药学学报, 2019, 54(3): 502-509
引用本文:
邹纯才, 鄢海燕, 王莉丽, 卞莹莹. 瓜蒌提取物抗血栓药效成分群的筛选与验证[J]. 药学学报, 2019, 54(3): 502-509.
ZOU Chun-cai, YAN Hai-yan, WANG Li-li, BIAN Ying-ying. Screening and validation of antithrombotic effective components group from Trichosanthes extract[J]. Acta Pharmaceutica Sinica, 2019, 54(3): 502-509.

瓜蒌提取物抗血栓药效成分群的筛选与验证
邹纯才, 鄢海燕, 王莉丽, 卞莹莹
皖南医学院药学院, 安徽 芜湖 241002
摘要:
筛选瓜蒌提取物抗血栓的药效成分群并进行药效学验证与作用机制分析。建立瓜蒌提取物的HPLC指纹图谱,以阿司匹林(0.01 g·kg-1)为阳性对照组,测定瓜蒌提取物(0.09、0.45和0.9 g·kg-1)抗大鼠血栓药效学指标(本实验所用动物经皖南医学院医学伦理委员会批准同意),采用灰色关联度法研究瓜蒌提取物抗血栓的谱效关系并筛选药效成分群。按药效成分群中各成分的含量制备单体化合物混合溶液(0.006、0.03和0.06 g·kg-1)并进行药效学和作用机制研究,以验证谱效关系结果的正确性。瓜蒌提取物22个成分与抗血栓药效间的关联度呈量效关系且关联度不同。胞嘧啶、尿嘧啶、鸟嘌呤、次黄嘌呤、黄嘌呤、腺嘌呤、鸟苷和腺苷8个成分是瓜蒌提取物抗血栓的主要药效成分群,这些成分比例为3:12:10:5:2:8:13:14。药效成分群各组与模型组比较均可有效降低血栓干重(P<0.01或P<0.05),但与瓜蒌提取物组(0.45 g·kg-1)比较无统计学意义。与模型组比较,药效成分群0.06 g·kg-1组和0.03 g·kg-1组均可有效降低TXB2含量(P<0.01或P<0.05),药效成分群各组均可升高6-keto-PGF1α含量(P<0.01),改善TXB2/6-keto-PGF1α趋于正常且呈量效关系,此效果优于瓜蒌提取物组(0.45 g·kg-1)(P<0.01)。药效成分群有较好的抗血栓作用,其作用机制为抑制血小板聚集及改善血管内皮功能。
关键词:   
Screening and validation of antithrombotic effective components group from Trichosanthes extract
ZOU Chun-cai, YAN Hai-yan, WANG Li-li, BIAN Ying-ying
Pharmacy School of Wannan Medical College, Wuhu 241002, China
Abstract:
To screen the antithrombotic effective components group of Trichosanthes extract, and to verify its pharmacodynamics and analyze its mechanism, the HPLC fingerprint of Trichosanthes extract (0.09, 0.45, 0.9 g·kg-1) was established, and the pharmacodynamic indexes of antithrombosis in rats with aspirin (0.01 g·kg-1) as positive control group were determined (the animals used in this experiment were approved by the Medical Ethics Committee of Wannan Medical College). The antithrombotic spectrum-activity relationship of Trichosanthes extract was studied and the effective antithrombotic ingredients group was screened by grey relational analysis. The monomer compound mixed solution (0.006, 0.03, 0.06 g·kg-1) was prepared according to the content of each component in the active component group, and the pharmacodynamics and action mechanism were studied to verify the correctness of the spectrum-effect relationship. The correlation between the 22 components of Trichosanthes extract and antithrombotic efficacy was different and showed dose-effect relationship. Cytosine, uracil, guanine, hypoxanthine, xanthine, adenine, guanosine, and adenosine are the main antithrombotic components of Trichosanthes extract. The ratio of cytosine, uracil, guanine, hypoxanthine, xanthine, adenine, guanosine and adenosine was 3:12:10:5:2:8:13:14. Compared with the model group, the thrombus dry weight of each effective components group could be effectively reduced (P<0.01 or P<0.05), but there was no significant difference between each effective components group and the Trichosanthes extract group. Compared with the model group, the TXB2 content in group (0.06 g·kg-1, 0.03 g·kg-1) could be effectively reduced (P<0.01 or P<0.05), and the content of 6-keto-PGF1α could be increased in each group (P<0.01), and the TXB2/6-keto-PGF1α tended to be normal and showed a dose-effect relationship. The effect was better than that in the Trichosanthes extract group (0.45 g·kg-1) (P<0.01). The effective ingredients group has a good antithrombotic effect, its mechanism is to inhibit platelet aggregation and improve vascular endothelial function.
