Molecular Mechanism of Puerarin Against Diabetes and its Complications

Bai, Yi-Ling; Han, Lingling; Qian, Jun-Hui; Wang, Haozhong

doi:10.3389/fphar.2021.780419

Cited by 27 publications

(15 citation statements)

References 64 publications

(82 reference statements)

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“…Recently, research studies have attempted to elucidate the mechanism of puerarin in type-2 diabetes and its related complications [ 21 , 22 , 23 ]. Various in vivo studies of puerarin described the hypoglycemic mechanism to work through the liver, pancreas, adipose tissue, and skeletal muscle [ 24 ]. In the pancreas, puerarin has been shown to enhance the glucagon-like peptide 1 (GLP-1R) signalling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…A small number of scientific investigations [ 21 , 22 , 23 ] were carried out to elucidate the antidiabetic activity and mechanisms of puerarin. Puerarin is reported to exhibit antihyperglycaemic activity by recovering the physiological homeostasis functions of the liver, pancreas, adipose tissue, and skeletal muscle [ 24 ]. It activates the glucagon-like peptide 1 (GLP-1R) signalling pathway in the pancreas of diabetic rats.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacodynamic Interactions between Puerarin and Metformin in Type-2 Diabetic Rats

Wang

et al. 2022

Molecules

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Herb–drug interactions are vital in effectively managing type-2-diabetes complications. Puerarin is a natural isoflavonoid in the Pueraria genus, and its pharmacological activities, including antidiabetic activity, are well established. The similar modes of action of puerarin and metformin in diabetic models suggest their positive pharmacodynamic interactions. This study investigated this in streptozotocin/nicotinamide-induced type-2 diabetic rats. Puerarin at doses of 80 mg/kg, 120 mg/kg and 160 mg/kg improved the activity of metformin in reversing hyperglycaemia, dysregulated lipid profiles, dysfunction of the liver, kidney, and pancreas, and inflammation. The treatment with either puerarin (high dose, 160 mg/kg intraperitoneally) or metformin (100 mg/kg intraperitoneally) did not bring the dysregulated biomarkers to normal levels in 4 weeks. By contrast, the combination of puerarin (160 mg/kg) and metformin (100 mg/kg) did. This study is the first to report scientific evidence for the positive pharmacodynamic interactions between puerarin and metformin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacodynamic Interactions between Puerarin and Metformin in Type-2 Diabetic Rats

Wang

et al. 2022

Molecules

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“…The STZ model is a well-established method for inducing type 1 or 2 diabetes in rats and, subsequently, diabetic complications [ 85 ]. For this purpose, our results represent that STZ aortic tissue levels significantly elevated VIP, E-selectin, endothelin-1, and ICAM-1 levels compared to the normal control group ( Figure 1 A).…”

Section: Discussionmentioning

confidence: 99%

Partial Synthetic PPARƳ Derivative Ameliorates Aorta Injury in Experimental Diabetic Rats Mediated by Activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR Expression

et al. 2022

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Type 2 diabetes mellitus (T2D) is a world wild health care issue marked by insulin resistance, a risk factor for the metabolic disorder that exaggerates endothelial dysfunction, increasing the risk of cardiovascular complications. Peroxisome proliferator-activated receptor PPAR) agonists have therapeutically mitigated hyperlipidemia and hyperglycemia in T2D patients. Therefore, we aimed to experimentally investigate the efficacy of newly designed synthetic PPARα/Ƴ partial agonists on a High-Fat Diet (HFD)/streptozotocin (STZ)-induced T2D. Female Wistar rats (200 ± 25 g body weight) were divided into four groups. The experimental groups were fed the HFD for three consecutive weeks before STZ injection (45 mg/kg/i.p) to induce T2D. Standard reference PPARƳ agonist pioglitazone and the partial synthetic PPARƳ (PIO; 20 mg/kg/BW, orally) were administered orally for 2 weeks after 72 h of STZ injection. The aorta tissue was isolated for biological ELISA, qRT-PCR, and Western blotting investigations for vascular inflammatory endothelial mediators endothelin-1 (ET-1), intracellular adhesion molecule 1 (ICAM-1), E-selectin, and anti-inflammatory vasoactive intestinal polypeptide (VIP), as well as microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR, endothelial Nitric Oxide Synthase (eNOS) immunohistochemical staining all are coupled with and histopathological examination. Our results revealed that HFD/STZ-induced T2D increased fasting blood glucose, ET-1, ICAM-1, E-selectin, and VIP levels, while decreasing the expression of both microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR phosphorylation. In contrast, the partial synthetic PPARƳ derivative evidenced a vascular alteration significantly more than reference PIO via decreasing (ET-1), ICAM-1, E-selectin, and VIP, along with increased expression of microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR. In conclusion, the partial synthetic PPARƳ derivative significantly affected HFD/STZ-induced T2D with vascular complications in the rat aorta.

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“…It had become the third epidemic following cardiovascular diseases and tumors. Significant and persistent hyperglycemia can lead to dysfunction in various cell types, efficiently inducing complications such as nephropathy, retinopathy, angiocardiopathy, cerebrovascular diseases, and neuropathy 1 . More than 400 million people already had DM, and the number of people with the disease continues to increase worldwide 2 .…”

Section: Introductionmentioning

confidence: 99%

Exploring the mechanism of active components from ginseng to manage diabetes mellitus based on network pharmacology and molecular docking

Jin

et al. 2023

Sci Rep

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A large body of literature has shown that ginseng had a role in diabetes mellitus management. Ginsenosides are the main active components of ginseng. But what ginsenosides can manage in diabetic are not systematic. The targets of these ginsenosides are still incomplete. Our aim was to identify which ginsenosides can manage diabetes mellitus through network pharmacology and molecular docking. To identify the targets of these ginsenosides. In this work, we retrieved and screened ginsenosides and corresponding diabetes mellitus targets across multiple databases. PPI networks of the genes were constructed using STRING, and the core targets were screened out through topological analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed by using the R language. Finally, molecular docking was performed after bioinformatics analysis for verification. Our research results showed that 28 ginsenosides in ginseng might be against diabetes mellitus by modulating related proteins such as VEGFA, Caspase 3, and TNF-α. Among the 28 ginsenosides, 20(R)-Protopanaxatriol, 20(R)-Protopanaxadiol, and Ginsenoside Rg1 might play a significant role. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis showed that the management of diabetes mellitus by ginsenosides may be related to the positive regulation of reactive oxygen metabolic processes, associated with the insulin signaling pathway, TNF signaling pathway, and AMPK signaling pathway. Molecular docking results and molecular dynamics simulation showed that most ginsenosides could stably bind to the core target, mainly hydrogen bonding and hydrophobic bond. This study suggests the management of ginseng on diabetes mellitus. We believe that our results can contribute to the systematic study of the mechanism of ginsenosides for the management of diabetes mellitus. At the same time, it can provide a theoretical basis for subsequent studies on the management of ginsenosides in diabetes mellitus.

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Molecular Mechanism of Puerarin Against Diabetes and its Complications

Cited by 27 publications

References 64 publications

Pharmacodynamic Interactions between Puerarin and Metformin in Type-2 Diabetic Rats

Pharmacodynamic Interactions between Puerarin and Metformin in Type-2 Diabetic Rats

Partial Synthetic PPARƳ Derivative Ameliorates Aorta Injury in Experimental Diabetic Rats Mediated by Activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR Expression

Exploring the mechanism of active components from ginseng to manage diabetes mellitus based on network pharmacology and molecular docking

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