The Ethanol Extract of Sugemule-3 Decoction Treats Isoproterenol-induced Heart Failure in Rats via PPARγ/PGC-1 Pathway

Abstract

Background: The herbs Baidoukou (the fruit of Amomum compactum Sol. ex Maton), Baijusheng (the fruit of Lactuca sativa L.), and Biba (Piper longum L.) make up the traditional Mongolian medicine known as Sugemule-3 decoction.Objectives: Heart failure (HF) is severely impacted; however, the pharmacological mechanism behind it is yet unclear. This investigation looked at the Sugemule-3 ethanol extract’s therapeutic mechanism for isoproterenol-induced HF in rats.Materials and Methods: To create a HF model, isoproterenol was administered to Wistar rats. Following the model’s successful establishment, various medications were administered for 4 weeks. The electrical signals of cardiac fluctuations, cardiac morphology, and function were observed using electrocardiogram (ECG) and echocardiography. The rats were killed 4 weeks later, and the hearts were observed using an electron microscope and HE staining. Cardiomyocyte apoptosis was observed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. The levels of markers in serum were determined using enzyme-linked immunosorbent assay (ELISA). Western blot and immunohistochemistry were used to detect the expression of proteins in rats.Results: Our findings show that isoproterenol injection subcutaneously interfered with the structure and function of the left ventricle, particularly during systole. In the model group, the level of oxidative stress index malondialdehyde (p < 0.01) increased with the decrease in antioxidant enzymes such as superoxide dismutase (p < 0.01) and glutathione peroxidase (p < 0.01). Sugemule-3 ethanol extract considerably reduced the harmful effects of isoproterenol on the rat myocardium. Additionally, isoproterenol increased the level of peroxisome proliferator-activated receptor (PPAR), carnitine palmitoyl transferase-1 (CPT-1), phosphoenolpyruvate carboxylase (PEPCK), stearyl CoA desaturase-1 (SCD-1), and ubiquitin-conjugating (UCB) expression while decreasing the level of peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) expression, leading to cardiometabolic diseases. Sugemule-3 ethanol extract improved cardiac metabolism.Conclusion: The findings demonstrate that Sugemule-3 ethanol extract may improve energy metabolism of cardiomyocytes and alleviate isoproterenol-induced HF through inhibiting the peroxisome proliferator-activated receptor gamma (PPARγ)/ PGC-1 signaling pathway.

Keywords: Sugemule-3 decoction; peroxisome proliferator-activated receptor gamma; peroxisome proliferator-activated receptor γ coactivator-1; heart failure; oxidative stress