Active ingredients and mechanisms of Phellinus linteus (grown on Rosa multiflora) for alleviation of Type 2 diabetes mellitus through network pharmacology

Gene ◽  
2021 ◽  
Vol 768 ◽  
pp. 145320
Author(s):  
Ki Kwang Oh ◽  
Md. Adnan ◽  
Dong Ha Cho
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Network Pharmacology ◽  
Phellinus Linteus ◽  
Rosa Multiflora ◽  
Active Ingredients

scholarly journals Use of Network Pharmacology to Explore the Mechanism of Gegen (Puerariae lobatae Radix) in the Treatment of Type 2 Diabetes Mellitus Associated with Hyperlipidemia

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Guozhen Yuan ◽  
Shuai Shi ◽  
Qiulei Jia ◽  
Jingjing Shi ◽  
Shuqing Shi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Signaling Pathway ◽  
Fluid Shear Stress ◽  
Chinese Herbs ◽  
Network Pharmacology ◽  
Biological Processes ◽  
Active Ingredients

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.

scholarly journals Investigation on the Enzymatic Profile of Mulberry Alkaloids by Enzymatic Study and Molecular Docking

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1776 ◽  
Author(s):  
Zhihua Liu ◽  
Ying Yang ◽  
Wujun Dong ◽  
Quan Liu ◽  
Renyun Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Molecular Docking ◽  
Side Effects ◽  
Inhibitory Effect ◽  
Active Ingredients ◽  
Wide Range ◽  
Consensus Score

α-glucosidase inhibitors (AGIs) have been an important category of oral antidiabetic drugs being widely exploited for the effective management of type 2 diabetes mellitus. However, the marketed AGIs not only inhibited the disaccharidases, but also exhibited an excessive inhibitory effect on α-amylase, resulting in undesirable gastrointestinal side effects. Compared to these agents, Ramulus Mori alkaloids (SZ-A), was a group of effective alkaloids from natural Morus alba L., and showed excellent hypoglycemic effect and fewer side effects in the Phase II/III clinical trials. Thus, this paper aims to investigate the selective inhibitory effect and mechanism of SZ-A and its major active ingredients (1-DNJ, FA and DAB) on different α-glucosidases (α-amylase and disaccharidases) by using a combination of kinetic analysis and molecular docking approaches. From the results, SZ-A displayed a strong inhibitory effect on maltase and sucrase with an IC50 of 0.06 μg/mL and 0.03 μg/mL, respectively, which was similar to the positive control of acarbose with an IC50 of 0.07 μg/mL and 0.68 μg/mL. With regard to α-amylase, SZ-A exhibited no inhibitory activity at 100 μg/mL, while acarbose showed an obvious inhibitory effect with an IC50 of 1.74 μg/mL. The above analysis demonstrated that SZ-A could selectively inhibit disaccharidase to reduce hyperglycemia with a reversible competitive inhibition, which was primarily attributed to the three major active ingredients of SZ-A, especially 1-DNJ molecule. In the light of these findings, molecular docking study was utilized to analyze their inhibition mechanisms at molecular level. It pointed out that acarbose with a four-ring structure could perform desirable interactions with various α-glucosidases, while the three active ingredients of SZ-A, belonging to monocyclic compounds, had a high affinity to the active site of disaccharidases through forming a wide range of hydrogen bonds, whose affinity and consensus score with α-amylase was significantly lower than that of acarbose. Our study illustrates the selective inhibition mechanism of SZ-A on α-glucosidase for the first time, which is of great importance for the treatment of type 2 diabetes mellitus.

scholarly journals The Mechanism of Jinqi Jiangtang Tablet in Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology

2020 ◽  
Author(s):  
Mingjun Yang ◽  
Boni Song ◽  
Zhitong Bing ◽  
Juxiang Liu ◽  
Rui Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Drug Targets ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Active Compounds ◽  
Online Tool

Abstract Background: Type 2 Diabetes Mellitus(T2DM) is an endocrine disease that caused mainly by insulin resistance (IR) and β cell dysfunction. The incidence of T2DM is quite high in the worldwide. To explore the molecular mechanism of Jinqi Jiangtang Tablet(JJT) in treating of T2DM based on Network Pharmacology. Methods: The active compounds, targets of three Traditional Chinese medicines in JJT were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） database and Uniprot database; The targets of T2DM were screened through the Drugbank database; The compound-target network was constructed via the Cytoscape 3.7.2 software and used the built-in Network analyzer to analyze and select the key active compounds; The overlapping targets of drug and disease targets were gained by the VENNY online tool and the targets were built by STRING website to select the key genes; Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed on the potential targets using DAVID6.8 online tool to study the mechanism of overlapping targets. Via Systems Dock platform to validate the interaction between compound and targets Results: Twenty-five active compounds of JJT were screened, 101 drug targets, 142 disease targets and twenty-one overlapping targets. GO enrichment analysis showed that the biological processes (BP)mainly included the blood circulation ,etc. Cell composition(CC) mainly affected the integral component of plasma membrane, etc. Molecular functions(MF) mainly involved alpha-adrenergic receptor activity, etc. KEGG pathway analysis showed that there were twelve pathways related to T2DM, among which PPAR signaling pathway was related to T2DM mostly. RXRA is one of key targets of JJT and berberine performed well. Conclusions: This study revealed the mechanism of JJT in treatment of T2DM preliminarily and supplied a further foundation for studying its mechanism.

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