Objective To explore the medication rules and mechanism of Xin'an physicians in the treatment of diabetes mellitus.
Methods The prescriptions for the treatment of diabetes mellitus in Xin'an medical writings were collected. The core drug prescriptions were obtained by using IBM SPSS Modeler 18.0 for dispensing association rules as well as complex network analysis, and the cluster analysis of high-frequency traditional Chinese medicines was carried out by using IBM SPSS Statistics 25.0. The active ingredients and targets of the core drugs were extracted from the BATMAN-TCM database. The GeneCards database was used to search for diabetes gene targets, and after obtaining the intersecting targets, the STRING online platform was imported to construct the protein interactions network, and screened the core genes by using the Cytoscape 3.9.1 software, and imported into the DAVID database for GO function and KEGG pathway enrichment analysis.
Results A total of 135 valid prescriptions were included, involving 184 flavors of traditional Chinese medicines, with cold and mild properties. Sweet, bitter and pungent flavors, and the main attributes of lung, spleen, kidney, stomach and heart meridians. The association rules mined 14 pairs of commonly used medicine pairs. Cluster analysis clustered the top 20 traditional Chinese medicines into five cluster groups. Complex network visualization analysis formed a core prescription consisting of honey-fried licorice root, ginseng, rhizoma anemarrhenae, ophiopogon japonicus, poria cocos. The core prescription drugs were screened for 164 effective active ingredients, 1,498 action targets, 1,995 diabetes gene targets, 404 intersecting targets, 10 core targets were extracted, and a total of 1,363 items covering BP were obtained from GO functional enrichment analysis, 129 items involving CC, 264 items containing MF, and 206 items of KEGG signaling pathway.
Conclusion The prescriptions and medicines used by Xin'an doctors in the treatment of diabetes mellitus reflect the academic idea of "treating both the symptoms and the root cause" as well as the therapeutic thought of "using cold and warmth, supplementing with sweetness and warmth, opening up and lowering with bitterness, cultivating the earth and generating gold, and consolidating the root and cultivating the elements", which provide references for the treatment of diabetes mellitus in today's clinics.
1.中华医学会糖尿病学分会, 国家基层糖尿病防治管理办公室. 国家基层糖尿病防治管理指南(2022)[J]. 中华内科杂志, 2022, 61(3): 249-262. [Chinese Diabetes Society, National Office for Primary Diabetes Care. National guidelines for the prevention and control of diabetes in primary care (2022) [J]. Chinese Journal of Internal Medicine, 2022, 61(3): 249-262.] DOI: 10.3760/cma.j.cn112138-20220120-000063.
2.刘洁. 糖尿病药物治疗的现状及进展研究[J]. 医学信息, 2022, 35(9): 69-72. [Liu J. Current situation and research progress of diabetic drug therapy[J]. Journal of Medical Information, 2022, 35(9): 69-72.] DOI: 10.3969/j.issn.1006-1959.2022.09.017.
3.Tegegne BA, Adugna A, Yenet A, et al. A critical review on diabetes mellitus type 1 and type 2 management approaches: from lifestyle modification to current and novel targets and therapeutic agents[J]. Front Endocrinol (Lausanne), 2024, 15: 1440456. DOI: 10.3389/fendo.2024.1440456.
4.刘剑, 方朝晖, 倪英群, 等. 丹蛭降糖胶囊联合达格列净治疗2型糖尿病周围血管病变的临床研究[J]. 北京中医药大学学报, 2024, 47(8): 1119-1125. [Liu J, Fang ZH, Ni YQ, et al. Clinical study on the combination of the Danzhi Jiangtang capsule and dapagliflozin for type 2 diabetes mellitus with peripheral vascular disease[J]. Journal of Beijing University of Traditional Chinese Medicine, 2024, 47(8): 1119-1125.] DOI: 10.3969/j.issn.1006-2157.2024.08.013.
5.吴吉萍, 赵进东, 陆瑞敏, 等. 丹蛭降糖胶囊治疗早期糖尿病肾病的临床疗效观察[J]. 现代中药研究与实践, 2023, 37(6): 74-78. [Wu JP, Zhao JD, Lu RM, et al. Clinical observation of Danzhi Jiangtang capsules in the treatment of early diabetic kidney disease[J]. Research and Practice on Chinese Medicines, 2023, 37(6): 74-78.] DOI: 10.13728/j.1673-6427.2023.06.014.
