Objective: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge.,(Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis(AP)using a network pharmac...Objective: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge.,(Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis(AP)using a network pharmacology approach and validate the findings in animal experiments. Methods: Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP. The reliability of the results was verified by molecular docking simulation and molecular dynamics simulation.Finally, the results of network pharmacology enrichment analysis were verified by immunohistochemistry,Western blot analysis and real-time quantitative PCR, respectively. Results: Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3(MAPK3), Janus kinase 2(JAK2), signal transducer and activator of transcription 3(STAT3), protein c-Fos(FOS) were identified as core targets in the protein interaction(PPI) network analysis. Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP, and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation. Molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3, STAT3 and FOS. Molecular dynamics simulation revealed that FOS-isotanshinone Ⅱ and STAT3-dan-shexinkum d had good binding capacity. Animal experiments indicated that compared with the AP model group, DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1β, interleukin-6 and tumor necrosis factor-α, and blocking the activation of Th17 cell differentiation(P<0.01). Conclusion: DH-DS could inhibit the expression of inflammatory factors and protect pancreatic tissues,which would be functioned by regulating Th17 cell differentiation-related m RNA and protein expressions.展开更多
BACKGROUND：Rheum ribes L.is a plant native to China,Iran,Turkey,India,and a few other countries.Antidiarrheal activity is considered to be one of its important properties according to various systems of traditional m...BACKGROUND：Rheum ribes L.is a plant native to China,Iran,Turkey,India,and a few other countries.Antidiarrheal activity is considered to be one of its important properties according to various systems of traditional medicine.An increasing rate of bacterial resistance to antibiotics has led to treatment failure in some cases of shigellosis in children,and underlines a need for safe,efficient and valid options.OBJECTIVE：The purpose of this study is to evaluate the efficacy of R.ribes syrup as a complementary medicine for treatment of shigellosis in children.DESIGN,SETTING,PARTICIPANTS AND INTERVENTIONS：This randomized,doubleblind,placebocontrolled trial started with a group of 150 children aged between 12–72 months with suspected Shigella dysentery.R.ribes syrup or placebo syrup was administered to the intervention and control groups,respectively for 5 days.In addition,the standard antibiotic treatment（ceftriaxone for the first 3 days and cefixime syrup for 2 further days）was administered to both groups.MAIN OUTCOME MEASURES：Body temperature,abdominal pain,need for antipyretics,defecation frequency,stool volume and consistency and microscopic stool examination were recorded as outcome measures.Any observed adverse effects were also recorded.RESULTS：Mean duration of fever and diarrhea in the R.ribes group was significantly lower than that in the placebo group（P=0.016 and 0.001,respectively）.In addition,patients in the R.ribes group showed shorter duration of need for antipyretics and shorter duration of abdominal pain（P=0.012 and 0.001,respectively）.However,there were no significant differences between the two groups regarding the microscopic stool analyses.Furthermore,no adverse effect was reported.CONCLUSION：R.ribes syrup can be recommended as a complementary treatment for children with Shigella dysentery.展开更多
基金Supported by National Natural Science Foundation of China (No.82160890, 82260899)Innovation Project of Guangxi Graduate Education (No.YCSW2023383)。
文摘Objective: To identify the core targets of Rheum palmatum L. and Salvia miltiorrhiza Bge.,(Dahuang-Danshen, DH-DS) and the mechanism underlying its therapeutic efficacy in acute pancreatitis(AP)using a network pharmacology approach and validate the findings in animal experiments. Methods: Network pharmacology analysis was used to elucidate the mechanisms underlying the therapeutic effects of DH-DS in AP. The reliability of the results was verified by molecular docking simulation and molecular dynamics simulation.Finally, the results of network pharmacology enrichment analysis were verified by immunohistochemistry,Western blot analysis and real-time quantitative PCR, respectively. Results: Sixty-seven common targets of DH-DS in AP were identified and mitogen-activated protein kinase 3(MAPK3), Janus kinase 2(JAK2), signal transducer and activator of transcription 3(STAT3), protein c-Fos(FOS) were identified as core targets in the protein interaction(PPI) network analysis. Gene ontology analysis showed that cellular response to organic substance was the main functions of DH-DS in AP, and Kyoto Encyclopedia of Genes and Genomes analysis showed that the main pathway included Th17 cell differentiation. Molecular docking simulation confirmed that DH-DS binds with strong affinity to MAPK3, STAT3 and FOS. Molecular dynamics simulation revealed that FOS-isotanshinone Ⅱ and STAT3-dan-shexinkum d had good binding capacity. Animal experiments indicated that compared with the AP model group, DH-DS treatment effectively alleviated AP by inhibiting the expression of interleukin-1β, interleukin-6 and tumor necrosis factor-α, and blocking the activation of Th17 cell differentiation(P<0.01). Conclusion: DH-DS could inhibit the expression of inflammatory factors and protect pancreatic tissues,which would be functioned by regulating Th17 cell differentiation-related m RNA and protein expressions.
文摘BACKGROUND：Rheum ribes L.is a plant native to China,Iran,Turkey,India,and a few other countries.Antidiarrheal activity is considered to be one of its important properties according to various systems of traditional medicine.An increasing rate of bacterial resistance to antibiotics has led to treatment failure in some cases of shigellosis in children,and underlines a need for safe,efficient and valid options.OBJECTIVE：The purpose of this study is to evaluate the efficacy of R.ribes syrup as a complementary medicine for treatment of shigellosis in children.DESIGN,SETTING,PARTICIPANTS AND INTERVENTIONS：This randomized,doubleblind,placebocontrolled trial started with a group of 150 children aged between 12–72 months with suspected Shigella dysentery.R.ribes syrup or placebo syrup was administered to the intervention and control groups,respectively for 5 days.In addition,the standard antibiotic treatment（ceftriaxone for the first 3 days and cefixime syrup for 2 further days）was administered to both groups.MAIN OUTCOME MEASURES：Body temperature,abdominal pain,need for antipyretics,defecation frequency,stool volume and consistency and microscopic stool examination were recorded as outcome measures.Any observed adverse effects were also recorded.RESULTS：Mean duration of fever and diarrhea in the R.ribes group was significantly lower than that in the placebo group（P=0.016 and 0.001,respectively）.In addition,patients in the R.ribes group showed shorter duration of need for antipyretics and shorter duration of abdominal pain（P=0.012 and 0.001,respectively）.However,there were no significant differences between the two groups regarding the microscopic stool analyses.Furthermore,no adverse effect was reported.CONCLUSION：R.ribes syrup can be recommended as a complementary treatment for children with Shigella dysentery.
