基于网络药理学方法探究中药肉桂治疗糖尿病的作用机制

doi:10.3976/j.issn.1002-4026.2020.06.007

Abstract

Abstract: To predict the active components and key targets of Cinnamomi Cortex in the treatment of diabetes and analyze its mechanisms using bioinformatics technology and network pharmacology. The effective compounds and the corresponding target proteins of Cinnamomi Cortex were determined and screened using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP) database and a literature search. Diabetes-related genes were obtained from the GeneCards Database, and the compound-target network and the protein-protein interaction (PPI) network were constructed. Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis were conducted using the Database for Annotation, Visualization and Integrated Discovery(DAVID) and STRING databases. Molecular docking was performed between active components and key targets. Overall, 32 active components were found to act on 131 related targets and 20 core genes such as INS, AKT1, IL6, TNF, and VEGFA. GO and KEGG analysis showed that Cinnamomi Cortex was mainly involved in biological processes such as positive regulation of transcription by RNA polymerase II promoter, as well as pathways covering the AGE/RAGE signaling pathway in diabetic complications and IL-17 signaling pathway. The results of molecular docking of 10 key components showed that quercetin and procyanidin B1 in Cinnamomi Cortex had better affinity with INS, IL6, VEGFA, and TNF. This study preliminarily explained the mechanism of Cinnamomi Cortex in in treatment of diabetes, which will be helpful to guide the clinical use of drugs.

Key words: Cinnamomi Cortex, diabetes, network pharmacology, molecular docking

CLC Number:

R285.5

WANG Jun, SU Ben-zheng, JIANG Hai-qiang, SUN Yu, YANG Yu-han, CUI Ning, YU Zong-yuan. Exploration of the mechanisms of Cinnamomi Cortex in the treatment of diabetes based on network pharmacology[J].Shandong Science, 2020, 33(6): 44-54.

