Objective: This study is designed to observe the chronic toxicity after the administration of mulberry sea-buckthorn beverage concentrate for 3 months on rats and to predict the possible adverse effect and the potenti...Objective: This study is designed to observe the chronic toxicity after the administration of mulberry sea-buckthorn beverage concentrate for 3 months on rats and to predict the possible adverse effect and the potential toxicity target organs. Method: The rats (SPF level) were randomly divided into high-dose (20 mL/kg BW), middle-dose (10 mL/kg BW), low-dose (5 mL/kg BW) groups and negative control group (20 mL/kg BW of purified water) with 30 rats in each group. Each group was orally given mulberry sea-buckthorn beverage concentrate for 3 months and recovered by stop feeding samples for 2 weeks for a recovery observation. The rats’ general condition, the organ coefficient, the indexes of hematology and blood biochemistry and the histological changes of the main organs were determined. Result: The appearance and behavior of activity in rats showed no anomalies in all these groups and all the rats put on weight during this period. Comparing to the negative control group, no obvious differences were observed in the weekly weight and organ coefficient of each dose group. After 3 months of administration, HGB in both mulberry sea-buckthorn beverage concentrate low-dose group and high-dose group were increased. No significant differences were observed in the indexes of hematology after 2 weeks of recovery. CREA in low-dose, middle-dose and high-dose groups were significantly increased after 3 months of administration and it remained in the high level in middle-dose and high-dose group even after 2 weeks of recovery. No drug-related lesions were observed in the histological changes of major organs. Conclusion: The results show that long term use of mulberry concentrated sea-buckthorn beverage can lead to increased CREA, which suggested kidney toxicity. Although no obvious pathological change was found in kidney, we should pay attention to chronic kidney damage in the further research.展开更多
目的:基于网络药理学预测沙棘治疗酒精性肝损伤(Alcohol Liver Injury)的作用机制,并通过建立斑马鱼酒精性肝损伤动物模型来验证沙棘治疗酒精性肝损伤的功效。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Sy...目的:基于网络药理学预测沙棘治疗酒精性肝损伤(Alcohol Liver Injury)的作用机制,并通过建立斑马鱼酒精性肝损伤动物模型来验证沙棘治疗酒精性肝损伤的功效。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP)、Uniprot数据库收集有效成分及其作用靶标,Venny2.1寻找交集靶点。通过GeneCards及OMIM数据库收集和筛选疾病靶点,STRING v12.0数据库进行PPI网络分析,PDB及PubChem进行蛋白质结构及小分子结构确认。通过Cytoscape(Version 3.9.1)软件网络图构建沙棘治疗酒精性肝损伤关联网络。利用Metascape数据库对共有靶点进行基因本体(Gene Ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Gene,KEGG)数据库通路富集分析。通过斑马鱼实验进行功能验证:选取受精后3 d(3 dpf)野生型AB品系斑马鱼,正常组喂养于正常饲养用水,其余各组饲养于2%的无水乙醇溶液中建立酒精性肝损伤模型。沙棘组给予不同浓度的沙棘溶液,28℃处理2 d后,确定沙棘对酒精性肝损伤模型斑马鱼的最大耐受浓度(MTC)剂量,并根据MTC结果进行下一步给药,测定样品肝保护功效评价表型实验结果。结果:筛选后得到沙棘活性成分33个,主要包括槲皮素、花葵素、儿茶酸等;治疗酒精性肝损伤的潜在靶点1434个,主要包括ADH1C、CTNNB1、TGFB1等。调控这些核心靶点的信号通路主要富集在Lipid and atherosclerosis、Fluid shear stress and atherosclerosis、PI3K-Akt signaling pathway等多条信号通路中。动物实验结果显示:与模型组相比,沙棘可显著降低酒精性肝损伤模型斑马鱼肝脏不透明值(P<0.01),改善肝脏和卵黄囊肿大(P<0.01),下调AST和ALT的活力值(P<0.001),改善肝细胞核肿大,减少肝组织脂肪空泡样变性的功效。结论:沙棘可改善酒精性肝损伤,其机制可能与改善脂肪酸氧化、细胞代谢和抑制细胞凋亡有关。展开更多
