降尿酸中药药效物质筛选方法学研究进展
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摘要
体内血清尿酸浓度长期过高时,可诱发痛风并引起一系列代谢性疾病。近20年来,由于生活水平的不断提高及饮食结构的改变,高尿酸血症及痛风的发病率不断增高。降低血清尿酸水平是高尿酸血症与痛风防治的首要方法,但目前临床应用的降尿酸西药均具有较严重的毒副作用。降尿酸中草药在长期的使用过程中安全有效,随着现代科学技术的迅速发展,应用及开发不同筛选方法从这些中草药中寻找高效、安全的药效物质已成为高尿酸血症及痛风防治药物研究的热点。本文对降尿酸中草药提取物、提取物部位及活性单体成分等药效物质筛选方法进行了综述,发现降尿酸药效物质筛选方法主要有体内法和体外法,体内法主要应用于筛选药材提取物降尿酸活性与机制,体外方法多用于单体活性成分筛选且以黄嘌呤氧化酶(XOD)抑制剂筛选为主,分子对接联用同源建模及亲和超滤联用液质联用(AUF-LC-MS)技术已成为促尿酸排泄成分及XOD抑制剂筛选的新趋势,而体外细胞模型将为促尿酸排泄药中草药药效物质筛选开辟新途径。综述为高尿酸血症及痛风的中草药药药效物质筛选及药物开发提供了一定的参考依据。
Gout is caused by the nucleation and growth of monosodium rate crystals in tissues and around joints,which is followed by long-standing hyperuricemia and serum urate of above the saturation threshold. It could cause a series of complications,such as cardiovascular,hypertension,and renal complications. Over the past two decades,the incidences of hyperuricemia and gout have been increasing due to the continuous improvement of living standards and the changes in dietary structure. The prime and most important therapy for hyperuricemia and gout is to reduce serum uric acid levels,but the western medicine for reducing uric acid in clinical application has serious toxic and side effects. With the rapid development of modern science and technology,the application and development of different screening methods for effective ingredients with a low toxicity and side effects from Chinese herbal medicines for reducing serum uric acid levels has attracted much attention in the research and development of drugs for the prevention and treatment of hyperuricemia and gout. In this study,the screening methods for extracts,fractions,active monomer components and other effective substances were reviewed and analyzed. According to the findings,the screening methods had a considerable progress both in vivo and in vitro. The results showed that the in vivo methods were mainly applied for studying the urate lowing effect and mechanisms of herbal extracts,while the studies for xanthine oxidase( XOD) inhibitors mainly depended on the in vitro methods. Molecular docking homology modeling and liquid chromatography-mass spectrometry have become a new trend for screening effective substances with XOD inhibitory activities and uric acid excretion activities,while cell model will open up a new way for screening effective substances for uric acid excretion. The review provides certain reference for effective components screening of hyperuricemia and gout.
Gout is caused by the nucleation and growth of monosodium rate crystals in tissues and around joints,which is followed by long-standing hyperuricemia and serum urate of above the saturation threshold. It could cause a series of complications,such as cardiovascular,hypertension,and renal complications. Over the past two decades,the incidences of hyperuricemia and gout have been increasing due to the continuous improvement of living standards and the changes in dietary structure. The prime and most important therapy for hyperuricemia and gout is to reduce serum uric acid levels,but the western medicine for reducing uric acid in clinical application has serious toxic and side effects. With the rapid development of modern science and technology,the application and development of different screening methods for effective ingredients with a low toxicity and side effects from Chinese herbal medicines for reducing serum uric acid levels has attracted much attention in the research and development of drugs for the prevention and treatment of hyperuricemia and gout. In this study,the screening methods for extracts,fractions,active monomer components and other effective substances were reviewed and analyzed. According to the findings,the screening methods had a considerable progress both in vivo and in vitro. The results showed that the in vivo methods were mainly applied for studying the urate lowing effect and mechanisms of herbal extracts,while the studies for xanthine oxidase( XOD) inhibitors mainly depended on the in vitro methods. Molecular docking homology modeling and liquid chromatography-mass spectrometry have become a new trend for screening effective substances with XOD inhibitory activities and uric acid excretion activities,while cell model will open up a new way for screening effective substances for uric acid excretion. The review provides certain reference for effective components screening of hyperuricemia and gout.
