交泰丸对糖尿病、抑郁和失眠症“异病同治”的网络药理学机制分析
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摘要
目的:从分子水平探讨交泰丸对糖尿病、抑郁和失眠症"异病同治"的作用机制。方法:运用网络药理学技术,通过数据库检索,以交泰丸的有效成分、作用靶点、治疗疾病种类为网络节点,使用Cytoscape构建相互作用网络,MAS进行生物信息学分析。结果:交泰丸中的20个化合物可作用于92个靶点发挥对3种疾病的治疗作用,HTR2A和HTR2C为交泰丸治疗糖尿病、抑郁和失眠的共同靶点。交泰丸治疗糖尿病的靶点主要富集在抗细胞凋亡生物过程和Toll样受体信号通路,治疗抑郁的靶点主要富集在信号转导生物过程和神经活性配体-受体相互作用通路,治疗失眠的靶点主要富集在5-羟色胺受体,磷脂酶C激活途径生物过程和神经活性配体-受体相互作用通路。结论:交泰丸具有多成分、多靶点、多途径的特点,该研究为交泰丸"异病同治"的作用机制提供参考。
This study was aimed to discuss mechanism of Jiao-Tai-Wan(JTW) in treating diabetes mellitus(DM),depressive disorder and insomnia with same method at a molecular level. The method of network pharmacology was used.Databases were retrieved and effective components of JTW, effect targets and disease types were used as network nodes to construct the interaction network by Cytoscape. MAS was applied to conduct bioinformatic analysis. The results showed that 20 compounds in JTW could act on 92 effect targets to exert the therapeutic action for three diseases.HTR2 A and HTR2 C are common effect targets for treating DM, depressive disorder and insomnia. Effect targets of JTW in DM treatment mainly enriched in anti-apoptosis biological process and toll-like receptor signaling pathway. Effect targets of JTW in treating depressive disorder mainly enriched in signal transduction biological process and neuroactive ligand-receptor interaction pathway. Effect targets of JTW in insomnia treatment mainly enriched in serotonin receptor,phospholipase C activating pathway biological process and neuroactive ligand-receptor interaction pathway. It was concluded that JTW showed characteristics of multi-component, multi-target and multi-pathway. This study can be used as a reference for the mechanism of"treating different diseases with same method"of JTW.
This study was aimed to discuss mechanism of Jiao-Tai-Wan(JTW) in treating diabetes mellitus(DM),depressive disorder and insomnia with same method at a molecular level. The method of network pharmacology was used.Databases were retrieved and effective components of JTW, effect targets and disease types were used as network nodes to construct the interaction network by Cytoscape. MAS was applied to conduct bioinformatic analysis. The results showed that 20 compounds in JTW could act on 92 effect targets to exert the therapeutic action for three diseases.HTR2 A and HTR2 C are common effect targets for treating DM, depressive disorder and insomnia. Effect targets of JTW in DM treatment mainly enriched in anti-apoptosis biological process and toll-like receptor signaling pathway. Effect targets of JTW in treating depressive disorder mainly enriched in signal transduction biological process and neuroactive ligand-receptor interaction pathway. Effect targets of JTW in insomnia treatment mainly enriched in serotonin receptor,phospholipase C activating pathway biological process and neuroactive ligand-receptor interaction pathway. It was concluded that JTW showed characteristics of multi-component, multi-target and multi-pathway. This study can be used as a reference for the mechanism of"treating different diseases with same method"of JTW.
引文
1蔡菲菲,李晓燕,董姝,等.基于网络药理学的茵陈蒿汤“异病同治”研究.世界科学技术:中医药现代化,2016,18(9):1507-1514.
2 赵振宇,沈霞,胡本祥,等.基于系统药理学研究柴胡治疗情志疾病异病同治的机制.中国药学杂志,2016,51(13):1131-1136.
3 高伯正.交泰丸释名.光明中医杂志,1996,(6):6-7.
