Greater Plantain (Plantago major) as a tool for helping with Cardiovascular / heart health

Advanced glycation end products (AGEs) have been identified to transduce fibrogenic signals via inducing the activation of their receptor (RAGE)-mediated pathway. Recently, disrupting AGE-RAGE interaction has become a promising therapeutic strategy for chronic heart failure (CHF). Endothelial-to-mesenchymal transition (EndMT) is close to the cardiac fibrosis pathological process. Our previous studies have demonstrated that knockout RAGE suppressed the autophagy-mediated EndMT, and thus alleviated cardiac fibrosis. Plantamajoside (PMS) is the major bioactive compound of Plantago Asiatica, and its activity of anti-fibrosis has been documented in many reports. However, its effect on CHF and the underlying mechanism remains elusive. Thus, we tried to elucidate the protective role of PMS in CHF from the viewpoint of the AGEs/RAGE/autophagy/EndMT axis. Herein, PMS was found to attenuate cardiac fibrosis and dysfunction, suppress EndMT, reduce autophagy levels and serum levels of AGEs, yet did not affect the expression of RAGE in CHF mice. Mechanically, PMS possibly binds to the V-domain of RAGE, which is similar to the interaction between AGEs and RAGE. Importantly, this competitive binding disturbed AGEs-induced the RAGE-autophagy-EndMT pathway in vitro. Collectively, our results indicated that PMS might exert an anti-cardiac fibrosis effect by specifically binding RAGE to suppress the AGEs-activated RAGE/autophagy/EndMT pathway.

Myocardial ischemia/reperfusion (I/R) injury has been found to be associated with oxidative stress. Plantamajoside (PMS) is a major compound of Plantago asiatica that was reported to possess cardioprotective and antioxidant effects. The current study was designed to investigate the effect of PMS on myocardial I/R injury. Rat cardiomyocytes H9c2 cells were exposed to hypoxia/reoxygenation (H/R) to establish in vitro model of myocardial I/R injury. MTT assay proved that H9c2 cells viability was significant reduced under H/R treatment, while the reduction was ameliorated by PMS. H/R-induced ROS production in H9c2 cells was suppressed by PMS. The decreased activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) in the H/R group were effectively elevated by PMS. In addition, treatment with PMS attenuated H/R-stimulated production of TNF-α, IL-6 and IL-1β in H9c2 cells. Besides, PMS significantly suppressed bax expression and caspase 3 activity, as well as increased bcl-2 expression in H/R-stimulated H9c2 cells. Furthermore, we also found that PMS significantly enhanced the activation of Akt/Nrf2/HO-1 signaling pathway and suppressed the activation of NF-κB signaling pathway in H/R-stimulated H9c2 cells. These results provided substantial evidence that PMS protected against myocardial I/R injury via attenuating oxidative stress, inflammatory response and apoptosis. The protective effects of PMS were attributed to the Akt/Nrf2/HO-1 and NF-κB signaling pathways.