RRP Regulates Autophagy through the AMPK Pathway to Alleviate the Effect of Cell Senescence on Atherosclerosis

Abstract

Autophagy is closely associated with atherosclerosis and other cardiovascular diseases (CVD). Compound Danshen prescription is widely used as a clinical antiatherosclerotic drug. In our previous studies, we have shown that the combined active component, ginsenoside Rg1-notoginsenoside R1-protocatechualdehyde (RRP), can effectively alleviate endothelial dysfunction and reduce atherosclerotic plaques. However, the association between cellular senescence, caused by reduced autophagy, and atherosclerosis remains unclear. In this study, we investigated whether RRP can enhance autophagy and alleviate cell senescence through the AMPK pathway. Our results showed that RRP reduced the secretion of inflammatory factors in the serum of atherosclerotic mice, enhanced autophagy, and alleviated aortic aging in mice, thus reducing atherosclerotic plaques. In human aortic endothelial cells (HAECs), RRP effectively enhanced autophagy and inhibited senescence by activating the AMPK pathway. When AMPKα was silenced, the effect of RRP was inhibited, thus reversing its antiaging effect. Overall, our results show that RRP regulates autophagy through the AMPK pathway, thereby inhibiting cell senescence and alleviating the progression of atherosclerosis, suggesting that RRP may be a potential candidate drug for the treatment of atherosclerosis.

Danshen-Shanzha formula for the treatment of atherosclerosis: ethnopharmacological relevance, preparation methods, chemical constituents, pharmacokinetic properties, and pharmacological effects

“…From Han Dynasty (202 BC) to modern Frontiers in Pharmacology frontiersin.org society, DS has been extensively utilized in conjunction with various herbs to address a wide range of health issues, including diabetes, hepatocirrhosis, osteoporosis, and particularly cerebrovascular as well as cardiovascular diseases (Zhang and Ren, 2017). Studies on phytochemistry have revealed that DS contains a variety amount of phenylpropionic acids and diterpenequinones (Liu et al, 2023). Shanzha, commonly considered to be the fruit of Crateagus pinnatifida Bge.…”

“…DS extracts have been observed to promote autophagy as well as prevent senescence in both human umbilical vein and aortic endothelial cell lines, where it could activate the AMPK signaling and its anti-aging benefits are abolished when AMPKα is suppressed. Also, it has been shown that DS extracts exhibit the activities to trigger autophagy which were exert by LC3 transformations and p62 degradations, decrease the release of pro-inflammatory cytokines in the blood and thus mitigated the degeneration of the aorta in atherosclerosis mouse models, all the actions helped to lower the incidence of atherosclerotic plaques (Ko et al, 2020;Liu et al, 2023). In order to investigate the potential association between Sal B and autophagy as well as apoptosis, Sun et al established a macrophage model of atherosclerosis induced by cholesterol crystals.…”