Ph.D. Program for Aging, China Medical University, Taichung, Taiwan.
Department of Chinese Medicine, Yuan Sheng Hospital, ChangHua, Taiwan.
Environ Toxicol. 2021 Dec;36(12):2475-2483. doi: 10.1002/tox.23360. Epub 2021 Sep 8.
The insulin-like growth factor II receptor (IGF-IIR) induces myocardial hypertrophy under various pathological conditions like diabetes and hypertension via G protein receptors like Gαq or Gαs. Increased expression of the ligand IGF II and IGF-IIR induces pathological hypertrophy through downstream signaling mediators such as calcineurin, nuclear factor of activated T cells 3 and calcium-calmodulin (CaM)-dependent kinase II (CaMKII)-histone deacetylase 4 (HDAC4). The dried stigma of Crocus sativus L. (saffron) has a long repute as a traditional medicine against various disorders. In the present study, we have investigated whether C. sativus extract (CSE) canameliorate Leu IGF-II triggered hypertrophy and have elucidated the underlying mechanism of protection. Additionally, the effects of oleic acid (OA), an activator of calcineurin and CaMKII was investigated thereof. The results demonstrate that CSE can ameliorate Leu IGF-II-induced hypertrophy seemingly through regulation of calcineurin-NFAT3 and CaMKII-HDAC4 signaling cascade.
胰岛素样生长因子 II 受体 (IGF-IIR) 通过 G 蛋白受体（如 Gαq 或 Gαs）在糖尿病和高血压等各种病理条件下诱导心肌肥厚。配体 IGF II 和 IGF-IIR 的表达增加通过下游信号转导介质如钙调神经磷酸酶、激活 T 细胞核因子 3 和钙调蛋白 (CaM)-依赖性激酶 II (CaMKII)-组蛋白去乙酰化酶 4 (HDAC4) 诱导病理性肥大。藏红花（番红花）的干燥柱头作为治疗各种疾病的传统药物已有悠久的历史。在本研究中，我们研究了藏红花提取物 (CSE) 是否可以改善亮氨酸 IGF-II 触发的肥大，并阐明了保护的潜在机制。此外，还研究了钙调神经磷酸酶和 CaMKII 的激活剂——油酸 (OA) 的作用。结果表明，CSE 可以通过调节钙调神经磷酸酶-NFAT3 和 CaMKII-HDAC4 信号级联来改善亮氨酸 IGF-II 诱导的肥大。
