Mustafa Nor Hidayah, Jalil Juriyati, Saleh Mohammed S M, Zainalabidin Satirah, Asmadi Ahmad Yusof, Kamisah Yusof
Centre for Drug and Herbal Development, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia.
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia.
Life (Basel). 2022 Dec 23;13(1):43. doi: 10.3390/life13010043.
Cardiac hypertrophy is an early hallmark during the clinical course of heart failure. Therapeutic strategies aiming to alleviate cardiac hypertrophy via the mitogen-activated protein kinase (MAPK)/calcineurin-nuclear factor of activated T-cells (NFAT) signaling pathway may help prevent cardiac dysfunction. Previously, empty pod ethanol crude extract of Hassk was shown to demonstrate protective effects against cardiomyocyte hypertrophy. Therefore, the current study aimed to investigate the effects of various fractions of the plant ethanol extract on the MAPK/NFAT signaling pathway in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. Simultaneous treatment with ethyl acetate (EA) fraction produced the most potent antihypertrophic effect evidenced by the reduced release of B-type natriuretic peptide (BNP). Subsequently, treatment with the EA fraction (6.25, 12.5, and 25 μg/mL) prevented an Ang II-induced increase in cell surface area, hypertrophic factors (atrial natriuretic peptide and BNP), reactive oxygen species, protein content, and NADPH oxidase 4 expression in the cells. Furthermore, EA treatment attenuated the activation of the MAPK pathway and calcineurin-related pathway (GATA-binding protein 4 and NFATC3), which was similar to the effects of valsartan (positive control). Our findings indicate that the EA fraction prevents Ang II-induced cardiac hypertrophy by regulating the MAPK/calcineurin-NFAT signaling pathway.
心脏肥大是心力衰竭临床过程中的早期标志。旨在通过丝裂原活化蛋白激酶（MAPK）/钙调神经磷酸酶-活化T细胞核因子（NFAT）信号通路减轻心脏肥大的治疗策略可能有助于预防心脏功能障碍。此前，哈斯克空荚乙醇粗提物已显示出对心肌细胞肥大的保护作用。因此，本研究旨在探讨该植物乙醇提取物的不同组分对血管紧张素II（Ang II）诱导的心肌细胞肥大中MAPK/NFAT信号通路的影响。乙酸乙酯（EA）组分同时处理产生了最有效的抗肥大作用，B型利钠肽（BNP）释放减少证明了这一点。随后，用EA组分（6.25、12.5和25μg/mL）处理可防止Ang II诱导的细胞表面积增加、肥大因子（心房利钠肽和BNP）、活性氧、蛋白质含量以及细胞中NADPH氧化酶4表达增加。此外，EA处理减弱了MAPK通路和钙调神经磷酸酶相关通路（GATA结合蛋白4和NFATC3）的激活，这与缬沙坦（阳性对照）的作用相似。我们的研究结果表明，EA组分通过调节MAPK/钙调神经磷酸酶-NFAT信号通路预防Ang II诱导的心脏肥大。
