Melissa officinalis extract attenuates gamma radiation-induced cardiac injury in rats: An integrated bioinformatics and experimental study

The detrimental effect of gamma radiation on cardiac tissue is an intricate problem in the field of nuclear medicine. Therefore, this study aimed to investigate the potential mechanism of Melissa officinalis (MO) against irradiation (IR)-induced cardiac toxicity using an integrated approach combining phytochemical profiling (HPLC and GC-MS), network pharmacology, molecular docking, and in vivo experimental validation. Phytochemical profiling, Network pharmacology and molecular docking analyses identified ellagic acid as a major bioactive constituent of MO and predicted the NRF2 and MAPK pathways as key targets. For in vivo validation, twenty-four male Wistar rats were divided into four groups: control, MO extract (75 mg/kg/day for 3 weeks), irradiated (5 Gy gamma radiation), and irradiated + MO extract. Cardiac injury was assessed by measuring cardiac enzymes (ALT, LDH), oxidative stress markers (MDA, GSH, SOD, CAT, and GPx), lipid profile, and gene expression of PGC-1α, β3AR, Na+/K+-ATPase, NRF2, MAPK, and JNK. MO extract significantly attenuated radiation-induced elevations in serum LDH and ALT, reduced lipid peroxidation, restored antioxidant defenses, and was associated with improved transcriptional markers of cardiac metabolism. These effects were mediated through upregulation of NRF2 and downregulation of MAPK and JNK signaling pathways, consistent with network pharmacology predictions. Collectively, these results suggest that MO may represent a promising candidate for mitigating acute radiation-induced biochemical alterations associated with cardiac injury by enhancing cardiac function and mitigating impaired oxidative status. The study revealed that MO could reduce cardiac toxicity in irradiated rats through its antioxidant activity, mediated by the NRF2 and MAPK pathways.