Insulin sensitizing and cardioprotective effects of Esculetin and Telmisartan combination by attenuating Ang II mediated vascular reactivity and cardiac fibrosis

Kadakol, Almesh; Pandey, Anuradha; Goru, Santosh Kumar; Malek, Vajir; Gaikwad, Anil Bhanudas

doi:10.1016/j.ejphar.2015.09.035

Cited by 13 publications

(12 citation statements)

References 33 publications

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“…D, and E, indicate the averaged I-V relationships of I K(erg) obtained in control (circle symbols) and during exposure to 10 μmol/L TEL (square symbols), respectively. The results shown in (D) and (E) were, respectively, obtained at the beginning (filled symbols) and end (open symbols) of voltage pulses (mean ± SEM; n = 9-12 for each point) receptor, 3,6,9,31,34 administration of TEL at clinically used concentrations may be effective at perturbing the activity of ion channels in heart cells.…”

Section: Discussionmentioning

confidence: 99%

“…This drug may increase the depolarization‐induced hyperexcitability of heart cells by preferentially interacting with the inactivated states of Na V 1.5 channels. Therefore, despite being an antagonist of AT 1 receptor, administration of TEL at clinically used concentrations may be effective at perturbing the activity of ion channels in heart cells.…”

Section: Discussionmentioning

confidence: 99%

“…Telmisartan (TEL; C33H30N4O2; 4′-[(1,4′-dimethyl-2′-propyl[ 2 ,6′-bi-1H-benzimidazol]-1′-yl)-1′-yl]methyl)-[1,1′-biphenyl]-2carboxylic acid), a non-peptide, orally active blocker of angiotensin II type 1 (AT1) receptor, is the newest available drug class for the treatment of hypertension and different types of cardiovascular disorders. [1][2][3][4][5][6][7][8][9] This drug has been demonstrated to exert anti-inflammatory actions that are closely linked to its activation of PPARγ activity. [10][11][12][13] However, growing evidence indicates that TEL may interact with ion channels to perturb the amplitude and kinetics of ion currents.…”

Section: Introductionmentioning

confidence: 99%

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Activation of voltage‐gated sodium current and inhibition of erg‐mediated potassium current caused by telmisartan, an antagonist of angiotensin II type‐1 receptor, in HL‐1 atrial cardiomyocytes

Chang

2018

Clin Exp Pharma Physio

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Telmisartan (TEL) is a non-peptide blocker of angiotensin II type-1 (AT ) receptor. However, the mechanisms through which this drug interacts directly with ion currents in hearts remain largely unclear. Herein, we aim to investigate the effects of TEL the on ionic currents and membrane potential of murine HL-1 cardiomyocytes. In whole-cell recordings, addition of TEL stimulated the peak and late components of voltage-gated Na currents (I ) with different potencies. The EC values required to achieve the stimulatory effect of this drug on peak and late I were 0.2 and 1.2 μmol/L, respectively, and the current-voltage relationship of peak I shifted toward less-depolarized potentials during exposure to TEL. Telmisartan not only increased peak I but also prolonged the inactivation time course of late I . Amiodarone (Amio) or ranolazine (Ran), but not angiotensin II, could reverse TEL-mediated effects. The drug enhanced the recovery rate of I inactivation and exerted an inhibitory effect on erg-mediated K and L-type Ca currents. In whole-cell current-clamp recordings, addition of the drug resulted in prolongation of the duration of action potentials (APs) in a dose-dependent manner in HL-1 cells; Amio or Ran could reverse this increase in AP durations. Telmisartan-mediated prolongation of AP was attenuated in KCNH2 siRNA-transfected HL-1 cells. In cultured smooth muscle cells of the human coronary artery, TEL enhanced I amplitudes and slowed current inactivation. Stimulation by TEL of I in HL-1 cells did not simply increase current magnitude but altered current kinetics, thereby suggesting state-dependent activation. Telmisartan may have greater affinity to the open/inactivated state than to the resting state residing in Na channels. Collectively, TEL-mediated stimulation of I and inhibition of I could be an important ionic mechanism underlying the increased cell excitability of HL-1 cells; these actions, however, cannot be entirely explained by its blockade of AT receptor.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activation of voltage‐gated sodium current and inhibition of erg‐mediated potassium current caused by telmisartan, an antagonist of angiotensin II type‐1 receptor, in HL‐1 atrial cardiomyocytes

Chang

2018

Clin Exp Pharma Physio

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“…After 4 weeks, T2D control (T2DC) rats were treated with either esculetin (50 mg/kg/day) or telmisartan (10 mg/kg/day) or their combination and respective control animals were treated with vehicle (0.5% sodium carboxymethyl cellulose) for 2 weeks and the rats were allowed to feed on their respective diets till the end of the study. [ 6 ] Body weight (BW), biochemical estimations, and blood pressure measurements were performed at the end of 6 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…[ 4 5 ] Recently, we have reported that combination of telmisartan with a functional food ingredient, esculetin-prevented oxidative stress, cardiac fibrosis, and vascular stiffness in high-fat diet (HFD) induced IR condition. [ 6 ]…”

Section: Introductionmentioning

confidence: 99%

Telmisartan and esculetin combination ameliorates type 2 diabetic cardiomyopathy by reversal of H3, H2A, and H2B histone modifications

et al. 2017

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Pharmacological and Nutritional Effects of Natural Coumarins and Their Structure–Activity Relationships

Zhu

Jiang

2018

Molecular Nutrition Food Res

126

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Coumarins are fused benzene and pyrone ring systems with a wide spectrum of bioactivities, including antitumor, anti-inflammation, antiviral, and antibacterial effects. In this paper, the current development of coumarin-based drugs is introduced, and their structure-activity relationship is discussed by reviewing the relevant literature published in the past 20 years. Coumarin molecules can be customized by the target site to prevent systemic side effects by virtue of structural modification. The ortho-phenolic hydroxyl on the benzene ring has remarkable antioxidant and antitumor activities. Coumarins with aryl groups at the C-4 position have good activities in anti-HIV, antitumor, anti-inflammation, and analgesia. C-3 phenylcoumarins have strong anti-HIV and antioxidant effects. Tetracycline pyranocoumarins can significantly inhibit HIV; osthol structural analogues have antimicrobial activity. Praeruptorin C and its derivatives play an important role in lowering blood pressure and dilating coronary arteries, and khellactone derivatives have significant inhibitory effects on AIDS, cancer, and cardiovascular diseases. It is concluded that the specific site on the core structure of coumarin exhibits one or more activities due to the electronic or steric effects of the substituents. This review is intended to be conducive to rational design and development of more active and less toxic agents with a coumarin scaffold.

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Insulin sensitizing and cardioprotective effects of Esculetin and Telmisartan combination by attenuating Ang II mediated vascular reactivity and cardiac fibrosis

Cited by 13 publications

References 33 publications

Activation of voltage‐gated sodium current and inhibition of erg‐mediated potassium current caused by telmisartan, an antagonist of angiotensin II type‐1 receptor, in HL‐1 atrial cardiomyocytes

Activation of voltage‐gated sodium current and inhibition of erg‐mediated potassium current caused by telmisartan, an antagonist of angiotensin II type‐1 receptor, in HL‐1 atrial cardiomyocytes

Telmisartan and esculetin combination ameliorates type 2 diabetic cardiomyopathy by reversal of H3, H2A, and H2B histone modifications

Pharmacological and Nutritional Effects of Natural Coumarins and Their Structure–Activity Relationships

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