Objective To observe the effects of Zhuang Gu Zhi Tong Formula (ZGZTF) on antagonist SOST in canonical Wnt/β-catenin signaling pathway in osteoporosis. Methods We analyzed the differential genes of patients with oste...Objective To observe the effects of Zhuang Gu Zhi Tong Formula (ZGZTF) on antagonist SOST in canonical Wnt/β-catenin signaling pathway in osteoporosis. Methods We analyzed the differential genes of patients with osteoporosis and normal subjects from the GEO database and then found SOST with specific expression. We analyzed SOST as an antagonist of the Wnt signaling pathway by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then we studied the effect of ZGZTF on SOST in Wnt signaling pathway. Osteoporosis model was induced by ovariectomy (OVX) in 8-week-old female Sprague–Dawley (SD) rats. After 12 weeks of treatment with ZGZTF by intragastric administration, the rats were put to death in batch. The changes of alkaline phosphatase (ALP), bone gla protein (BGP) and estradiol (E2) in serum were determined, and bone mineral density (BMD) and histomorphology of right femur were observed. Biomechanics of lumbar vertebra were measured, and the expression of SOST, Wnt3a,β-catenin, LRP5, Runx2, Osx and their mRNA involving the canonical Wnt/β-catenin signaling pathway were detected by Western blot, RT-PCR and Immunohistochemical analysis. All data were analyzed by SPSS 22.0. Results Twelve weeks of treatment with ZGZTF could significantly decrease the level of ALP and BGP in serum, increase the BMD of femurs, and improve the biomechanical capability of vertebral body in maximum loading and elastic modulus. Concerning histomorphology, we found ordered arrangement of trabeculae, slightly thinning of trabeculae and none obvious slight fractures in femurs after 12 weeks of treatment with ZGZTF. The expression of LRP5,β-catenin, Runx2 and Osx involved in the canonical Wnt/β-catenin signaling pathway was significantly up-regulated in the presence of ZGZTF,and the expression of SOST in this pathway was down-regulated. Conclusions These results suggest that ZGZTF may be antiosteoporosis by down-regulating SOST protein to promote Wnt/β-catenin signaling pathway.展开更多
Objective Pharmacological methods were used to screen targets and signaling pathways of Ma Xing Shi Gan Decoction(MXSGD)during influenza treatments,and mechanisms underlying antiinfluenza effects were elucidated.Metho...Objective Pharmacological methods were used to screen targets and signaling pathways of Ma Xing Shi Gan Decoction(MXSGD)during influenza treatments,and mechanisms underlying antiinfluenza effects were elucidated.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and relevant literature were searched under predefined conditions to identify the main compounds and their targets.Interactions between the target proteins were predicted using the STRING database.Gene Ontology(GO)functional enrichment analyses and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed on the core targets involved in the influenza protein-protein interaction(PPI)network,using WebGestalt and the reactome database.iGEMDOCK was used for molecular docking of receptors and ligands to produce docking scores,and the results were visualized using Autodock and PyMOL.Results In total,126 major compounds and their respective targets were screened.355 influenza target proteins and 1221 influenza protein interactions were predicted using the STRING database.Influenza-related signaling pathways were strongly enriched in pharmacodynamic targets of MXSGD such as cytokine signaling in immune system and signaling by interleukin.The main biological process was response to the stimulates.Molecular docking results showed that RELALicochalcone A docking elicited by MXSGD,was superior to that of other target proteins and active compounds,suggesting that the docking site is also the main effector site of MXSGD during influenza treatments.Conclusions The results showed that MXSGD exerts antiinfluenza effects by interfering with virus adsorption,inhibiting virus proliferation,influencing immune functions and protecting host cells,which may prevent inflammation-induced tissue damage.展开更多
