Carthamus tinctorius L. prevents LPS-induced TNF signaling activation and cell apoptosis through JNK1/2–NF B pathway inhibition in H9c2 cardiomyoblast cells

[[abstract]]Aim of the study: Severe and potentially fatal hypotension and cardiac contractile dysfunction are common symptoms in patients with sepsis. In our previous study, we found that estradiol and estrogen-receptor a have cardio-protective effects in myocardial cells exposed to LPS. Estradiol supplementation has been shown to induce breast and cervical cancers. Flos Carthami, the flower of Carthamus tinctorius L (Compositae) is an important traditional Chinese medicine used for the treatment of heart disease and inflammation, and therefore might be a potential alternative to Estradiol in the prevention of heart damage. This study investigated the effect of Flos Carthami (FC(EtOH)) ethanolic extract on LPS-induced apoptosis in H9c2 cardiomyoblast cells. Materials and methods: H9c2 cells induced apoptosis with LPS administration (1 mu g/mL). H9c2 cells were divided into five groups: Control, LPS (1 mu g/mL), and three FC(EtOH) (31.25, 62.5,and 125 mu g/mL). We detected apoptosis using MTT, LDH, TUNEL assay. JC-1 staining and Western blot were used to detect pro-apoptosis proteins, anti-apoptosis proteins, MAPK proteins (JNK, ERK, and P38), and NF kappa B expression. Results: FC(EtOH) (62.5 mu g/mL) inhibited LPS-induced apoptosis by suppressing JNK1/2 activity, which resulted in the reduction of both I kappa B degradation and NF kappa B activation. In addition, FC(EtOH) led to the activation of anti-apoptotic proteins, Bcl-2 and Bcl-xL, the stabilization of the mitochondria membrane and the down-regulation of extrinsic and intrinsic pro-apoptotic proteins, such as TNF alpha, active caspase-8, t-Bid, Bax, active caspases-9, and -3. Conclusions: Carthamus tinctorius L possesses the ability to suppress JNK activity and inhibit LPS-induced TNF alpha activation and apoptosis in H9c2 cardiomyoblast cells. Carthamus tinctorius L could potentially serve as a cardio-protective agent against LPS-induced apoptosis. (C) 2010 Elsevier Ireland Ltd. All rights reserved