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Network pharmacology, molecular docking and in vivo experiments were used to explore the pharmacodynamic basis and potential mechanism of Danggui Sini Decoction in the treatment of primary dysmenorrhea(PD). The chemical constituents of Danggui(Angelicae Sinensis Radix), Guizhi(Cinnamomi Ramulus), Tongcao(Tetrapanacis Medulla), Baishao(Paeoniae Radix Alba), Xixin(Asari Radix et Rhizoma), Gancao(Glycyrrhizae Radix et Rhizoma), and Dazao(Jujubae Fructus) from Danggui Sini Decoction were retrieved through TCMSP(Traditional Chinese Medicine Systems Pharmacology Database), and the action targets of Danggui Sini Decoction were collected through DrugBank. "Primary dysmenorrhea" and "dysmenorrhea" were used as the key words to search the corresponding targets in the GeneCards, OMIM and TTD databases, and then the intersection targets of Danggui Sini Decoction and the primary dysmenorrhea targets were taken for reverse screening to obtain the corresponding active ingredients. Cytoscape 3.6.1 software was used to construct a traditional Chinese medicine-compound-target-disease network; STRING database was used to build a protein-protein interaction(PPI) network; Gene ontology(GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were conducted by using DAVID database. The action mechanism of the intersection targets were then predicted, and a histogram chart and bubble chart were drawn for visualization. Then the top five targets in the PPI network were used for docking with the most compounds. In animal experiments, Sprague Dawley(SD) female rats were used to establish a primary dysmenorrhea model by intraperitoneal injection of diethylstilbestrol once a day. A total of 60 SD female rats were randomly divided into 6 groups, namely control group, model group, Danggui Sini Decoction low(1.5 g·kg~(-1)), medium(3.0 g·kg~(-1)), high(6.0 g·kg~(-1)) dose groups, and ibuprofen(20 mg·kg~(-1)) positive control group, with 10 rats in each group. From day 4, except for the control group, rats in the other groups were given intragastric administration of corresponding drugs, and the control group received intragastric administration of normal saline for 7 consecutive days. The number of writhing before and after the administration, the ute-rine contraction inhibition rate and the uterine index after administration were observed, and ELISA assay was used to detect the levels of prostaglandin-endoperoxide synthase 2(PTGS2) and vascular endothelial growth factor A(VEGFA) in the tissues of each group as well as the levels of serum inflammatory factors interleukin 1(IL-1), interleukin 6(IL-6), and tumor necrosis factor-alpha(TNF-α). According to network analysis, 7 Chinese medicines contained 114 active ingredients, 149 targets, and 30 common target genes with PD were obtained. The key targets included VEGFA, IL6, PTGS2, TNF, etc.; GO function enrichment analysis showed a total of 399 terms(P<0.05) were obtained, 353 of which were biological process(BP) terms, 21 were cell composition(CC) terms, and 25 were molecular function(MF) terms. In KEGG pathway enrichment analysis, 14 signaling pathways were obtained, 3 of which were related to inflammation, namely arachidonic acid metabolism, MAPK signaling pathway and NOD-like receptor signaling pathway. The compounds in Danggui Sini Decoction can play a therapeutic role in the treatment of PD by acting on VEGFA, IL-6, PTGS2, TNF and other targets to regulate arachidonic acid and inflammatory signaling pathways.
Assuntos
Medicamentos de Ervas Chinesas , Dismenorreia , Animais , Dismenorreia/tratamento farmacológico , Feminino , Glycyrrhiza , Humanos , Simulação de Acoplamento Molecular , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio VascularRESUMO
Diabetic retinopathy (DR) is one of the common microvascular complications of diabetes mellitus and is the main cause of visual impairment in diabetic patients. The pathogenesis of DR is still unclear. The complement system, as an important component of the innate immune system in addition to defending against the invasion of foreign microorganisms, is involved in the occurrence and development of DR through 3 widely recognized complement activation pathways, the complement regulatory system, and many other pathways. Molecules such as C3a, C5a, and membrane attacking complex, as important molecules of the complement system, are involved in the pathologenesus of DR, either through direct damaging effects or by activating cells (microglia, macroglia, etc.) in the retinal microenvironment to contribute to the pathological damage of DR indirectly. We review the integral association of the complement system and DR to further understand the pathogenesis of DR and possibly provide a new strategy for itstreatment.
