基于整合药理学策略分析小儿扶脾颗粒对功能性消化不良的精准应用
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摘要
通过整合药理学研究策略,预测小儿扶脾颗粒治疗功能性消化不良(FD)的作用靶标和信号通路,探讨其可能的作用机制。通过DISEASES和Uni Prot数据库收集疾病靶标信息,利用整合药理学平台预测中药化学成分、靶标、蛋白基因本体(GO)功能、京都基因与基因组百科全书(KEGG)通路,构建小儿扶脾颗粒治疗FD的候选靶标关键网络和"中药-化学成分-核心靶标-关键通路"网络。预测潜在作用靶标2 882个,候选靶标通路信息96条,预测得到β-1,4-半乳糖基转移酶(β-1,4-Gal T)亚型(B4GALT4,B4GALT2,B4GALT1),磷酸化蛋白激酶C亚性D型(PRKCD),腺苷酸环化酶2(ADCY2)等关键靶标。富集得到神经系统、内分泌系统、甲状腺激素信号通路、长时程抑制作用等与FD相关的通路,预测小儿扶脾颗粒治疗FD是通过调节胃肠激素、抗抑郁、调节神经和内分泌系统来发挥疗效的,为该药物的临床精准应用及定位提供了依据,同时有助于阐明该药物的作用机制。
Integrated pharmacological approach was used to predict the target genes and signal pathways of Xiaoer Fupi granules in the treatment of functional dyspepsia( FD),and the possible mechanism was discussed.The disease target information was collected by the DISEASES and Uni Prot databases,integrated pharmacological platform of traditional Chinese medicine( TCM-IP) was used to predict chemical composition,target,protein gene ontology( GO) function and Kyoto encyclopedia of genes and genomes( KEGG) pathway,and the networks of candidate target and TCMs-chemical components-core targets-key pathways were constructed. A total of 2 882 potential targets and 96 candidate target pathways were predicted,and β-1,4-galactosyltransferase( β-1,4-Gal T) subtypes( B4 GALT4,B4 GALT2,B4 GALT1) and phosphorylated protein kinase C subtype D( PRKCD),adenylate cyclase 2( ADCY2) and other targets were predicted. Some pathways were enriched,such as nervous system,endocrine system,thyroid hormone signaling pathway,long-term depression and other pathways related to FD. It was predicted that Xiaoer Fupi granules for treating FD by regulating gastrointestinal hormones,antidepression,and regulating nerves and endocrine system. This study provides a basis for the precise clinical application and positioning of Xiaoer Fupi granules,and helps to clarify the mechanism of this drug.
Integrated pharmacological approach was used to predict the target genes and signal pathways of Xiaoer Fupi granules in the treatment of functional dyspepsia( FD),and the possible mechanism was discussed.The disease target information was collected by the DISEASES and Uni Prot databases,integrated pharmacological platform of traditional Chinese medicine( TCM-IP) was used to predict chemical composition,target,protein gene ontology( GO) function and Kyoto encyclopedia of genes and genomes( KEGG) pathway,and the networks of candidate target and TCMs-chemical components-core targets-key pathways were constructed. A total of 2 882 potential targets and 96 candidate target pathways were predicted,and β-1,4-galactosyltransferase( β-1,4-Gal T) subtypes( B4 GALT4,B4 GALT2,B4 GALT1) and phosphorylated protein kinase C subtype D( PRKCD),adenylate cyclase 2( ADCY2) and other targets were predicted. Some pathways were enriched,such as nervous system,endocrine system,thyroid hormone signaling pathway,long-term depression and other pathways related to FD. It was predicted that Xiaoer Fupi granules for treating FD by regulating gastrointestinal hormones,antidepression,and regulating nerves and endocrine system. This study provides a basis for the precise clinical application and positioning of Xiaoer Fupi granules,and helps to clarify the mechanism of this drug.
引文
[1]许海玉,侯文彬,李珂,等.基于整合药理学的中药质量标志物发现与应用[J].中国实验方剂学杂志,2019,25(6):1-8.
[2]章轶立,魏戌,谢雁鸣,等.基于整合药理学策略探究补肾活血法治疗骨质疏松症作用机制-以补骨脂-三七药对为例[J].中国实验方剂学杂志,2018,24(21):163-169.
[3]李朝平,黄建良.小儿扶脾颗粒治疗小儿厌食症疗效观察[J].实用医药杂志,2015,32(7):627-628.
[4]袁杰,胡以信.小儿扶脾颗粒治疗小儿畏食症的疗效观察[J].临床医药实践,2013,22(2):93-94.
[5]龙红萍,李欣,王婷婷,等.基于UPLC-LTQ-OrbitrapMS的小儿扶脾颗粒的化学成分研究[J].中草药,2018,49(23):5522-5531.
[6]管志美,彭艳梅,龚年春,等.小儿扶脾颗粒指纹图谱研究[J].湖南中医杂志,2018,34(11):148-151.
