Younis Nancy Safwat
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Hasa 31982, Kingdom of Saudi Arabia.
Department of Pharmacology, Zagazig University, Zagazig 44519, Egypt.
Korean J Physiol Pharmacol. 2020 May 1;24(3):259-266. doi: 10.4196/kjpp.2020.24.3.259.
Cardiovascular diseases are the primary reason of mortality, among which myocardial infarction (MI) is the most dominant and prevalent. This study was considered to examine D-Limonene protective action against isoproterenol (ISO) induced MI. Wister male rats were dispersed into four groups. Normal and D-Limonene control group in which rats administered saline or D-Limonene. ISO control animals were administered saline for 21 days then challenged with ISO (85 mg/kg, subcutaneously) on 20th and 21st day for MI induction. D-Limonene pretreated group in which animals were pretreated with D-Limonene 50 mg/kg orally for 21 days then administered ISO on 20th and 21st day. MI prompted variations were assessed by myocardial infarction area determination, blood pressure (BP) alterations, cardiac injury biomarkers and inflammatory mediators measurements. For more depth investigation, both the apoptotic status was evaluated measuring mRNA expression of Bcl-2 and Bax as well as mitogen-activated protein kinase-extracellular signal-regulated kinase (MAPK-ERK) signal transduction were investigated Western blotting. MI group revealed significant infarcted area, blood pressure alterations, myocardial injury enzymes intensification together with inflammatory cytokines amplification. MI was associated with activation of MAPK-ERK signal pathway and apoptotic status within the myocardium. On the other hand, pretreated with D-Limonene demonstrated deterred infracted area, reduced myocardial enzymes, improved BP indices, lessened inflammatory levels. Furthermore, D-Limonene pretreatment caused a decline in MAPK proteins pathway and Bax relative mRNA expression, while intensifying Bcl-2 mRNA expression promoting that D-Limonene may constrain MI induced myocardial apoptosis. D-Limonene mitigated MI injury through MAPK/NF-κB pathway inhibition and anti-apoptotic effect.
心血管疾病是死亡的主要原因，其中心肌梗死（MI）最为常见和普遍。本研究旨在探讨D-柠檬烯对异丙肾上腺素（ISO）诱导的心肌梗死的保护作用。将雄性Wister大鼠分为四组。正常组和D-柠檬烯对照组分别给予生理盐水或D-柠檬烯。ISO对照组动物连续21天给予生理盐水，然后在第20天和第21天皮下注射ISO（85mg/kg）诱导心肌梗死。D-柠檬烯预处理组动物口服50mg/kg D-柠檬烯预处理21天，然后在第20天和第21天给予ISO。通过测定心肌梗死面积、血压（BP）变化、心脏损伤生物标志物和炎症介质来评估心肌梗死引起的变化。为了进行更深入的研究，通过测量Bcl-2和Bax的mRNA表达来评估凋亡状态，并通过蛋白质印迹法研究丝裂原活化蛋白激酶-细胞外信号调节激酶（MAPK-ERK）信号转导。心肌梗死组显示出明显的梗死面积、血压变化、心肌损伤酶升高以及炎症细胞因子增加。心肌梗死与心肌内MAPK-ERK信号通路的激活和凋亡状态有关。另一方面，用D-柠檬烯预处理可减少梗死面积、降低心肌酶、改善血压指标、减轻炎症水平。此外，D-柠檬烯预处理导致MAPK蛋白通路和Bax相对mRNA表达下降，同时增强Bcl-2 mRNA表达，表明D-柠檬烯可能抑制心肌梗死诱导的心肌细胞凋亡。D-柠檬烯通过抑制MAPK/NF-κB通路和抗凋亡作用减轻心肌梗死损伤。
