Efficacy and safety of dietary polyphenols in rheumatoid arthritis: A systematic review and meta-analysis of 47 randomized controlled trials.

Objective: To evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA). Methods: CNKI, Pubmed, Cochrane library, Embase were searched to collect randomized controlled trials (RCTs) of dietary polyphenols in the treatment of RA. The databases were searched from the time of their establishment to November 8nd, 2022. After 2 reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies, Meta-analysis was performed using RevMan5.4 software. Results: A total of 49 records (47 RCTs) were finally included, involving 3852 participants and 15 types of dietary polyphenols (Cinnamon extract, Cranberry extract, Crocus sativus L. extract, Curcumin, Garlic extract, Ginger extract, Hesperidin, Olive oil, Pomegranate extract, Puerarin, Quercetin, Resveratrol, Sesamin, Tea polyphenols, Total glucosides of paeony). Pomegranate extract, Resveratrol, Garlic extract, Puerarin, Hesperidin, Ginger extract, Cinnamon extract, Sesamin only involve in 1 RCT. Cranberry extract, Crocus sativus L. extract, Olive oil, Quercetin, Tea polyphenols involve in 2 RCTs. Total glucosides of paeony and Curcumin involve in more than 3 RCTs. These RCTs showed that these dietary polyphenols could improve disease activity score for 28 joints (DAS28), inflammation levels or oxidative stress levels in RA. The addition of dietary polyphenols did not increase adverse events. Conclusion: Dietary polyphenols may improve DAS28, reduce C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and improve oxidative stress, etc. However, more RCTs are needed to verify or modify the efficacy and safety of dietary polyphenols. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022315645.

Study on the Antioxidant Effect of Tanshinone IIA on Diabetic Retinopathy and Its Mechanism Based on Integrated Pharmacology.

Aim: To explore the effect of tanshinone IIA on diabetic retinopathy (DR) and its mechanism. Methods: GeneCards and OMM databases were used to mine DR-related genes. The chemical structure of tanshinone IIA was searched by PubChem, and the potential target was predicted by PharmMapper. Cystape 3.8.2 was used to visualize and analyze the tanshinone IIA-DR protein interaction network. DAVID ver 6.8 data were used to perform enrichment analysis of the tanshinone IIA-DR protein interaction network. Then animal experiments were carried out to further explore the mechanism of tanshinone IIA in the treatment of DR. Male SD rats were intraperitoneally injected with streptozotocin to establish a diabetes model and were randomly divided into a model group, a low-dose tanshinone IIA group and a high-dose group. Normal rats served as the control group. Hematoxylin-eosin (HE) staining was used to observe the structural changes of the retina; the SOD, GSH-Px, and MDA levels in the retina were detected by the xanthine oxidase method; the expression of VEGF, IL-1ß, IL-6, TNF-α, and caspase-3 mRNA were detected by qRT-PCR; and the Bcl-2, Bax, and VEGFA proteins were determined by the western blot. Results: A total of 213 tanshinone IIA potential targets and 223 DR-related genes were obtained. The enrichment analysis showed that tanshinone IIA may regulate hypoxia, oxidative stress, positive regulation of ERK1 and ERK2 cascade, steroid hormone-mediated signaling pathway, inflammatory response, angiogenesis, VEGF signaling pathway, apoptosis, PI3K-Akt signaling pathway, TNF signaling pathway, and biological processes and signaling pathways. The structure of the retina in the normal control group was clear, the retina in the model group was not clear, the nerve fiber layer was edema, the retinal cell layers of the tanshinone IIA low-dose group are arranged neatly, the inner and outer nuclear layers are slightly disordered, and the tanshinone IIA low-dose group was large. The structure of the mouse retina was further improved compared with the low-dose tanshinone IIA group. Compared with the model group, the retinal tissue SOD and GSH-PX of rats in the tanshinone IIA group increased, and the MDA level decreased (P < 0.05). Compared with the model group, the expression of VEGF, IL-1ß, IL-6, TNF-α, and caspase-3 mRNA in the retina of tanshinone IIA groups was significantly reduced (P < 0.01). Compared with the model group, the Bcl-2 protein in the tanshinone IIA groups increased, while the Bax and VEGFA proteins decreased (P < 0.05). Conclusion: Tanshinone IIA may improve the morphological performance of the retina of diabetic rats and inhibit DR, the mechanism of which may be anti-inflammatory, antiangiogenesis, etc.

Research on the Mechanism of Liuwei Dihuang Decoction for Osteoporosis Based on Systematic Biological Strategies.

