scholarly journals Does In Vitro Cytochrome P450 Downregulation Translate to In Vivo Drug‐Drug Interactions? Preclinical and Clinical Studies With 13‐ cis ‐Retinoic Acid

2019 ◽  
Vol 12 (4) ◽  
pp. 350-360 ◽  
Author(s):  
Faith Stevison ◽  
Mika Kosaka ◽  
Jane R. Kenny ◽  
Susan Wong ◽  
Cathryn Hogarth ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Retinoic Acid ◽  
Drug Interactions ◽  
Clinical Studies ◽  
Preclinical And Clinical Studies

scholarly journals Essential Oils as Treatment Strategy for Alzheimerʼs Disease: Current and Future Perspectives

Planta Medica ◽  
2018 ◽  
Vol 85 (03) ◽  
pp. 239-248 ◽  
Author(s):  
Anju Benny ◽  
Jaya Thomas
Keyword(s):  
Essential Oils ◽  
Clinical Studies ◽  
Symptomatic Relief ◽  
Memory Loss ◽  
Clinical Trial Data ◽  
In Vivo Studies ◽  
Scientific Databases ◽  
Preclinical And Clinical Studies

AbstractAlzheimerʼs disease is a multifarious neurodegenerative disease that causes cognitive impairment and gradual memory loss. Several hypotheses have been put forward to postulate its pathophysiology. Currently, few drugs are available for the management of Alzheimerʼs disease and the treatment provides only symptomatic relief. Our aim is to review the relevant in vitro, in vivo, and clinical studies focused toward the potential uses of essential oils in the treatment of Alzheimerʼs disease. Scientific databases such as PubMed, ScienceDirect, Scopus, and Google Scholar from April 1998 to June 2018 were explored to collect data. We have conducted wide search on various essential oils used in different models of Alzheimerʼs disease. Out of 55 essential oils identified for Alzheimerʼs intervention, 28 have been included in the present review. A short description of in vivo studies of 13 essential oils together with clinical trial data of Salvia officinalis, Salvia lavandulifolia, Melissa officinalis, Lavandula angustifolia, and Rosmarinus officinalis have been highlighted. In vitro studies of remaining essential oils that possess antioxidant and anticholinesterase potential are also mentioned. Our literary survey revealed encouraging results regarding the various essential oils being studied in preclinical and clinical studies of Alzheimerʼs disease with significant effects in modulating the pathology through anti-amyloid, antioxidants, anticholinesterase, and memory-enhancement activity.

scholarly journals Cytochrome P450-Based Drug-Drug Interactions of Vonoprazan In Vitro and In Vivo

2020 ◽  
Vol 11 ◽  
Author(s):  
Yiran Wang ◽  
Changxiong Wang ◽  
Shuanghu Wang ◽  
Quan Zhou ◽  
Dapeng Dai ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions

Inhibition of Desipramine Hydroxylation (Cytochrome P450-2D6) in Vitro by Quinidine and by Viral Protease Inhibitors: Relation to Drug Interactions in Vivo

1998 ◽  
Vol 87 (10) ◽  
pp. 1184-1189 ◽  
Author(s):  
Lisa L. von Moltke ◽  
David J. Greenblatt ◽  
Su Xiang Duan ◽  
Johanna P. Daily ◽  
Jerold S. Harmatz ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Protease Inhibitors ◽  
Cytochrome P450 2D6 ◽  
Viral Protease ◽  
P450 2D6

scholarly journals A Novel Cytochrome P450, Zebrafish Cyp26D1, Is Involved in Metabolism of All-trans Retinoic Acid

2006 ◽  
Vol 20 (7) ◽  
pp. 1661-1672 ◽  
Author(s):  
Xingxing Gu ◽  
Fang Xu ◽  
Wei Song ◽  
Xiaolin Wang ◽  
Ping Hu ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Retinoic Acid ◽  
Critical Concentration ◽  
Zebrafish Embryos ◽  
Retinoid Signaling ◽  
All Trans Retinoic Acid ◽  
Left Right Asymmetry ◽  
X Receptors

Abstract Retinoid signaling is essential for development of vertebrate embryos, and its action is mainly through retinoic acid (RA) binding to its RA receptors and retinoid-X receptors, while the critical concentration and localization of RA in embryos are determined by the presence and activity of retinal dehydrogenases (for RA synthesis) and cytochrome P450 RAs (Cyp26s) (for degradation of RA). Previously, we identified a novel cyp26 gene (cyp26d1) in zebrafish that is expressed in hindbrain during early development. Using reverse-phase HPLC analyses, we show here that zebrafish Cyp26D1 expressed in 293T cells could metabolize all-trans RA, 9-cis RA, and 13-cis RA, but could not metabolize retinol or retinal. The metabolites of all-trans RA produced by Cyp26D1 were the same as that produced by Cyp26A1, which are mainly 4-hydroxy-all-trans-RA and 4-oxo-all-trans-RA. Performing mRNA microinjection into zebrafish embryos, we demonstrated that overexpression of Cyp26D1 in embryos not only caused the distance between rhombomere 5 and the first somite of the injected embryos to be shorter than control embryos but also resulted in left-right asymmetry of somitogenesis in the injected embryos. These alterations were similar to those caused by the overexpression of cyp26a1 in zebrafish embryos and to that which resulted from treating embryos with 1 μm 4-diethylamino-benzaldehyde (retinal dehydrogenase inhibitor), implying that cyp26d1 can antagonize RA activity in vivo. Together, our in vitro and in vivo results provided direct evidence that zebrafish Cyp26D1 is involved in RA metabolism.