4 张焕萍.交泰丸加减治疗心肾不交型失眠32例.内蒙古医学杂志,2009,41(S2):61.
5 周志焕,高杉,李琳,等.交泰丸临床及药理研究述要.天津中医药,2014,31(3):190-192.
6 王芳.糖尿病、失眠与精神心理因素的关系及中医的认识.国际中医中药杂志,2009,31(3):256-258.
7 王蓓蕾,洪肖娟,黄家兴,等.针灸治疗糖尿病抑郁的临床研究进展.湖南中医杂志,2016,32(3):182-185.
8 Cappuccio F P,D'Elia L,Strazzullo P,et al.Quantity and quality of sleep and incidence of type 2 diabetes:a systematic review and metaanalysis.Diabetes Care,2010,33(2):414-420.
9 李佳琦,严悦蓉,余叶蓉.睡眠障碍与糖尿病的关系及其对糖代谢的影响研究进展.中国全科医学,2017,20(11):1300-1304.
10 Knol M J,Twisk J W,Beekman A T,et al.Depression as a risk factor for the onset of type 2 diabetes mellitus.A meta-analysis.Diabetologia,2006,49(5):837.
11 高树明,李沛纯,杨帅,等.试从心肾不交论交泰丸临床辨治.天津中医药大学学报,2016,35(2):73-76.
12 张建永,张滨,段灿灿.交泰丸治疗糖尿病的理论基础及应用.世界中医药,2016,11(3):554-557.
13 全世建,王红丹,刘彦凤.交泰丸化学成分及药理作用的研究进展.河南中医学院学报,2007,22(4):83-84.
14 秦娟娟,刘振华,梁艳,等.5-羟色胺及其受体与抑郁症.国际药学研究杂志,2012,39(5):409-413.
15 杨岑,冉明梓,欧阳鹏荣,等.五羟色胺在睡眠-觉醒中作用.现代生物医学进展,2015,15(11):2191-2194.
16 García-Pedraza Já,Ferreira-Santos P,Aparicio R,et al.Blocking 5-HT2 receptor restores cardiovascular disorders in type 1 experimental diabetes.Sci Rep,2016,6:33979.
17 蒋延超,蒋世云,傅凤鸣,等.鸡血藤中黄酮类化合物与环氧合酶-2对接研究.天然产物研究与开发,2015,27(5):809-815.
18 Ga?ecki P P,Talarowska M,Bobińska K,et al.COX-2 gene expression is correlated with cognitive function in recurrent depressive disorder.Psychiatry Res,2014,215(2):488-490.
19 Szerafin T,Erdei N,Fül?p T,et al.Increased cyclooxygenase-2 expres-sion and prostaglandin-mediated dilation in coronary arterioles of patients with diabetes mellitus.Circ Res,2006,99(5):e12-17.
20余运龙,全世建.交泰丸对PCPA大鼠下丘脑5-HT、NE的影响.时珍国医国药,2011,22(11):2803-2804.
21 杨帅,潘晔,宋彦奇,等.交泰丸对抑郁大鼠行为学及脑内单胺类神经递质的影响.中草药,2016,47(23):4218-4223.
22 余运龙,全世建.交泰丸对PCPA失眠大鼠大脑γ-氨基丁酸及受体的影响.时珍国医国药,2010,21(06):1417-1418.
23 张娜.单胺氧化酶抑制剂治疗神经退行性疾病的研究进展.医学理论与实践,2015,28(13):1713-1715+1718.
24 吕妍,徐金娥.PPAR与糖尿病脂代谢的相关性.齐鲁医学杂志,2013,28(3):277-279.
25 胡娜,袁琳,李慧姣,等.交泰丸对db/db小鼠肾脏的保护作用及脂肪组织PPARγ基因表达调节作用的实验研究.中国中医药科技,2017,24(5):567-571.
