Numerous polysaccharides isolated from plants have been used to augment traditional drugs in the treatment of cancer.In order to explore the influence to hepatocellular carcinoma,a novel cold water-soluble polysacchar...Numerous polysaccharides isolated from plants have been used to augment traditional drugs in the treatment of cancer.In order to explore the influence to hepatocellular carcinoma,a novel cold water-soluble polysaccharide was separated from Rhodiola rosea L.root(RLP)and then its structure and anti-cancer activities were tested.The chemical compositions and high performance gel permeation chromatography(HPGPC)results indicated that RLP was an acid heteropolysaccharide with the molecular weight of about1.15×10~6 Da.Furthermore,ion chromatography(IC),Fourier transform infrared(FT-IR)and nuclear magnetic resoance(NMR)further indicated that RLP was main composed of→2,4)-α-Rha(1→,→5)-α-L-Araf-(1→,α-D-Glu,→6)-β-D-Galp-(1→,β-D-Man and→4)-α-GalpA-(1→.In vivo antitumor activities of RLP were carried out by using H22 tumor-bearing mice model.The results shown that RLP(100 and 300 mg/kg)could inhibit tumor growth of H22 cells from 23.59%to 45.52%and protect thymuses and spleen without damage.In addition,according to cell cycle,AV-FITC/PI and JC-1,RLP could induce dose-dependent apopto sis of H22 cells via S phase arrested which was through a mitochondrial related pathway.Our data indicated that RLP has a broader application prospect in anti-tumor preparations.展开更多
Aim Rhodiola rosea L. possesses a wide range of pharmacological properties including lung-protective, and it has been implemented in folk medicine for several 100 years. However, the accurate mechanisms of its lung- p...Aim Rhodiola rosea L. possesses a wide range of pharmacological properties including lung-protective, and it has been implemented in folk medicine for several 100 years. However, the accurate mechanisms of its lung- protective activity remain unclear. This study aimed at investigating the possible mechanisms of lung-protective activity of Rhodiola rosea L. in pulmonary fibrosis model. Methods Pathological observation, ROS detection and measure- ments of biochemical indexes on rat models proved lung-protective effect of Rhodiola rosea L. Identification of active compounds in Rhodiola rosea L. was executed through several methods including UPLC-TOF-MS. SEA docking, too- lecular modeling, molecular docking, and molecular dynamics （MD） simulation were applied in this study to explore possible mechanisms of the lung-protective potential of Rhodiola rosea L. Furthermore, in vitro cytological examina- tion and Western blot were used for validating the efficacy of the selected compounds. Results Experiments on rat models showed a potent lung-protective effect of Rhodiola rosea L. Then we analyzed the chemical composition of Rhodiola rosea L. and found out their key targets. Moreover, in silico analysis results testified good interaction be- tween selected compound 13 and key targets Akt-1/Caspase-1, and compound 10 also interacts well with Akt-1. Fur- ther Western blot analysis proved changed expression levels of those target proteins, indicating that selected small compounds indeed acted on those targets. Conclusion In silico analysis and experimental validation together demon- strated that selected compound 10 in Rhodiola rosea L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both Caspase-1 and Akt-1. These small compounds may ameliorate pulmonary fibrosis by acting on their targets which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Rhodiola rosea L. acting on pneumonocyte and ameliorating pulmonary fibrosis.展开更多
目的基于网络药理学和分子对接方法探究红景天防治急性高原病的作用机制。方法通过TCMID和ETCM数据库检索红景天的化学成分,再经过SwissTarget和STITCH数据库筛选红景天成分作用靶点;通过DisGeNET、Genecards及GEO数据库筛选急性高原病...目的基于网络药理学和分子对接方法探究红景天防治急性高原病的作用机制。方法通过TCMID和ETCM数据库检索红景天的化学成分,再经过SwissTarget和STITCH数据库筛选红景天成分作用靶点;通过DisGeNET、Genecards及GEO数据库筛选急性高原病相关靶点;利用STRING数据库获取蛋白质相互作用(Protein-protein interaction,PPI)网络;利用DAVID数据库进行基因本体(Gene ontology,GO)功能富集分析及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;采用Cytoscape软件构建“药物-成分-靶点-疾病”网络及“成分-靶点-通路”网络;利用Autodock软件进行分子对接研究;采用2018年国际路易斯湖评分系统对患者症状进行评分;使用ELISA试剂盒对患者血清IL6、IL10及HIF1A水平进行测定。结果从红景天中筛选得到31个化学成分和2295个作用靶点,与1083个急性高原病相关靶点取交集,得到125个共同靶点,PPI网络中心主要涉及IL6、VEGFA、CAT、IL10、IL2、HIF1A等关键靶蛋白。KEGG富集分析主要涉及HIF-1信号通路、PI3K-AKT信号通路、VEGF信号通路等相关通路。分子对接验证显示红景天成分槲皮素、山奈酚、没食子酸、咖啡酸、红景天苷与关键靶点IL6、VEGFA、CAT、IL2、HIF1A的结合活性较好。此外,急性高原病患者在服用红景天胶囊后头痛、胃肠道症状、疲乏以及头晕情况明显缓解,症状总评分显著降低;血清中IL6和HIF1A水平显著降低,IL10水平显著升高。结论红景天能够通过多成分、多靶点、多通路的方式,发挥防治急性高原病的作用。展开更多
