目的 利用网络药理学技术预测延胡索生物碱的抗糖尿病作用并加以验证。方法 全面收集 Pubmed、CNKI、万方和维普数据库中与延胡索的生物碱成分相关的靶点信息。在OMIM数据库检索糖尿病相关疾病的靶点, 通过共享靶点实现与生物碱成分的关联, 构建并分析延胡索生物碱“成分-靶点-糖尿病”网络。采用胰岛素抵抗模型和糖尿病模型验证预测结果。结果 延胡索生物碱的“成分-靶点”网络中, 延胡索各成分的靶点涉及神经递质及其代谢酶、离子通道、信号蛋白和酪氨酸激酶样受体和G蛋白偶联受体。延胡索“成分-靶点”网络和“糖尿病相关疾病-靶点”网络共享多个靶点, 其中涉及多种重要枢纽节点, 如NOS3、VEGF等, 多种成分的靶点与2型糖尿病、高血压、肥胖、胰岛素抵抗等疾病关联, 提示延胡索生物碱可能具有抗糖尿病相关疾病作用。延胡索醇提物明显降低对正常和糖尿病小鼠血糖、高脂诱导胰岛素抵抗小鼠糖耐量, 这些结果与网络药理学预测结果较为一致。结论 延胡索生物碱有潜在抗糖尿病、糖尿病并发症的作用。
Abstract
OBJECTIVE To predict the anti-diabetes effects of Corydalis yanhusuo alkaloids with pharmacological network technology and verify the results in animal models. METHODS Targets of Corydalis yanhusuo alkaloids were collected from Pubmed, CNKI, Wangfang and VIP databases, and targets for treatment of diabetes and diabetic complications were searched from OMIM database. The “components-targets-diabetes” network was constructed and analyzed with cytoscape 2.8.2. Diabetes model was established by STZ injection. RESULTS The targets of Corydalis yanhusuo alkaloids covered many kinds of protein, including ion channel, G coupled protein, and signal proteins such as potassium channel, MAPK/ERK, VEGF and NOS3. In the network, Corydalis yanhusuo alkaloids associated with diabetes and diabetic complications, especially, non-insulin dependent diabetes, obesity, and diabetic complications via modulation of NOS3, VEGF, INSR, KCNJ11 and IRS1, indicating potential effects of Corydalis yanhusuo for diabetes and diabetic complications. Corydalis yanhusuo alkaloids decreased blood glucose in normal and diabetic ICR mice and improved sugar tolerance in insulin-resistant mice, which was in conformity with the prediction. CONCLUSION Corydalis yanhusuo alkaloids show potential effects on diabetes and diabetic complications.
关键词
延胡索 /
生物碱 /
网络药理学 /
糖尿病 /
并发症 /
胰岛素抵抗 /
新用途
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Key words
Corydalis yanhusuo /
alkaloid /
pharmacological network /
diabetes /
complications /
insulin resistance /
novel application
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参考文献
[1] KUBO M, MATSUDA H, TOKUOKA K, et al. Anti-inflammatory activities of methanolic extract and alkaloidal components from Corydalis tuber. Biol Pharm Bull, 1994, 17 (2):262-265. [2] MATSUDA H, TOKUOKA K, WU J, et al. Inhibitory effects of methanolic extract from Corydalis tuber against types Ⅰ-Ⅳ allergic models. Biol Pharm Bull, 1995, 18 (7):963-967. [3] LING H, WU L, LI L. Corydalis yanhusuo rhizoma extract reduces infarct size and improves heart function during myocardial ischemia/reperfusion by inhibiting apoptosis in rats. Phytother Res, 2006, 20 (6):448-453. [4] WEN C, WU L, LING H, et al. Salutary effects of Corydalis yanhusuo extract on cardiac hypertrophy due to pressure overload in rats. J Pharm Pharmacol, 2007, 59 (8):1159-1165. [5] WU L, LING H, LI L, et al. Beneficial effects of the extract from Corydalis yanhusuo in rats with heart failure following myocardial infarction. J Pharm Pharmacol, 2007, 59 (5):695-701. [6] LIU X, YANG Z, LI R, et al. Responses of dopaminergic, serotonergic and noradrenergic networks to acute levo-tetrahydropalmatine administration in naive rats detected at 9. 