6.王彩霞. 参芪地黄汤加减治疗糖尿病的效果分析[J]. 中国民族医药杂志, 2024, 30(9): 14-16. [Wang CX. Analysis of the effect of the addition and subtraction of Shenqi Dihuang decoction in the treatment of diabetes[J]. Journal of Medicine & Pharmacy of Chinese Minorities, 2024, 30(9): 14-16.] DOI: 10.3969/j.issn.1006-6810.2024.09.006.
7.朱善勇. 消渴丸联合六味地黄丸治疗2型气阴两虚糖尿病的临床效果观察[J]. 内蒙古中医药, 2024, 43(5): 12-14. [Zhu SY. Observation of the clinical effect of thirst quenching pills combined with Liuwei Dihuang pills in the treatment of type 2 qi and yin deficiency diabetes mellitus[J]. Inner Mongolia Journal of Traditional Chinese Medicine, 2024, 43(5): 12-14.] DOI: 10.16040/j.cnki.cn15-1101.2024.05.016.
8.王婷, 汪洋, 董鹏, 等. 基于数据挖掘及网络药理学分析新安医家治疗哮喘的用药规律及作用机制[J]. 现代中药研究与实践, 2023, 37(5): 41-47. [Wang T, Wang Y, Dong P, et al. Medication rules and mechanism of Xin'an physicians in the treatment of asthma based on data mining and network pharmacology[J]. Research and Practice on Chinese Medicines, 2023, 37(5): 41-47.] DOI: 10.13728/j.1673-6427.2023.05.008.
9.薛茜尹, 张怡, 李国辉, 等. 基于数据挖掘和网络药理学探讨中药复方治疗抑郁症的用药规律与作用机制[J]. 广州中医药大学学报, 2024, 41(10): 2804-2814. [Xue QY, Zhang Y, Li GH, et al. Exploration on the medication rules and mechanism of chinese herbal compound in the treatment of depression based on data mining and network pharmacology[J]. Journal of Guangzhou University of Traditional Chinese Medicine, 2024, 41(10): 2804-2814.] DOI: 10.13359/j.cnki.gzxbtcm.2024.10.040.
10.任思思, 陆璐, 潘家姝, 等. 基于网络药理学与实验验证探究马齿苋治疗结直肠癌的作用机制[J]. 世界科学技术-中医药现代化, 2024, 26(9): 2265-2277. [Ren SS, Lu L, Pan JS, et al. Network-Based pharmacology and experimental validation to explore the Portulaca oleracea L. mechanism of action in the treatment of colorectal cancer[J]. Modernization of Traditional Chinese Medicine and Materia Medica-world Science and Technology, 2024, 26(9): 2265-2277.] DOI: 10.11842/wst.20231212002.
11.张艺凡, 贾苏杰, 刘静远, 等. 基于网络药理学和动物实验探讨黄连解毒汤通过Bcl-2/Bax/Caspase-3信号通路抗结直肠腺瘤作用机制[J]. 中医药导报, 2024, 30(11): 32-40, 47. [Zhang YF, Jia SJ, Liu JY, et al. The Mechanism of Huanglian Jiedu decoction against colorectaladenoma via Bcl-2/Bax/Caspase-3 pathway based on network pharmacology and animal experiments[J]. Guiding Journal of Traditional Chinese Medicine and Pharmacy, 2024, 30(11): 32-40, 47.] DOI: 10.13862/j.cn43-1446/r.2024.11.007.
12.消渴的诊断依据、证候分类、疗效评定——中华人民共和国中医药行业标准《中医内科病证诊断疗效标准》(ZY/T001.1-94)[S]. 2016.
13.中国药典2020年版. 一部[S]. 2020: 52-455.
14.南京中医药大学, 编著. 中药大辞典[M]. 上海: 上海科技出版社, 2013: 1-3874.
15.国家中医药管理局《中华本草》编委会, 编著. 中华本草[M]. 上海: 上海科技大学出版社, 1999: 1-533.
