Pharmacogenetics in the Treatment of Cardiovascular Diseases and Its Current Progress Regarding Implementation in the Clinical Routine

Dávila-Fajardo, Cristina Lucía; Díaz-Villamarín, Xando; Antúnez-Rodríguez, Alba; Fernández-Gómez, Ana Estefanía; García-Navas, Paloma; Martínez-González, Luis Javier; Dávila-Fajardo, José Augusto; Barrera, J Cabeza

doi:10.3390/genes10040261

Cited by 19 publications

(16 citation statements)

References 116 publications

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“…Nowadays, several attempts have focused on coumarins, as an abundant secondary metabolite, considered an effective bioactive molecule that present a promising therapeutic option. Coumarins are found in several plant families and essential oils and are used as fragrant additives in food and cosmetics [12]. Many reports have suggested that the coumarins possess a huge array of biological roles, such as antithrombotic, neuroprotective, antidiabetic, anticoagulant, anti-inflammatory, antioxidant, and antiplasmodial activities [13][14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

(E)-N′-(1-(7-Hydroxy-2-Oxo-2H-Chromen-3-Yl) Ethylidene) Benzohydrazide, a Novel Synthesized Coumarin, Ameliorates Isoproterenol-Induced Myocardial Infarction in Rats through Attenuating Oxidative Stress, Inflammation, and Apoptosis

Feriani

Khdhiri

Tir

et al. 2020

Oxidative Medicine and Cellular Longevity

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The present study was directed to investigate the effect of precotreatment with (E)-N′-(1-(7-hydroxy-2-oxo-2H-chromen-3-yl) ethylidene) benzohydrazide (7-hyd.HC), a novel potent synthesized coumarin, on isoproterenol- (ISO-) induced myocardial infarction (MI) in rats. The hydrazone compound was characterized by IR, 1D, and 2D NMR analyses. Experimental induction of MI in rats was established by ISO (85 mg/kg/day, s.c) for two consecutive days (6th and 7th days). 7-hyd.HC or sintrom was given for 7 days prior and simultaneous to ISO injection. 7-hyd.HC offered a cardiopreventive effect by preventing heart injury marker leakage (LDH, ALT, AST, CK-MB, and cTn-I) from cardiomyocytes and normalizing cardiac function and ECG pattern, as well as improving lipid profile (TC, TG, LDL-C, and HDL-C), which were altered by ISO administration. Moreover, 7-hyd.HC precotreatment significantly mitigated the oxidative stress biomarkers, as evidenced by the decrease of lipid peroxidation and the increased level of the myocardial GSH level together with the SOD, GSH-Px, and catalase activities. 7-hyd.HC inhibited the cardiac apoptosis by upregulating the expression of Bcl-2 and downregulating the expression of Bax and caspase-3 genes. In addition, 7-hyd.HC reduced the elevated fibrinogen rate and better prevented the myocardial necrosis and improved the interstitial edema and neutrophil infiltration than sintrom. Overall, 7-hyd.HC ameliorated the severity of ISO-induced myocardial infarction through improving the oxidative status, attenuating apoptosis, and reducing fibrinogen production. The 7-hyd.HC actions could be mediated by its antioxidant, antiapoptotic, and anti-inflammatory capacities.

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Section: Introductionmentioning

confidence: 99%

(E)-N′-(1-(7-Hydroxy-2-Oxo-2H-Chromen-3-Yl) Ethylidene) Benzohydrazide, a Novel Synthesized Coumarin, Ameliorates Isoproterenol-Induced Myocardial Infarction in Rats through Attenuating Oxidative Stress, Inflammation, and Apoptosis

Feriani

Khdhiri

Tir

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Coumarins have a wide range of biological properties including antiviral, antimicrobial, anti-inflammatory, and other bioactivities. Some coumarins are approved for use in the treatment of various diseases [ 28 , 29 , 30 , 31 ]. The most important are vitamin K antagonists, such as warfarin, phenprocumone, or acenocumarol, which are used as anticoagulants [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Coumarin’s Anti-Quorum Sensing Activity Can Be Enhanced When Combined with Other Plant-Derived Small Molecules