引文
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[3] Sorensen L B. Role of the intestinal tract in the elimination of uric acid[J]. Arthritis Rheum,2010,8(4):694-706.
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[7]张晨辉,谢雄雄,曾金祥,等.药用植物中黄嘌呤氧化酶抑制剂的研究进展[J].中成药,2018,40(10):2255-2260.
[8]张雪,俸婷婷,黄俊飞,等.降尿酸药物筛选方法学研究进展[J].亚太传统医药,2015,11(6):48-49,50.
[9]朱玲玲,陈宝军.七叶莲总皂苷体内外降尿酸作用及对高尿酸血症小鼠尿酸转运蛋白的影响[J].新中医,2018,50(5):41-44.
[10]曾金祥,许兵兵,李敏,等.藏药短管兔耳草醇提物降低急性高尿酸血症小鼠血尿酸水平及机制研究[J].中国新药杂志,2015,24(21):2489-2493.
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[12] Chien S C,YANG C W,Tseng Y H,et al. Lonicera hypoglauca inhibits xanthine oxidase and reduces serum uric acid in mice[J]. Planta Med,2009,75(4):302-306.
[13]林华,袁丽仙,高丽辉,等.芒果苷对高尿酸血症小鼠血尿酸及嘌呤代谢相关酶表达的影响[J].中国实验方剂学杂志,2019,25(2):55-59.
[14]施琬,李钟,顾祖莲,等.虎杖-桂枝药对配伍对大鼠慢性高尿酸血症和肾、肠尿酸转运体表达的影响[J].中国实验方剂学杂志,2016,22(2):107-112.
[15]任丽,欧水平,陈灵,等.虎杖提取物及其有效部位的大鼠抗痛风性关节炎试验[J].中国实验方剂学杂志,2016,22(19):111-115.
[16]熊雯雯,张红阳,文乐,等.短穗兔耳草提取物对高尿酸血症小鼠黄嘌呤氧化酶和肾脏尿酸转运体的影响研究[J].中国新药杂志,2018,27(13):1538-1543.
[17]朱明敏,师晓毅,孙维峰.复方土茯苓颗粒对HUA大鼠XO活性及其mRNA的抑制作用[J].中国实验方剂学杂志,2016,22(5):127-130.
[18] LIU Y W,SUN W F,ZHANG X X,et al. Compound tufuling granules regulate glucose transporter 9expression in kidney to influence serum uric acid level in hyperuricemia mice[J]. Chin J Integr Med,2015,21(11):823-829.
[19]周盼.基于肠道转运体研究大黄酸干预尿酸代谢的分子机制[D].泉州:华侨大学,2017.
[20]王雨,林志健,边猛,等.维药菊苣提取物对高尿酸血症状态下肠道屏障的影响[J].中华中医药杂志,2018,33(5):1718-1723.
[21]徐象威,牛艳芬,高丽辉,等.基于肠道尿酸转运体ABCG2的芒果苷降尿酸作用机制分析[J].中国实验方剂学杂志,2018,24(17):145-149.
[22] Umamaheswari M,Asokkumar K,Sivashanmugam A T,et al. In vitro xanthine oxidase inhibitory activity of the fractions of Erythrina stricta Roxb.[J]. J Ethnopharmacol,2009,124(3):646-648.
[23]杨道茂,欧阳明安. 9种中药提取物黄嘌呤氧化酶抑制活性研究[J].天然产物研究与开发,2014,26(4):597-600,578.
[24] ZHU J X,WANG Y,KONG L D,et al. Effects of Biota orientalis extract and its flavonoid constituents,quercetin and rutin on serum uric acid levels in oxonate-induced mice and xanthine dehydrogenase and xanthine oxidase activities in mouse liver[J]. J Ethnopharmacol,2004,93(1):133-140.
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