[7]赵昕,何彦瑶.一测多评法同时测定小儿扶脾颗粒中党参炔苷、柚皮芸香苷、橙皮苷、白术内酯Ⅲ和白术内酯Ⅰ[J].中国药师,2018,21(11):2045-2048.
[8]黄晓燕,胡亮,丁野,等.小儿扶脾颗粒的质量标准研究[J].海峡药学,2018,30(10):51-54.
[9]张雯,唐仕欢,张毅,等.基于整合药理学的越鞠丸“异病同治”研究[J].中国中药杂志,2018,43(7):1352-1359.
[10]Shatkay H,Brady S,Wong A. Text as data:using textbased features for proteins representation and for computational prediction of their characteristics[J].Methods,2015,74:54-64.
[11]张声生,赵鲁卿.功能性消化不良中医诊疗专家共识意见(2017)[J].中华中医药杂志,2017,32(6):2595-2598.
[12]田子钰,刘素香,陈常青.中药治疗小儿功能性消化不良的研究进展[J].中草药,2017,48(4):803-807.
[13]张栎婧,战丽彬.基于整合药理学平台探究参苓白术散治疗2型糖尿病的物质基础和作用机制[J].中国实验方剂学杂志,2018,24(21):157-162.
[14]田亚欣,王凤云,张娇,等.功能性消化不良的常用方剂及药对规律总结[J].中国实验方剂学杂志,2016,22(21):182-185.
[15]倪静.不同运动模型诱发大鼠应激性胃溃疡的实验研究及党参的防治作用[D].西安:陕西师范大学,2007.
[16]郭军鹏,孟超,刘宏岩.补气中药对小鼠胃肠动力和激素水平的影响[J].中国老年学杂志,2015,35(11):2920-2921.
[17]孟萍,尹建康,高晓静,等.白术对慢传输型便秘大鼠结肠组织Cajal间质细胞的影响[J].中医研究,2012,25(9):58-60.
[18]李淑芬,李希.β-1,4半乳糖基转移酶的生物学功能研究进展[J].生命的化学,2016,36(5):589-595.
[19]Vanhooren V,Vandenbroucke R E,Dewaele S,et al.Mice overexpressingβ-1,4-galactosyltransferaseⅠare resistant to TNF-induced inflammation and DSS-induced colitis[J]. PLo S One,2013,8(12):e79883.
[20]谢正,李恒芬,刘纪猛.抑郁模型大鼠中枢腺苷酸环化酶、蛋白激酶C的变化及抗抑郁药物的影响[J].中国神经精神疾病杂志,2010,36(4):225-228.
[21]Mawe G M,Coates M D,Moses P L. Review article:intestinal serotonin signalling in irritable bowel syndrome[J]. Aliment Pharmacol Ther,2006,23(8):1067-1076.
[22]Witte A B,D'Amato M,Poulsen S S,et al. Duodenal epithelial transport in functional dyspepsia:role of serotonin[J]. World J Gastrointest Pathophysiol,2013,4(2):28-36.
[23]Clark A,Mach N. Exercise-induced stress behavior,gutmicrobiota-brain axis and diet:a systematic review for athletes[J]. J Int Soc Sports Nutr,2016,13:43.
[24]Sam A H,Troke R C,TAN T M,et al. The role of the gut/brain axis in modulating food intake[J].Neuropharmacology,2012,63(1):46-56.
[25]Talley N J. Functional dyspepsia:new insights into pathogenesis and therapy[J]. Korean J Intern Med,2016,31(3):444-456.
[26]LIU J,LI F,TANG X D,et al. Xiangsha Liujunzi decoction alleviates the symptoms of functional dyspepsia by regulating brain-gut axis and production of neuropeptides[J]. BMC Complement Altern Med,2015,doi:10. 1186/s12906-015-0913-z.
[27]梁乾坤.基于脑肠轴探讨功能性消化不良大鼠胃肠动力及脑肠肽水平[D].兰州:兰州大学,2016.
[28]朱金照,许其增,王雯,等.中药白术对肝硬化大鼠肠动力及胃肠激素的影响[J].第二军医大学学报,2005,26(11):1307-1308.
[29]Nakada K,Matsuhashi N,Joh T,et al. The influence of depression and anxiety status on the therapeutic efficacy of PPI on the gerd and FD symptoms. New insights by the cross-lagged effects model[J]. Gastroenterology,2017,152(5):S467-S468.
[2]章轶立,魏戌,谢雁鸣,等.基于整合药理学策略探究补肾活血法治疗骨质疏松症作用机制-以补骨脂-三七药对为例[J].中国实验方剂学杂志,2018,24(21):163-169.
[3]李朝平,黄建良.小儿扶脾颗粒治疗小儿厌食症疗效观察[J].实用医药杂志,2015,32(7):627-628.
