Zhan Xiang, Wang Wen-Yu, Fu Jun, Deng Ran, Li Feng, Dai Xue-Jing, Wang Yan, Wu Hong
Anhui University of Chinese Medicine Hefei 230012,China Key Laboratory of Xin'an Medicine,Ministry of Education Hefei 230038,China Anhui Province Key Laboratory of Chinese Herbal Compound Hefei 230012,China.
Zhongguo Zhong Yao Za Zhi. 2019 Jan;44(2):364-371. doi: 10.19540/j.cnki.cjcmm.20181101.006.
To investigate the " drug-guide" effect of Achyranthes bidentata saponins( ABS) and geniposide( GE) in the treatment on adjuvant arthritis( AA) rats. A UHPLC-MS/MS method for the quantitative determination of GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa in rat blood and joint dialysate was established. After single or combined administration with ABS and GE was given to AA rat model,a microdialysis sampling method for rat joint cavity and jugular vein blood vessels was established to collect microdialysis samples. Waters Acquity HSS C_(18) column was used to separate the above four components,with mobile phase as acetonitrile-0. 1% formic acid water as mobile phase for gradient elution. ESI source was adopted for mass spectra in a negative ion scanning mode. Multiple reaction monitoring( MRM) mode was applied to detect the above four components. The methodological results showed that GE,zingibroside R1,ginsenoside Ro and chikusetsu saponin Ⅳa demonstrated a good linear relationship within the concentration ranges of 2-4 000,16-4 096,14-3 584,23-5 888 μg·L-1 respectively. The precision,accuracy,stability and matrix effect of these four ingredients reached the requirements of quantitative analysis of biological samples. The pharmacokinetic results demonstrated that the combined administration of ABS and GE( 60 mg·kg(-1)+60 mg·kg(-1)) can increase the degree of GE in joint cavity distribution,and the AUCjoint/AUCplasmwere twice of that of single administration of GE( 60 mg·kg~(-1)),which indicated that ABS might played a vital role in GE's distribution to joint cavity. Moreover,there was no significant difference between the distribution trend of total three ABS and GE in rats. The pharmacodynamics results showed that the combined administration of ABS and GE has stronger effects on paw swelling,arthritis index and synovial pathomorphology of AA rats than single administration of GE,which suggested that ABS might improve GE's anti-inflammatory effect in AA rats. Based on the above results,ABS has a targeting effect in increasing GE's concentration in joint cavity,with a synergy in efficacy.
探讨牛膝皂苷（ABS）和栀子苷（GE）对佐剂性关节炎（AA）大鼠的“药物导向”作用。建立了大鼠血液和关节透析液中GE、紫菀皂苷R1、人参皂苷Ro和竹节参皂苷Ⅳa的超高效液相色谱-串联质谱（UHPLC-MS/MS）定量测定方法。对AA大鼠模型单次或联合给予ABS和GE后，建立大鼠关节腔和颈静脉血管微透析采样方法采集微透析样品。采用Waters Acquity HSS C18色谱柱分离上述4种成分，以乙腈-0.1%甲酸水为流动相进行梯度洗脱。采用电喷雾离子源（ESI），在负离子扫描模式下进行质谱分析，采用多反应监测（MRM）模式检测上述4种成分。方法学结果表明，GE、紫菀皂苷R1、人参皂苷Ro和竹节参皂苷Ⅳa在2～4 000、16～4 096、14～3 584、23～5 888 μg·L-1浓度范围内线性关系良好，4种成分的精密度、准确度、稳定性和基质效应均达到生物样品定量分析要求。药代动力学结果表明，ABS与GE联合给药（60 mg·kg-1+60 mg·kg-1）可提高GE在关节腔的分布程度，关节腔与血浆的药时曲线下面积（AUCjoint/AUCplasm）为GE单次给药（60 mg·kg-1）的2倍，提示ABS对GE向关节腔的分布可能起重要作用。此外，3种ABS总量与GE在大鼠体内的分布趋势无明显差异。药效学结果表明，ABS与GE联合给药对AA大鼠足肿胀、关节炎指数及滑膜病理形态学的影响较GE单次给药更强，提示ABS可能增强GE对AA大鼠的抗炎作用。基于上述结果，ABS对提高GE在关节腔的浓度具有靶向作用，且在药效上具有协同作用。
