penetration of drugs into a range of important pharmacological sanctuaries, such as brain, testis, and fetus, and the penetration into specific cell- and tissue compartments can be extensively limited by ABC transporters. These interactions with ABC transporters determine to a large extent the clinical usefulness, side effects and toxicity risks of drugs. Many other xenotoxins, (pre-)carcinogens and endogenous compounds are also influenced by the ABC transporters, with corresponding consequences for the well-being of the individual. We aim to provide an overview of properties of the mammalian ABC transporters known to mediate significant transport of clinically relevant drugs.
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              Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glycoprotein.

              Multidrug resistance (MDR) is a significant obstacle to providing effective chemotherapy to many patients. Multifactorial in etiology, classic MDR is associated with the overexpression of P-glycoprotein (P-gp), resulting in increased efflux of chemotherapy from cancer cells. Inhibiting P-gp as a method to reverse MDR in cancer patients has been studied extensively, but the results have generally been disappointing. The development of P-gp inhibitors is reviewed, including a discussion of early agents that are no longer being developed and third-generation agents that are currently in clinical trials. First-generation agents (eg, cyclosporin, verapamil) were limited by unacceptable toxicity, whereas second-generation agents (eg, valspodar, biricodar) had better tolerability but were confounded by unpredictable pharmacokinetic interactions and interactions with other transporter proteins. Third-generation inhibitors (tariquidar XR9576, zosuquidar LY335979, laniquidar R101933, and ONT-093) have high potency and specificity for P-gp. Furthermore, pharmacokinetic studies to date have shown no appreciable impact on cytochrome P450 3A4 drug metabolism and no clinically significant drug interactions with common chemotherapy agents. Third-generation P-gp inhibitors have shown promise in clinical trials. The continued development of these agents may establish the true therapeutic potential of P-gp-mediated MDR reversal.
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                Author and article information

                Journal
                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                ECAM
                Evidence-based Complementary and Alternative Medicine : eCAM
                Hindawi Publishing Corporation
                1741-427X
                1741-4288
                2017
                31 January 2017
                : 2017
                : 2582463
                Affiliations
                1School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Nankai District, Tianjin 300193, China
                2Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin 300193, China
                Author notes

                Academic Editor: Olumayokun A. Olajide

                Author information
                http://orcid.org/0000-0001-8431-3167
                http://orcid.org/0000-0002-6123-2070
                http://orcid.org/0000-0001-7869-5736
                Article
                10.1155/2017/2582463
                5307007
                f840185f-7c73-4e63-bc49-5e0aacead2ec
                Copyright © 2017 Gregory Ondieki et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 November 2016
                : 26 December 2016
                : 4 January 2017
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81373890
                Award ID: 81430096
                Funded by: Open Topic Fund for State Key Laboratory of Bioactive Substance and Function of Natural Medicines
                Award ID: GTZK201514
                Funded by: Program for Changjiang Scholars and Innovative Research Team
                Award ID: IRT_14R41
                Categories
                Review Article

                Complementary & Alternative medicine
                Complementary & Alternative medicine

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