Influence of Ginsenoside Rh2 on Cardiomyocyte Pyroptosis in Rats with Acute Myocardial Infarction

Abstract

Objective. This paper intends to verify through in vivo experiments whether ginsenoside Rh2 (G-Rh2) can play an anti-inflammatory role by modulating cardiomyocyte (CM) pyroptosis in rats with acute myocardial infarction (AMI), thereby alleviating myocardial injury. Methods. Twenty SD rats were randomized into control, L-Rh2, M-Rh2, and H-Rh2 groups, among which the latter three groups were modeled for AMI and given an intraperitoneal injection of G-Rh2 (L-Rh2: 2 mg/kg; M-Rh2: 4 mg/kg; H-Rh2: 8 mg/kg), while the control group was only treated with thoracotomy and sodium chloride injection. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), and left ventricular end-diastolic pressure (LVEDP) were recorded by ultrasonic diagnosis. Rats were killed under anesthesia, and the morphological characteristics of ventricular tissue were observed by electron microscope. Additionally, cardiac blood and ventricular tissues were collected to quantify the contents of myocardial injury markers (creatine phosphate kinase (CK), creatine phosphokinase-MB isoenzyme (CK-MB), and lactate dehydrogenase (LDH) by ELISA, as well as the expression of pyroptosis-related genes cysteinyl aspartate specific proteinase 1 (Caspase-1), gasdermin D (GSDMD), interleukin (IL)-1β, and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) by qRT-PCR and Western blot). Results. Ultrasonic examination identified lower HR, SBP, DBP, MAP, and LVSP in the three Rh2 injection groups compared with the control group ( P < 0.05); and in comparison with M- and H-Rh2 groups, HR, SBP, DBP, MAP, and LVSP were all lower in L-Rh2 group, while LVEDP was higher ( P < 0.05). Microscopically, CMs and organelles in the L-RH2, M-RH2, and H-RH2 groups were damaged to varying degrees compared with the control group, with those in the L-RH2 group being the most serious. CK, CK-MB, and LDH were also the highest in the L-Rh2 group and the lowest in the control group, while their levels were obviously reduced in M- and H-Rh2 groups ( P < 0.05). Finally, GSDMD, IL-1β, NLRP3, and Caspase-1 were found to be reduced in the control group, while pyroptosis-related gene expression in the M-Rh2 group was improved markedly ( P < 0.05). Conclusion. G-Rh2 can inhibit the pathological development of AMI by relieving the focal death of CM and inhibiting the release of proinflammatory factors in the body, and the effect is significantly related to the dosage, which is expected to become a new treatment option for AMI in the future.

The Role of Pyroptosis in Coronary Heart Disease

“… 68 At present, a number of traditional Chinese herbal medicine preparations broadly applied in clinical practice to treat MI, such as Qishen Granules and Ginsenoside Rh2(G-Rh2), have also been confirmed to inhibit the development of AMI by alleviating CM pyroptosis. 69 , 70 G-Rh2, a hydrolysate derived from ginsenoside which is the active constituent of ginseng, was recently found to significantly ameliorate the severe damage to CMs and organelles in AMI-modeled rat CMs, with marked inhibition of both NLRP3 and caspase-1 levels. 70 …”

“… 69 , 70 G-Rh2, a hydrolysate derived from ginsenoside which is the active constituent of ginseng, was recently found to significantly ameliorate the severe damage to CMs and organelles in AMI-modeled rat CMs, with marked inhibition of both NLRP3 and caspase-1 levels. 70 …”

Ginsenoside Rk2, a dehydroprotopanaxadiol saponin, alleviates alcoholic liver disease via regulating NLRP3 and NLRP6 inflammasome signaling pathways in mice

“…Ginsenosides were considered the main bioactive components contributing to these actions. Several minor ginsenosides were reported to exert inhibitory effects on NLRP3 inflammasome in a variety of animal models, including depression [ 30 ], myocardial infarction [ 31 ], and d -galactosamine/LPS-induced liver injury [ 32 ]. Our pilot study indicated that ginsenoside Rk2 (Rk2) showed the most potent anti-inflammatory activity induced by activation of NLRP3 inflammasome without overt cytotoxicity, among the tested minor ginsenosides ( Fig.…”