基金the funding support from the National Natural Science Foundation of China (No. 81573956)Natural Science Foundation of Hunan Province (No. 2018JJ2297)+3 种基金Key Program of Chinese Medicine Science Research Plan of Hunan Province (No. 201612)Key Program of Scientific Research Fund of Hunan Provincial Education Department (No. 16A162)National College Students Innovation and Entrepreneurship Project (No. 201710541002)The Project of Research Learning and Innovative Experiment for College Students in Hunan (No. 2015217, No. 2015220, No. 2016284 and No. 2016281)
文摘Objective To observe the effects of Zhuang Gu Zhi Tong Formula (ZGZTF) on antagonist SOST in canonical Wnt/β-catenin signaling pathway in osteoporosis. Methods We analyzed the differential genes of patients with osteoporosis and normal subjects from the GEO database and then found SOST with specific expression. We analyzed SOST as an antagonist of the Wnt signaling pathway by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Then we studied the effect of ZGZTF on SOST in Wnt signaling pathway. Osteoporosis model was induced by ovariectomy (OVX) in 8-week-old female Sprague–Dawley (SD) rats. After 12 weeks of treatment with ZGZTF by intragastric administration, the rats were put to death in batch. The changes of alkaline phosphatase (ALP), bone gla protein (BGP) and estradiol (E2) in serum were determined, and bone mineral density (BMD) and histomorphology of right femur were observed. Biomechanics of lumbar vertebra were measured, and the expression of SOST, Wnt3a,β-catenin, LRP5, Runx2, Osx and their mRNA involving the canonical Wnt/β-catenin signaling pathway were detected by Western blot, RT-PCR and Immunohistochemical analysis. All data were analyzed by SPSS 22.0. Results Twelve weeks of treatment with ZGZTF could significantly decrease the level of ALP and BGP in serum, increase the BMD of femurs, and improve the biomechanical capability of vertebral body in maximum loading and elastic modulus. Concerning histomorphology, we found ordered arrangement of trabeculae, slightly thinning of trabeculae and none obvious slight fractures in femurs after 12 weeks of treatment with ZGZTF. The expression of LRP5,β-catenin, Runx2 and Osx involved in the canonical Wnt/β-catenin signaling pathway was significantly up-regulated in the presence of ZGZTF,and the expression of SOST in this pathway was down-regulated. Conclusions These results suggest that ZGZTF may be antiosteoporosis by down-regulating SOST protein to promote Wnt/β-catenin signaling pathway.
基金We thank for the funding support from the National Natural Science Foundation of China(No.81973670)the Natural Science Foundation of Hunan Province(No.2018JJ2297)+1 种基金the Key Program of Scientific Research Fund of Hunan Provincial Education Department(No.19A370)the Project of Research Learning and Innovative Experiment for College Students in Hunan(No.2016284,No.2016281,No.2017281and No.2018420).
文摘Objective Pharmacological methods were used to screen targets and signaling pathways of Ma Xing Shi Gan Decoction(MXSGD)during influenza treatments,and mechanisms underlying antiinfluenza effects were elucidated.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and relevant literature were searched under predefined conditions to identify the main compounds and their targets.Interactions between the target proteins were predicted using the STRING database.Gene Ontology(GO)functional enrichment analyses and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed on the core targets involved in the influenza protein-protein interaction(PPI)network,using WebGestalt and the reactome database.iGEMDOCK was used for molecular docking of receptors and ligands to produce docking scores,and the results were visualized using Autodock and PyMOL.Results In total,126 major compounds and their respective targets were screened.355 influenza target proteins and 1221 influenza protein interactions were predicted using the STRING database.Influenza-related signaling pathways were strongly enriched in pharmacodynamic targets of MXSGD such as cytokine signaling in immune system and signaling by interleukin.The main biological process was response to the stimulates.Molecular docking results showed that RELALicochalcone A docking elicited by MXSGD,was superior to that of other target proteins and active compounds,suggesting that the docking site is also the main effector site of MXSGD during influenza treatments.Conclusions The results showed that MXSGD exerts antiinfluenza effects by interfering with virus adsorption,inhibiting virus proliferation,influencing immune functions and protecting host cells,which may prevent inflammation-induced tissue damage.
