首页|猫爪草活性多糖RTP-60-3V-Ⅲ化学结构及抗药物性肝损伤的作用

猫爪草活性多糖RTP-60-3V-Ⅲ化学结构及抗药物性肝损伤的作用

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目的:分离和纯化制备猫爪草的多糖成分RTP-60-3V-Ⅲ,研究其理化性质及化学结构特征,评价其对药物诱导肝细胞损伤的影响.方法:猫爪草粗多糖RTP-60 经乙醇分级沉淀,DEAE纤维素、凝胶Sephdex G50 和G-100 柱色谱分离和纯化,获得分子量均一多糖RTP-60-3V-Ⅲ.高效凝胶过滤法测定分子量分布,PMP衍生和毛细管电泳法测定单糖组成.采用高碘酸氧化-Smith降解和甲基化反应,再结合IR,NMR和GC-MS等技术对RTP-60-3V-Ⅲ进行化学结构特征的研究.采用MTT法评价RTP-60-3V-Ⅲ对阿托伐他汀、地塞米松、阿奇霉素、紫杉醇和利福平药物体外诱导LO2 肝细胞损伤的影响.结果:RTP-60-3V-Ⅲ为葡聚糖,峰高分子量为 4 628 Da,骨架结构主要为→4,6)-α-D-Glcp-(1→以及α-D-Glcp-(1→,→4)-α-D-Glcp-(1→和→6)-α-D-Glcp-(1→这3 种侧链.该多糖对阿托伐他汀、地塞米松、阿奇霉素、紫杉醇和利福平诱导的LO2 细胞死亡具有明显的抑制活性,且呈良好的浓度-效应关系.结论:猫爪草多糖RTP-60-3V-Ⅲ具有明显的抗药物性肝损伤活性,未来有望成为治疗药物肝损伤的候选药物.
The chemical structure of an active polysaccharide RTP-60-3V-Ⅲ from roots of Ranunculus ternatus and its effect on drug-induced liver injury
Objective:To isolate and purify an active polysaccharide(RTP-60-3V-Ⅲ)from the roots of Ranunculus ternatus and investigate its antidrug-induced liver injury effects.Methods:The crude polysaccharides from the roots of R.ternatus were isolated and purified with graded alcohol precipitation,DEAE-cellulose column and Sephadex gel G100 and G50 columns to obtain the homogeneous polysaccharide.The molecular weight of RTP-60-3V-Ⅲ was determined with gel filtration chromatography and its monosaccharide composition was analyzed with capillary electrophoresis after acid hydrolysis and PMP derivation.The methods of periodate oxidation-Smith degradation,methylation analysis,FT-IR,NMR and GC-MS were used to investigate the chemical structural features of RTP-60-3V-Ⅲ.The effects of the polysaccharide on drug-induced liver injury in human LO2 liver cell model were estimated by MTT method using atorvastatin,dexamethasone,azithromycin,paclitaxel,and rifampicin.Results:RTP-60-3V-Ⅲ is a glucan and its peak height weight is 4 628 Da.Its backbone chain is →4,6)-α-D-Glcp-(1→ and with three branch chains of α-D-Glcp-(1→,→4)-α-D-Glcp-(1→and→6)-α-D-Glcp-(1→.The polysaccharide significantly reduced LO2 cell death induced by atorvastatin,dexamethasone,azithromycin,paclitaxel and rifampicin and exhibited good concentration-effect relations.Conclusion:The polysaccharide of RTP-60-3V-Ⅲ from Ranunculus ternatus possesses remarked effects on drug-induced liver injury,and it might be a good candidate in this field in future.

Ranunculus ternatuspolysaccharideschemical structuredrug-induced liver injury

姚蕙、麻浩、骆芙瑶、顾嘉楠、赵修南、高月求、单俊杰

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军事医学研究院毒物药物研究所,北京 100850

上海中医药大学曙光医院肝病科,上海 201203

猫爪草 多糖 化学结构 药物性肝损伤

国家"重大新药创制"科技重大专项资助项目

2018ZX10205504

2024

中国新药杂志
中国医药科技出版社 中国医药集团总公司 中国药学会

中国新药杂志

CSTPCD北大核心
影响因子:1.039
ISSN:1003-3734
年,卷(期):2024.33(4)
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