16.朱江, 张蔚钱, 庞祖才, 等. 基于数据挖掘、GEO基因芯片及网络药理学探讨中医药治疗骨不连的用药规律及药理分析[J]. 中国医药导报, 2024, 21(33): 162-170, 179. [Zhu J, Zhang WQ, Pang ZC, et al. Exploring medication pattern and pharmacological analysis of traditional Chinese medicine in the treatment of bone nonunion based on data mining, GEO gene chip, and network pharmacology[J]. China Medical Herald, 2024, 21(33): 162-170, 179.] DOI: 10.20047/j.issn1673-7210.2024.33.30.
17.王玲玲, 付桃芳, 杜俊英, 等. 基于SPSS Clementine的关联规则分析在中医药数据挖掘中的应用优势和局限[J]. 云南中医学院学报, 2016, 39(6): 98-102. [Wang LL, Fu TF, Du JY, et al. The Application advantages and limitations of association rules analysis based on SPSS clementine in traditional Chinese medicine data mining[J]. Journal of Yunnan University of Chinese Medicine, 2016, 39(6): 98-102.] DOI: 10.19288/j.cnki.issn.1000-2723.2016.06.024.
18.温莉珍, 肖婷, 沈燕珊, 等. 国家中药复方专利治疗高尿酸血症用药规律研究[J]. 海峡药学, 2024, 36(6): 33-38. [Wen LZ, Xiao T, Shen YS, et al. Study on medication rules for treating hyperuricemia with Chinese herbal compounds based on the national patent database[J]. Strait Pharmaceutical Journal, 2024, 36(6): 33-38.] DOI: 10.3969/j.issn.1006-3765.2024.06.007.
19.信立媛, 郑亮. 基于数据挖掘和网络药理学研究中药免疫增强剂的作用机制及用药规律[J]. 南京中医药大学学报, 2024, 40(2): 174-183. [Xin LY, Zheng L. Study on the medication rule and action mechanism of traditional Chinese medicine immune enhancer based on data mining and network pharmacology[J]. Journal of Nanjing University of Traditional Chinese Medicine, 2024, 40(2): 174-183.] DOI: 10.14148/j.issn.1672-0482. 2024.0174.
20.Kong X, Liu C, Zhang Z, et al. BATMAN-TCM 2.0: an enhanced integrative database for known and predicted interactions between traditional Chinese medicine ingredients and target proteins[J]. Nucleic Acids Res, 2024, 52(D1): D1110-D1120. DOI: 10.1093/nar/gkad926.
21.Stelzer G, Rosen N, Plaschkes I, et al. The GeneCards suite: from gene data mining to disease genome sequence analyses[J]. Curr Protoc Bioinformatics, 2016, 54: 1.30.31-31.30.33. DOI: 10.1002/cpbi.5.
22.Szklarczyk D, Kirsch R, Koutrouli M, et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest[J]. Nucleic Acids Res, 2023, 51(D1): D638-D646. DOI: 10.1093/nar/gkac1000.
23.袁明洋, 付锦洲, 黄中强, 等. 基于网络药理学和UPLC-MS/MS探讨消石利胆丸治疗胆石症的作用机制[J]. 药物流行病学杂志, 2024, 33(9): 1006-1016. [Yuan MY, Fu JZ, Huang ZQ, et al. Exploring the mechanism of Xiaoshi Lidan pills in the treatment of cholelithiasis based on network pharmacology and UPLC-MS/MS[J]. Chinese Journal of Pharmacoepidemiology, 2024, 33(9): 1006-1016.] DOI: 10.12173/j.issn.1005-0698.202403143.
24.Sherman BT, Hao M, Qiu J, et al. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update)[J]. Nucleic Acids Res, 2022, 50(W1): W216-W221. DOI: 10.1093/nar/gkac194.
25.Tang D, Chen M, Huang X, et al. SRplot: a free online platform for data visualization and graphing[J]. PLoS One, 2023, 18(11): e0294236. DOI: 10.1371/journal.pone.0294236.
