scholarly journals Exploring the Regulatory Mechanism of Modified Huanglian Maidong Decoction on Type 2 Diabetes Mellitus Biological Network Based on Systematic Pharmacology

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Qi He ◽  
Tianqing Zhang ◽  
Bing Jin ◽  
Yonghe Wu ◽  
Jiamin Wu ◽  
...  

Objective. To explore the mechanism of modified Huanglian Maidong decoction (Maidong-Sanqi-Huanglian Compounds, MSHCs) intervention in type 2 diabetes mellitus (T2DM). Method. This study used PubChem and SciFinder to collect the molecular structure of MSHCs, used PharmMapper to predict the potential targets of MSHC, and combined them with the T2DM gene to construct MSHC-T2DM protein-protein interaction (PPI) network. The plugin MCODE in Cytoscape 3.7.1 was then used to perform cluster analysis on the MSHC-T2DM PPI network. The genes and targets were input into DAVID for Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were performed to verify the therapeutic effect of MSHC on T2DM. Results. Several T2DM-related targets, clusters, signaling pathways, and biological processes are found. The experimental results showed that compared with the blank group, the content of fasting blood glucose (FBG) in the model group was higher ( P < 0.01 ). Compared with the model group, the content of FBG decreased and the insulin level increased in the MSHC medium-dose (0.15 g/kg) and high-dose (0.45 g/kg) groups and metformin group after 4 weeks of drug administration ( P < 0.05 ). MSHC can also improve blood liquid levels and inflammatory factor levels ( P < 0.05 ). Conclusion. MSHC may achieve therapeutic effects through regulating the T2DM-related targets, biological processes, and pathways, such as insulin resistance, energy metabolism, oxidative stress, and inflammation, found in this research.

Author(s):  
Zhigui Wu ◽  
Li Gu ◽  
Yuankai Si ◽  
Wenxian Yin ◽  
Meng Zhao ◽  
...  

Objective: The aim of this study was to examine the effect of berberine in diabetes mellitus in vivo and in vitro, and elucidate the underlying mechanisms. Methods: Rat models of type 2 diabetes mellitus (T2DM) were established, which were treated with berberine. Pathological changes in the thoracic aorta, and inflammatory factor and adiponectin levels were investigated. Vascular smooth muscle cells (VSMCs) of the thoracic aorta were cultured and treated with berberine. Cellular proliferation, migration, and inflammatory factor levels were investigated. Responses of vascular rings to phenylephrine (PE) and sodium nitroprusside (SNP) after berberine intervention, and the changes of relaxation responses to SNP after adding Iberiotoxin (IbTX) were investigated. Results: Berberine ameliorated the pathological status of the thoracic aorta in the T2DM rats. Berberine significantly inhibited the C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) production, and increased the adiponectin level compared with the model group. Compared with the model group, berberine inhibited the proliferation and migration of VSMCs in vitro, and reduced tumor growth factor-β1 (TGF-β1), IL-6, and TNF-α levels. Furthermore, the contraction of thoracic aorta to PE was reduced, while the relaxation response of thoracic aorta to SNP was increased, after the berberine intervention in the T2DM rats. The relaxation of thoracic aorta to SNP in the model and berberine groups were decreased after the IbTX treatment. Conclusions: Protective effects of berberine against macrovascular complications induced by diabetes mellitus may be attributed to inhibiting the inflammation and intervening the calcium-activated potassium (BKCa).


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Guoxiu Zu ◽  
Keyun Sun ◽  
Ling Li ◽  
Xiuli Zu ◽  
Tao Han ◽  
...  

