Improvised cardiac function of siddha formulation Sikkanjar elixir® through CAMK2 and VEGF mechanism-in experimentally induced cardiac hypertrophy model in rats

BACKGROUND: Sikkanjar elixir® (SE) contains 29 herbs, honey and fermented rice water. It is a modified and fortified form of Sikkanjar Manappagu (Manappagu means syrup), a Siddha traditional medicine. SE has its reference to treat vascular block, high cholesterol, varicose vein, hypertension; improved cardiac efficiency and blood circulation. However, the validation of Siddha claim of SE has not been carried out in experimentally conditions. OBJECTIVE: The present study designed to validate the scientific claim of SE and investigate the cardio-protective prospective of SE, in a rat model of cardiac hypertrophy (CH). MATERIALS AND METHODS: CH was induced in Sprague-Dawley rats via ligation of the descending abdominal aorta. The cardio-protective effects of SE were evaluated through behavioral assessments, biochemical parameters, antioxidant profiling, liver and kidney function tests, ATP, troponin I levels measurement. The cardiac hypertrophy markers like CAMK2, VEGF, and SIRT3 expression were measured through qRTPCR. RESULTS: HPTLC evaluation of SE denotes 1.221 mg RUE/g and 4.604 mg GAE/g, of total flavonoid and phenolics content respectively. CH induction led to elevated heart rate, troponin I, and liver/kidney function markers, along with decreased plasma glucose, cholesterol, tissue ATP, catalase, glutathione, and VEGF levels. SE treatment significantly reversed these changes, as evidenced by reduced heart rate, normalization of biochemical markers, and improved antioxidant status. Notably, SE treatment suppressed CAMK2 expression and upregulated VEGF, suggesting enhanced myocardial contractility. Histopathological analysis further supported these findings, showing reduced myocyte fibre thickness and septal volume. CONCLUSION: SE reversed the CH induced pathology through restoration of cardiac pumping efficiency (ejection fraction) via CAMK2 and VEGF mechanism. Normalization of cardiac output might contribute to the recovery of kidney, metabolic functions and promotion of anti-oxidant effect. These observations can also be extrapolated in CCF or MI conditions in clinical situations.