Icariin Protects Rat Cardiac H9c2 Cells from Apoptosis by Inhibiting Endoplasmic Reticulum Stress

Abstract

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.

Activation of endoplasmic reticulum stress is involved in the activity of icariin against human lung adenocarcinoma cells

“…As a natural prenylated flavonol glycoside, ICA has been shown to suppress the proliferation of various types of cancer cells [11][12][13][14]. Various molecules and signaling pathways are involved in the anti-tumor effects of ICA.…”

“…Experimentally, ICA can induce apoptosis through a ROS/JNK-dependent mitochondrial pathway in human hepatoma SMMC-7721 cells [28]. Additionally, ICA can protect rat cardiac H9c2 cells from apoptosis by inhibiting ERS [14]. However, the role of ERS signaling in the anti-NSCLC activity of ICA has not been examined.…”

“…Many studies has been shown that ICA has potent antitumor activities in various cancer types, including breast cancer, human burkitt lymphoma and liver cancer [11][12][13]. Recently, Zhang et al have reported that ICA protected rat cardiac H9c2 cells from apoptosis by inhibiting ERS [14], indicating that ICA might be a cancer-fighting agent through the regulation of the ERS. However, by literature retrieval, the effects of ICA on human lung adenocarcinoma and the mechanisms responsible for these effects have not been elucidated.…”

EGFR inhibition attenuates diabetic nephropathy through decreasing ROS and endoplasmic reticulum stress

“…Interestingly, NAC, a scavenger of ROS, could also inhibit ER stress, suggesting that ROS accumulation could trigger ER stress. ROS is linked to ER stress in other systems, such as rat cardiac cells, and human hepatoma cells [33, 34]. Reports on the interactions between ROS and ER stress are still controversial and not clear [9, 35, 36].…”

Icariin Exerts Protective Effect Against Myocardial Ischemia/Reperfusion Injury in Rats

“…Another study by Song et al revealed that icariin reduced cardiac remodeling through down-regulating myocardial apoptosis and matrix metalloproteinase activity in rats with congestive heart failure [4]. Moreover, a recent in vitro study has shown that Icariin protects rat cardiac H9c2 cells from apoptosis by inhibiting endoplasmic reticulum stress [5]. These results suggested that icariin could exert cardioprotective effects.…”