文摘Objective: This study is designed to observe the chronic toxicity after the administration of mulberry sea-buckthorn beverage concentrate for 3 months on rats and to predict the possible adverse effect and the potential toxicity target organs. Method: The rats (SPF level) were randomly divided into high-dose (20 mL/kg BW), middle-dose (10 mL/kg BW), low-dose (5 mL/kg BW) groups and negative control group (20 mL/kg BW of purified water) with 30 rats in each group. Each group was orally given mulberry sea-buckthorn beverage concentrate for 3 months and recovered by stop feeding samples for 2 weeks for a recovery observation. The rats’ general condition, the organ coefficient, the indexes of hematology and blood biochemistry and the histological changes of the main organs were determined. Result: The appearance and behavior of activity in rats showed no anomalies in all these groups and all the rats put on weight during this period. Comparing to the negative control group, no obvious differences were observed in the weekly weight and organ coefficient of each dose group. After 3 months of administration, HGB in both mulberry sea-buckthorn beverage concentrate low-dose group and high-dose group were increased. No significant differences were observed in the indexes of hematology after 2 weeks of recovery. CREA in low-dose, middle-dose and high-dose groups were significantly increased after 3 months of administration and it remained in the high level in middle-dose and high-dose group even after 2 weeks of recovery. No drug-related lesions were observed in the histological changes of major organs. Conclusion: The results show that long term use of mulberry concentrated sea-buckthorn beverage can lead to increased CREA, which suggested kidney toxicity. Although no obvious pathological change was found in kidney, we should pay attention to chronic kidney damage in the further research.
文摘目的:基于网络药理学预测沙棘治疗酒精性肝损伤(Alcohol Liver Injury)的作用机制,并通过建立斑马鱼酒精性肝损伤动物模型来验证沙棘治疗酒精性肝损伤的功效。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP)、Uniprot数据库收集有效成分及其作用靶标,Venny2.1寻找交集靶点。通过GeneCards及OMIM数据库收集和筛选疾病靶点,STRING v12.0数据库进行PPI网络分析,PDB及PubChem进行蛋白质结构及小分子结构确认。通过Cytoscape(Version 3.9.1)软件网络图构建沙棘治疗酒精性肝损伤关联网络。利用Metascape数据库对共有靶点进行基因本体(Gene Ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Gene,KEGG)数据库通路富集分析。通过斑马鱼实验进行功能验证:选取受精后3 d(3 dpf)野生型AB品系斑马鱼,正常组喂养于正常饲养用水,其余各组饲养于2%的无水乙醇溶液中建立酒精性肝损伤模型。沙棘组给予不同浓度的沙棘溶液,28℃处理2 d后,确定沙棘对酒精性肝损伤模型斑马鱼的最大耐受浓度(MTC)剂量,并根据MTC结果进行下一步给药,测定样品肝保护功效评价表型实验结果。结果:筛选后得到沙棘活性成分33个,主要包括槲皮素、花葵素、儿茶酸等;治疗酒精性肝损伤的潜在靶点1434个,主要包括ADH1C、CTNNB1、TGFB1等。调控这些核心靶点的信号通路主要富集在Lipid and atherosclerosis、Fluid shear stress and atherosclerosis、PI3K-Akt signaling pathway等多条信号通路中。动物实验结果显示:与模型组相比,沙棘可显著降低酒精性肝损伤模型斑马鱼肝脏不透明值(P<0.01),改善肝脏和卵黄囊肿大(P<0.01),下调AST和ALT的活力值(P<0.001),改善肝细胞核肿大,减少肝组织脂肪空泡样变性的功效。结论:沙棘可改善酒精性肝损伤,其机制可能与改善脂肪酸氧化、细胞代谢和抑制细胞凋亡有关。
