以网络药理学技术挖掘、发现“黄连-厚朴”药对中活性组分
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摘要
基于网络药理学技术,挖掘、发现"黄连-厚朴"药对中防治疾病的活性组分,并对潜在的靶点与机制进行整合与分析。采用TCMSP数据库筛选活性成分、利用TTD和Drug Bank数据库配合文献挖掘潜在靶点进行预测、利用通路注释技术对黄连和厚朴活性组分及潜在靶点进行通路的富集与分析。通过该技术的应用共筛选出"黄连-厚朴"药对具有潜在靶点活性成分29个,其中主要包括氢化小檗碱、小檗碱、黄连碱、巴马汀等在内的12个生物碱类组分;厚朴酚、和厚朴酚以及和厚朴新酚在内的3个木脂素类组分;α-桉叶醇,β-桉叶醇,桉油等在内的6个挥发油类组分以及含有槲皮素和新橙皮苷的黄酮类组分。另外,筛选出与之相对应的作用靶点199个,主要包含PTGS2,PTGS1,NCOA2,Hsp90AB1等;共涉及疾病信号通路72条,如前列腺癌、膀胱癌、胰腺癌等在内的8条肿瘤类通路;催产素信号通路、胰岛素信号通路、甲状腺激素信号通路等在内的9条内分泌类通路以及炎症等相关通路。该研究初步挖掘发现了"黄连-厚朴"药对的主要活性组分及潜在靶点,为组分中药制剂研究提供了物料来源。
To mine and discover the active components of " Coptidis Rhizome-Magnoliae Officinalis Cortex( C&M) " based on the network pharmacology,integrate and analyze the potential targets and mechanisms. The TCMSP database was used to screen active ingredients. TTD and Drug Bank databases were used to predict the potential targets by referring to relevant literature,and the pathway annotation technology was used to enrich and analyze the active ingredients and potential targets of " C&M". A total of 29 potential target active ingredients were screened from " C&M",including 12 alkaloids components such as( R)-canadine,berberine,coptisine,and palmatine; 3 lignans consisting of magnolol,honokiol and obovatol; 6 volatile oils consisting of α-eudesmol,β-eudesmol,eucalyptol and so on,and flavonoids including quercetin and neohesperidin. Corresponding 199 predicted targets were screened out,mainly including PTGS2,PTGS1,NCOA2,Hsp90 AB1,and so on. 72 signaling pathways were involved,8 of which were related to cancer,such as prostate cancer,bladder cancer,and pancreatic cancer; 9 of which were related to endocrine,including oxytocin signaling pathway,insulin signaling pathway,thyroid hormone signaling pathway and so on,as well as inflammation-related pathway. This study has preliminarily mined and discovered the main active components and potential targets of " C&M",providing material source for the study on the preparation of structural components of traditional Chinese medicine.
To mine and discover the active components of " Coptidis Rhizome-Magnoliae Officinalis Cortex( C&M) " based on the network pharmacology,integrate and analyze the potential targets and mechanisms. The TCMSP database was used to screen active ingredients. TTD and Drug Bank databases were used to predict the potential targets by referring to relevant literature,and the pathway annotation technology was used to enrich and analyze the active ingredients and potential targets of " C&M". A total of 29 potential target active ingredients were screened from " C&M",including 12 alkaloids components such as( R)-canadine,berberine,coptisine,and palmatine; 3 lignans consisting of magnolol,honokiol and obovatol; 6 volatile oils consisting of α-eudesmol,β-eudesmol,eucalyptol and so on,and flavonoids including quercetin and neohesperidin. Corresponding 199 predicted targets were screened out,mainly including PTGS2,PTGS1,NCOA2,Hsp90 AB1,and so on. 72 signaling pathways were involved,8 of which were related to cancer,such as prostate cancer,bladder cancer,and pancreatic cancer; 9 of which were related to endocrine,including oxytocin signaling pathway,insulin signaling pathway,thyroid hormone signaling pathway and so on,as well as inflammation-related pathway. This study has preliminarily mined and discovered the main active components and potential targets of " C&M",providing material source for the study on the preparation of structural components of traditional Chinese medicine.
引文
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[21] Suh K S,Chon S,Jung W W,et al. Magnolol protects pancreaticb-cells against methylglyoxal-induced cellular dysfunction[J].Chem Biol Interact,2017,227:101.
[22]龚敏敏,董慧.黄连及其复方治疗抑郁症的临床应用和现代研究进展[J].中国医院药学杂志,2018(13):2.
[23]黄世敬,陈宇霞,张颖.厚朴治疗抑郁症及抗抑郁机理探讨[J].世界中西医结合杂志,2015,10(7):1023.
[24] Li M,Zhang F,Wang X,et al. Magnolol inhibits growth of gall-bladder cancer cells through the p53 pathway[J]. Cancer Sci,2015,106(10):1341.
[25] Zhang F H,Ren H Y,Shen J X,et al. Magnolol suppresses theproliferation and invasion of cholangiocarcinoma cells via inhibi-ting the NF-kB signaling pathway[J]. Biomed Pharmacother,2017,94:474.