基金the National Natural Science Foundation of China(31801568)the Natural Science Foundation of Tianjin City of China(18JCQNJC79300)+1 种基金the Science and Technology Major Special Projects and Engineering of Tianjin City(17ZXYENC00010)the Science and Technology Project of Gaoyou City,Jiangsu Province(GY201812)。
文摘Numerous polysaccharides isolated from plants have been used to augment traditional drugs in the treatment of cancer.In order to explore the influence to hepatocellular carcinoma,a novel cold water-soluble polysaccharide was separated from Rhodiola rosea L.root(RLP)and then its structure and anti-cancer activities were tested.The chemical compositions and high performance gel permeation chromatography(HPGPC)results indicated that RLP was an acid heteropolysaccharide with the molecular weight of about1.15×10~6 Da.Furthermore,ion chromatography(IC),Fourier transform infrared(FT-IR)and nuclear magnetic resoance(NMR)further indicated that RLP was main composed of→2,4)-α-Rha(1→,→5)-α-L-Araf-(1→,α-D-Glu,→6)-β-D-Galp-(1→,β-D-Man and→4)-α-GalpA-(1→.In vivo antitumor activities of RLP were carried out by using H22 tumor-bearing mice model.The results shown that RLP(100 and 300 mg/kg)could inhibit tumor growth of H22 cells from 23.59%to 45.52%and protect thymuses and spleen without damage.In addition,according to cell cycle,AV-FITC/PI and JC-1,RLP could induce dose-dependent apopto sis of H22 cells via S phase arrested which was through a mitochondrial related pathway.Our data indicated that RLP has a broader application prospect in anti-tumor preparations.
文摘Aim Rhodiola rosea L. possesses a wide range of pharmacological properties including lung-protective, and it has been implemented in folk medicine for several 100 years. However, the accurate mechanisms of its lung- protective activity remain unclear. This study aimed at investigating the possible mechanisms of lung-protective activity of Rhodiola rosea L. in pulmonary fibrosis model. Methods Pathological observation, ROS detection and measure- ments of biochemical indexes on rat models proved lung-protective effect of Rhodiola rosea L. Identification of active compounds in Rhodiola rosea L. was executed through several methods including UPLC-TOF-MS. SEA docking, too- lecular modeling, molecular docking, and molecular dynamics （MD） simulation were applied in this study to explore possible mechanisms of the lung-protective potential of Rhodiola rosea L. Furthermore, in vitro cytological examina- tion and Western blot were used for validating the efficacy of the selected compounds. Results Experiments on rat models showed a potent lung-protective effect of Rhodiola rosea L. Then we analyzed the chemical composition of Rhodiola rosea L. and found out their key targets. Moreover, in silico analysis results testified good interaction be- tween selected compound 13 and key targets Akt-1/Caspase-1, and compound 10 also interacts well with Akt-1. Fur- ther Western blot analysis proved changed expression levels of those target proteins, indicating that selected small compounds indeed acted on those targets. Conclusion In silico analysis and experimental validation together demon- strated that selected compound 10 in Rhodiola rosea L. targeted Akt-1 in hepatocytes. Besides, compound 13 targeted both Caspase-1 and Akt-1. These small compounds may ameliorate pulmonary fibrosis by acting on their targets which are related to apoptosis or autophagy. The conclusions above may shed light on the complex molecular mechanisms of Rhodiola rosea L. acting on pneumonocyte and ameliorating pulmonary fibrosis.
文摘目的基于网络药理学和分子对接方法探究红景天防治急性高原病的作用机制。方法通过TCMID和ETCM数据库检索红景天的化学成分,再经过SwissTarget和STITCH数据库筛选红景天成分作用靶点;通过DisGeNET、Genecards及GEO数据库筛选急性高原病相关靶点;利用STRING数据库获取蛋白质相互作用(Protein-protein interaction,PPI)网络;利用DAVID数据库进行基因本体(Gene ontology,GO)功能富集分析及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析;采用Cytoscape软件构建“药物-成分-靶点-疾病”网络及“成分-靶点-通路”网络;利用Autodock软件进行分子对接研究;采用2018年国际路易斯湖评分系统对患者症状进行评分;使用ELISA试剂盒对患者血清IL6、IL10及HIF1A水平进行测定。结果从红景天中筛选得到31个化学成分和2295个作用靶点,与1083个急性高原病相关靶点取交集,得到125个共同靶点,PPI网络中心主要涉及IL6、VEGFA、CAT、IL10、IL2、HIF1A等关键靶蛋白。KEGG富集分析主要涉及HIF-1信号通路、PI3K-AKT信号通路、VEGF信号通路等相关通路。分子对接验证显示红景天成分槲皮素、山奈酚、没食子酸、咖啡酸、红景天苷与关键靶点IL6、VEGFA、CAT、IL2、HIF1A的结合活性较好。此外,急性高原病患者在服用红景天胶囊后头痛、胃肠道症状、疲乏以及头晕情况明显缓解,症状总评分显著降低;血清中IL6和HIF1A水平显著降低,IL10水平显著升高。结论红景天能够通过多成分、多靶点、多通路的方式,发挥防治急性高原病的作用。
