Akomolafe_2025_J.Mol.Histol_56_157

Cardiovascular diseases are among the top killer diseases globally. This work assessed the cardioprotective ability of raw and roasted pumpkin (Cucurbita pepo L.) seed-supplemented diets on cisplatin-induced heart damage in rats. The cardiotoxicity was induced with cisplatin (7 mg/kg) intraperitoneally. The rats' six groups were treated for 14 days: control rats fed a normal diet; group 2: cisplatin-induced (CIS) untreated; groups 3 and 4: CIS + 5% raw pumpkin seed (RW) and CIS + 10% RW; groups 5 and 6: CIS + 5% and 10% roasted pumpkin seed (RT). The biochemical assays were done using standard procedures, and Schrodinger suites were used for in silico studies of C. pepo phytocompounds with phosphodiesterase 5. There was a significant (p < 0.05) elevation in arginase, phosphodiesterase-5, adenosine deaminase, acetylcholinesterase, and butyrylcholinesterase activities, ROS and TBARS in cisplatin-induced rats relative to control. Cisplatin-induced rats also have their nitric oxide, antioxidant (catalase, GST, and GSH) levels reduced, and the heart's histoarchitectural structure degenerated relative to control. These conditions were reversed upon treatment with raw and roasted pumpkin seeds (5% and 10%). Molecular docking of C. pepo phytocompounds like chlorogenic acid (-11.4 kcal/mol), beta-sitosterol (-11.013 kcal/mol), quercetin (-10.323 kcal/mol), and epicatechin (-10.168 kcal/mol) suggests that they are potent inhibitors of phosphodiesterase 5, better than standard drug pravastatin (-9.809 kcal/mol), with a good pharmacotoxicity profile. The study suggests that the cardioprotective effect of raw and roasted pumpkin seeds could be via their ability to inhibit phosphodiesterase 5, improve vasodilation, increase antioxidant levels, and alleviate oxidative stress.