The structure-activity relationship of ginsenosides on hypoxia-reoxygenation induced apoptosis of cardiomyocytes

Abstract

Ginsenosides have been studied extensively in recent years due to their therapeutic effects in cardiovascular diseases. While most studies examined the different ginsenosides individually, few studies compare the therapeutic effects among the different types. This study examined how effective protopanaxadiol, protopanaxatriol ginsenosides Rh2, Rg3, Rh1, and Rg2 of the ginsenoside family are in protecting H9c2 cardiomyocytes from damage caused by hypoxia/reoxygenation. In the current study, a model of myocardial ischemia and reperfusion was induced in H9c2 cardiomyocytes by oxygen deprivation via a hypoxia chamber followed by reoxygenation. Our data show that structures similar to that of protopanaxadiol, which lacked the hydroxide group at C6, were more effective in lowering apoptosis than structures similar to protopanaxatriol with a hydroxide group at C6. As the compounds increased in size and complexity, the cardioprotective effects diminished. In addition, the S enantiomer proved to be more effective in cardioprotection than the R enantiomer. Furthermore, the immunoblotting analysis demonstrated that ginsenosides activate AMPK but suppress JNK signaling pathways during hypoxia/reoxygenation. Thus, ginsenosides treatment attenuated hypoxia/reoxygenation-induced apoptosis via modulating cardioprotective AMPK and inflammation-related JNK signaling pathways.

miR‑155 inhibition represents a potential valuable regulator in mitigating myocardial hypoxia/reoxygenation injury through targeting BAG5 and MAPK/JNK signaling

“…Hypoxia/reoxygenation (H/r) injury, a mimic in vitro model of myocardial I/R injury, has been widely used to explore the underlying molecular mechanism of myocardial i/r injury (3)(4)(5). At present, a number of studies have explored myocardial H/R injury from the perspectives of the inflammatory response (6), cell apoptosis (7) and cell signal transduction (8), but the exact molecular mechanism remains unknown. Therefore, it is important to explore the potential molecular mechanisms of myocardial iri.…”

American Ginseng (Panax quinquefolium L.) as a Source of Bioactive Phytochemicals with Pro-Health Properties

“…Most ginsenosides consist of a dammarane skeleton with 17 carbon atoms arranged in four rings. Due to the number of hydroxyl groups these compounds can be classified into two main categories: protopanaxadiol (PPD) and protopanaxatriol (PPT) [33].…”

Saponins as chemosensitizing substances that improve effectiveness and selectivity of anticancer drug—Minireview of in vitro studies

“…Saponins are a very diverse group of plant metabolites, and many reports have indicated that their activity is affected by their structure, namely, by the nature of aglycone as well as the number and monosaccharide composition of sugar chains, which may be linear or branched (Chwalek, Lalun, Bobichon, Plé, & Voutquenne‐Nazabadioko, ; Feng et al, ; Vo et al, ). Most triterpene saponins are based on aglycone of the three most common types: dammarane, which is a tetracyclic structure, and two pentacyclic skeletons such as ursane and oleanane (Figure ), the latter of which is considered to be most abundant in nature.…”