Icariin protects rat cardiac H9c2 cells from apoptosis by inhibiting endoplasmic reticulum stress.

Endoplasmic reticulum stress (ERS) is one of the mechanisms of apoptotic cell death. Inhibiting the apoptosis induced by ERS may be a novel therapeutic target in cardiovascular diseases. Icariin, a flavonoid isolated from Epimedium brevicornum Maxim, has been demonstrated to have cardiovascular protective effects, but its effects on ERS are unknown. In the present study, we focused on icariin and investigated whether it might protect the cardiac cell from apoptosis via inhibition of ERS. In H9c2 rat cardiomyoblast cells, pretreatment of icariin significantly inhibited cell apoptosis by tunicamycin, an ERS inducer. Icariin also decreased generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential and activation of caspase-3. Moreover, icariin inhibited upregulation of endoplasmic reticulum markers, GRP78, GRP94 and CHOP, elicited by tunicamycin. These results indicated that icariin could protect H9c2 cardiomyoblast cells from ERS-mitochondrial apoptosis in vitro, the mechanisms may be associated with its inhibiting of GRP78, GRP94 and CHOP and decreasing ROS generation directly. It may be a potential agent for treating cardiovascular disease.

内质网应激（ERS）是细胞凋亡的机制之一。抑制ERS诱导的细胞凋亡可能是心血管疾病的一个新的治疗靶点。淫羊藿苷是从淫羊藿中分离出的一种黄酮类化合物，已被证明具有心血管保护作用，但其对ERS的影响尚不清楚。在本研究中，我们聚焦于淫羊藿苷，研究它是否可以通过抑制ERS来保护心肌细胞免于凋亡。在H9c2大鼠心肌细胞中，淫羊藿苷预处理显著抑制了衣霉素（一种ERS诱导剂）诱导的细胞凋亡。淫羊藿苷还减少了活性氧（ROS）的产生、线粒体膜电位的丧失以及半胱天冬酶 - 3的激活。此外，淫羊藿苷抑制了衣霉素引起的内质网标志物GRP78、GRP94和CHOP的上调。这些结果表明，淫羊藿苷在体外能够保护H9c2心肌细胞免受ERS - 线粒体凋亡的影响，其机制可能与其直接抑制GRP78、GRP94和CHOP以及减少ROS的产生有关。它可能是一种治疗心血管疾病的潜在药物。