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Tumors are new organisms formed by uncontrollable cell proliferation of local tissues driven by various oncogenic factors. The cause of tumors is unknown with life-threating outcome. Tumors can be classified into benign tumors， borderline tumors， and malignant tumors according to their pathological properties. Among them， malignant tumor is commonly known as cancer， with no specific medicines or reliable cure means， so this is a hot spot and difficult point in current medical research. In ancient literatures， there are many records about the efficacy of Chinese herbal medicine in treating tumor， and modern pharmacological researches have shown that more and more active ingredients of traditional Chinese medicine（TCM） have gradually highlighted their inhibitory effect on various types of tumor. Caulis sinomenii has been used for treatment of rheumatic diseases in TCM for a long history. Sinomenine is a major bioactive alkaloid presented in C. sinomenii， which has demonstrated a wide range of pharmacological activities such as anti-inflammation， immunosuppression， analgesia and sedation， and due to its slightly soluble in water， it is commonly used in clinic in the form of hydrochloride， with its commercial name of Zhengqing Fengtongning. Recent studies show that sinomenine alone or combined with chemoradiotherapy can inhibit growth of several tumors significantly or in a synergistic way， so it is termed as an inhibitor of tumors. Anti-tumor effect of sinomenine involve inhibition of tumor cell proliferation， induction of tumor cell apoptosis， blockade of tumor cell cycle， suppression of tumor invasion and metastasis， induction of autophagy of tumor cells， and reversal of multidrug resistance of tumor cells. Upon combination with nanomaterials， it can enhance efficiency and reduce toxicity. Here we summarized and reviewed recent advances on basic anti-tumor research of sinomenine， and then made a classification and description according to its in vivo and in vitro pharmacological action and mechanism of action， so as to elucidate the great potential of sinomenine as a promising anti-tumor drug， and provide reference for further research on its anti-tumor mechanism.
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Objective:To explore the molecular mechanism of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma (FLRSM) in the treatment of retinitis pigmentosa (RP) based on network pharmacology and bioinformatics. Method:Possible intake active components and targets of FLRSM were screened out and predicted by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP). Gene targets related to RP were mined through disease gene databases. Protein-protein interaction (PPI) network of component-targets and disease-targets were mapped by functional protein association networks (STRING), and the intersection of the two networks was obtained. The gene ontology and kyoto encyclopedia of genes and genomes(KEGG) pathway of the intersection network were analyzed by the database for annotation, visualization and integrated discovery(DAVID). CytoHubba analysis was used to screen out the key targets. Result:A total of 390 active ingredients related to FLRSM were retrieved from TCMSP. According to pharmacokinetic parameters, 110 active ingredients were screened out, 19 active ingredients were further screened out, and 208 targets related to these constituents were retrieved. Totally 206 genes directly related to RP were obtained from the disease gene databases. And 79 genes were obtained from the intersection of PPI networks of component targets and disease targets. These genes mainly involved in biological processes, such as protein autophosphorylation, transcriptional regulation and cell proliferation, and the molecular functions mainly involved adenosine triphosphate binding, transcription factor activity, core promoter binding, and were enriched in nuclear, transcription factor complex, nucleus, cytoplasm and other regions. It was mainly related to neurotrophin signaling pathway, cell cycle related pathway and Wnt signaling pathway. And 8 key gene targets for FLRSM treatment of RP were identified by further screening. Conclusion:The material basis of pharmacodynamic action of FLRSM involves 19 active ingredients, such as porous sterol and tanshinone ⅡA. The key targets of FLRSM in the treatment of RP include 8 genes, such as E2F transcription factor 1(E2F1) and retinoblastoma gene1(RB1).The main mechanism is related to the regulation of neurotrophin signaling pathways, cell cycle related pathways and other signaling networks.
