Key result
Ginsenoside Rh2 (2 μM) prevented OGD-induced H9c2 cell death and reduced IL-18 and IL-1β levels by decreasing NLRP3 inflammasome activation and pyroptosis.
Why the study?
QiShen YiQi pills treat myocardial infarction in clinical practice, but the molecular mechanism regulating post-MI pyroptosis remains not fully known.
Ginsenoside Rh2, an active ingredient of QiShen YiQi pills, protects cardiomyocytes from OGD-induced injury by inhibiting pyroptosis pathways.
Hypothesis-generating for ginsenoside Rh2 in ischemic injury; leaves open clinical translation and should not change practice.
Background: QiShen YiQi pills (QSYQ) is a Traditional Chinese Medicine (TCM) formula, which has a significant effect on the treatment of patients with myocardial infarction (MI) in clinical practice. However, the molecular mechanism of QSYQ regulation pyroptosis after MI is still not fully known. Hence, this study was designed to reveal the mechanism of the active ingredient in QSYQ. Methods: Integrated approach of network pharmacology and molecular docking, were conducted to screen active components and corresponding common target genes of QSYQ in intervening pyroptosis after MI. Subsequently, STRING and Cytoscape were applied to construct a PPI network, and obtain candidate active compounds. Molecular docking was performed to verify the binding ability of candidate components to pyroptosis proteins and oxygen-glucose deprivation (OGD) induced cardiomyocytes injuries were applied to explore the protective effect and mechanism of the candidate drug. Results: Two drug-likeness compounds were preliminarily selected, and the binding capacity between Ginsenoside Rh2 (Rh2) and key target High Mobility Group Box 1 (HMGB1)was validated in the form of hydrogen bonding. 2 μM Rh2 prevented OGD-induced H9c2 death and reduced IL-18 and IL-1β levels, possibly by decreasing the activation of the NLRP3 inflammasome, inhibiting the expression of p12-caspase1, and attenuating the level of pyroptosis executive protein GSDMD-N. Conclusions: We propose that Rh2 of QSYQ can protect myocardial cells partially by ameliorating pyroptosis, which seems to have a new insight regarding the therapeutic potential for MI.
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Qi et al. (2022) studied Myocardial infarction / OGD-induced cardiomyocytes injuries. Ginsenoside Rh2 (Rh2) was evaluated on OGD-induced H9c2 death and pyroptosis markers. Ginsenoside Rh2 (2 μM) prevented OGD-induced H9c2 cell death and reduced IL-18 and IL-1β levels by decreasing NLRP3 inflammasome activation and pyroptosis.
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