Exploring the synergistic and complementary effects of berberine and paeoniflorin in the treatment of type 2 diabetes mellitus by network pharmacology

Zhang, Lili; Lin, Han Chieh; Ma, Jiang; Wu, Tingchao; Yu, Wei; Zhao, Linhua; Tong, Xiaolin

doi:10.1016/j.ejphar.2022.174769

Cited by 16 publications

(6 citation statements)

References 34 publications

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“…The results indicated that the administration of AFr could increase the expression of these three proteins, especially AKT1 and PPARG. Previous studies showed that AKT1 might play a role in insulin−related pathways [ 27 ], and the increased expression of AKT1 plays a role in the treatment of T2DM and prevented its complications [ 28 ]. PPARG is a transcription factor revolving around adipocyte differentiation, lipid metabolism, and inflammation [ 29 ].…”

Section: Resultsmentioning

confidence: 99%

Exploring Active Ingredients, Beneficial Effects, and Potential Mechanism of Allium tenuissimum L. Flower for Treating T2DM Mice Based on Network Pharmacology and Gut Microbiota

et al. 2022

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Forty compounds were isolated and characterized from A. tenuissimum flower. Among them, twelve flavonoids showed higher α−glucosidase inhibition activities in vitro than acarbose, especially kaempferol. The molecular docking results showed that the binding of kaempferol to α−glucosidase (GAA) could reduce the hydrolysis of substrates by GAA and reduce the glucose produced by hydrolysis, thus exhibiting α−glucosidase inhibition activities. The in vivo experiment results showed that flavonoids−rich A. tenuissimum flower could decrease blood glucose and reduce lipid accumulation. The protein expression levels of RAC−alpha serine/threonine−protein kinase (AKT1), peroxisome proliferator activated receptor gamma (PPARG), and prostaglandin G/H synthase 2 (PTGS2) in liver tissue were increased. In addition, the Firmicutes/Bacteroidetes (F/B) ratio was increased, the level of gut probiotics Bifidobacterium was increased, and the levels of Enterobacteriaceae and Staphylococcus were decreased. The carbohydrate metabolism, lipid metabolism, and other pathways related to type 2 diabetes mellitus were activated. This study indicating flavonoids−rich A. tenuissimum flower could improve glycolipid metabolic disorders and inflammation in diabetic mice by modulating the protein expression and gut microbiota.

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Section: Resultsmentioning

confidence: 99%

Exploring Active Ingredients, Beneficial Effects, and Potential Mechanism of Allium tenuissimum L. Flower for Treating T2DM Mice Based on Network Pharmacology and Gut Microbiota

et al. 2022

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“…ESR1 and islet β apoptosis are closely related, and it is also one of the biological indicators for clinical diagnosis of gestational diabetes in early pregnancy [ 22 ]. MAPK1 can reduce blood glucose levels in patients with DM, improve oxidative stress, and protect pancreatic β cells by regulating MAPK/ERK cascade reaction [ 23 ]. AKT1 is an important target downstream of insulin signaling pathway, which can regulate glucose transport and blood glucose level by blocking insulin receptor dephosphorylation [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Investigating the Mechanism of Rhizoma Coptidis‐Eupatorium fortunei Medicine in the Treatment of Type 2 Diabetes Based on Network Pharmacology and Molecular Docking

Luo

Wei

et al. 2022

BioMed Research International

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Objective. This study systematically explored the mechanism of Rhizoma Coptidis-Eupatorium fortunei in treating type 2 diabetes mellitus (T2DM) by using network pharmacology and molecular docking methods. Methods. The TCMSP database was used to screen out the active ingredients and related targets of Rhizoma Coptidis-Eupatorium fortunei (R-E) drug pair. GeneCards, OMIM, DrugBank, and other databases were used to screen the related targets of T2DM, and then, the UniProt database was used to standardize the relevant targets of T2DM. Then, the Venn analysis was performed on the active ingredient-related targets and disease-related targets of R-E drugs to find the intersection targets. Using the STRING database and Cytoscape software, the PPI network and “drug-active ingredient-target-disease” network are constructed by intersecting targets and corresponding active ingredients. Through the cluster profiler package in the R software, GO function enrichment analysis and KEGG pathway enrichment analysis were carried out on the intersection targets and the screened core targets, and the prediction results were verified by molecular docking. Results. Taking OB ≥ 30 % and DL ≥ 0.18 as the standard, a total of 25 effective active ingredients of R-E drug pairs were screened, including berberine, palmatine, coptisine, and so on. After corresponding, 19 effective chemical components and 284 targets of the R-E drug pair were obtained. After searching multiple disease databases, 1289 T2DM-related targets were screened. After the summary, 159 common targets were obtained in this study. Finally, in the bioinformatics analysis, this study concluded that quercetin, luteolin, berberine, palmatine, and coptisine are the main chemical components of the R-E drug pair. ESR1, MAPK1, AKT1, TP53, IL6, and JUN are the important core targets. GO and KEGG enrichment analyses showed that Rhizoma Coptidis-Eupatorium fortunei could improve T2DM by regulating multiple biological processes and pathways. Molecular docking results showed that berberine, palmatine, and coptisine had higher binding to the core target, and MAPK1, AKT1, and IL6 could stably bind to the active ingredients of Rhizoma Coptidis-Eupatorium fortunei. Conclusion. Rhizoma Coptidis-Eupatorium fortunei may have therapeutic effects on T2DM such as anti-inflammatory and regulating glucose and lipid metabolism through multiple components, multiple targets, and multiple signaling pathways, which provides a scientific basis for further research on the hypoglycemic effect of Rhizoma Coptidis-Eupatorium fortunei drug pair.

