Nepeta deflersiana attenuates isoproterenol-induced myocardial injuries in rats: Possible involvement of oxidative stress, apoptosis, inflammation through nuclear factor (NF)-κB downregulation

Background: Nepeta deflersiana (Lamiaceae) is a perennial herb used in the Saudi and Yemeni folk medicine as an anti-inflammatory, carminative, and antirheumatic agent. Purpose: This study explores the phytochemistry of the plant and the cardioprotective effect of N. deflersiana ethanolic extract (NDEE) against isoproterenol (ISP)-induced myocardial injury in rats. Design/Methods: Cardiac function, serum cardiac enzymes, myocardial antioxidants, inflammatory, and apoptotic biomarkers, and histopathological parameters were studied in ISP-injured Wistar rat heart tissues. Results: To the best of our knowledge, this is the first study to report the isolation of nine secondary metabolites from this plant: 1 alpha-hydroxy-7 alpha, 14 alpha, 18-triacetoxy-isopimara-8,15-diene (1), beta-sitosterol (2), lupeol (3), ursolic acid (4), 2,3-dihydroxy ursolic acid (5), caffeic acid (6), methyl rosmarinate (7), rosmarinic acid (8), and an irridoid glucoside 8-epi-7-deoxyloganic acid (9). To explain the mechanisms underlying the cardioprotective effect of NDEE, we evaluated the redox-sensitivity of NDEE in ISP-induced cardiac injury. The oral administration of NDEE (50 and 100 mg/kg b.w) prevented the depletion of endogenous antioxidants (CAT, SOD, NP-SH, and NO) and myocyte injury marker enzymes and inhibited lipid peroxidation (MDA, MPO). Moreover, NDEE downregulated the expression of pro-inflammatory cytokines (TNF alpha, IL-6, and IL-10) and apoptotic markers (caspase-3 and Bax) and upregulated the anti-apoptotic protein Bcl2. Furthermore, NDEE pretreatment significantly downregulated cardiac NF-kappa B (p65) expression, NF-kappa B-DNA binding activity, and MPO activity. Histological data showed that NDEE pretreatment reduced myonecrosis, edema, and infiltration of inflammatory cells and restored the architecture of cardiomyocytes. Conclusion: NDEE demonstrated strong antioxidant, cardioprotective, anti-inflammatory, and anti-apoptotic potential against myocardial damage. This further endorses the use of N. deflersiana in Yemeni folk medicine against cardiovascular diseases.