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补骨脂炮制品水提和醇沉物化学成分及肝毒性研究
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          李卓柯    1, 2* ,刘 洋 ,李 晔 ,王春柳 ,刘 峰 ,孙婷婷 ,张 红 (1.陕西中医药大学药学院,陕西 咸阳
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          712046;2.陕西省中医药研究院,西安 710003;3.陕西步长制药有限公司,西安 710075)
          中图分类号  R283.1      文献标志码  A      文章编号  1001-0408(2023)12-1443-06
          DOI  10.6039/j.issn.1001-0408.2023.12.07
          摘  要  目的  研究补骨脂不同炮制品水提及醇沉物中5种化学成分的含量变化情况,并初步评价其肝毒性。方法  制备补骨脂
          生品和雷公法、流水漂洗法、盐炙法炮制品的水提样品,以及雷公法、盐炙法炮制品的醇沉样品,采用高效液相色谱法测定其中补
          骨脂苷、异补骨脂苷、补骨脂素、异补骨脂素、补骨脂酚的含量并进行比较;以不同质量浓度补骨脂生品、流水漂洗法、雷公法、盐炙
          法水提样品和雷公法、盐炙法醇沉样品作用72 h,计算各样品对野生型斑马鱼的半数致死浓度(LC50 )和最大非致死浓度(MNLC);
          以对乙酰氨基酚为阳性对照,以上述样品(MNLC)作用 72 h,观察野生型斑马鱼的基本形态和转基因斑马鱼的肝脏表型。采用
          Pearson相关性分析评价成分含量与肝毒性的相关性。结果  与生品水提物比较,不同炮制品水提样品中补骨脂苷、异补骨脂苷的
          含量均显著降低(P<0.05),而雷公法、盐炙法醇沉样品中补骨脂素、异补骨脂素、补骨脂酚的含量均显著升高(P<0.05)。生品、
          流水漂洗法、雷公法、盐炙法水提样品和雷公法、盐炙法醇沉样品的LC50分别为2.45、5.00、5.38、1.55、2.36、0.64 g/L(以生药量计),
          MNLC分别为2.21、4.53、5.02、1.37、2.13、0.53 g/L(以生药量计);与空白对照组比较,各样品处理组斑马鱼幼鱼均表现出不同程度
          的畸形,肝脏相对荧光强度均显著减弱(P<0.05或P<0.01)。补骨脂酚、异补骨脂素、补骨脂素等脂溶性成分与肝脏相对荧光强
          度的相关性较高(R >0.7)。结论  补骨脂炮制品经水提后以补骨脂苷、异补骨脂苷为主,经醇沉后补骨脂素、异补骨脂素、补骨脂
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          酚的含量增加;醇沉样品的肝毒性更强,且肝毒性与补骨脂脂溶性成分的含量呈正相关。
          关键词  补骨脂;炮制品;水提物;醇沉物;肝毒性;成分含量

          Study  on  chemical  compositions  and  hepatotoxicity  of  water  extract  and  ethanol  precipitate  of  processed
          products of Psoralea corylifolia
          LI Zhuoke ,LIU Yang ,LI Ye ,WANG Chunliu ,LIU Feng ,SUN Tingting ,ZHANG Hong (1.  College  of
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          Pharmacy,  Shaanxi  University  of  Chinese  Medicine,  Shaanxi  Xianyang  712046,  China;2.  Shaanxi Academy  of
          Traditional  Chinese  Medicine,  Xi’an  710003,  China;3.  Shaanxi  Buchang  Pharmaceutical  Co.,  Ltd.,  Xi’an
          710075, China)
          ABSTRACT   OBJECTIVE  To  study  the  content  changes  of  5  chemical  compositions  in  water  extract  and  ethanol  precipitate  of
          different processed products of Psoralea corylifolia, and to preliminarily evaluate its hepatotoxicity. METHODS The water extracts
          from crude product of P. corylifolia and processed products by Leigong method, running water rinsing method, and salt stir-frying
          method were prepared, as well as the ethanol precipitates of processed products by Leigong method and salt stir-frying method were
          prepared.  The  contents  of  psoralenoside,  isopsoralenoside,  psoralen,  isopsoralen  and  bakuchiol  were  determined  by  high-
          performance  liquid  chromatography  and  compared.  The  median  lethal  concentration (LC50 )  and  maximum  non-lethal  concentration
         (MNLC)  of  each  sample  to  wild-type  zebrafish  juveniles  were  calculated  after  72  h  of  treatment  with  different  concentrations  of
          water  extracts  from  raw  product  and  processed  products  by  running  water  rinsing  method,  Leigong  method  and  salt  stir-frying
          method,  different  concentrations  of  ethanol  precipitates  from  processed  products  by  Leigong  method  and  salt  stir-frying  method,
          and  the  acetaminophen  was  used  as  the  positive  control.  The  basic  morphology  of  wild-type  zebrafish  juveniles  and  the  liver
          phenotype  of  transgenic  zebrafish  juveniles  were  observed  after  72  h  of  treatment  with  the  above  samples (MNLC).  Pearson
          correlation analysis was used to evaluate the correlation between component content and hepatotoxicity. RESULTS  Compared with
                                                             the  water  extract  of  raw  products,  the  contents  of  psoralenoside
             Δ 基金项目 陕西省重点研发计划项目(No.2021ZDLSF04-06,No.
                                                             and  isopsoralenoside  in  the  water  extract  of  different  processed
          2022ZDXM-SF-06,No.2022SF-183)
             *第一作者 研究实习员,硕士。研究方向:中药药效物质基础与                   products were generally decreased (P<0.05), while the contents
          质量控制。E-mail:yc020630vv@163.com                     of  psoralen,  isopsoralen  and  bakuchiol  in  the  ethanol  precipitate
             #a 通信作者 副研究员,博士。研究方向:中药炮制机制及饮片质                 of Leigong method and salt stir-frying products were significantly
          量标准。E-mail:sttlt@126.com
                                                             increased (P<0.05).  The  LC50  of  water  extracts  of  crude
             #b 通信作者 研究员,博士。研究方向:中药药效物质基础与质量
          控制。E-mail:zhanghong919919@163.com                  product  and  processed  products  by  running  water  rinsing


          中国药房  2023年第34卷第12期                                              China Pharmacy  2023 Vol. 34  No. 12    · 1443 ·
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