[26] Airi F,Tetsuya O,Koji W,et al. Identification of anti-inflam-matory constituents in Phellodendri Cortex and Coptidis Rhizomaby monitoring the suppression of nitric oxide production[J]. JNat Med,2017,71:745.
[27] Ranaware A M,Banik K,Deshpande V,et al. Magnolol:a neol-ignan from the Magnolia family for the prevention and treatment ofcancer[J]. Int J Mol Sci,2018,19:2362.
[2]王萍萍,刘保秀,杨桃,等.和厚朴酚对急慢性应激小鼠的抗抑郁作用及机制研究[J].中国药学杂志,2017,52(24):2161.
[3]周霞,彭耀宗,黄涛,等.黄连生物碱对体外培养的小鼠腹腔巨噬细胞的影响[J].中国中药杂志,2015,40(23):4660.
[4] Wan N,Tan H Y,Li L,et al. Berberine and Coptidis Rhizomaas potential anticancer agents:recent updates and future perspec-tives[J]. J Ethnopharmacol,2015,176:35.
[5]张淑洁,钟凌云.厚朴化学成分及其现代药理研究进展[J].中药材,2013,36(5):83.
[6]杨楠,封亮,贾晓斌.组分结构理论指导下创新中药制剂的拓展与外延[J].中国中药杂志,2016,41(1):144.
[7]张青,李琰,陈磊.黄连素对2型糖尿病及其并发症的治疗作用及相关机制研究进展[J].中国中药杂志,2015,40(9):1660.
[8]张志琴,朱双雪.槲皮素的药理活性与临床应用研究进展[J].药学研究,2013,32(7):400.
[9]陈红英,李学刚,叶小利,等.黄连中阿魏酸对小檗碱在HepG2细胞中降糖活性的影响[J].食品工业科技,2015,36(1):361.
[10]郭晶.基于抗氧活性的厚朴有效组分的研究[D].上海:华东理工大学,2012.
[11]黄杰,李莎,伍春莲.厚朴酚抗肿瘤机制的研究进展[J].天然产物研究与开发,2016,28(4):637.
[12] Lee H,Lee S J,Bae G U,et al. Canadine from Corydalisturtschaninovii stimulates myoblast differentiation and protectsagainst myotube atrophy[J]. Int J Mol Sci,2017,18:2748.
[13] Guo S,Jiang K F,Wu H C,et al. Magnoflorine ameliorates li-popolysaccharide-induced acute lung injury via suppressing NF-κB and MAPK activation[J]. Front Pharmacol,2018,9:982.
[14]杨燕,李晓东,季枚,等. COX-2/PGE2与肿瘤相关免疫细胞[J].临床检验杂志,2016,34(4):284.
[15]杨帆. NCOA2激活Wnt信号通路导致胃癌发生和转移的机制[D].福州:福建医科大学,2017.
[16]王明慧,冯林,李萍,等. Hsp90AB1在非小细胞肺癌中高表达并且与肺腺癌患者不良预后相关[J].中国肺癌杂志,2016,19(2):64.
[17] Cheng Y C,Hueng D Y,Huang H Y,et al. Magnolol and hono-kiol exert a synergistic anti-tumor effect through autophagy andapoptosis in human glioblastomas[J]. Oncotarget,2016,7(20):29116.
[18]胡诚毅,莫志贤.黄连素的药理作用及机制研究进展[J].中国实验方剂学杂志,2017,23(20):213.
[19] Geng F H,Li G H,Zhang X,et al. Berberine improves mesen-teric artery insulin sensitivity through up-regulating insulin re-ceptor-mediated signalling in diabetic rats[J]. Br J Pharmacol,2016,173:1569.
[20]李骋,何金枝,周学东,等.黄连素调控胰岛素抵抗相关2型糖尿病的研究进展[J].中国中药杂志,2017,42(12):2254.
[21] Suh K S,Chon S,Jung W W,et al. Magnolol protects pancreaticb-cells against methylglyoxal-induced cellular dysfunction[J].Chem Biol Interact,2017,227:101.
[22]龚敏敏,董慧.黄连及其复方治疗抑郁症的临床应用和现代研究进展[J].中国医院药学杂志,2018(13):2.
[23]黄世敬,陈宇霞,张颖.厚朴治疗抑郁症及抗抑郁机理探讨[J].世界中西医结合杂志,2015,10(7):1023.
[24] Li M,Zhang F,Wang X,et al. Magnolol inhibits growth of gall-bladder cancer cells through the p53 pathway[J]. Cancer Sci,2015,106(10):1341.
[25] Zhang F H,Ren H Y,Shen J X,et al. Magnolol suppresses theproliferation and invasion of cholangiocarcinoma cells via inhibi-ting the NF-kB signaling pathway[J]. Biomed Pharmacother,2017,94:474.
[26] Airi F,Tetsuya O,Koji W,et al. Identification of anti-inflam-matory constituents in Phellodendri Cortex and Coptidis Rhizomaby monitoring the suppression of nitric oxide production[J]. JNat Med,2017,71:745.
[27] Ranaware A M,Banik K,Deshpande V,et al. Magnolol:a neol-ignan from the Magnolia family for the prevention and treatment ofcancer[J]. Int J Mol Sci,2018,19:2362.