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Resveratrol and quercetin have effects on polycystic ovary syndrome (PCOS). Hence, resveratrol combined with quercetin may have better effects on it. However, because of the limitations in animal and human experiments, the pharmacological and molecular mechanism of quercetin-resveratrol combination (QRC) remains to be clarified. In this research, a systematic pharmacological approach comprising multiple compound target collection, multiple potential target prediction, and network analysis was used for comparing the characteristic of resveratrol, quercetin and QRC, and exploring the mechanism of QRC. After that, four networks were constructed and analyzed: (1) compound-compound target network; (2) compound-potential target network; (3) QRC-PCOS PPI network; (4) QRC-PCOS-other human proteins (protein-protein interaction) PPI network. Through GO and pathway enrichment analysis, it can be found that three compounds focus on different biological processes and pathways; and it seems that QRC combines the characteristics of resveratrol and quercetin. The in-depth study of QRC further showed  more PCOS-related biological processes and pathways. Hence, this research not only offers clues to the researcher who is interested in comparing the differences among resveratrol, quercetin and QRC, but also provides hints for the researcher who wants to explore QRC’s various synergies and its pharmacological and molecular mechanism.

BackgroundOsteoporosis is an important health problem worldwide. Siwu decoction (SWD) and its modification have a good clinical effect on osteoporosis. However, the molecular mechanism of SWD on osteoporosis has not been thoroughly explained.Material/MethodsA systematic pharmacological methodology was utilized to predict the active compounds and potential targets of SWD, collect the genes of osteoporosis and the known targets of SWD, and analyze the osteoporosis and SWD’s network.ResultsFive networks were constructed and analyzed: (1) Osteoporosis genes’ protein–protein interaction (PPI) network; (2) Compound-compound target network of SWD; (3) SWD-osteoporosis PPI network; (4) Compound-known target network of SWD; and (5) SWD known target- osteoporosis PPI network. Several osteoporosis and treatment-related targets (eg.,. HSP90AB1, FGFR1, HRAS, GRB2, and PGF), clusters, biological processes, and signaling pathways (e.g., PI3K-Akt signaling pathway, insulin signaling pathway, MAPK signaling pathway and FoxO signaling pathway) were found.ConclusionsThe therapeutic effect of SWD on osteoporosis may be achieved by interfering with the biological processes and signaling pathways related to the development of osteoporosis.

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Aim. To explore the mechanism of resveratrol in reducing the soft tissue damage of osteoarthritis (OA) based on network pharmacology. Methods. Pharmmapper was used to predict the target of resveratrol, OMIM and Genecards were used to collect OA-related disease genes, and David ver 6.8 was used for enrichment analysis. Then, animal experiments were carried out for verification. The rat OA model was established and the rats were randomly divided into 4 groups: model group, resveratrol low-dose group, resveratrol high-dose group, and blank control group for follow-up experiments. Hematoxylin-eosin (HE) staining was used to detect the degree of pathological damage of rat bones and joints. Enzyme-linked immunosorbent assay (ELISA) was used for the content of inflammatory factors. Western blot was used to detect the expression of Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (MyD88), nuclear factor kappa B protein (NF-κB), cysteine protease-9 (CASP-9), Bcl-2 protein, and Bax protein. Results. Through network pharmacological analysis, this study found that resveratrol may regulate the TLR4 signaling pathway, PI3K-Akt signaling pathway, FoxO signaling pathway, Osteoclast differentiation, Rheumatoid arthritis, etc. Animal experiments showed that compared with the model group, the pathological damage of bone and joint in the resveratrol low-dose and high-dose groups was significantly improved. Compared with the model group, the serum levels of IL-1beta, IL-6, IL-17, TNF-α, and MCP-1 in the resveratrol low-dose and high-dose groups were significantly reduced ( P  < 0.05); protein levels of TLR-4, MyD88, and NF-κB p65 were significantly reduced ( P  < 0.05); caspase-9 and Bax protein levels were significantly reduced ( P  < 0.05), and Bcl-2 was significantly increased ( P  < 0.05). Conclusion. Resveratrol may inhibit the activation of the TLR4-mediated NF-κB signaling pathway and has a repairing effect on soft tissue damage in OA.

Objective: To explore the mechanism of Shengmai Yin (SMY) for coronary heart disease (CHD) by systemic pharmacology and chemoinformatics. Methods: Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), traditional Chinese medicine integrative database (TCMID) and the traditional Chinese medicine (TCM) Database@Taiwan were used to screen and predict the bioactive components of SMY. Pharmmapper were utilized to predict the potential targets of SMY, the TCMSP was utilized to obtain the known targets of SMY. The Genecards and OMIM database were utilized to collect CHD genes. Cytoscape was then used for network construction and analysis, and DAVID was used for Gene Ontology (GO) and pathway enrichment analysis. After that, animal experiments were then performed to further validate the results of systemic pharmacology and chemoinformatics. Results: Three major networks were constructed: (1) CHD genes’ protein–protein interaction (PPI) network; (2) SMY–CHD PPI network; (3) SMY known target–CHD PPI network. The other networks are minor networks generated by analyzing the three major networks. Experimental results showed that compared with the model group, the Shengmai injection (SMI) can reduce the myocardial injury score and the activities of serum aspartate aminoconvertase (AST), CK and lactate dehydrogenase (LDH) in rats (P&lt;0.05), and reduce serum lipid peroxide (LPO) content and increase serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in myocardial infarction rats (P&lt;0.05). SMI can also decrease the expression of MMP-9 mRNA and increase that of TIMP-1 mRNA (P&lt;0.01). Conclusion: SMY may regulate the signaling pathways (such as PPAR, FoxO, VEGF signaling), biological processes (such as angiogenesis, blood pressure formation, inflammatory response) and targets (such as AKT1, EGFR, MAPK1) so as to play a therapeutic role in CHD.

ObjectiveTo evaluate safety and efficacy of dietary polyphenols in the treatment of rheumatoid arthritis (RA).MethodsCNKI, 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.ResultsA 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.ConclusionDietary 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 registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022315645.

Background With the aging of the world’s population, the incidence of osteoporosis (OP) has become a public health problem of worldwide concern. Research shows that icariin may have a therapeutic effect on OP. Material/Methods PharmMapper was utilized to predict the potential targets of icariin. GeneCards and Online Mendelian Inheritance in Man (OMIM) were used for the collection of OP genes. The STRING database was utilized to obtain the protein-protein interaction (PPI) data. We used Cytoscape 3.7.2 to construct and analyze the networks. The genes and targets in the networks were input into the Database for Annotation, Visualization and Integrated Discovery (DAVID) to undergo Gene Ontology (GO) and pathway enrichment analysis. Finally, animal experiments were performed to verify the prediction results of this study. Results A total of 297 icariin potential targets and 262 OP genes were obtained, and an icariin-OP PPI network was constructed and analyzed. The results of the GO enrichment analysis showed that icariin can regulate the steroid hormone-mediated signaling pathway, skeletal system development, extracellular space, cytosol, and steroid hormone receptor activity. The results of the pathway enrichment analysis showed that icariin can regulate osteoclast differentiation, FoxO, estrogen, and PPAR signaling pathways. The results of the experiments showed that icariin can increase estradiol, β-catenin, and Receptor Activator of Nuclear Factor-κ B Ligand (RANKL)/osteoprotegerin (OPG) ratio in postmenopausal OP rats ( P <0.05). Conclusions This research found that the icariin can regulate OP-related biological processes, cell components, molecular functions, and signaling pathways.