4 T. Magnetic Resonance Imaging, 2012, 30 (2):261-270. [7] HENKES H, FRANZ M, KENDALL O, et al. Evaluation of the anxiolytic properties of tetrahydropalmatine, a Corydalis yanhusuo compound, in the male Sprague-Dawley rat. AANA J, 2011, 79 (4 suppl):75-80. [8] SHEN N, HUAN Y, SHEN Z F. Berberine inhibits mouse insulin gene promoter through activation of AMP activated protein kinase and may exert beneficial effect on pancreatic beta-cell. Eur J Pharmacol, 2012, 694(1-3):120-126. [9] LIU L Z, CHEUNG S C, LAN L L, et al. Berberine modulates insulin signaling transduction in insulin-resistant cells. Mol Cell Endocrinol, 2010, 317 (1-2):148-153. ZHANG P. Mechanisms of yanhusuo extracts underlying the arryhrmias induced by coronary heart disease. Beijing:Beijing University of Chinese Medicine, 2012. LUO S Y, GUO P, QIAN G, et al. Study on acting mechanism of anti-morphine conditioned place preference between aqueous extract of Corydalis yanhusuo and L-THP and comparison of their effects. China J Chin Mater Med(中国中药杂志), 2012, 47(22):3457-3561. SAITO S Y, TANAKA M, MATSUNAGA K, et al. The combination of rat mast cell and rabbit aortic smooth muscle is the simple bioassay for the screening of anti-allergic ingredient from methanolic extract of Corydalis tuber. Biol Pharm Bull, 2004, 27 (8):1270-1274. GAO J L, SHI J M, HE K, et al. Yanhusuo extract inhibits metastasis of breast cancer cells by modulating mitogen-activated protein kinase signaling pathways. Oncol Rep, 2008, 20 (4):819-824. WANG W, XIAO W, YU R, et al. Study on chemical composition from Chinese traditional medicine of Corydalis yanhusuo. Journal of The Central University for Nationalities(Nat Sci Ed) (中央民族大学学报:自然科学版), 2007, 16(1):80-82, 86. LU Z, SUN W, DUAN X, et al. Chemical constituents from Corydalis yanhusuo. China J Chin Mater Med(中国中药杂志), 2012, 37 (2):235-237. ZHANG X, QU Y, HOU J, et al. Chemical constituents from the bulb of Corydalis yanhusuo W. T wang. J Shengyang Pharm Univ(沈阳药科大学学报), 2008, 25 (7):537-540. SHI J, HAN W, YE W, et al. Phytochemical investigation of Corydalis yanhusuo. Nat Prod Res Dev(天然产物研究与开发), 2011, 23 (4):647-651. ZHAO M, LI L, SHEN J, et al. Inhibitory and inductive effects of(-)-and(+)-tetrahydropalmatine on CYP450 in mice. J Zhejiang Univ(Med Sci) (浙江大学学报:医学版), 2011, 40 (1):33-39. YU J, HUA B, PIAO B, et al. Effect of tetrahydropalmatine on irradiation-induced endothelial cell injury. Chin J Cancer Preve Treat(中华肿瘤防治杂志), 2011, 18(8):584-587, 601. HAN Y, ZHANG W, TANG Y, et al. l-Tetrahydropalmatine, an active component of Corydalis yanhusuo W. T. Wang, protects against myocardial ischaemia-reperfusion injury in rats. PLoS One, 2012, 7 (6):e38627. ZHAO Y, HELLUM B H, LIANG A, et al. The in vitro inhibition of human CYP1A2, CYP2D6 and CYP3A4 by tetrahydropalmatine, neferine and berberine. Phytother Res, 2012, 26 (2):277-283. LI X, WU L, FAN X, et al. Network pharmacology study on major active compounds of Fufang Danshen formula. China J Chin Mater Med(中国中药杂志), 2011, 36(21):2911-2915. WU L, GAO X, WANG L, et al. Prediction of multi-target of Aconiti Lateralis Radix Praeparata and its network pharmacology. China J Chin Mater Med(中国中药杂志), 2011, 36(21):2907-2910. LING H, WU L, LI L. Corydalis yanhusuo rhizoma extract reduces infarct size and improves heart function during myocardial ischemia/reperfusion by inhibiting apoptosis in rats. Phytother Res, 2006, 20 (6):448-453. ZHOU Y. Effects of Yanhusuo on ET, 6-Keto-PGF1α and TXB2 in II type diabetic rat. Hubei University of Chinese Medicine, 2006. PATEL M B, MISHRA S. Hypoglycemic activity of alkaloidal fraction of Tinospora cordifolia. Phytomedicine, 2011, 18 (12):1045-1052.
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脚注
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基金
浙江省科技计划实验动物科技计划项目(2013C37005);温州市科技计划项目(Y20130047, Y20100049, Y20100048)
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