雷公藤萜类组分提取及其抗炎药效-毒性时间节律性研究  

Study on the Extraction of Terpenoids From Leigongteng(Tripterygium Wilfordii)and Its Time Rhythm of Anti-inflammatory Efficacy and Toxicity

作　　者：房雨彤 潘荣华[2] 唐婷婷 曹杰 李秋桐 嵇晶[1] 黄仕文[1] 程建明[1] 刘陶世[1] FANG Yutong;PAN Ronghua;TANG Tingting;CAO Jie;LI Qiutong;JI Jing;HUANG Shiwen;CHENG Jianming;LIU Taoshi(Nanjing University of Chinese Medicine,Nanjing 210023,Jiangsu,China;Liyang Hospital of Chinese Medicine,Liyang 213300,Jiangsu,China)

机构地区：[1]南京中医药大学,江苏南京210023 [2]溧阳市中医院,江苏溧阳213300

出　　处：《辽宁中医药大学学报》2022年第7期43-49,共7页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：江苏省自然科学基金面上项目(BK20181424)。

摘　　要：目的优选雷公藤萜类组分的提取参数,阐明雷公藤萜类组分抗炎药效与毒性的时间节律性以探讨雷公藤的新型增效减毒方法。方法采用HPLC法同时测定雷公藤中雷公藤甲素和雷公藤晋碱等5种萜类成分的含量,采用单因素法与正交试验法优选雷公藤的提取工艺参数。采用巴豆油混合致炎液建立小鼠耳肿胀的急性炎症模型,对比白天给药(10:00)和夜间给药(22:00)药效与毒性的差异,采用Elisa法测定小鼠血清生化指标肿瘤坏死因子-α(TNF-α)、白细胞介素-2(IL-2)、谷丙转氨酶(ALT)和谷草转氨酶(AST)含量,并测定小鼠心脏、肝脏、肾脏和脾脏的脏器指数。结果(1)雷公藤萜类组分的优化提取参数:取雷公藤饮片加85%乙醇回流提取2次(11倍量1.5 h,9倍量1 h)。提取物中雷公藤甲素、雷公藤内酯酮、雷公藤晋碱、雷公藤次碱、雷公藤红素的平均含量分别为40.59、12.71、139.19、578.58、2.67μg·g^(-1)。(2)雷公藤提取物在0.45~1.80 g·kg^(-1)剂量范围能够显著降低小鼠耳肿胀率,降低小鼠血清IL-2、TNF-α含量,同时使ALT、AST含量升高,脏器指数增大。与白天给药相比,夜间给药对小鼠耳肿胀率及血清IL-2、TNF-α含量的降低效果更显著,且脏器指数及ALT、AST含量低于白天给药。结论雷公藤萜类组分具有显著的抗炎作用,但同时会引起肝肾等毒性。雷公藤夜间给药的抗炎作用强于白天给药,但毒性低于白天给药,提示雷公藤的抗炎作用和毒性均具有明显时间节律性,该结果对制定雷公藤给药方案和研制择时给药系统具有重要参考价值。Objective To optimize the extraction parameters of terpenoids from Leigongteng(Tripterygium wilfordii),clarify the time rhythm of anti-inflammatory efficacy and toxicity of terpenoids from Tripterygium wilfordii,and explore a new method of enhancing efficacy and reducing toxicity of Leigongteng(Tripterygium wilfordii).Methods The contents of triptolide and triptolide in Leigongteng(Tripterygium wilfordii)were determined by HPLC,and the extraction parameters of Leigongteng(Tripterygium wilfordii)were optimized by single factor method and orthogonal test.The acute inflammation model of mice ear swelling induced by croton oil mixed with inflammatory liquid was used to compare the difference of efficacy and toxicity between daytime(10:00 am)and nighttime(10:00 pm).The serum biochemical index of tumor necrosis factor was determined by ELISA.The contents of tumor necrosis factor-α(TNF-α),interleukin-2(IL-2),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured,and the organ indexes of heart,liver,kidney and spleen were measured.Results(1)The optimal extraction parameters of terpenoids from Leigongteng(Tripterygium wilfordii)were as follows:Leigongteng(Tripterygium wilfordii)decoction pieces were refluxed with 85%ethanol twice(11 times volume for 1.5 h,9 times volume for 1 h).The contents of triptolide,triptolide,triptolide,triptolidine,triptolidine and triptolide were 40.59,12.71,139.19,578.58 and 2.67μg·g^(-1),respectively.(2)Leigongteng(Tripterygium wilfordii)extract in the dose range of 0.45-1.80 g·kg^(-1) could significantly reduce the ear swelling rate of mice,reduce the serum IL-2 and TNF-α.At the same time,the content of ALT and AST increased,and the organ coefficient increased.Compared with daytime administration,nighttime administration had significant effects on ear swelling rate,serum IL-2 and TNF-αThe content of ALT and AST was lower than that in daytime.Conclusion The terpenoids from Leigongteng(Tripterygium wilfordii)have significant anti-inflammatory effect,but at the same

关 键 词：雷公藤 提取 抗炎 时间节律性 择时给药 

分 类 号：R284[医药卫生—中药学]