Aromadendrin attenuates isoproterenol-induced myocardial injury via modulation of oxidative stress, apoptosis, and mitogen-activated protein kinase/nuclear factor erythroid 2-related factor 2 signaling pathways

BACKGROUND: Myocardial injury (MI) generated by excessive β-adrenergic stimulation, such as with isoproterenol (ISO), is intimately related to oxidative stress, inflammation, and apoptosis. Aromadendrin (AD), a well-known flavonoid, has anti-inflammatory and antioxidant properties and is being investigated for its potential in various diseases. The aim of the current investigation was to explore the cardioprotective effect of ISO-induced MI in rats and the underlying mechanism. MATERIALS AND METHODS: Intraperitoneal administration of ISO (100 mg/kg) was used for the induction of MI in rats, and rats received the oral administration of AD (2.5, 5, and 10 mg/kg). The body weight, heart weight, heart/body weight ratio, hemodynamic parameters, hemodynamic function, membrane-bound enzymes, cardiac 5HT, serum 5HT, serum, cardiac total calcium (Ca2), antioxidant, lipid, inflammatory, matrix metalloproteinase (MMP), and apoptosis parameters were estimated. The mRNA expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), B-cell lymphoma 2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), cysteine-aspartic acid protease-3 (Caspase-3), protein kinase B (Akt), mechanistic target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 MAPK (p38) were estimated. RESULTS: AD treatment altered the hemodynamic parameters left ventricular systolic pressure, left ventricular end-diastolic pressure, ±dP/dt, hemodynamic functional (heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure), lipid parameters (total cholesterol, triglyceride, low density lipoprotein (LDL), very LDL, high density lipoprotein), membrane bound enzymes (Na⁺/K⁺-ATPase, Mg2⁺- ATPase, Ca2⁺-ATPase), antioxidant parameters (superoxide dismutase, catalase, glutathione, malonaldehyde), inflammatory cytokines (Tumor necrosis factor-α, interleukin-1β [IL-1β], IL-6, IL-10), inflammatory parameters (nuclear factor kappa B, cyclooxygenase-2, inducible nitric oxide synthetase), apoptosis parameters (Bax, Bcl-2, caspase-3, caspase-9, caspase-c), MMP (MMP-2, MMP-3, and MMP-9), HO-1, and Nrf2. AS altered the mRNA expression of Nrf2, HO-1, Bax, Bcl-2, caspase-3, Akt, mTOR, and MAPK (ERK, JNK, and p38). CONCLUSION: AD confers potent cardioprotective effects against ISO induced MI in rats via alteration of oxidative stress, apoptosis, and MAPK/Nrf2 signaling pathways.