References 31

1	达德丽, 封歌俊, 罗晓红. 黄芪桂枝五物汤联合血府逐瘀汤内服外用治疗消渴痹证经验[J]. 亚太传统医药, 2019, 15(2): 93-94. doi: 10.11954/ytctyy.201902029
2	赵思怡, 黄帆, 冯子桐, 等. 六味地黄丸(汤)联合二甲双胍治疗2型糖尿病的Meta分析和试验序贯分析[J]. 中国医院药学杂志, 2019, 39(11): 1158-1165. doi: 10.13286/j.cnki.chinhosppharmacyj.2019.11.11
3	张泽鑫,吴汶丰,谢丹,等.基于网络药理学联合GEO芯片分析干姜黄芩黄连人参汤治疗2型糖尿病的机理和分子靶点[J]. 广东药科大学学报, 2020, 36(3):361-368. doi: 10.16809/j.cnki.2096-3653.2020022602
4	蔡宝石, 李玲, 李梅, 等. 血府逐瘀汤联合双胍类降糖药治疗糖尿病疗效研究[J]. 陕西中医, 2020, 41(6):774-776. doi: 10.3969/j.issn.1000-7369.2020.06.020
5	敖君. 对于抗糖尿病药物不良反应分析研究[J]. 糖尿病新世界, 2014(11): 22. doi: 10.3969/j.issn.1672-4062.2014.11.014
6	国家药典委员会. 中华人民共和国药典2015年版一部[M]. 北京:中国医药科技出版社, 2015.
7	叶菲, 许东航. 肉桂提取物醇质体透皮吸收研究[J]. 药物评价研究, 2013, 36(2): 119-122. doi: 10.7501/j.issn.1674-6376.2013.02.010
8	ZHANG C L, FAN L H, FAN S M, et al.Cinnamomum cassia Presl.: a review of its traditional uses, phytochemistry, pharmacology and toxicology[J]. Molecules, 2019, 24(19): 3473. doi: 10.3390/molecules24193473
9	姚平安, 崔肖华, 卫克昭, 等. 肉桂对糖尿病大鼠肝损伤的保护作用[J]. 上海中医药杂志, 2017, 51(7): 76-79. doi: 10.16305/j.1007-1334.2017.07.022
10	徐洁, 钟丽娟. 肉桂对2型糖尿病大鼠肝糖原、肌糖原的影响[J]. 中国中医药科技, 2007, 14(3): 171-172. doi: 10.3969/j.issn.1005-7072.2007.03.013
11	LI J, MA X R, LIU C, et al. Exploring the mechanism of Danshen against myelofibrosis by network pharmacology and molecular docking[J]. Evidence-Based Complementary and Alternative Medicine, 2018, 2018: 1-11. doi: 10.1155/2018/8363295
12	METZ J T, HAJDUK P J. Rational approaches to targeted polypharmacology: creating and navigating protein-ligand interaction networks[J]. Current Opinion in Chemical Biology, 2010, 14(4): 498-504. doi: 10.1016/j.cbpa.2010.06.166
13	LUO Q, SHI X, DING J R, et al. Network pharmacology integrated molecular docking reveals the antiosteosarcoma mechanism of biochanin A[J]. Evidence-Based Complementary and Alternative Medicine, 2019, 2019: 1410495. doi: 10.1155/2019/1410495
14	黄友, 杨莎莎, 林夏, 等. 基于网络药理-分子对接研究附子理中丸治疗溃疡性结肠炎的作用机制[J]. 药学学报, 2020, 55(8): 1812-1822. doi: 10.16438/j.0513-4870.2019-0936
15	田会东, 郭丽娜, 贾明璐, 等. 苍术-玄参药对治疗2型糖尿病作用机制的网络药理学研究[J]. 现代药物与临床, 2019, 34(5): 1274-1278. doi: 10.7501/j.issn.1674-5515.2019.05.002
16	DAVIS P A, YOKOYAMA W. Cinnamon intake lowers fasting blood glucose: meta-analysis[J]. Journal of Medicinal Food, 2011, 14(9): 884-889. doi: 10.1089/jmf.2010.0180
17	SAHIB A S. Anti-diabetic and antioxidant effect of cinnamon in poorly controlled type-2 diabetic Iraqi patients: a randomized, placebo-controlled clinicaltrial[J]. Journal of Intercultural Ethnopharmacology, 2016, 5(2): 108-113. doi: 10.5455/jice.20160217044511
18	CHEN L, SUN P, WANG T, et al. Diverse mechanisms of antidiabetic effects of the different procyanidin oligomer types of two different cinnamon species on db/db mice[J]. Journal of Agricultural and Food Chemistry, 2012, 60(36): 9144-9150. doi: 10.1021/jf3024535
19	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): 400-403. doi: 10.13506/j.cnki.jpr.2013.07.011
20	CHIS I C, SOCACIU M, MOLDOVAN R, et al. Vascular impact of quercetin administration in association with moderate exercise training in experimental type 1 diabetes[J]. Revista Romana De Medicina De Laborator, 2019, 27(3): 269-279. doi: 10.2478/rrlm-2019-0028
21	ZHU R Y, LIU H X, LIU C Y, et al. Cinnamaldehyde in diabetes:a review of pharmacology, pharmacokinetics and safety[J]. Pharmacological Research, 2017, 122: 78-89. doi: 10.1016/j.phrs.2017.05.019
22	LU Z L, JIA Q, WANG R, et al. Hypoglycemic activities of A- and B-type procyanidin oligomer-rich extracts from different Cinnamon barks[J]. Phytomedicine, 2011, 18(4): 298-302. doi: 10.1016/j.phymed.2010.08.008
23	KONHEIM Y L, WOLFORD J K. Association of a promoter variant in the inducible cyclooxygenase-2 gene (PTGS2) with type 2 diabetes mellitus in Pima Indians[J]. Human Genetics, 2003, 113(5): 377-381. doi: 10.1007/s00439-003-1000-y
24	SALTIEL A R, KAHN C R. Insulin signalling and the regulation of glucose and lipid metabolism[J]. Nature, 2001, 414(6865): 799-806. doi: 10.1038/414799a
25	MATSUBARA A, WASSON J C, DONELAN S S, et al. Isolation and characterization of the human AKT1 gene, identification of 13 single nucleotide polymorphisms (SNPs), and their lack of association with Type II diabetes[J]. Diabetologia, 2001, 44(7): 910-913. doi: 10.1007/s001250100577
26	ALWHAIBI A, VERMA A, ADIL M S, et al. The unconventional role of Akt1 in the advanced cancers and in diabetes-promoted carcinogenesis[J]. Pharmacological Research, 2019, 145: 104270. doi: 10.1016/j.phrs.2019.104270
27	张晓川, 朱春胜, 周政, 等. 人参-黄芪药对治疗2型糖尿病作用机制的网络药理学研究[J]. 现代药物与临床, 2020, 35(5):842-848. doi: 10.7501/j.issn.1674-5515.2020.05.004
28	胡波, 许珏, 陈忠诚, 等. 2型糖尿病患者IL-2,IL-6及TNF-α水平检测[J]. 广东医学, 2006, 27(5): 735-737. doi: 10.3969/j.issn.1001-9448.2006.05.063
29	VON HOLSTEIN-RATHLOU S, BONDURANT L D, PELTEKIAN L, et al. FGF21 mediates endocrine control of simple sugar intake and sweet taste preference by the liver[J]. Cell Metabolism, 2016, 23(2): 335-343. doi: 10.1016/j.cmet.2015.12.003
30	王超, 张会欣, 邢邯英, 等. 氧化苦参碱抑制p38MAPK通路减轻高脂喂养胰岛素抵抗小鼠氧化应激[J]. 中国中药杂志, 2016, 41(15): 2872-2876. doi: 10.4268/cjcmm20161521
31	YUAN X, HAN L, FU P, et al. Cinnamaldehyde accelerates wound healing by promoting angiogenesis via up-regulation of PI3K and MAPK signaling pathways[J]. Laboratory Investigation, 2018, 98(6): 783-798. doi: 10.1038/s41374-018-0025-8