AbstractQuercetin has demonstrated antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic activities, suggesting therapeutic potential against type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). In this study, potential molecular targets of quercetin were first identified using the Swiss Target Prediction platform and pathogenic targets of T2DM and AD were identified using online Mendelian inheritance in man (OMIM), DisGeNET, TTD, DrugBank, and GeneCards databases. The 95 targets shared among quercetin, T2DM, and AD were used to establish a protein–protein interaction (PPI) network, top 25 core genes, and protein functional modules using MCODE. Metascape was then used for gene ontology and kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. A protein functional module with best score was obtained from the PPI network using CytoHubba, and 6 high-probability quercetin targets (AKT1, JUN, MAPK, TNF, VEGFA, and EGFR) were confirmed by docking simulations. Molecular dynamics simulation was carried out according to the molecular docking results. KEGG pathway enrichment analysis suggested that the major shared mechanisms for T2DM and AD include “AGE-RAGE signaling pathway in diabetic complications,” “pathways in cancer,” and “MAPK signaling pathway” (the key pathway). We speculate that quercetin may have therapeutic applications in T2DM and AD by targeting MAPK signaling, providing a theoretical foundation for future clinical research.


2021 ◽  
Author(s):  
Guoxiu Zu ◽  
Keyun Sun ◽  
Ling Li ◽  
Xiuli Zu ◽  
Tao Han ◽  
...  

Abstract Quercetin has demonstrated antioxidant, anti-inflammatory, hypoglycemic, and hypolipidemic activities, suggesting therapeutic potential against type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). In this study, potential molecular targets of quercetin were first identified using the Swiss Target Prediction platform and pathogenic targets of T2DM and AD were identified using Online Mendelian Inheritance in Man (OMIM), DisGeNET, TTD, DrugBank, and GeneCards databases. The 95 targets shared among quercetin, T2DM, and AD were used to establish a protein–protein interaction (PPI) network, top 25 core genes, and protein functional modules using MCODE. Metascape was then used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A protein functional module with best score was obtained from the PPI network using CytoHubba, and 6 high-probability quercetin targets (AKT1, JUN, MAPK, TNF, VEGFA, and EGFR) were confirmed by docking simulations. KEGG pathway enrichment analysis suggested that the major shared mechanisms for T2DM and AD include “AGE-RAGE signaling pathway in diabetic complications,” “pathways in cancer,” and “MAPK signaling pathway” (the key pathway). We speculate that quercetin may have therapeutic applications in T2DM and AD by targeting MAPK signaling, providing a theoretical foundation for future clinical research.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 570
Author(s):  
Marina Yazigi Solis ◽  
Guilherme Giannini Artioli ◽  
Bruno Gualano

Creatine is one of the most popular supplements worldwide, and it is frequently used by both athletic and non-athletic populations to improve power, strength, muscle mass and performance. A growing body of evidence has been identified potential therapeutic effects of creatine in a wide variety of clinical conditions, such as cancer, muscle dystrophy and neurodegenerative disorders. Evidence has suggested that creatine supplementation alone, and mainly in combination with exercise training, may improve glucose metabolism in health individuals and insulin-resistant individuals, such as in those with type 2 diabetes mellitus. Creatine itself may stimulate insulin secretion in vitro, improve muscle glycogen stores and ameliorate hyperglycemia in animals. In addition, exercise induces numerous metabolic benefits, including increases in insulin-independent muscle glucose uptake and insulin sensitivity. It has been speculated that creatine supplementation combined with exercise training could result in additional improvements in glucose metabolism when compared with each intervention separately. The possible mechanism underlying the effects of combined exercise and creatine supplementation is an enhanced glucose transport into muscle cell by type 4 glucose transporter (GLUT-4) translocation to sarcolemma. Although preliminary findings from small-scale trials involving patients with type 2 diabetes mellitus are promising, the efficacy of creatine for improving glycemic control is yet to be confirmed. In this review, we aim to explore the possible therapeutic role of creatine supplementation on glucose management and as a potential anti-diabetic intervention, summarizing the current knowledge and highlighting the research gaps.


2020 ◽  
Vol 11 (6) ◽  
pp. 5538-5552 ◽  
Author(s):  
Yulan Li ◽  
Dan Chen ◽  
Chengmei Xu ◽  
Qingyujing Zhao ◽  
Yage Ma ◽  
...  

