Plantamajoside attenuates cardiac fibrosis via inhibiting AGEs activated-RAGE/autophagy/EndMT pathway.

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.

[Protective effect of puerarin against calcium overload after focal cerebral ischemia injury in rats].

OBJECTIVE: To observe the temporal and spatial changes in the distribution of Ca2+ in the rat brain following focal cerebral ischemia injury and explore the protective effect of puerarin against calcium overload. METHODS: Focal cerebral ischemia was induced by middle cerebral artery occlusion in rats. After cerebral ischemia, puerarin was administered in the rats at different time points. The volume of ischemic cerebral tissue was assessed by TTC staining, and the fluorescence intensity of Ca2+ in the cortex and corpora striata was determined under laser scanning confocal microscope. RESULTS: The fluorescence intensity of Ca2+ in the infracted cortex and corpora striata begun to increase 2 h after the ischemia and was further enhanced with the prolongation of the ischemic time. No significance was found in the fluorescence intensity of Ca2+ between the cortex and corpora striata. The fluorescence intensity of Ca2+ in the infarcted corpora striata was obviously higher than that in the cortex after ischemia. Compared with that in the ischemic model group, the fluorescence intensity of Ca2+ in the infarcted cortex and corpora striata decreased significantly at 2 and 12 h following puerarin intervention (P<0.05). CONCLUSION: Puerarin treatment can relieve calcium overload, reduce cerebral ischemic volume and play a neuroprotective role against focal cerebral ischemia. Twelve hours following cerebral ischemic injury may be the time window for administering puerarin intervention.