Abstract:Capsaicin (trans‐8‐methyl‐N‐vanillyl‐6‐nonenamide, CAP) is an important ingredient in spicy foods consumed throughout the world. Vinblastine (VBL) is a naturally occurring alkaloid prescribed to cancer patients. Many cancer patients treated with VBL were taking CAP at the same time. This study attempted to investigate the effect of CAP on the pharmacokinetics of VBL, which is the substrate of CYP3A, P‐gp, and Mrp2. CAP, cyclosporine (CsA) or olive oil was given to rats for seven consecutive days, and on the se… Show more
“…In repression, Pchs like flavonoids, decrease the mRNA levels of CYP3A and P-gp by unknown mechanisms (Figure 1). 28-41 Figure 1.Mechanisms involved in the modulation: (1) Some Pch such as hyperforin and some flavonoids modulate cyp3a and abcb1 gene expression by activation or repression modify mRNA transcription for CYP3A and P-gp. 8,31,35,93,94 However, the exact mechanism by which the repression of both proteins is carried out is unknown.…”
Section: Cytochromementioning
confidence: 99%
“…In repression, Pchs like flavonoids, decrease the mRNA levels of CYP3A and P-gp by unknown mechanisms (Figure 1). [28][29][30][31][32][33][34][35][36][37][38][39][40][41] Inhibition of Protein Activity (Metabolism or Transport). Some Pchs inhibit CYP3A and P-gp by binding directly to the protein: in the CYP3A, Pchs bind to the catalytic site; meanwhile for P-gp, they bind to the cytosolic site (Figure 1).…”
Phytochemicals (Pch) present in fruits, vegetables and other foods, are known to inhibit or induce drug metabolism and transport. An exhaustive search was performed in five databases covering from 2000 to 2021. Twenty-one compounds from plants were found to modulate CYP3A and/or P-gp activities and modified the pharmacokinetics and the therapeutic effect of 27 different drugs. Flavonols, flavanones, flavones, stilbenes, diferuloylmethanes, tannins, protoalkaloids, flavans, hyperforin and terpenes, reduce plasma concentration of cyclosporine, simvastatin, celiprolol, midazolam, saquinavir, buspirone, everolimus, nadolol, tamoxifen, alprazolam, verapamil, quazepam, digoxin, fexofenadine, theophylline, indinavir, clopidogrel. Anthocyanins, flavonols, flavones, flavanones, flavonoid glycosides, stilbenes, diferuloylmethanes, catechin, hyperforin, alkaloids, terpenes, tannins and protoalkaloids increase of plasma concentration of buspirone, losartan, diltiazem, felodipine, midazolam, cyclosporine, triazolam, verapamil, carbamazepine, diltiazem, aripiprazole, tamoxifen, doxorubicin, paclitaxel, nicardipine. Interactions between Pchs and drugs affect the gene expression and enzymatic activity of CYP3A and P-gp transporter, which has an impact on their bioavailability; such that co-administration of drugs with food, beverages and food supplements can cause a subtherapeutic effect or overdose. Therefore, it is important for the clinician to consider these interactions to obtain a better therapeutic effect.
“…In repression, Pchs like flavonoids, decrease the mRNA levels of CYP3A and P-gp by unknown mechanisms (Figure 1). 28-41 Figure 1.Mechanisms involved in the modulation: (1) Some Pch such as hyperforin and some flavonoids modulate cyp3a and abcb1 gene expression by activation or repression modify mRNA transcription for CYP3A and P-gp. 8,31,35,93,94 However, the exact mechanism by which the repression of both proteins is carried out is unknown.…”
Section: Cytochromementioning
confidence: 99%
“…In repression, Pchs like flavonoids, decrease the mRNA levels of CYP3A and P-gp by unknown mechanisms (Figure 1). [28][29][30][31][32][33][34][35][36][37][38][39][40][41] Inhibition of Protein Activity (Metabolism or Transport). Some Pchs inhibit CYP3A and P-gp by binding directly to the protein: in the CYP3A, Pchs bind to the catalytic site; meanwhile for P-gp, they bind to the cytosolic site (Figure 1).…”
Phytochemicals (Pch) present in fruits, vegetables and other foods, are known to inhibit or induce drug metabolism and transport. An exhaustive search was performed in five databases covering from 2000 to 2021. Twenty-one compounds from plants were found to modulate CYP3A and/or P-gp activities and modified the pharmacokinetics and the therapeutic effect of 27 different drugs. Flavonols, flavanones, flavones, stilbenes, diferuloylmethanes, tannins, protoalkaloids, flavans, hyperforin and terpenes, reduce plasma concentration of cyclosporine, simvastatin, celiprolol, midazolam, saquinavir, buspirone, everolimus, nadolol, tamoxifen, alprazolam, verapamil, quazepam, digoxin, fexofenadine, theophylline, indinavir, clopidogrel. Anthocyanins, flavonols, flavones, flavanones, flavonoid glycosides, stilbenes, diferuloylmethanes, catechin, hyperforin, alkaloids, terpenes, tannins and protoalkaloids increase of plasma concentration of buspirone, losartan, diltiazem, felodipine, midazolam, cyclosporine, triazolam, verapamil, carbamazepine, diltiazem, aripiprazole, tamoxifen, doxorubicin, paclitaxel, nicardipine. Interactions between Pchs and drugs affect the gene expression and enzymatic activity of CYP3A and P-gp transporter, which has an impact on their bioavailability; such that co-administration of drugs with food, beverages and food supplements can cause a subtherapeutic effect or overdose. Therefore, it is important for the clinician to consider these interactions to obtain a better therapeutic effect.
“…Vinca alkaloids inhibit cellular proliferation by binding to tubulin and hindering the activities of the mitotic spindle in lower concentrations, though in higher concentrations, the entire microtubule can be destabilized 70 . As is typically seem in anti-cancer chemotherapies, they are metabolized by CYP3A4 and CYP3A5 with the former being generally more critical for vinblastine and the latter for vincristine 71 , 72 . The use of these vinca alkaloids for clinical treatment has been approved by the U.S. department of agriculture (USDA) as far back as 1963 due to their ability to prolong life in cancer patients however, they quickly evolved for use primarily in combination therapies (often with DNA-replication inhibitors) for NSCLC patients 73 , 74 , 75 .…”
Non-small cell lung cancer is recognized as the deadliest cancer across the globe. In some areas, it is more common in women than even breast and cervical cancer. Its rise, vaulted by smoking habits and increasing air pollution, has garnered much attention and resource in the medical field. The first lung cancer treatments were developed more than half a century ago. Unfortunately, many of the earlier chemotherapies often did more harm than good, especially when they were used to treat genetically unsuitable patients. With the introduction of personalized medicine, physicians are increasingly aware of when, how, and in whom, to use certain anti-cancer agents. Drugs such as tyrosine kinase inhibitors, anaplastic lymphoma kinase inhibitors, and monoclonal antibodies possess limited utility because they target specific oncogenic mutations, but other drugs that target mechanisms universal to all cancers do not. In this review, we discuss many of these non-oncogene-targeting anti-cancer agents including DNA replication inhibitors (
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., alkylating agents and topoisomerase inhibitors) and cytoskeletal function inhibitors to highlight their application in the setting of personalized medicine as well as their limitations and resistance factors.
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