26 Sun X,Chen R,Yang Z,et al.Taxifolin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of oxidative stress and cell apoptosis.Food Chem Toxicol,2014,63:221-232.
27 Wu Y,Chen Y,Wu Q,et al.Minocycline inhibits PARP-1 expression and decreases apoptosis in diabetic retinopathy.Molecular medicine reports,2015,12(4):4887-4894.
28 Anuradha R,Saraswati M,Kumar K G,et al.Apoptosis of beta cells in diabetes mellitus.DNA and cell biology,2014,33(11):743-748.
29 宋春雨,杜联.论糖尿病及糖尿病并发症与细胞凋亡关系.辽宁中医药大学学报,2015,17(11):71-73.
30 邹欣,刘德亮,陆付耳,等.交泰丸对2型糖尿病大鼠胰腺脂肪沉积和胰岛细胞凋亡的影响.中国中药杂志,2014,39(11):2106-2111.
31 罗旭异,高健生,潘琳.交泰丸对链脲佐菌素性糖尿病大鼠视网膜血管病理改变的作用.中国中医眼科杂志,2007,17(1):27-31.
32 吴珺,鲁一兵,刘超.Toll样受体和糖尿病.国际内分泌代谢杂志,2008,28(2):116-118.
33 吴冕,陈海冰.Toll样受体与2型糖尿病及其并发症的关系及分子机制.医学综述,2013,19(20):3754-3757.
34 徐向青,唐启盛.抑郁症与细胞信号转导研究进展.中国医药导报,2012,9(36):49-50.
35 潘玲珍.蜘蛛香药物依赖性评价的毒理基因组学研究.成都:西南交通大学,2011.
36 陈爱琴,陈晓春,周瑞祥,等.5-HT2受体-磷脂酶C的激活易化大鼠基底外侧杏仁核突触可塑性的研究.神经解剖学杂志,2008,24(5):529-532.
2 赵振宇,沈霞,胡本祥,等.基于系统药理学研究柴胡治疗情志疾病异病同治的机制.中国药学杂志,2016,51(13):1131-1136.
3 高伯正.交泰丸释名.光明中医杂志,1996,(6):6-7.
4 张焕萍.交泰丸加减治疗心肾不交型失眠32例.内蒙古医学杂志,2009,41(S2):61.
5 周志焕,高杉,李琳,等.交泰丸临床及药理研究述要.天津中医药,2014,31(3):190-192.
6 王芳.糖尿病、失眠与精神心理因素的关系及中医的认识.国际中医中药杂志,2009,31(3):256-258.
7 王蓓蕾,洪肖娟,黄家兴,等.针灸治疗糖尿病抑郁的临床研究进展.湖南中医杂志,2016,32(3):182-185.
8 Cappuccio F P,D'Elia L,Strazzullo P,et al.Quantity and quality of sleep and incidence of type 2 diabetes:a systematic review and metaanalysis.Diabetes Care,2010,33(2):414-420.
9 李佳琦,严悦蓉,余叶蓉.睡眠障碍与糖尿病的关系及其对糖代谢的影响研究进展.中国全科医学,2017,20(11):1300-1304.
10 Knol M J,Twisk J W,Beekman A T,et al.Depression as a risk factor for the onset of type 2 diabetes mellitus.A meta-analysis.Diabetologia,2006,49(5):837.
11 高树明,李沛纯,杨帅,等.试从心肾不交论交泰丸临床辨治.天津中医药大学学报,2016,35(2):73-76.
12 张建永,张滨,段灿灿.交泰丸治疗糖尿病的理论基础及应用.世界中医药,2016,11(3):554-557.
13 全世建,王红丹,刘彦凤.交泰丸化学成分及药理作用的研究进展.河南中医学院学报,2007,22(4):83-84.
14 秦娟娟,刘振华,梁艳,等.5-羟色胺及其受体与抑郁症.国际药学研究杂志,2012,39(5):409-413.