[1]	MU Nana, LIAO Binbin, LI Zhen, LI Jipin, LI Yihua, WANG Ying, CHEN Xubing. Investigating the mechanism of action of Elephantopus scaber L. in the treatment of ulcerative colitis based on network pharmacology and molecular docking [J]. Shandong Science, 2023, 36(6): 48-55.
[2]	WANG Yifan, ZHANG Zhe, TIAN Caijun. Mechanism of Sanhuang Xiexin decoction in treatment of Alzheimer's disease based on network pharmacology and molecular docking method [J]. Shandong Science, 2023, 36(5): 19-26.
[3]	FU Mengya, AO Huihao, BU Chao, PENG Tangyi, WU Deling, HAN Yanquan, HONG Yan. Forecast analysis of the quality markers of Zingiberis Rhizoma based on fingerprints and network pharmacology [J]. Shandong Science, 2023, 36(4): 35-41.
[4]	YIN Zhipeng, GAO Yunyun, LIU Wenwen, GUO Pengbo, ZHAO Yinghui. Exploring the mechanism of Xiangsha Liujunzi Decoction in treating Helicobacter pylori-associated gastritis based on network pharmacology and molecular docking technology [J]. Shandong Science, 2023, 36(4): 52-60.
[5]	ZHAO Xin, HUANG Biyun, WU Dan, ZHANG Mei. The mechanism of Guishaozhenxian Tablet in the treatment of temporal lobe epilepsy based on network pharmacology and molecular docking [J]. Shandong Science, 2023, 36(3): 27-37.
[6]	WANG Yifan, ZHANG Yanyan, TIAN Caijun. Network pharmacology to explore the mechanism of Wangbi formula in the treatment of rheumatoid arthritis [J]. Shandong Science, 2023, 36(3): 38-45.
[7]	LIU Wenwen, GAO Yunyun, YIN Zhipeng, LÜ Gang, WANG Yu, ZHAO Yinghui. Network pharmacology and molecular docking analysis of the mechanism of Huanglian Wendan Decoction in the treatment of Helicobacter pylori associated gastritis [J]. Shandong Science, 2023, 36(2): 23-32.
[8]	LIU Wenwen, LI Changgeng, KONG Na, LIU Shuang, DONG Hongjing. Study on the mechanism of Shiweiyipi Granules based on network pharmacology and molecular docking [J]. Shandong Science, 2023, 36(2): 33-40.
[9]	SHEN Fengxia, FAN Jianwei, LI Qian, MA Yun, FENG Qun, GUAN Yongxia. Analysis of the mechanism of Yinzhihuang Granules in liver fibrosis treatment based on network pharmacology and molecular docking [J]. Shandong Science, 2023, 36(1): 23-33.
[10]	YU Guofang, TIAN Liwei, ZHAO Chenling, WU Mengting, YANG Wenming, DONG Ting. Mechanisms of Zhinao Capsules in the treatment of Alzheimer's disease based on network pharmacology and molecular docking [J]. Shandong Science, 2023, 36(1): 34-40.
[11]	LI Yan, LI Ziwen, LI Limin, WANG Mengxia, ZHANG Peng, WU Zhengzhi. Exploring the mechanism of Mori Cortex in the treatment of type 2 diabetes mellitus based on network pharmacology [J]. Shandong Science, 2023, 36(1): 41-50.
[12]	PAN Wu-liang, ZHANG Jiang-yu, XU Chun-yan, ZENG Yi, PAN Zong-yu, YOU Yuan-yuan. Exploring the mechanism of Salviae Miltiorrhizae Radix Et Rhizoma in treating plasma cell mastitis based on network pharmacology and molecular docking [J]. Shandong Science, 2022, 35(6): 33-41.
[13]	JIANG Ye-ke, CHEN Yan, PAN Ling-yu, HAN Yan-quan, HE Ning, WANG Yong-zhong. Mechanism of Clematidis Radix Rhizoma in the treatment of rheumatoid arthritis based on network pharmacology and molecular docking [J]. Shandong Science, 2022, 35(6): 42-49.
[14]	KE Chang-hu, PAN Chang-jiang, YAN Hui, LIU Jia-ling, CHEN Miao, LI Zhi-hao. Using network pharmacology and molecular docking to determine the mechanism of Cnidii Fructus in the treatment of breast cancer [J]. Shandong Science, 2022, 35(6): 50-57.
[15]	HUANG Yue, FANG Chong-kai, NIE Duo-rui, LAN Qing-xia, LI Yue-jun, HUANG Xue-wu. Prediction of the mechanism of Astragali Radix - Curcumae Rhizomain in the treatment of gastric cancer using network pharmacology and molecular docking [J]. Shandong Science, 2022, 35(5): 16-25.

Exploration of the mechanisms of Cinnamomi Cortex in the treatment of diabetes based on network pharmacology

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References 31

Related Articles 15

Metrics

Comments

Recommended 0