Objective: The current study aimed to evaluate the protective role of Manilkara hexandra methanolic bark extract (MHBE) against cisplatin-induced renal injuries and its effects on the cardiovascular system in Wistar rats using in-silico and in-vivo approaches.
Materials and methods: In-silico studies, including network pharmacology and molecular docking, identified key MHBE phytochemicals and their target proteins. Nephrotoxicity was induced with a single intraperitoneal dose of cisplatin (5 mg/kg), followed by oral MHBE treatment at low (100 mg/kg) and high (200 mg/kg) doses for 21 days. Renal and cardiac biochemical markers were measured weekly, alongside urine analysis and ECG monitoring. Histopathological examinations of kidney and heart tissues were conducted.
Results: In-silico findings revealed that bioactives such as taxifolin, catechin, and quercetin effectively targeted poly (ADP-ribose) polymerase 1 (PARP1), tumor necrosis factor ligand superfamily member 11 (TNFSF11), and interleukin-6 (IL-6), providing protection against cisplatin-induced damage. Cisplatin administration elevated serum creatinine, blood urea nitrogen (BUN), uric acid, lactate dehydrogenase (LDH), and creatine kinase-myocardial band (CK-MB), increased urinary sodium and potassium, and reduced serum total protein and albumin. Electrocardiogram (ECG) showed prolonged PR, QT, and QRS intervals with bradycardia in cisplatin-treated rats. MHBE treatment significantly attenuated these biochemical and electrophysiological alterations. Histopathological observations confirmed MHBE ability to restore renal and cardiac architecture.
Conclusion: The findings of in silico and in vivo studies demonstrate that Manilkara hexandra methanolic bark extract mitigates cisplatin-induced renal and cardiac toxicities.