WMP (extract of pressed degreased walnut meal) is rich in polyphenols which exhibit multiple therapeutic effects.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Guozhen Yuan ◽  
Shuai Shi ◽  
Qiulei Jia ◽  
Jingjing Shi ◽  
Shuqing Shi ◽  
...  

Rapid increases in metabolic disorders, such as type 2 diabetes mellitus (T2DM) and hyperlipidemia, are becoming a substantial challenge to worldwide public health. Traditional Chinese medicine has a long history and abundant experience in the treatment of diabetes and hyperlipidemia, and Puerariae lobatae Radix (known as Gegen in Chinese) is one of the most prevalent Chinese herbs applied to treat these diseases. The underlying mechanism by which Gegen simultaneously treats diabetes and hyperlipidemia, however, has not been clearly elucidated to date. Therefore, we systematically explored the potential mechanism of Gegen in the treatment of T2DM complicated with hyperlipidemia based on network pharmacology. We screened the potential targets of Gegen, T2DM, and hyperlipidemia in several online databases. Then, the hub targets were analyzed by performing protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays, and finally, the complicated connections among compounds, targets, and pathways were visualized in Cytoscape. We found that isoflavones, including daidzein, genistein, and puerarin, as well as β-sitosterol, are the key active ingredients of Gegen responsible for its antidiabetic and antihyperlipidemia effects, which mainly target AKR1B1, EGFR, ESR, TNF, NOS3, MAPK3, PPAR, CYP19A1, INS, IL6, and SORD and multiple pathways, such as the PI3K-Akt signaling pathway; the AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis; the PPAR signaling pathway; insulin resistance; the HIF-1 signaling pathway; the TNF signaling pathway; and others. These active ingredients also target multiple biological processes, including the regulation of glucose and lipid metabolism, the maintenance of metabolic homeostasis, and anti-inflammatory and antioxidant pathways. In conclusion, Gegen is a promising therapeutic phytomedicine for T2DM with hyperlipidemia that targets multiple proteins, biological processes, and pathways.


2017 ◽  
Vol 4 (S) ◽  
pp. 88
Author(s):  
Phuong Thi-Bich Le ◽  
Phuc Van Pham ◽  
Ngoc Bich Vu ◽  
Loan Thi-Tung Dang ◽  
Ngoc Kim Phan

Introduction: Type 2 diabetes mellitus (T2D) is the most common form of diabetes mellitus, accounting for 90% of diabetes mellitus in patients. At the present time, although T2D can be treated by various drugs and therapies using insulin replacement, reports have shown that complications including microvascular, macrovascular complications and therapy resistance can occur in patients on long term treatment. Stem cell therapy is regarded as a promising therapy for diabetes mellitus, including T2D. The aim of this study was to evaluate the safety and therapeutic effect of expanded autologous adipose derived stem cell (ADSC) transplantation for T2D treatment; the pilot study included 3 patients who were followed for 3 months. Methods: The ADSCs were isolated from stromal vascular fractions, harvested from the belly of the patient,and expanded for 21 days per previously published studies. Before transplantation, ADSCs were evaluated for endotoxin, mycoplasma contamination, and karyotype. All patients were transfused with ADSCs at 1-2x106 cells/kg of body weight.Patients were evaluated for criteria related to transplantation safety and therapeutic effects; these included fever, blood glucose level before transplantation of ADSCs, and blood glucose level after transplantation (at 1, 2 and 3 months). Results: The results showed that all samples of ADSCs exhibited the MSC phenotype with stable karyotype (2n=46), there was no contamination of mycoplasma, and endotoxin levels were low (<0.25 EU/mL). No adverse effects were detected after 3 months of transplantation. Decreases of blood glucose levels were recorded in all patients. Conclusion: The findings from this initial study show that expanded autologous ADSCs may be a promising treatment for T2D.


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