Journal
PHYTOTHERAPY RESEARCH
Volume 37, Issue 3, Pages 834-847Publisher
WILEY
DOI: 10.1002/ptr.7663
Keywords
cardiac fibrosis; chronic heart failure; endothelial to mesenchymal transition; pharmacology; plantamajoside; receptor of advanced glycation end products
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This study found that Plantamajoside (PMS) has a protective effect in chronic heart failure (CHF), attenuating cardiac fibrosis and dysfunction, suppressing EndMT, reducing autophagy levels and serum levels of AGEs. Mechanistically, PMS possibly binds to the V-domain of RAGE, disrupting the AGEs-induced RAGE-autophagy-EndMT pathway. These findings suggest that PMS may exert an anti-cardiac fibrosis effect by inhibiting the 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.
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