Astragaloside IV Ameliorates Diabetic Cardiomyopathy by Suppressing the GNG2/MRAS-ERK Signaling Pathway

Ying Dong,1,* Yidi Ma,2,* Shi-Jan Liu,3 Hong-Yan Zhang,4 Gen Li,5 Shi Yan,6 Qiang Fu2 1The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, People’s Republic of China; 2School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, People’s Republic of China; 3Department of Kidney, the Second Affliated of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 4Department of Kidney, Beidahuang Industry Group General Hospital, Harbin, Heilongjiang, People’s Republic of China; 5Department of Radiation Therapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People’s Republic of China; 6Medical Oncology, Cancer Hospital Affiliated of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shi Yan, Email [email protected] Qiang Fu, Email [email protected]: This study aims to investigate the mechanism of AGS-IV in treating diabetic cardiomyopathy (DCM) by establishing animal and cellular models of the disease.Methods: A DCM rat model was established by feeding a high-fat diet combined with streptozotocin (STZ) injection, and a DCM cell model was created through glucose induction. In model rats, the cardiac weight-to-body weight ratio, the left ventricular weight-to-heart weight ratio, and ventricular wall thickness were measured. ELISA was used to detect Collagen1 and MMP-2 levels in myocardial tissue, serum, and cultured cells. The mRNA levels of GNG2, MRAS, and ERK in myocardial tissue and cultured cells were measured using RT-PCR.Results: In vivo, experiments demonstrated that AGS-IV effectively reduced the cardiac weight-to-body weight ratio, left ventricular weight-to-heart weight ratio, and ventricular wall thickness in DCM rat models. It also decreased Collagen I levels in myocardial tissue and MMP-2 levels in serum, accompanied by downregulated mRNA expression of GNG2, MRAS, and ERK in myocardial tissue. In vitro, AGS-IV significantly reduced Collagen I and MMP-2 levels in DCM cell models and downregulated GNG2, MRAS, and ERK mRNA expression.Conclusion: AGS-IV exerts therapeutic effects on DCM by regulating the GNG2/MRAS-ERK signaling pathway.Keywords: AGS-IV, diabetic cardiomyopathy, in vivo, in vitro