[4]袁杰,胡以信.小儿扶脾颗粒治疗小儿畏食症的疗效观察[J].临床医药实践,2013,22(2):93-94.
[5]龙红萍,李欣,王婷婷,等.基于UPLC-LTQ-OrbitrapMS的小儿扶脾颗粒的化学成分研究[J].中草药,2018,49(23):5522-5531.
[6]管志美,彭艳梅,龚年春,等.小儿扶脾颗粒指纹图谱研究[J].湖南中医杂志,2018,34(11):148-151.
[7]赵昕,何彦瑶.一测多评法同时测定小儿扶脾颗粒中党参炔苷、柚皮芸香苷、橙皮苷、白术内酯Ⅲ和白术内酯Ⅰ[J].中国药师,2018,21(11):2045-2048.
[8]黄晓燕,胡亮,丁野,等.小儿扶脾颗粒的质量标准研究[J].海峡药学,2018,30(10):51-54.
[9]张雯,唐仕欢,张毅,等.基于整合药理学的越鞠丸“异病同治”研究[J].中国中药杂志,2018,43(7):1352-1359.
[10]Shatkay H,Brady S,Wong A. Text as data:using textbased features for proteins representation and for computational prediction of their characteristics[J].Methods,2015,74:54-64.
[11]张声生,赵鲁卿.功能性消化不良中医诊疗专家共识意见(2017)[J].中华中医药杂志,2017,32(6):2595-2598.
[12]田子钰,刘素香,陈常青.中药治疗小儿功能性消化不良的研究进展[J].中草药,2017,48(4):803-807.
[13]张栎婧,战丽彬.基于整合药理学平台探究参苓白术散治疗2型糖尿病的物质基础和作用机制[J].中国实验方剂学杂志,2018,24(21):157-162.
[14]田亚欣,王凤云,张娇,等.功能性消化不良的常用方剂及药对规律总结[J].中国实验方剂学杂志,2016,22(21):182-185.
[15]倪静.不同运动模型诱发大鼠应激性胃溃疡的实验研究及党参的防治作用[D].西安:陕西师范大学,2007.
[16]郭军鹏,孟超,刘宏岩.补气中药对小鼠胃肠动力和激素水平的影响[J].中国老年学杂志,2015,35(11):2920-2921.
[17]孟萍,尹建康,高晓静,等.白术对慢传输型便秘大鼠结肠组织Cajal间质细胞的影响[J].中医研究,2012,25(9):58-60.
[18]李淑芬,李希.β-1,4半乳糖基转移酶的生物学功能研究进展[J].生命的化学,2016,36(5):589-595.
[19]Vanhooren V,Vandenbroucke R E,Dewaele S,et al.Mice overexpressingβ-1,4-galactosyltransferaseⅠare resistant to TNF-induced inflammation and DSS-induced colitis[J]. PLo S One,2013,8(12):e79883.
[20]谢正,李恒芬,刘纪猛.抑郁模型大鼠中枢腺苷酸环化酶、蛋白激酶C的变化及抗抑郁药物的影响[J].中国神经精神疾病杂志,2010,36(4):225-228.
[21]Mawe G M,Coates M D,Moses P L. Review article:intestinal serotonin signalling in irritable bowel syndrome[J]. Aliment Pharmacol Ther,2006,23(8):1067-1076.
[22]Witte A B,D'Amato M,Poulsen S S,et al. Duodenal epithelial transport in functional dyspepsia:role of serotonin[J]. World J Gastrointest Pathophysiol,2013,4(2):28-36.
[23]Clark A,Mach N. Exercise-induced stress behavior,gutmicrobiota-brain axis and diet:a systematic review for athletes[J]. J Int Soc Sports Nutr,2016,13:43.
[24]Sam A H,Troke R C,TAN T M,et al. The role of the gut/brain axis in modulating food intake[J].Neuropharmacology,2012,63(1):46-56.
[25]Talley N J. Functional dyspepsia:new insights into pathogenesis and therapy[J]. Korean J Intern Med,2016,31(3):444-456.
[26]LIU J,LI F,TANG X D,et al. Xiangsha Liujunzi decoction alleviates the symptoms of functional dyspepsia by regulating brain-gut axis and production of neuropeptides[J]. BMC Complement Altern Med,2015,doi:10. 1186/s12906-015-0913-z.
[27]梁乾坤.基于脑肠轴探讨功能性消化不良大鼠胃肠动力及脑肠肽水平[D].兰州:兰州大学,2016.
[28]朱金照,许其增,王雯,等.中药白术对肝硬化大鼠肠动力及胃肠激素的影响[J].第二军医大学学报,2005,26(11):1307-1308.
[29]Nakada K,Matsuhashi N,Joh T,et al. The influence of depression and anxiety status on the therapeutic efficacy of PPI on the gerd and FD symptoms. New insights by the cross-lagged effects model[J]. Gastroenterology,2017,152(5):S467-S468.