15 杨岑,冉明梓,欧阳鹏荣,等.五羟色胺在睡眠-觉醒中作用.现代生物医学进展,2015,15(11):2191-2194.
16 García-Pedraza Já,Ferreira-Santos P,Aparicio R,et al.Blocking 5-HT2 receptor restores cardiovascular disorders in type 1 experimental diabetes.Sci Rep,2016,6:33979.
17 蒋延超,蒋世云,傅凤鸣,等.鸡血藤中黄酮类化合物与环氧合酶-2对接研究.天然产物研究与开发,2015,27(5):809-815.
18 Ga?ecki P P,Talarowska M,Bobińska K,et al.COX-2 gene expression is correlated with cognitive function in recurrent depressive disorder.Psychiatry Res,2014,215(2):488-490.
19 Szerafin T,Erdei N,Fül?p T,et al.Increased cyclooxygenase-2 expres-sion and prostaglandin-mediated dilation in coronary arterioles of patients with diabetes mellitus.Circ Res,2006,99(5):e12-17.
20余运龙,全世建.交泰丸对PCPA大鼠下丘脑5-HT、NE的影响.时珍国医国药,2011,22(11):2803-2804.
21 杨帅,潘晔,宋彦奇,等.交泰丸对抑郁大鼠行为学及脑内单胺类神经递质的影响.中草药,2016,47(23):4218-4223.
22 余运龙,全世建.交泰丸对PCPA失眠大鼠大脑γ-氨基丁酸及受体的影响.时珍国医国药,2010,21(06):1417-1418.
23 张娜.单胺氧化酶抑制剂治疗神经退行性疾病的研究进展.医学理论与实践,2015,28(13):1713-1715+1718.
24 吕妍,徐金娥.PPAR与糖尿病脂代谢的相关性.齐鲁医学杂志,2013,28(3):277-279.
25 胡娜,袁琳,李慧姣,等.交泰丸对db/db小鼠肾脏的保护作用及脂肪组织PPARγ基因表达调节作用的实验研究.中国中医药科技,2017,24(5):567-571.
26 Sun X,Chen R,Yang Z,et al.Taxifolin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of oxidative stress and cell apoptosis.Food Chem Toxicol,2014,63:221-232.
27 Wu Y,Chen Y,Wu Q,et al.Minocycline inhibits PARP-1 expression and decreases apoptosis in diabetic retinopathy.Molecular medicine reports,2015,12(4):4887-4894.
28 Anuradha R,Saraswati M,Kumar K G,et al.Apoptosis of beta cells in diabetes mellitus.DNA and cell biology,2014,33(11):743-748.
29 宋春雨,杜联.论糖尿病及糖尿病并发症与细胞凋亡关系.辽宁中医药大学学报,2015,17(11):71-73.
30 邹欣,刘德亮,陆付耳,等.交泰丸对2型糖尿病大鼠胰腺脂肪沉积和胰岛细胞凋亡的影响.中国中药杂志,2014,39(11):2106-2111.
31 罗旭异,高健生,潘琳.交泰丸对链脲佐菌素性糖尿病大鼠视网膜血管病理改变的作用.中国中医眼科杂志,2007,17(1):27-31.
32 吴珺,鲁一兵,刘超.Toll样受体和糖尿病.国际内分泌代谢杂志,2008,28(2):116-118.
33 吴冕,陈海冰.Toll样受体与2型糖尿病及其并发症的关系及分子机制.医学综述,2013,19(20):3754-3757.
34 徐向青,唐启盛.抑郁症与细胞信号转导研究进展.中国医药导报,2012,9(36):49-50.
35 潘玲珍.蜘蛛香药物依赖性评价的毒理基因组学研究.成都:西南交通大学,2011.
36 陈爱琴,陈晓春,周瑞祥,等.5-HT2受体-磷脂酶C的激活易化大鼠基底外侧杏仁核突触可塑性的研究.神经解剖学杂志,2008,24(5):529-532.