不同辅料模拟炮制下黄草乌碱丙的转化规律及其转化产物的毒效研究  

Exploring the transformation rule of Vilmorrianine C and the toxicity-efficacy of its transformation products under simulated processing with different excipients

作　　者：胡林 苏东雪 庄馨瑛 段小花 马晓霞 HU Lin;SU Dong-xue;ZHUANG Xin-ying;DUAN Xiao-hua;MA Xiao-xia(Yunnan University of Chinese Medicine,Kunming 650500,China;Key Laboratory of Yunnan Provincial Department of Education for Processing Research on Characteristic Prepared Pieces,Kunming 650500,China)

机构地区：[1]云南中医药大学,云南昆明650500 [2]云南省教育厅云南特色饮片炮制研究重点实验室,云南昆明650500

出　　处：《时珍国医国药》2025年第2期273-279,共7页Lishizhen Medicine and Materia Medica Research

基　　金：云南省应用基础研究-中医联合专项项目(202301AZ070001-003);云南省“万人计划”青年拔尖人才专项(YNWR-QNBJ-2019-011);云南省傣医药与彝医药重点实验室开放课题(202210SS2216)。

摘　　要：目的研究不同辅料炮制对黄草乌碱丙转化的影响,比较黄草乌碱丙与转化产物的急性毒性和镇痛活性。方法采用TLC和HPLC法鉴别不同辅料炮制黄草乌碱丙的主要转化产物,分析其不同炮制时间下主要产物的含量变化;采用小鼠急性毒性实验评价黄草乌碱丙及其转化产物的毒性,采用热板致小鼠疼痛和醋酸致小鼠扭体疼痛法比较其镇痛活性。结果黄草乌碱丙加辅料炮制转化产物主要包括Acoforesticine、Chasmanine和对甲氧基苯甲酸;黄草乌碱丙炮制前的浓度为47.33μg/mL,加辅料白矾炮制6 h后,几乎仍以原型形式存在,其含量为37.32μg/mL;加辅料甘草、黑豆炮制时主要转化产物为Acoforesticine,在炮制6 h后,Acoforesticine含量分别为7.23,6.43μg/mL;加辅料生姜炮制的主要转化产物为Acoforesticine和对甲氧基苯甲酸,6 h时含量分别为7.79,7.01μg/mL;不加辅料(清水)炮制6 h后,转化产物以对甲氧基苯甲酸为主,含量为8.86μg/mL;黄草乌碱丙和Acoforesticine腹腔注射的LD50值分别为3.5735、35.5050 mg/kg,Chasmanine最大给药量为67.15 mg/kg;黄草乌碱丙和Acoforesticine低、中、高剂量对热板和醋酸致小鼠疼痛均有显著的镇痛作用,而Chasmanine仅有镇痛作用趋势。结论加辅料甘草、黑豆和生姜炮制黄草乌碱丙能不同程度的抑制其单酯型转化产物的进一步降解,在毒性降低的同时更多保留其镇痛活性。Objective To investigate the effect of different processing excipients on the transformation of Vilmorrianine C(VC)and to compare the acute toxicity and analgesic activity of VC with its transformation products.Methods The main transformation products of VC processed with different excipients were identified by TLC and the contents change of the main products in different processing periods analyzed by HPLC.The toxicity of VC and its transformation products were evaluated by acute toxicity test in mice,and their analgesic activities was compared by hot plate-induced pain and acetic acid-induced writhing pain methods in mice.Results The transformation products of VC under different processing excipients mainly included Acoforesticine,Chasmanine and p-methoxybenzoic acid.The initial concentration of VC was 47.33μg/mL,and it almost remained the prototype form with a concentration of 37.32μg/mL after 6 hours processed with the excipient alum.The main transformation product is Acoforesticine when licorice and black beans were added as excipients for processing,and the content of Acoforesticine is 7.23μg/mL and 6.43μg/ml respectively after 6 hours.The main transformation products are Acoforesticine and p-methoxybenzoic acid and their contents are 7.79μg/mL and 7.01μg/mL respectively when processed with ginger for 6 hours.When boiled in water for 6 hours(adding no processing excipient),p-methoxybenzoic acid could be tested as the main processed product with the content of 8.86μg/mL.The LD50 values of VC and Acoforesticine by intraperitoneal injection were 3.5735 and 35.5050 mg/kg respectively,while the maximum dose for Chasmanine was 67.15 mg/kg.The low,medium and high doses of VC and Acoforesticine showed significant inhibitory effects on the pain induced by hot plates and acetic acid in mice,while Chasmanine only had a tendency of inhibition.Conclusion The processing excipients licorice,black bean and ginger could inhibit the further degradation of the monoester-type transformation products of VC in different d

关 键 词：黄草乌碱丙 炮制辅料 模拟炮制 急性毒性 镇痛活性 

分 类 号：R283.1[医药卫生—中药学] R283.2[医药卫生—中医学]