Shengmai San Alleviates Diabetic Cardiomyopathy Through Improvement of Mitochondrial Lipid Metabolic Disorder

Abstract

Background/Aims: Shengmai San (SMS), prepared from Panax ginseng, Ophiopogon japonicus, and Schisandra chinensisin, has been widely used to treat ischemic disease. In this study, we investigated whether SMS may exert a beneficial effect in diabetic cardiomyopathy through improvement of mitochondrial lipid metabolism. Methods: A leptin receptor-deficient db/db mouse model was utilized, and lean age-matched C57BLKS mice served as non-diabetic controls. Glucose and lipid profiles, myocardial structure, dimension, and function, and heart weight to tibial length ratio were determined. Myocardial ultrastructural morphology was observed with transmission electron microscopy. Protein expression and activity of oxidative phosphorylation (OXPHOS) complex were assessed using western blotting and microplate assay kits. We also observed cellular viability, mitochondrial membrane potential, OXPHOS complex activity, and cellular ATP level in palmitic acid-stimulated H9C2 cardiomyocytes. Changes in the sirtuin (SIRT1)/AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) pathway and mitochondrial uncoupling signaling were assessed using western blotting and quantitative real-time PCR. Results: Leptin receptor-deficient db/db mice exhibit obesity, hyperglycemia, and hyperlipidemia, accompanied by distinct myocardial hypertrophy and diastolic dysfunction. SMS at a dose of 3 g/kg body weight contributed to a recovery of diabetes-induced myocardial hypertrophy and diastolic dysfunction. SMS administration led to an effective restoration of mitochondrial structure and function both in vivo and in vitro. Furthermore, SMS markedly enhanced SIRT1 and p-AMPKα protein levels and decreased the expression of acetylated-PGC-1α and uncoupling protein 2 protein. SMS also restored the depletion of NRF1 and TFAM levels in diabetic hearts and H9C2 cardiomyocytes. Conclusion: The results indicate that SMS may alleviate diabetes-induced myocardial hypertrophy and diastolic dysfunction by improving mitochondrial lipid metabolism.

The three syndromes and six Chinese patent medicine study during the recovery phase of COVID-19

“…Twenty one Compounds of Shengmaiyin include 14 saponins, 6 lignans [ 76 ]. It is often used to treat chronic obstructive pulmonary disease [ 77 ], diabetic myocardium disease [ 78 ], and coronary atherosclerotic heart disease [ 79 ]. It exerts its action primarily by improving mitochondrial lipid metabolism and inhibiting oxidative stress damage [ 80 ].…”

Use of a Systematic Pharmacological Methodology to Explore the Mechanism of Shengmai Powder in Treating Diabetic Cardiomyopathy

“…SMP significantly enhanced the protein levels of SIRT1 and p-AMPKa and decreased the expression of acetylated PGC-1a. SMP also restores NRF1 and TFAM levels [12,15,81]. These results are shown in Table 4.…”

“…Experiments show that upregulation of SIRT1/AMPK/PGC1 signaling may contribute to the cardioprotective effects of SMP [12,15,81]. Western blot analysis showed a decrease in SIRT1 and p-AMPK (Thr172) protein levels in diabetic hearts, accompanied by an increase in acetylated PGC-1a levels (acetylated lysine sites at 110 KDa), although expression of PGC-1a was not altered [82][83][84].…”

Remedying the Mitochondria to Cure Human Diseases by Natural Products

“…QiDiTangShen granules [77] Shengmai San [78] Water extracts of Liuwei Dihuang [79] Salidroside [82] Hydroxytyrosol [85] Oxidative stress Water extracts of Liuwei Dihuang [79] Anthocyanins [80] Ginsenoside Rb1 [84] Hydroxytyrosol [85] Apoptosis Anthocyanins [80] Orientin [81] Astragalus polysaccharides [83] Ginsenoside Rb1 [84] Mitochondrial membrane potential imbalance Orientin [81] Water extracts of Liuwei Dihuang [79] Mitochondrial fusion, division, and autophagy Orientin [81] QiDiTangShen granules [77] Salidroside [82] Obesity Energy metabolism obstruction Melinjo (Gnetum gnemon L.) seed extract [88] 12 Oxidative Medicine and Cellular Longevity Table 8: Continued.…”