Ginsenoside Rg3 ameliorates myocardial glucose metabolism and insulin resistance via activating the AMPK signaling pathway

Ni, Jingyu; Liu, Zhihao; Jiang, Miaomiao; Li, Lan; Deng, Jie; Wang, Xiaodan; Su, Jing; Zhu, Yan; He, Feng; Mao, Jingyuan; Gao, Xiumei; Fan, Guanwei

doi:10.1016/j.jgr.2021.06.001

Cited by 16 publications

(14 citation statements)

References 38 publications

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“…Interestingly, most of them exhibited significant biological activity related to COVID-19 and heart failure. For instance, Ginsenoside Rg3 (DL = 0.22, AlogP = 2.3 and LogS = −3.9) was found to exert significant regulatory effect on glucose metabolism and insulin resistance through activation of the AMPK pathway in chronic heart failure induced by transverse aortic coarctation [ 41 ]. Ginsenoside Rf (DL = 0.24, AlogP = 1.13 and LogS = −3.28) has been reported to exhibit anti-inflammatory activities on inhibiting hypoxia-induced cyclooxygenase 2 expression through binding to peroxisome proliferator-activated receptor γ70 [ 42 ].…”

Section: Resultsmentioning

confidence: 99%

Network analysis for elucidating the mechanisms of Shenfu injection in preventing and treating COVID-19 combined with heart failure

Zhou

Chen

Zheng

et al. 2022

Computers in Biology and Medicine

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Section: Resultsmentioning

confidence: 99%

Network analysis for elucidating the mechanisms of Shenfu injection in preventing and treating COVID-19 combined with heart failure

Zhou

Chen

Zheng

et al. 2022

Computers in Biology and Medicine

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“…Our prior work demonstrated that Rg3 regulated glucose metabolism [ 26 ]. Therefore, we reconstructed the myocardial glucose metabolic pathways and integrated the proteomics and metabolomics data to systematically overview the myocardial glucose metabolism process (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Plasma metabolic profiling based on NMR measurements was using the same methodology used in the previous paper [ 26 ]. The glucose content in Fig.…”

Section: Methodsmentioning

confidence: 99%

Rg3 regulates myocardial pyruvate metabolism via P300-mediated dihydrolipoamide dehydrogenase 2-hydroxyisobutyrylation in TAC-induced cardiac hypertrophy

Zhang

Wang

et al. 2022

Cell Death Dis

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The failing heart is characterized by an increase in glucose uptake and glycolytic rates that is not accompanied by a concomitant increase in glucose oxidation. Lower coupling of glucose oxidation to glycolysis possibly owes to unchanged or reduced pyruvate oxidation in mitochondria. Therefore, increasing pyruvate oxidation may lead to new therapies for heart disease. Dihydrolipoamide dehydrogenase (DLD) is a component of the pyruvate dehydrogenase complex (PDH). DLD mutations or defects are closely associated with metabolic diseases. However, few studies explore the effects of DLD mutants or acylation status on PDH activity and pyruvate metabolism. P300 is protein 2-hydroxyisobutyryltransferases in cells, and P300-dependent lysine 2-hydroxyisobutyrylation of glycolytic enzymes affects glucose metabolism. However, there are no relevant reports on the effect of 2-hydroxyisobutyrylation on the energy metabolism of heart failure, and it is worth further in-depth study. In this study, we showed that 2-hydroxyisobutyrylation is an essential protein translational modification (PTM) that regulates the activity of pyruvate dehydrogenase complex (PDHc). In a mouse model of transverse aortic constriction (TAC)-induced cardiac hypertrophy, the 2-hydroxyisobutylation of DLD was significantly increased, related to the decrease in PDH activity. In addition, our data provide clear evidence that DLD is a direct substrate of P300. As one of the main active ingredients of ginseng, ginsenoside Rg3 (Rg3) can reduce the 2-hydroxyisobutylation levels of DLD and restore the PDH activity by inhibiting the acyltransferase activity of P300, thereby producing beneficial effects whenever the heart is injured. Therefore, this study suggests a novel strategy for reversing myocardial hypertrophy.

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“…Ginsenosides, the major compounds of P. ginseng, have been veri ed to have antidiabetic properties because of their antihyperglycemic, antiinflammatory, and antioxidant actions [8]. Current research on the mechanisms of P. ginseng compounds in the treatment of diabetes has concentrated on isolating compounds and studying their hypoglycemic effects in vitro and in vivo [9][10][11]. However, because of the multicompound and multitarget properties of traditional medicine, the underlying mechanisms of P. ginseng in T2DM treatment have not been comprehensively revealed.…”

Section: Introductionmentioning

confidence: 99%

The Molecular Mechanisms of Panax ginseng in Treating Type 2 Diabetes Mellitus: Network Pharmacology Analysis and Molecular Docking Validation

Tran

2022

Evidence-Based Complementary and Alternative Medicine

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Background. Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder with a high global incidence. Panax ginseng has been used to treat T2DM in traditional medicine, with previous in vitro, in vivo, and clinical trial studies demonstrating its e cacy. is study aimed to determine the mechanism of P. ginseng in treating T2DM by network pharmacology. Methods. e bioactive compounds of P. ginseng and corresponding targets of P. ginseng-T2DM were retrieved across multiple databases. e proteinprotein interaction network was established using the STRING database and topological analysis helped identify the core target. Using the DAVID tool, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, we checked the binding of core targets and bioactive compounds using molecular docking. Results. e P. ginseng-T2DM networks mainly contained 22 bioactive compounds and 314 overlapping targets. e ve most signi cant core targets were SRC, STAT3, MAPK1, AKT1, and PIK3R1. ere were 244 GO terms and 95 KEGG pathways (adjusted p < 0.01) that were strongly correlated with diabetes-related signaling pathways, such as insulin resistance, the HIF-1 signaling pathway, the PI3K/Akt signaling pathway, the prolactin signaling pathway, the Rap1 signaling pathway, the Ras signaling pathway, the calcium signaling pathway, and the FoxO signaling pathway. Molecular docking results revealed that the top ve core targets had a high binding a nity with the bioactive compounds of P. ginseng. Conclusion. e bioactive compounds and targets in P. ginseng ameliorate T2DM by regulating insulin resistance and multiple signaling pathways.

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Ginsenoside Rg3 ameliorates myocardial glucose metabolism and insulin resistance via activating the AMPK signaling pathway

Cited by 16 publications

References 38 publications

Network analysis for elucidating the mechanisms of Shenfu injection in preventing and treating COVID-19 combined with heart failure

Network analysis for elucidating the mechanisms of Shenfu injection in preventing and treating COVID-19 combined with heart failure

Rg3 regulates myocardial pyruvate metabolism via P300-mediated dihydrolipoamide dehydrogenase 2-hydroxyisobutyrylation in TAC-induced cardiac hypertrophy

The Molecular Mechanisms of Panax ginseng in Treating Type 2 Diabetes Mellitus: Network Pharmacology Analysis and Molecular Docking Validation

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