Background: Osteoporosis is an important health problem worldwide. Liuwei Dihuang Decoction (LDD) and its main ingredients may have a good clinical effect on osteoporosis. Meanwhile, its mechanism for treating osteoporosis needs to be further revealed in order to provide a basis for future drug development. Methods: A systematic biological methodology was utilized to construct and analyze the LDD-osteoporosis network. After that, the human transcription data of LDD intervention in patients with osteoporosis and protein arrays data of LDD intervention in osteoporosis rats were collected. The human transcription data analysis, protein arrays data analysis, and molecular docking were performed to validate the findings of the prediction network (LDD-osteoporosis PPI network). Finally, animal experiments were conducted to verify the prediction results of systematic pharmacology. Results: (1) LDD-osteoporosis PPI network shows the potential compounds, potential targets (such as ALB, IGF1, SRC, and ESR1), clusters, biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and signaling and Reactome pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) of LDD intervention in osteoporosis. (2) Human transcriptomics data and protein arrays data validated the findings of the LDD-osteoporosis PPI network. (3) The animal experiments showed that LDD can improve bone mineral density (BMD), increase serum estradiol (E2) and alkaline phosphatase (ALP) levels, and upregulate Wnt3a and ß-catenin mRNA expression (P < 0.05). (4) Molecular docking results showed that alisol A, dioscin, loganin, oleanolic acid, pachymic acid, and ursolic acid may stably bind to JAK2, ESR1, and CTNNB1. Conclusion: LDD may have a therapeutic effect on osteoporosis through regulating the targets (such as ALB, IGF1, SRC, and ESR1), biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) found in this research.

Corrigendum to "Exploring the Pharmacological Mechanism of Liuwei Dihuang Decoction for Diabetic Retinopathy: A Systematic Biological Strategy-Based Research".

[This corrects the article DOI: 10.1155/2021/5544518.].

Mechanism of Radix Rhei Et Rhizome Intervention in Cerebral Infarction: A Research Based on Chemoinformatics and Systematic Pharmacology.

OBJECTIVE: To explore the therapeutic targets, network modules, and coexpressed genes of Radix Rhei Et Rhizome intervention in cerebral infarction (CI), and to predict significant biological processes and pathways through network pharmacology. To explore the differential proteins of Radix Rhei Et Rhizome intervention in CI, conduct bioinformatics verification, and initially explain the possible therapeutic mechanism of Radix Rhei Et Rhizome intervention in CI through proteomics. METHODS: The TCM database was used to predict the potential compounds of Radix Rhei Et Rhizome, and the PharmMapper was used to predict its potential targets. GeneCards and OMIM were used to search for CI-related genes. Cytoscape was used to construct a protein-protein interaction (PPI) network and to screen out core genes and detection network modules. Then, DAVID and Metascape were used for enrichment analysis. After that, in-depth analysis of the proteomics data was carried out to further explore the mechanism of Radix Rhei Et Rhizome intervention in CI. RESULTS: (1) A total of 14 Radix Rhei Et Rhizome potential components and 425 potential targets were obtained. The core components include sennoside A, palmidin A, emodin, toralactone, and so on. The potential targets were combined with 297 CI genes to construct a PPI network. The targets shared by Radix Rhei Et Rhizome and CI include ALB, AKT1, MMP9, IGF1, CASP3, etc. The biological processes that Radix Rhei Et Rhizome may treat CI include platelet degranulation, cell migration, fibrinolysis, platelet activation, hypoxia, angiogenesis, endothelial cell apoptosis, coagulation, and neuronal apoptosis. The signaling pathways include Ras, PI3K-Akt, TNF, FoxO, HIF-1, and Rap1 signaling pathways. (2) Proteomics shows that the top 20 proteins in the differential protein PPI network were Syp, Syn1, Mbp, Gap43, Aif1, Camk2a, Syt1, Calm1, Calb1, Nsf, Nefl, Hspa5, Nefh, Ncam1, Dcx, Unc13a, Mapk1, Syt2, Dnm1, and Cltc. Differential protein enrichment results show that these proteins may be related to synaptic vesicle cycle, vesicle-mediated transport in synapse, presynaptic endocytosis, synaptic vesicle endocytosis, axon guidance, calcium signaling pathway, and so on. CONCLUSION: This study combined network pharmacology and proteomics to explore the main material basis of Radix Rhei Et Rhizome for the treatment of CI such as sennoside A, palmidin A, emodin, and toralactone. The mechanism may be related to the regulation of biological processes (such as synaptic vesicle cycle, vesicle-mediated transport in synapse, presynaptic endocytosis, and synaptic vesicle endocytosis) and signaling pathways (such as Ras, PI3K-Akt, TNF, FoxO, HIF-1, Rap1, and axon guidance).

Exploring the mechanism of Danggui Buxue Decoction in regulating atherosclerotic disease network based on integrated pharmacological methods.