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Ativação do Complemento , Proteínas do Sistema Complemento , Retinopatia Diabética , Humanos , Retinopatia Diabética/imunologia , Proteínas do Sistema Complemento/metabolismo , Ativação do Complemento/fisiologiaRESUMO
AIM: To investigate the association between central serous chorioretinopathy (CSC) and Helicobacter pylori (Hp) by summarizing all available evidence. METHODS: The Scopus, Embase, EBSCO, PubMed, Web of Science, and Cochrane Library databases for all relevant studies published from inception to October 2022 were searched, and manually searched for relevant reference lists as a supplement. Studies investigating the association between CSC and Hp infection were included. Finally, 8 case-control studies were included in the Meta-analysis after study selection. RESULTS: The results showed no significant correlation between Hp infection and CSC [odds ratio (OR) 1.89, 95% confidential interval (CI) 0.58-6.15, I 2=96%, P=0.29]. After subgroup analysis based on the degree of development of the study (developing/developed countries), it was found that the results of the two subgroups were the same as the whole, and no significant difference between the two subgroups existed. Meta-regression showed that the effect of sample size on heterogeneity among studies was more prominent (P<0.01, adjusted R 2=89.72%), which can explain 89.72% of the sources of heterogeneity. CONCLUSION: This Meta-analysis reveals no significant correlation between Hp infection and CSC, which still warrants further well-designed extensive sample studies to reach a more reliable conclusion and promote a better understanding of the treatment of CSC.
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Objective: This study is designed to find out the molecular targets of effective Chinese medicine Ziyin Mingmu pills (ZMPs) in treating age-related macular degeneration (AMD) based on network pharmacology and experimental data. Methods: A comprehensive network pharmacology strategy that consists of three sequential modules (drug-disease target molecular docking, enrichment analysis, and external verification) was carried out to identify potential targets of ZMPs acting on AMD. Results: The active ingredients of ZMPs targeting 66 genes have effects on the process of AMD. GO and KEGG pathway enrichment analyses suggested that response to oxidative stress, regulation of angiogenesis, and lipid and atherosclerosis might serve as the most important signaling pathways in ZMPs for AMD treatment. Combined with the GSE29801 dataset for further analysis, two key genes, EGFR and VEGFA, were identified. Immune infiltration analysis showed that there was a strong association between EGFR and immune cell content. In addition, images were acquired following 24 h in the scratch experiment showed that ZMPs can reduce the percentage of wound healing distance. The Western blot assay found that ZMPs increased the expression of EGFR and decreased the expression of VEGFA. Conclusion: This study sheds light on some mechanisms of ZMP therapy for AMD, particularly the effect of ZMP on the oxidative stress in RPE and cell survival and angiogenesis in AMD. We propound ZMPs as a promising strategy to intervene in the process of AMD.
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Skin fibrosis is a physiopathological process featuring the excessive deposition of extracellular matrix (ECM), which is the main architecture that provides structural support and constitutes the microenvironment for various cellular behaviors. Recently, increasing interest has been drawn to the relationship between the mechanical properties of the ECM and the initiation and modulation of skin fibrosis, with the engagement of a complex network of signaling pathways, the activation of mechanosensitive proteins, and changes in immunoregulation and metabolism. Simultaneous with the progression of skin fibrosis, the stiffness of ECM increases, which in turn perturbs mechanical and humoral homeostasis to drive cell fate toward an outcome that maintains and enhances the fibrosis process, thus forming a pro-fibrotic "positive feedback loop". In this review, we highlighted the central role of the ECM and its dynamic changes at both the molecular and cellular levels in skin fibrosis. We paid special attention to signaling pathways regulated by mechanical cues in ECM remodeling. We also systematically summarized antifibrotic interventions targeting the ECM, hopefully enlightening new strategies for fibrotic diseases.