Deryabin¹,

Inchagova²,

Rusakova³

et al. 2021

Molecules

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Coumarins are class of natural aromatic compounds based on benzopyrones (2H-1-benzopyran-2-ones). They are identified as secondary metabolites in about 150 different plant species. The ability of coumarins to inhibit cell-to-cell communication in bacterial communities (quorum sensing; QS) has been previously described. Coumarin and its derivatives in plant extracts are often found together with other small molecules that show anti-QS properties too. The aim of this study was to find the most effective combinations of coumarins and small plant-derived molecules identified in various plants extracts that inhibit QS in Chromobacterium violaceum ATCC 31532 violacein production bioassay. The coumarin and its derivatives: 7-hydroxycoumarin, 7.8-dihydroxy-4-methylcoumarin, were included in the study. Combinations of coumarins with gamma-octalactone, 4-hexyl-1.3-benzenediol, 3.4.5-trimethoxyphenol and vanillin, previously identified in oak bark (Quercus cortex), and eucalyptus leaves (Eucalyptus viminalis) extracts, were analyzed in a bioassay. When testing two-component compositions, it was shown that 7.8-dihydroxy-4-methylcoumarin, 4-hexyl-1.3-benzendiol, and gamma-octalactone showed a supra-additive anti-QS effect. Combinations of all three molecules resulted in a three- to five-fold reduction in the concentration of each compound needed to achieve EC50 (half maximal effective concentration) against QS in C. violaceum ATCC 31532.

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“…In cancer management, targeted therapy based on genetic data is widely applied (e.g., cetuximab for KRAS wild-type colorectal cancer, dabrafenib for cancers with V600E BRAF mutation). In cardiovascular disease, pharmacogenetic profiling for clopidogrel, warfarin, acenocoumarol, and simvastatin dosing is recommended [110,111]. At the same time, there are some obstacles that need to be overcome to fully implement pharmacogenetic testing in the clinical practice: we need robust evidence for cost effectiveness, physicians and patients need to be aware and trained, and commercial pharmacogenetic panels need to be developed [111].…”

Section: Discussionmentioning

confidence: 99%

“…In cardiovascular disease, pharmacogenetic profiling for clopidogrel, warfarin, acenocoumarol, and simvastatin dosing is recommended [110,111]. At the same time, there are some obstacles that need to be overcome to fully implement pharmacogenetic testing in the clinical practice: we need robust evidence for cost effectiveness, physicians and patients need to be aware and trained, and commercial pharmacogenetic panels need to be developed [111]. For IBD, to date, pharmacogenetic research has also produced the most success in the context of molecular patient profiling (e.g., TPMT and NUDT15 genetic testing in the context of thiopurine-induced myelotoxicity, Table 2).…”

Section: Discussionmentioning

confidence: 99%

Molecular Profiling of Inflammatory Bowel Disease: Is It Ready for Use in Clinical Decision-Making?

Lee

Cleynen

2019

Cells

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Inflammatory bowel disease (IBD) is a heterogeneous disorder in terms of age at onset, clinical phenotypes, severity, disease course, and response to therapy. This underlines the need for predictive and precision medicine that can optimize diagnosis and disease management, provide more cost-effective strategies, and minimize the risk of adverse events. Ideally, we can leverage molecular profiling to predict the risk to develop IBD and disease progression. Despite substantial successes of genome-wide association studies in the identification of genetic variants affecting IBD susceptibility, molecular profiling of disease onset and progression as well as of treatment responses has lagged behind. Still, thanks to technological advances and good study designs, predicting phenotypes using genomics and transcriptomics in IBD has been rapidly evolving. In this review, we summarize the current status of prediction of disease risk, clinical course, and response to therapy based on clinical case presentations. We also discuss the potential and limitations of the currently used approaches.

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Pharmacogenetics in the Treatment of Cardiovascular Diseases and Its Current Progress Regarding Implementation in the Clinical Routine

Cited by 19 publications

References 116 publications

(E)-N′-(1-(7-Hydroxy-2-Oxo-2H-Chromen-3-Yl) Ethylidene) Benzohydrazide, a Novel Synthesized Coumarin, Ameliorates Isoproterenol-Induced Myocardial Infarction in Rats through Attenuating Oxidative Stress, Inflammation, and Apoptosis

(E)-N′-(1-(7-Hydroxy-2-Oxo-2H-Chromen-3-Yl) Ethylidene) Benzohydrazide, a Novel Synthesized Coumarin, Ameliorates Isoproterenol-Induced Myocardial Infarction in Rats through Attenuating Oxidative Stress, Inflammation, and Apoptosis

Coumarin’s Anti-Quorum Sensing Activity Can Be Enhanced When Combined with Other Plant-Derived Small Molecules

Molecular Profiling of Inflammatory Bowel Disease: Is It Ready for Use in Clinical Decision-Making?

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