Abstract
Objective: The present study was carried out to evaluate the combined cardioprotective effect of standardized extract of Tinospora cordifolia extract (TCE) with atenolol (AT) and propranolol (PP) in isoproterenol (ISO) induced cardiac necrosis in rats. 
 Methods: Myocardial infarction (MI) or cardiac necrosis was induced by subcutaneous administration of ISO for two days consecutively at an interval of 24 h. Rats were pre-administered with test drugs for 21 d followed by ISO was administration on 20 and 21st day. 24 h after final ISO administration, mean arterial blood pressure (MAB), Heart rate (HR), electrocardiogram (ECG), heart bio-marker enzyme, and histopathological study of cardiac tissue were evaluated from control and experimental groups and analyzed statistically by one-way ANOVA followed by Tukeys’s test. 
 Results: Rats administered with ISO showed significant (p<0.001) changes in ECG, HR, MAB, heart bio-marker enzyme, antioxidant parameters, and histopathology of the heart. The activities of biomarkers have reduced in serum and there is a significant (p<0.001) increase in antioxidants in the heart tissue of animals treated with drug combination. Similarly, ECG, MAB, and HR were restored to normalcy in drug-treated animals. 
 Conclusion: It may be concluded that the herb-drug combinations i. e TCE (500 mg/kg)+AT (10 mg/kg) and TCE (500 mg/kg)+PP (10 mg/kg) has shown increased cardioprotective activity than they were used alone.
Highlights
Cardiovascular diseases are major contributors to the high incidence of mortality occurring globally
Severe oxidative stress is caused by ISO in the myocardial cells, and at increased doses, it produces Myocardial infarction (MI)-like changes in the heart tissue [1]
Creatine kinase-MB (CK-MB), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) standard kits were purchased from ARKRAY Healthcare Pvt
Summary
Cardiovascular diseases are major contributors to the high incidence of mortality occurring globally. There is a need for extensive research for the effective treatment of these cardiovascular diseases. Severe oxidative stress is caused by ISO in the myocardial cells, and at increased doses, it produces MI-like changes in the heart tissue [1]. It is a well-known fact that the ISOgenerated free radicals initiate the lipid peroxidation of membranebound polyunsaturated fatty acids, which leads to structural as well as functional cardiac tissue injury [2, 3]. Tinospora cordifolia (Menispermaceae) is reported in scientific literature as a constituent of many active compound formulations used in the treatment of general diseases like dyspepsia, fever, and urinary diseases. An attempt was made to evaluate the combined effect of TCE with AT and PP if any, in the ISOinduced myocardial damage that is known to induce myocardial necrosis and cardiotoxicity [6,7,8]
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