Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology, Banaras Hindu University (BHU), Uttar Pradesh, Varanasi, 221005, India.
School of Biomedical Engineering, Indian Institute of Technology, Banaras Hindu University (BHU), Uttar Pradesh, Varanasi, 221005, India.
Naunyn Schmiedebergs Arch Pharmacol. 2022 Oct;395(10):1189-1207. doi: 10.1007/s00210-022-02273-9. Epub 2022 Jul 25.
Depression and coronary heart diseases are the common comorbid disorder affecting humans globally. The present study evaluated the effectiveness of rosmarinic acid (RA) against myocardial infarction (MI) in comorbid depression induced by maternal separation in rats. Maternal stress is one of the childhood crises that may be a potential risk factor for coronary heart disease in later part of life. As per protocol, 70-80% of pups were separated daily for 3 h between postnatal day 1 (PND1) and postnatal day 21 (PND21). Forced-swim test, sucrose preference test, and electrocardiography were performed during the experiment. Body weight was measured on PND0, PND35, and PND55. Orally rosmarinic acid (25 mg/kg and 50 mg/kg) and fluoxetine (10 mg/kg) was done from PND35 to PND55. On PND53 and PND54, isoproterenol (100 mg/kg, subcutaneously) was administered to induce myocardial infarction. On PND55, blood was collected and animals sacrificed, and plasma corticosterone, brain-derived neurotrophic factor, cardiac biomarkers, interleukine-10, and anti-oxidant parameters were measured. Rosmarinic acid and fluoxetine ameliorated the maternal separation-induced increase in immobility period, anhedonia, body weight, ST elevation, corticosterone, creatine kinase-MB (CK-MB), and lactate dehydrogenase (LDH). At the same time, both drugs elevated the tissue levels of BDNF, IL-10, glutathione, and superoxide dismutase activity. This study provides the first experimental evidence that maternal stress is an independent risk factor of cardiac abnormalities in rats. Moreover, maternal stress synergistically increases the severity of cardiac abnormalities induced by isoproterenol. Interestingly, fluoxetine and rosmarinic acid effectively ameliorated behavioral anomalies and myocardial infarction in maternally separated rats. Schematic representation of possible molecular mechanism of action of rosmarinic acid against MS-induced myocardial infarction. RA, rosmarinic acid; MS, maternal separation; PND, postnatal days; ISO, isoproterenol; BDNF, brain-derived neurotrophic factor; GSH, glutathione; SOD, superoxide dismutase; IL-10, interleukin-10; MI, myocardial infarction.
抑郁和冠心病是影响全球人类的常见共病。本研究评估了迷迭香酸（RA）对母体分离诱导的合并抑郁大鼠心肌梗死（MI）的疗效。母体应激是儿童危机之一，可能是生命后期冠心病的潜在危险因素。按照方案，70-80%的幼崽在产后第 1 天（PND1）和第 21 天（PND21）之间每天分离 3 小时。在实验过程中进行强迫游泳试验、蔗糖偏好试验和心电图检查。在 PND0、PND35 和 PND55 测量体重。从 PND35 到 PND55 给予口服迷迭香酸（25mg/kg 和 50mg/kg）和氟西汀（10mg/kg）。在 PND53 和 PND54，皮下给予异丙肾上腺素（100mg/kg）诱导心肌梗死。在 PND55 时，收集血液并处死动物，测量血浆皮质酮、脑源性神经营养因子、心脏生物标志物、白细胞介素-10 和抗氧化参数。迷迭香酸和氟西汀改善了母体分离引起的不动期、快感缺失、体重、ST 抬高、皮质酮、肌酸激酶-MB（CK-MB）和乳酸脱氢酶（LDH）的增加。同时，两种药物都提高了 BDNF、IL-10、谷胱甘肽和超氧化物歧化酶活性的组织水平。这项研究提供了第一个实验证据，证明母体应激是大鼠心脏异常的独立危险因素。此外，母体应激协同增加异丙肾上腺素诱导的心脏异常的严重程度。有趣的是，氟西汀和迷迭香酸有效地改善了母体分离大鼠的行为异常和心肌梗死。迷迭香酸对 MS 诱导的心肌梗死作用的可能分子机制示意图。RA，迷迭香酸；MS，母体分离；PND，产后天数；ISO，异丙肾上腺素；BDNF，脑源性神经营养因子；GSH，谷胱甘肽；SOD，超氧化物歧化酶；IL-10，白细胞介素-10；MI，心肌梗死。
