Evaluation of cardioprotection and bio-efficacy enhancement of stevioside and diltiazem in rats

Abstract

Background: Cardiovascular diseases and resultant complications of cardio-therapeutic regimens are one of the leading causes of mortalities in developing countries. Diltiazem is a calcium channel blocker primarily used in treatment of supraventricular arrhythmias, systemic hypertension, and hypertrophic cardiomyopathy. Stevioside, the chief component of Stevia plant, is a natural sweetener that has significant therapeutic properties. Stevioside is a known bioenhancer that acts by synergizing pharmacological activities of other drugs. Present study was designed to evaluate cardioprotective activity of stevioside and possible bioenhancement upon co-administration with diltiazem. Standard cardiotoxicity models-isoproterenol-induced myocardial infarction and ischemia-reperfusion injury (IRI) through modified Langendorff setup was used to test this hypothesis. Rats were randomly divided into control groups (normal-physiological saline and toxic-isoproterenol, 150 mg/kg, s.c., and IRI induced in normal control animals) and treatment groups (diltiazem-17.5 mg/kg, p.o., stevioside-100 and 200 mg/kg, p.o. and combination groups). At the end of the treatment period, animals were sacrificed and biochemical, electrocardiographic, and histopathological changes were measured. Results: Pre-treatment with stevioside prevented leakage of biomarkers and normalized serum and perfusate levels of CK-MB, CK-NAC, LDH, AST, and ALT enzymes. It displayed lipid-lowering effect on TC and TG levels dose dependently. STV also showed protective action on levels of tissue antioxidant enzymes (SOD and Catalase), electrocardiographic parameters (HR, RR, QRS, QT, PR), and heart tissue histopathology when compared to concurrent toxic control groups. Combination of stevioside (200 mg/kg) and diltiazem (17.5 mg/kg) exerted a more significant pharmacodynamic response, significantly restored biomarkers, antioxidants levels, and myocardial histology, and normalized electrocardiographic parameters. Conclusion: Stevioside and diltiazem both displayed cardioprotective effect when given alone. Co-administration displayed improved restorative action on antioxidant status, biomarkers, electrocardiographic parameters, and histology.

Cardioprotective potential of the antioxidant-rich bioactive fraction of Garcinia pedunculata Roxb. ex Buch.-Ham. against isoproterenol-induced myocardial infarction in Wistar rats

“…These results positively indicate that GC could preserve the typical membrane architecture of the myocardium, acting against the induction of cardiac hypertrophy and cardiotoxicity. These GC results align with the earlier reports of ( Hu et al, 2019 ; Bhatt et al, 2020 ; Feriani et al, 2020 ; Soumya et al, 2021 ).…”

“…It also shows a noticeable increase in all the pathological markers mentioned above. These changes indicate the presence of myocardial necrosis, damaged membrane integrity, and ischemic injury ( Panda et al, 2017 ; Bhatt et al, 2020 ). With GC pretreatment, successful reduction of these hypertrophic and pathological markers down to their normal levels was recorded in this study.…”

A Mixture of Tocopherol Acetate and L-Menthol Synergistically Promotes Hair Growth in C57BL/6 Mice

“…Additional investigation needs to be carried out to determine whether this compound contributes to the promotion of hair growth. Stevioside is known to cause the inhibition of calcium influx via the blockage of calcium channels, inhibition of extracellular calcium influx, and release of prostaglandins [ 29 , 30 ]. In addition, stevioside exerts anti-inflammatory and immunomodulatory activities by actively attenuating the nuclear factor (NF)-kappa B pathway [ 31 ].…”

Stevia rebaudiana, a Versatile Food Ingredient: The Chemical Composition and Medicinal Properties

“…Stevioside, a chemical component found in Stevia, has a synergic pharmacological activity. Bhatt et al [30] designed an experiment to evaluate the cardioprotective properties of stevioside and possible synergistic effects upon coadministration with diltiazem. The team made use of standard cardiotoxicity models to test the hypothesis: ischemiareperfusion injury (IRI) and isoproterenol-induced myocardial infarction through Langendoff set up.…”