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  被引量:3

The chemical structure of an active polysaccharide RTP-60-3V-Ⅲ from roots of Ranunculus ternatus and its effect on drug-induced liver injury

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作  者:姚蕙 麻浩 骆芙瑶 顾嘉楠 赵修南 高月求[2] 单俊杰 YAO Hui;MA Hao;LUO Fu-yao;GU Jia-nan;ZHAO Xiu-nan;GAO Yue-qiu;SHAN Jun-jie(Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;Department of Liver Diseases,Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区:[1]军事医学研究院毒物药物研究所,北京100850 [2]上海中医药大学曙光医院肝病科,上海201203

出  处:《中国新药杂志》2024年第4期360-371,共12页Chinese Journal of New Drugs

基  金:国家“重大新药创制”科技重大专项资助项目(2018ZX10205504)。

摘  要: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4628 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。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 4628 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.

关 键 词:猫爪草 多糖 化学结构 药物性肝损伤 

分 类 号:R965[医药卫生—药理学]

 

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