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Objective: To investigate the molecular mechanism of Salvia miltiorrhiza (SM) in the treatment of retinitis pigmentosa (RP) by interfering with the expression of characteristic genes and key protein in Müller cells (MC) based on the methods of network pharmacology and bioinformatics. Methods: Retrieval and screening of active ingredients and therapeutic targets of SM in blood was performed by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Differentially expressed genes of MC in normal and RP mice were obtained by searching GEO database. RP-related gene targets were retrieved through disease database. Cytoscape was used to construct protein-protein interaction networks of differentially expressed MC genes, disease targets and component targets and the intersection was extracted. Gene Ontology and KEGG signaling pathway analysis of characteristic genes were carried out by DAVID. CytoHubba was used to analyze and screen the key protein targets. Results: A total of 202 chemical constituents related to SM were retrieved, 65 active ingredients were screened according to ADME parameters, of which 13 were active ingredients in blood. A total of 117 possible targets were obtained by further searching and matching. A total of 242 differentially expressed genes in MC of normal and RP mice were obtained from chip data. A total of 206 targets closely related to RP were obtained from disease databases. A total of 85 characteristic genes of SM affecting MC in RP pathological process were extracted and intersected. These genes were mainly involved in transcriptional regulation, apoptotic signaling pathway regulation, DNA nuclear replication regulation and other biological processes. Molecular functions mainly include transcriptional coactivator activity, protein kinase activity, core promoter binding, etc. They were enriched in nuclear, nucleoplasm, transcription factor complex, Rb-E2F complex and other regions. The signaling pathways involved include splicer signaling pathway, actin cytoskeleton signaling pathway, cell cycle signaling pathway and so on. A total of eight key protein targets of SM on MC in RP pathological process were analyzed and screened. Conclusion: The substance basis of the pharmacodynamics of SM is 13 chemical constituents, such as cryptotanshinone, luteolin, tanshinone IIA, etc. The MC characteristic genes involved in the pathological process of RP intervened by SM are related to spliceosome signaling pathway, actin cytoskeleton signaling pathway, cell cycle regulation pathway, etc. The key targets include eight protein such as RB1, E2F1, TFDP1, etc.
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Aim To study the therapeutic effect of Huangqi Jianzhong decoction ( HQJZ) on duodenal ul-cer(DU) in rats and its effect on intestinal mucosal immune barrier function mediated by TLR-2. Methods SD rats were divided into normal group, model group, positive drug group and HQJZ group. DU model was established by methods of multiple factors. The body weight, food intake, and rectal temperature were measured. The ulcer index (UI) was calculated. The pathological changes of duodenal mucosa were observed by HE staining. The contents of cytokines were detec-ted by EL1SA. The expression of mRNx
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Objective: To study the effect of Astragalus membranaceus polysaccharides (AMP) on migration, intracellular polyamines content, cytosolic free Ca2+ concentration ([Ca2+]cyto), and RhoA protein expression of intestinal epithelial (IEC-6) cells, so as to explore the repairing mechanism of Astragalus membranaceus (AM) on gastrointestinal injury. Methods: AM was extracted by water and precipitated by ethanol, AM crude polysaccharides were obtained after removing protein. AMP I, II, III, and IV were obtained by DEAE cellulose column chromatography. AMP V was further obtained by Sephadex LH-20 gel column chromatography from AMP I. Cell migration model was established by Tips scratch method; High performance liquid chromatography was used to determine the polyamines content; Flow cytometry was used to detect the [Ca2+]cyto; Western blotting analysis was used to detect RhoA protein expression. The improving effect of AMP on migration, [Ca2+]cyto, and RhoA protein expression of normal and polyamine-depleted IEC-6 cells was observed. Results: AM crude polysaccharides, AMP I, and AMP V (100 mg /L or 200 mg /L) promoted cell migration and reversed the inhibition of cell migration induced by DFMO (P < 0.01); AMP V increased the intracellular polyamines content in normal and polyamine-deficient IEC-6 cells; AMP V also enhanced [Ca2+]cyto in the process of IEC-6 cell migration and reversed the reduction of [Ca2+]cyto induced by DFMO (P < 0.01); Further study suggested that AMP V increased RhoA protein expression in normal and polyamine-deficient IEC-6 cells (P < 0.01). Conclusion: These results indicate that the repairing effect of AM on the gastrointestinal mucosa damage may be related to its role of increasing polyamines content, then improving [Ca2+]cyto and RhoA protein expression and thereby promoting cell migration.