In silico network pharmacology and in vivo analysis of berberine-related mechanisms against type 2 diabetes mellitus and its complications

Sha, Di; Lin, Han Chieh; An, Xuedong; Kong, Ran; Gao, Zezheng; Yang, Yingying; Wang, Xinmiao; Zhang, Pei; Ding, Qiyou; Wu, Haoran; Wang, Han; Zhao, Linhua; Tong, Xiaolin

doi:10.1016/j.jep.2021.114180

“…Among the different alkaloids, berberine is an important lead compound with a wide spectrum of pharmacological activities, including antitumor, anti-inflammatory, hypoglycemic, hypolipidemic, and antiobesity effects [ 13 ]. Additionally, evidence has shown that berberine regulates the gut microbiota as well [ 14 , 15 ], which is closely associated with systematic inflammation that adds to the progression of T2DM. Systematic reviews have previously reported the efficacy of berberine on the regulation of glycemic and lipid metabolisms [ 16 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Guo

¹

,

Chen

²

,

Zhang

³

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Objective. Rhizoma Coptidis is an herb that has been frequently used in many traditional formulas for the treatment of diabetic mellitus (DM) over thousands of years. Berberine, the main active component of Rhizoma Coptidis, has been demonstrated to have the potential effect of hypoglycemia. To determine the potential advantages of berberine for diabetic care, we conducted this systematic review and meta-analysis to examine the efficacy and safety of berberine in the treatment of patients with type 2 DM. Methods. Eight databases including PubMed, Embase, Web of Science, the Cochrane library, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (SinoMed), Wanfang Database, and Chinese VIP Information was searched for randomized controlled trials (RCTs) reporting clinical data regarding the use of berberine for the treatment of DM. Publication qualities were also considered to augment the credibility of the evidence. Glycemic metabolisms were the main factors studied, including glycosylated hemoglobin (HbA1c), fasting plasm glucose (FPG), and 2-hour postprandial blood glucose (2hPG). Insulin resistance was estimated by fasting blood insulin (FINS), homeostasis model assessment-insulin resistance (HOMA-IR), and body mass index (BMI). Lipid profiles were also assessed, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), along with inflammation factors such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Serum creatinine (Scr), blood urea nitrogen (BUN), and adverse events were applied to evaluate the safety of berberine. Results. Forty-six trials were assessed. Analysis of berberine applied alone or with standard diabetic therapies versus the control group revealed significant reductions in HbA1c ( MD = − 0.73 ; 95% CI (−0.97, −0.51)), FPG ( MD = − 0.86 , 95% CI (−1.10, −0.62)), and 2hPG ( MD = − 1.26 , 95% CI (−1.64, −0.89)). Improved insulin resistance was assessed by lowering FINS ( MD = − 2.05 , 95% CI (−2.62, −1.48)), HOMA-IR ( MD = − 0.71 , 95% CI (−1.03, −0.39)), and BMI ( MD = − 1.07 , 95% CI (−1.76, −0.37)). Lipid metabolisms were also ameliorated via the reduction of TG ( MD = − 0.5 , 95% CI (−0.61, −0.39)), TC ( MD = 0.64 , 95% CI (−0.78, −0.49)), and LDL ( MD = 0.86 , 95% CI (−1.06, −0.65)) and the upregulation of HDL ( MD = 0.17 , 95% CI (0.09, 0.25)). Additionally, berberine improved the inflammation factor. Conclusion. There is strong evidence supporting the clinical efficacy and safety of berberine in the treatment of DM, especially as an adjunctive therapy. In the future, this may be used to guide targeted clinical use of berberine and the development of medications seeking to treat patients with T2DM and dyslipidemia.

show abstract

“…In this study, we searched for the chemical composition of EUO and TT through the pharmacology platform of the Chinese medicine network. We extracted the main active compounds of each medicine with the screening conditions of oral bioavailability ≥30% and drug-likeness ≥0.18 ( 36 ).…”

Section: Methodsmentioning

confidence: 99%

Eucommia ulmoides Oliver-Tribulus terrestris L. Drug Pair Regulates Ferroptosis by Mediating the Neurovascular-Related Ligand-Receptor Interaction Pathway- A Potential Drug Pair for Treatment Hypertension and Prevention Ischemic Stroke