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“…It is reported that kaempferol significantly inhibits concanavalin A (ConA) stimulation in early activation of mice T lymphocytes, arrests cell cycle, and inhibits ConA stimulation T cell proliferation. us, kaempferol can reduce autoimmune disease and organ transplant rejection caused by the excessive activation and proliferation of T lymphocytes [20,51,52]. Some studies reported that kaempferol could promote activating the Ampk/Nrf2/HO-1 signaling pathway and relieve the ox-LDL-induced endothelial injury [53][54][55].…”

Section: Discussionmentioning

confidence: 99%

“…Network pharmacology is a new strategy based on system biology, bioinformatics, and multidisciplines, which can systematically and comprehensively observe the intervention of drugs on disease networks [14][15][16][17][18][19][20]. It is especially suitable for TCM research in treating complex diseases [21,22].…”

Section: Introductionmentioning

confidence: 99%

Decoding the Mechanism of CheReCunJin Formula in Treating Sjögren’s Syndrome Based on Network Pharmacology and Molecular Docking

Wang

Chen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by progressive oral and ocular dryness that correlates poorly with autoimmune damage to the glands. CheReCunJin (CRCJ) formula is a prescription formulated according to the Chinese medicine theory for SS treatment. Objective. This study aimed to explore the underlying mechanisms of CRCJ against SS. Methods. The databases, including Traditional Chinese Medicine System Pharmacology, Encyclopedia of Traditional Chinese Medicine, Bioinformatics Analysis Tool for the molecular mechanism of Traditional Chinese Medicine, and Traditional Chinese Medicine Integrated Databases, obtained the active ingredients and predicted targets of CRCJ. Then, DrugBank, Therapeutic Target Database, Genecards, Comparative Toxicogenomics Database, and DisGeNET disease databases were used to screen the predicted targets of SS. Intersected targets of CRCJ and SS were visualized by using Venn diagrams. The overlapping targets were uploaded to the protein–protein interaction network analysis search tool. Cytoscape 3.8.2 software constructed a “compound-targets-disease” network. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses characterized potential targets’ biological functions and pathways. AutoDock Vina 1.1.2 software was used to research and verify chemical effective drug components and critical targets. Results. From the database, we identified 878 active components and 2578 targets of CRCJ, and 827 SS-related targets. 246 SS-related genes in CRCJ were identified by intersection analysis, and then ten hub genes were identified as crucial potential targets from PPI, including ALB, IL-6, TNF, INS, AKT1, IL1B, VEGFA, TP53, JUN, and TLR4. The process of CRCJ action against SS was mainly involved in human cytomegalovirus infection and Th17 cell differentiation, as well as the toll-like receptor signaling and p53 signaling pathways. Molecular docking showed that the bioactive compounds of CRCJ had a good binding affinity with hub targets. Conclusions. The results showed that CRCJ could activate multiple pathways and treat SS through multiple compounds and targets. This study lays a foundation for better elucidation of the molecular mechanism of CRCJ in the treatment of SS, and also provides basic guidance for future research on Chinese herbal compounds.

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Exploring the synergistic and complementary effects of berberine and paeoniflorin in the treatment of type 2 diabetes mellitus by network pharmacology

Cited by 16 publications

References 34 publications

Exploring Active Ingredients, Beneficial Effects, and Potential Mechanism of Allium tenuissimum L. Flower for Treating T2DM Mice Based on Network Pharmacology and Gut Microbiota

Exploring Active Ingredients, Beneficial Effects, and Potential Mechanism of Allium tenuissimum L. Flower for Treating T2DM Mice Based on Network Pharmacology and Gut Microbiota

Investigating the Mechanism of Rhizoma Coptidis‐Eupatorium fortunei Medicine in the Treatment of Type 2 Diabetes Based on Network Pharmacology and Molecular Docking

Decoding the Mechanism of CheReCunJin Formula in Treating Sjögren’s Syndrome Based on Network Pharmacology and Molecular Docking

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