OBJECTIVE: To explore the mechanism of Danggui Buxue Decoction (DGBXD) in regulating Atherosclerosis (AS) network based on integrated pharmacological methods. METHODS: The active ingredients and targets of DGBXD are obtained from TCMSP database and ETCM. AS-related targets were collected from the Genecards and OMIM databases. The drug-disease protein interaction (PPI) networks were constructed by Cytoscape. Meanwhile, it was used to screen out densely interacting regions, namely clusters. Finally, Gene Ontology (GO) annotations are performed on the targets and genes in the cluster to obtain biological processes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations are performed on the targets of the PPI network to obtain signaling pathways. RESULTS: A total of 212 known targets, 265 potential targets and 229 AS genes were obtained. The 'DGBXD known-AS PPI network' and 'DGBXD-AS PPI Network' were constructed and analyzed. DGBXD can regulate inflammation, platelet activation, endothelial cell apoptosis, oxidative stress, lipid metabolism, vascular smooth muscle proliferation, angiogenesis, TNF, HIF-1, FoxO signaling pathway, etc. The experimental data showed that compared with the model group, the expressions of ICAM-1, VCAM-1, and interleukin (IL)-1ß protein and mRNA in the DGBXD group decreased (P<0.05). However, plasma IL-1ß, TNF-α, and MCP-1 in the DGBXD group were not significantly different from the model group (P>0.05). CONCLUSION: The mechanism of DGBXD in the treatment of AS may be related to the improvement of extracellular matrix (ECM) deposition in the blood vessel wall and the anti-vascular local inflammatory response, which may provide a reference for the study of the mechanism of DGBXD.

Exploring the Pharmacological Mechanism of Liuwei Dihuang Decoction for Diabetic Retinopathy: A Systematic Biological Strategy-Based Research.

OBJECTIVE: To explore the pharmacological mechanism of Liuwei Dihuang decoction (LDD) for diabetic retinopathy (DR). METHODS: The potential targets of LDD were predicted by PharmMapper. GeneCards and other databases were used to collect DR genes. Cytoscape was used to construct and analyze network DR and LDD's network, and DAVID was used for Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were carried out to verify the results of systematic pharmacology. RESULTS: Five networks were constructed and analyzed: (1) diabetic retinopathy genes' PPI network; (2) compound-compound target network of LDD; (3) LDD-DR PPI network; (4) compound-known target network of LDD; (5) LDD known target-DR PPI network. Several DR and treatment-related targets, clusters, signaling pathways, and biological processes were found. Animal experiments found that LDD can improve the histopathological changes of the retina. LDD can also increase erythrocyte filtration rate and decrease the platelet adhesion rate (P < 0.05) and decrease MDA and TXB2 (P < 0.05). Compared with the model group, the retinal VEGF and HIF-1α expression in the LDD group decreased significantly (P < 0.05). CONCLUSION: The therapeutic effect of LDD on DR may be achieved by interfering with the biological processes (such as response to insulin, glucose homeostasis, and regulation of angiogenesis) and signaling pathways (such as insulin, VEGF, HIF-1, and ErbB signaling pathway) related to the development of DR that was found in this research.

Integrating systematic biological and proteomics strategies to explore the pharmacological mechanism of danshen yin modified on atherosclerosis.

This research utilized the systematic biological and proteomics strategies to explore the regulatory mechanism of Danshen Yin Modified (DSYM) on atherosclerosis (AS) biological network. The traditional Chinese medicine database and HPLC was used to find the active compounds of DSYM, Pharmmapper database was used to predict potential targets, and OMIM database and GeneCards database were used to collect AS targets. String database was utilized to obtain the other protein of proteomics proteins and the protein-protein interaction (PPI) data of DSYM targets, AS genes, proteomics proteins and other proteins. The Cytoscape 3.7.1 software was utilized to construct and analyse the network. The DAVID database is used to discover the biological processes and signalling pathways that these proteins aggregate. Finally, animal experiments and proteomics analysis were used to further verify the prediction results. The results showed that 140 active compounds, 405 DSYM targets and 590 AS genes were obtained, and 51 differentially expressed proteins were identified in the DSYM-treated ApoE-/- mouse AS model. A total of 4 major networks and a number of their derivative networks were constructed and analysed. The prediction results showed that DSYM can regulate AS-related biological processes and signalling pathways. Animal experiments have also shown that DSYM has a therapeutic effect on ApoE-/-mouse AS model (P < .05). Therefore, this study proposed a new method based on systems biology, proteomics, and experimental pharmacology, and analysed the pharmacological mechanism of DSYM. DSYM may achieve therapeutic effects by regulating AS-related signalling pathways and biological processes found in this research.