Zhang

¹

,

Yang

²

,

Yang

³

et al. 2022

View full text Add to dashboard Cite

BackgroundIn this study, we used the network pharmacology approach to explore the potential disease targets of the Eucommia ulmoides Oliver (EUO)-Tribulus terrestris L. (TT) drug pair in the treatment of hypertension-associated neurovascular lesions and IS via the ferroptosis pathway.MethodsWe used the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform to search for the key active compounds and targets of the drug pair. Based on the GeneCards database, the relevant targets for the drug pair were obtained. Then, we performed the molecular docking of the screened core active ingredients and proteins using the DAVID database and the R AutoDock Vina software. Based on the GSE22255 dataset, these screened target proteins were used to build random forest (RF) and support vector machine (SVM) models. Finally, a new IS nomogram prediction model was constructed and evaluated.ResultsThere were 36 active compounds in the EUO-TT drug pair. CHRM1, NR3C1, ADRB2, and OPRD1 proteins of the neuroactive ligand-receptor interaction pathway interacted with the proteins related to the ferroptosis pathway. Molecular docking experiments identified 12 active ingredients of the drug pair that may tightly bind to those target proteins. We constructed a visual IS nomogram prediction model using four genes (CHRM1, NR3C1, ADRB2, and OPRD1). The calibration curve, DCA, and clinical impact curves all indicated that the nomogram model is clinically applicable and diagnostically capable. CHRM1, NR3C1, ADRB2, and OPRD1, the target genes of the four effective components of the EUO-TT drug pair, were considered as risk markers for IS.ConclusionsThe active ingredients of EUO-TT drug pair may act on proteins associated with the neuroactive ligand-receptor interaction pathway to regulate ferroptosis in vascular neurons cells, ultimately affecting the onset and progression of hypertension.

show abstract

“…In this study, chemical compositions of the Yiqi Qingre Ziyin method were determined through the pharmacology platform of the Chinese Medicine Network [including Traditional Chinese Medicine Database, Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM)] (Chen et al, 2014;Ru et al, 2014;Liu et al, 2016). The main active ingredients of each drug were extracted under the following screening conditions: oral bioavailability of ≥30% and drug similarity of ≥0.18 (Di et al, 2021). The active ingredient targets of the Yiqi Qingre Ziyin method were obtained from the TCMSP database.…”

Section: Composite Compounds and Drugmentioning

confidence: 99%

Based on Network Pharmacology and Molecular Dynamics Simulations, Baicalein, an Active Ingredient of Yiqi Qingre Ziyin Method, Potentially Protects Patients With Atrophic Rhinitis From Cognitive Impairment

Kang

¹

,

Sun

²

,

Yi

³

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

Cognition may be improved by the active ingredients of the Yiqi Qingre Ziyin method in patients with atrophic rhinitis (AR). This study aimed to identify potential targets of the Yiqi Qingre Ziyin method for the treatment of patients with cognitive impairment. Nasal mucosal tissue samples from patients with AR were subjected to proteomic assays, and differentially expressed proteins were obtained. To explore the mechanism of AR leading to mild cognitive impairment (MCI), a differential analysis of AR related differential proteins in the MCI related GSE140831 dataset was performed. Most AR-related differential proteins are also differentially expressed in peripheral blood tissues of MCI, have similar biological functions and are enriched in similar pathways. These co-expressed differential factors in AR and MCI are known as common differential proteins of AR and MCI (CDPAM). Based on the analysis and validation of the random forest, support vector machine and neural network models, CDPAM acted as a diagnostic marker for MCI risk. Cytochrome C (CYCS) was significantly upregulated in the peripheral blood of patients with MCI. The active ingredients in the Yiqi Qingre Ziqin method were obtained and targeted 137 proteins. Among these targeted proteins, CYCS belong to the CDPAM set. Molecular docking and molecular dynamics analysis revealed that baicalein, an active ingredient in the Yiqi Qingre Ziyin method, stably targeted the CYCS protein. Results of the enrichment analysis revealed that the up-regulation of CYCS expression may have a defensive effect on the cells to resist foreign stimuli. Therefore, baicalein, an active ingredient in the Yiqi Qingre Ziyin method, may prevent the development and progression of MCI by targeting the CYCS protein.

show abstract

In silico network pharmacology and in vivo analysis of berberine-related mechanisms against type 2 diabetes mellitus and its complications

Cited by 28 publications

References 64 publications

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Eucommia ulmoides Oliver-Tribulus terrestris L. Drug Pair Regulates Ferroptosis by Mediating the Neurovascular-Related Ligand-Receptor Interaction Pathway- A Potential Drug Pair for Treatment Hypertension and Prevention Ischemic Stroke

Based on Network Pharmacology and Molecular Dynamics Simulations, Baicalein, an Active Ingredient of Yiqi Qingre Ziyin Method, Potentially Protects Patients With Atrophic Rhinitis From Cognitive Impairment

Contact Info

Product

Resources

About