scholarly journals Metabolic Drug-Drug Interaction Potential of Macrolactin A and 7-O-Succinyl Macrolactin A Assessed by Evaluating Cytochrome P450 Inhibition and Induction and UDP-Glucuronosyltransferase InhibitionIn Vitro

2014 ◽  
Vol 58 (9) ◽  
pp. 5036-5046 ◽  
Author(s):  
Soo Hyeon Bae ◽  
Min Jo Kwon ◽  
Jung Bae Park ◽  
Doyun Kim ◽  
Dong-Hee Kim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interactions ◽  
Antitumor Agents ◽  
Content Type ◽  
Dependent Inactivation ◽  
Competitive Inhibitors ◽  
Macrolactin A ◽  
Clinically Significant

ABSTRACTMacrolactin A (MA) and 7-O-succinyl macrolactin A (SMA), polyene macrolides containing a 24-membered lactone ring, show antibiotic effects superior to those of teicoplanin against vancomycin-resistant enterococci and methicillin-resistantStaphylococcus aureus. MA and SMA are currently being evaluated as antitumor agents in preclinical studies in Korea. We evaluated the potential of MA and SMA for the inhibition or induction of human liver cytochrome P450 (CYP) enzymes and UDP-glucuronosyltransferases (UGTs)in vitroto assess their safety as new molecular entities. We demonstrated that MA and SMA are potent competitive inhibitors of CYP2C9, withKivalues of 4.06 μM and 10.6 μM, respectively. MA and SMA also weakly inhibited UGT1A1 activity, withKivalues of 40.1 μM and 65.3 μM, respectively. However, these macrolactins showed no time-dependent inactivation of the nine CYPs studied. In addition, MA and SMA did not induce CYP1A2, CYP2B6, or CYP3A4/5. On the basis of anin vitro-in vivoextrapolation, our data strongly suggested that MA and SMA are unlikely to cause clinically significant drug-drug interactions mediated via inhibition or induction of most of the CYPs involved in drug metabolismin vivo, except for the inhibition of CYP2C9 by MA. Similarly, MA and SMA are unlikely to inhibit the activity of UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7 enzymesin vivo. Although further investigations will be required to clarify thein vivointeractions of MA with CYP2C9-targeted drugs, our findings offer a clearer understanding and prediction of drug-drug interactions for the safe use of MA and SMA in clinical practice.

scholarly journals Genome Editing Technologies: From Bench Side to Bedside

Acta Medica ◽  
2018 ◽  
Vol 49 (3) ◽  
pp. 30
Author(s):  
Fulya Yaylacıoğlu Tuncay ◽  
Pervin Rukiye Dinçer
Keyword(s):  
Gene Therapy ◽  
Animal Models ◽  
Genome Editing ◽  
Clinical Studies ◽  
Human Gene ◽  
Human Gene Therapy ◽  
Novel Technologies ◽  
Preclinical And Clinical Studies

The development of genome editing technologies has given the chance to researchers to manipulate any genomic sequences precisely. This ability is very useful for creating animal models to study human diseases in vivo; for easy creation of isogenic cell lines to study in vitro and most importantly for overcoming many disadvantages that the researchers faced during the human gene therapy trials. Here we review the basic mechanisms of genome editing technology and the four genome-editing platforms. We also discuss the applications of these novel technologies in preclinical and clinical studies in four groups according to the mechanism used, and lastly, summarize the problems in these technologies.

scholarly journals Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1028 ◽  
Author(s):  
Anshul Sharma ◽  
Hae-Jeung Lee
Keyword(s):  
Clinical Studies ◽  
Water Solubility ◽  
Parent Compound ◽  
Clinical Trial Data ◽  
In Vivo Studies ◽  
Compound K ◽  
Health Promoting ◽  
Preclinical And Clinical Studies

Ginseng (Panax ginseng) is an herb popular for its medicinal and health properties. Compound K (CK) is a secondary ginsenoside biotransformed from major ginsenosides. Compound K is more bioavailable and soluble than its parent ginsenosides and hence of immense importance. The review summarizes health-promoting in vitro and in vivo studies of CK between 2015 and 2020, including hepatoprotective, anti-inflammatory, anti-atherosclerosis, anti-diabetic, anti-cancer, neuroprotective, anti-aging/skin protective, and others. Clinical trial data are minimal and are primarily based on CK-rich fermented ginseng. Besides, numerous preclinical and clinical studies indicating the pharmacokinetic behavior of CK, its parent compound (Rb1), and processed ginseng extracts are also summarized. With the limited evidence available from animal and clinical studies, it can be stated that CK is safe and well-tolerated. However, lower water solubility, membrane permeability, and efflux significantly diminish the efficacy of CK and restrict its clinical application. We found that the use of nanocarriers and cyclodextrin for CK delivery could overcome these limitations as well as improve the health benefits associated with them. However, these derivatives have not been clinically evaluated, thus requiring a safety assessment for human therapy application. Future studies should be aimed at investigating clinical evidence of CK.

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