Key words:   
收稿日期: 2018-10-07
DOI: 10.16438/j.0513-4870.2018-0898
基金项目: 安徽高校省级自然科学研究重大项目(KJ2015ZD41,KJ2016SD60).
通讯作者: 鄢海燕
Email: yhy0801@126.com
相关功能
PDF(498KB) Free
打印本文
0
作者相关文章

参考文献:
[1] China Pharmacopoeia Commission. Chinese Pharmacopoeia:Vol I (中华人民共和国药典:一部)[S]. Beijing:China Medical Science Press, 2015:112.
[2] Zou CC, Yan HY, Wei ML. Study of the anti-heart failure mechanisms of compatibility of Gualou with Xiebai in basis of network pharmacology[J]. Acta Pharm Sin (药学学报), 2018, 53:1406-1413.
[3] Yang H, Qi LW, Li HJ, et al. "Bioactive equivalent combinatorial components" as defined labeled amount of active constituents for quality control of traditional Chinese medicines[J]. World Sci Technol Mod Tradit Chin Med Mat Med (世界科学技术-中医药现代化), 2014, 16:510-513.
[4] Li ZY, Duan YH, Qin XM, et al. Study of difference in quality of traditional Chinese medicines[J]. Acta Pharm Sin (药学学报), 2017, 52:1820-1826.
[5] Zhang JX, Hu Q, Yu H, et al. Rapid and intelligentized identification of the constituents in Gualoupi injection by HILIC/ESI-Orbitrap HRMS combined with Compound Discoverer software[J]. Acta Pharm Sin (药学学报), 2018, 53:1705-1712.
[6] Fan JX, Wang S, Meng XS, et al. Study of cancer cell apoptosis induced by Schizonepeta tenuifolia with microfluidic chip technology[J]. Acta Pharm Sin (药学学报), 2017, 52:126-131.
[7] Zeng LJ, Lin B, Song HT. Progress in study of spectrum-effect relationship of traditional Chinese medicine and discussions[J].China J Chin Mater Med (中国中药杂志), 2015, 40:1425-1432.
[8] Fan HY. Antiplatelet and Antithrombotic Activities of Salvianolic Acid A (丹酚酸A抗血小板及抗血栓作用的研究)[D].Changchun:Jilin University, 2012.
[9] Zou CC, Zong QN, Yan HY. Spectrum-activity relationship of trichosanthis fructus and trichosanthis fructus strip pieces for rat myocardial ischemia-reperfusion injury[J]. China J Chin Mater Med (中国中药杂志), 2018, 43:92-99.
[10] Yan HY, Zou CC, Wei ML, et al. Spectrum-effect relationship of Gualou Xiebai dropping pills on myocardial ischemia[J]. J Med Mater (中药材), 2015, 38:1912-1918.
[11] Zou CC, Hong GJ, Yan HY. Effect of different data standardization methods on spectrum-effect relationship for anticoagulation of Trichosanthis Fructus dropping pills[J].China J Chin Mater Med (中国中药杂志), 2018, 43:1864-1870.
[12] Zhang XD. The Study of Antithrombotic Effects of Kangxian Yixin Concentrated Pill(抗纤益心浓缩丸抗血栓作用研究)[D].Zhengzhou:Henan University of Chinese Medicine, 2017.
[13] Yan CH, Feng YP. Effects of butylphthalide on extracellular 6-keto-PGF1α, TXB2 and 6-keto-PGF1α/TXB2 ratio in cultured rat cortical neurons[J]. Acta Pharm Sin (药学学报), 1998, 33:881-885.
[14] Luo CY. Hemostatic Effects Study of Callicarpa nudiflora Hook (裸花紫珠的止血活性研究)[D]. Nanchang:Nanchang University, 2016.
[15] Wang FQ, Chen C, Xia ZN, et al. Applications of platelets in studies on traditional Chinese medicines promoting blood circulation to remove blood stasis[J]. China J Chin Mater Med (中国中药杂志), 2014, 39:2993-3003.