Ginsenoside-Rb1 Protects Hypoxic- and Ischemic-Damaged Cardiomyocytes by Regulating Expression of miRNAs

Abstract

Ginsenoside (GS-Rb1) is one of the most important active compounds of ginseng, with extensive evidence of its cardioprotective properties. However, the miRNA mediated mechanism of GS-Rb1 on cardiomyocytes remains unclear. Here, the roles of miRNAs in cardioprotective activity of GS-Rb1 were investigated in hypoxic- and ischemic-damaged cardiomyocytes. Neonatal rat cardiomyocytes (NRCMs) were first isolated, cultured, and then incubated with or without GS-Rb1 (2.5–40 μM) in vitro under conditions of hypoxia and ischemia. Cell growth, proliferation, and apoptosis were detected by MTT and flow cytometry. Expressions of various microRNAs were analyzed by real-time PCR. Compared with that of the control group, GS-Rb1 significantly decreased cell death in a dose-dependent manner and expressions of mir-1, mir-29a, and mir-208 obviously increased in the experimental model groups. In contrast, expressions of mir-21 and mir-320 were significantly downregulated and GS-Rb1 could reverse the differences in a certain extent. The miRNAs might be involved in the protective effect of GS-Rb1 on the hypoxia/ischemia injuries in cardiomyocytes. The effect might be based on the upregulation of mir-1, mir-29a, and mir-208 and downregulation of mir-21 and mir-320. This might provide us a new target to explore the novel strategy for ischemic cardioprotection.

Hormesis and Ginseng: Ginseng Mixtures and Individual Constituents Commonly Display Hormesis Dose Responses, Especially for Neuroprotective Effects

“…Rb1 also protected against myocardial ischemia injury via the enhanced expression of eNOS [76]. These initial findings lead to follow-up investigations concerning whether Rb1 could protect neonate rat cardiomyocytes from hypoxia/ischemia (HI) oxygen (10%) induced damage using either a preconditioning or co-exposure protocol [79][80][81]. The HI experimental study utilized a six-hour preconditioning period followed by a 12 h HI exposure period.…”

“…The HI experimental study utilized a six-hour preconditioning period followed by a 12 h HI exposure period. Rb1, which was tested over a concentration range of 3-160 µM, demonstrated a biphasic concentration response with protection being optimized at 40 µM, dropping significantly off from 80-160 µM ( Figure 17) [80]. An assessment of five MiRNA, at the optimal Rb1 concentration (i.e., 40 µM) revealed that three MiR (Mir-1, Mir 29a, and Mir 208) were markedly increased.…”

Ginsenoside Rb1 protects cardiomyocytes from oxygen‑glucose deprivation injuries by targeting microRNA‑21

“…Previous studies have only identified differentially expressed miRNAs in OGD-injured NRCMs with GS-Rb1 treatment (12,13). The present study is the first to verify the miRNA target of GS-Rb1 in the OGD induced cardiomyocytes apoptosis.…”

“…Culture of neonatal rat cardiomyocytes (NRCMs) from heart tissues. Primary cultures of NRCMs from a total of 180 12-24 h-old male Sprague Dawley rats (weight range, 5-6 g; Laboratory Animal Center, Jilin University, Changchun, China) were prepared through gentle serial trypsinization, as described previously (12)(13)(14). All animal protocols were approved by the Animal Care Center and Use Committee of Jilin University (Changchun, China).…”

“…Ginsenoside Rb1 (GS-Rb1) is the most active and abundant monomer in ginseng (11). Although a number of studies have demonstrated the protective effects of GS-Rb1 on the heart (11)(12)(13)(14) and recent studies have revealed that GS-Rb1 could impact miR expression in hypoxia/ischemia-injured cardiomyocytes (12,13), the miR targets involved and their roles in the heart remain unknown. Therefore, in the current study, the roles and mechanisms of miR-21 and its target gene, which encodes PDCD4, in the protection of cardiomyocytes treated with GS-Rb1 were studied by constructing an oxygen-glucose deprivation (OGD) injury model in vitro.…”