Why the study?
Ventricular remodeling after AMI drives chronic heart failure, but the mechanism of Ling-Gui-Zhu-Gan decoction against ventricular remodeling remains unclear.
Does Ling-Gui-Zhu-Gan decoction improve ventricular remodeling after acute myocardial infarction in a rat model?
Does Ling-Gui-Zhu-Gan decoction improve ventricular remodeling after acute myocardial infarction in a rat model?
Ling-Gui-Zhu-Gan decoction protects against ventricular remodeling after acute myocardial infarction via the NLRP3/Caspase-1/GSDMD signaling pathway in a rat model.
May warrant preclinical follow-up of LGZGD for post-AMI remodeling; leaves open any clinical role pending human trials.
Ventricular remodeling (VR) after acute myocardial infarction (AMI) is an important pathophysiological basis for the development of chronic heart failure (CHF). At present, Ling-Gui-Zhu-Gan decoction (LGZGD) has been widely reported in the clinical treatment and basic research of cardiovascular diseases (CVDs), such as myocardial infarction, heart failure, and angina pectoris. However, the mechanism of LGZGD against VR after AMI remains unclear. Ultra-performance liquid chromatography (UPLC) was applied to investigate the major constituents of LGZGD, and molecular docking was used to predict the targets on the NLRP3/Caspase-1/GSDMD signaling pathway. In vivo, histological changes in the myocardium were visualized using HE staining and Masson staining, and cardiomyocyte apoptosis was detected using TUNEL. IL-1β activity in rat serum was determined by ELISA. Finally, NLRP3, Caspase-1, and GSDMD expressions were analyzed through RT-qPCR and Western blotting. The results showed that 8 authentic reference substances have been detected in LGZGD. Molecular docking showed that the major chemical constituents of LGZGD had a good binding activity with NLRP3, Caspase-1, and GSDMD. Our results showed that LGZGD treatment markedly improved cardiac pathology, decreased cardiomyocyte apoptosis, reduced IL-1β activity, and regulated the expression of genes and proteins related to the NLRP3/Caspase-1/GSDMD signal pathway. These results suggest that LGZGD protects against VR after AMI through NLRP3/Caspase-1/GSDMD signal pathway.
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Zhou et al. (2022) studied this question.
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