Large Cardamom Extract Enhances Ramipril's Vasoprotective Action by Modulating Endothelial Redox Biology. An Evaluation based on in-silico and in-vitro Research

Background: The mechanisms that cause a patient's blood pressure to rise are diverse. Controlling blood pressure with monotherapy acting through a single pathway may be unachievable. Combining clinically used drug with herbal remedy can have two to five times greater antihypertensive response than monotherapy. Methods: This study examined the effects of aqueous extracts of large cardamom and ramipril on the redox biology of nitric oxide and vascular reactivity in the isolated aorta incubated with a nitro- L-arginine methyl ester. Molecular docking study was performed to predict the affinity of constituents of large cardamom extracts with the NOX 2 gene. Results: Nitric oxide (NO) levels, disordered antioxidant enzymes (glutathione and catalase), NADPH oxidase and lipid peroxidation were recovered when aqueous extract of large cardamomand ramipril were combined. A gradual increase in the percentage relaxation of acetylcholine in phenylephrine pre-contracted aorta indicates that the combination therapy prevents endothelial damage. Molecular docking study reveals the important phytoconstituents present in the large cardamom that can effectively bind with the NADPH oxidase for its antioxidant activity. Consculsion: According to our findings, it was evidenced that the large cardamom extract's vasoprotective action was was primarily due to its ability to restore endothelial redox biology by suppressing NADPH oxidase activity. Our findings suggest that ramipril's direct impact on the eNOS/NO system, along with the antioxidant properties of AELC, could have a synergetic benefit in the treatment of hypertension, as well as could minimize ramipril's existing side effects.