摘要
目的基于药性理论,通过对临床医保目录中抗白癜风中成药方药活性成分的筛选,对其有效成分进行初步药效学评价及机制探讨。方法收集抗白癜风中成药组方、药性和物质基础以筛选主药。通过TCMSP和TCMIP数据库得到主要化合物类型。使用admetSAR分析成药性得出关键化合物。通过成年斑马鱼和斑马鱼幼鱼的形态学、黑色素含量测定观察体内药效学。通过斑马鱼幼鱼存活率进行安全性评价。通过RT-PCR显示化合物在转录水平中的作用机制。使用分子对接预测化合物与蛋白晶体结构的结合能力。结果使用频次最高的主药为红花、紫草、蒺藜、龙胆、补骨脂和驱虫斑鸠菊。通过TCMSP和TCMIP数据库得到主要化合物类型为黄酮类,共有81个。根据成药性和稳定性筛选出甲氧基黄酮类化合物山柰素和异鼠李素。32μmol/L山柰素、32μmol/L异鼠李素和25μmol/L甲氧沙林均能促进斑马鱼黑色素再生。基于斑马鱼胚胎模型,3个化合物均能加速胚胎黑色素生成,且其有效浓度下斑马鱼幼鱼的存活率在90%以上。RT-PCR结果显示山柰素与异鼠李素上调黑色素生成关键基因黑素皮质素1受体(MCIR)和小眼畸形相关转录因子(MITF)mRNA水平。分子对接结果显示山柰素、异鼠李素与底物酶结合分数高于甲氧沙林。结论临床抗白癜风中成药组方中活性成分山柰素与异鼠李素促进斑马鱼模型黑色素生成且通过上调MC1R/MITF信号通路作用。
Objective Based on the Chinese herbal property, the pharmacodynamic evaluation and mechanism discussion of active components were carried out through screening the active components of Chinese patent medicine in the clinical medical insurance catalog. Methods The most frequently used main herbs were screened through the collection of anti-vitiligo Chinese patent medicine prescriptions, drug properties and material basis. The main compound types were acquired through TCMSP and TCMIP databases. The drug properties were analyzed by admetSAR method to obtain key compounds. The pharmacodynamics were observed by measuring the morphology and melanin content of adult zebrafish and larvae. The safety evaluation was indicated by the survival rate of larvae. RT-PCR was used to reveal the mechanism of the compounds at the transcriptional level. The binding ability of compounds to protein crystal structure was predicted by molecular docking. Results The most frequently used main herbs were Carthamus tinctorius, Lithospermum erythrorhizon, Tribulus terrestris, Gentianae Radix et Rhizoma., Psoraleae Fructus, and Vernonia anthelmintica. The main compound types through TCMSP and TCMIP database were flavonoids with a total of 81. Based on the druggability and stability, the methoxyflavones kaempferide and isorhamnetin were screened out. Kaempferide(32 μmol/L), isorhamnetin(32 μmol/L) and me t hoxsa le n(25 μmol/L) c oul d promote t he re ge ne ra ti on of me lani n i n ze bra fi sh. Ba se d on t he ze bra fish embryo model, kaempferide, isorhamnetin and methoxsalen all could accelerate melanogenesis in larvas, and the survival rates of larvas were more than 90% under effective concentration. RT-PCR showed that kaempferide and isorhamnetin upregulated the mRNA levels of MC1 R and MITF genes related to melanogenesis. The results of molecular docking between the structures of proteins(MITF, TYR, TYRP1) and kaempferide, isorhamnetin, methoxsalen showed that the binding score of kaempferide or isorhamnetin was higher than that of me
作者
于兰
唐辉
陈韩英
王晓琴
张波
YU Lan;TANG Hui;CHEN Han-ying;WANG Xiao-qin;ZHANG Bo(Key Laboratory of Xinjiang Phytomedicine Resources and Utilization,Ministry of Education,Shihezi University,Shihezi 832002,China;School of Pharmacy,Shihezi University,Shihezi 832002,China)
出处
《中草药》
CAS
CSCD
北大核心
2020年第23期6023-6034,共12页
Chinese Traditional and Herbal Drugs
基金
国家自然科学基金资助项目(U1603122)
兵团科技创新领域中青年领军人才资助项目(2018CB019)
2019年二批次兵团英才项目。
