Carthamus tinctorius L. prevents LPS-induced TNFα signaling activation and cell apoptosis through JNK1/2–NFκB 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 α 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 μg/mL). H9c2 cells were divided into five groups: Control, LPS (1 μg/mL), and three FC EtOH (31.25, 62.5,and 125 μg/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 NFκB expression. Results FC EtOH (62.5 μg/mL) inhibited LPS-induced apoptosis by suppressing JNK1/2 activity, which resulted in the reduction of both IκB degradation and NFκB 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 TNFα, 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 TNFα activation and apoptosis in H9c2 cardiomyoblast cells. Carthamus tinctorius L could potentially serve as a cardio-protective agent against LPS-induced apoptosis.