26.冯亚娟, 胡滨青, 周建华. 甘草黄酮对糖尿病大鼠血糖、血脂水平及抗氧化能力的影响[J]. 山东医药, 2016, 56(3): 23-25. [Feng YJ, Hu BQ, Zhou JH. Effects of licorice flavonoids on blood glucose, blood lipid levels and antioxidant capacity in diabetic rats[J]. Shandong Medical Journal, 2016, 56(3): 23-25.] DOI: 10.3969/j.issn.1002-266X.2016.03.008.
27.黄蕾, 汪燕燕, 孙冉, 等. 人参皂苷Rg1通过抑制MAPK-NLRP1通路减轻2型糖尿病诱导的神经元损伤[J]. 中国药理学通报, 2023, 39(11): 2034-2042. [Huang L,Wang YY, Sun R, et al. Ginsenoside Rg1 attenuates type 2 diabetes-induced neuronal damage by inhibiting MAPK-NLRP1 pathway[J].Chinese Pharmacological Bulletin, 2023, 39(11): 2034-2042.] DOI: 10.12360/CPB202306009.
28.洪凌, 杨振. 人参多糖对高脂饲料联合链脲菌素诱导糖尿病小鼠的影响[J]. 人参研究, 2023, 35(4): 6-8. [Hong L, Yang Z. Effect of ginseng polysaccharides on high-fat diet combined with streptozonacin-induced diabetic mice[J]. Ginseng Research, 2023, 35(4): 6-8.] DOI: 10.19403/j.cnki.1671-1521.2023.04.002.
29.王芳, 邓雪慧, 许平翠, 等. 知母黄柏药对治疗糖尿病骨质疏松症的药效物质和作用机制研究进展[J]. 中国现代应用药学, 2023, 40(21): 3039-3046. [Wang F, Deng XH, Xu PC, et al. Research progress on pharmacodynamic substances and mechanism of Anemarrhenae Rhizoma-Phellodendri Chinensis cortex herb pair in the treatment of diabetic osteoporosis[J]. Chinese Journal of Modern Applied Pharmacy, 2023, 40(21): 3039-3046.] DOI: 10.13748/j.cnki.issn1007-7693.20223030.
30.张杰, 林炳锋, 许平翠, 等. 麦冬提取物治疗2型糖尿病小鼠的血清代谢组学研究[J]. 中国生物工程杂志, 2022, 42(11): 99-108. [Zhang J, Lin BF, Xu PC, et al. Serum metabolomics of Ophiopogon japonicus extract against type 2 diabetes in mice[J]. China Biotechnology, 2022, 42(11): 99-108.] DOI: 10.13523/j.cb.2209009.
31.李乔, 张博. 茯苓多糖对2型糖尿病大鼠丝裂原激活的蛋白激酶通路及胰岛素抵抗的影响[J]. 安徽医药, 2022, 26(12): 2379-2382. [Li Q, Zhang B. Effect of pachyman on mitogen-activated protein kinase pathway and insulin resistance in type 2 diabetic rats[J]. Anhui Medical and Pharmaceutical Journal, 2022, 26(12): 2379-2382.] DOI: 10.3969/j.issn.1009-6469. 2022.12.010.
32.何晶晶, 庞书勤, 蔡秀群, 等. 山药对2型糖尿病慢性低度炎症影响的研究进展[J]. 糖尿病新世界, 2021, 24(17): 194-198. [He JJ, Pang SQ, Cai XQ, et al. Research progress of the effect of Chinese yam on chronic low-grade inflammation of type 2 diabetes[J]. Diabetes New World, 2021, 24(17): 194-198.] DOI: 10.16658/j.cnki.1672-4062.2021.17.194.
33.李阳, 李静, 贺琼, 等. 艾塞那肽周制剂联合二甲双胍对2型糖尿病病人血糖变异及慢性低度炎症的影响[J]. 中西医结合心脑血管病杂志, 2021, 19(4): 639-642. [Li Y, Li J, He Q, et al. Effect of exenatide weekly preparation combined with metformin on blood glucose variability and chronic low-grade inflammation in patients with type 2 diabetes mellitus[J]. Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease, 2021, 19(4): 639-642.] DOI: 10.12102/j.issn.1672-1349.2021.04.029.
34.刘佳, 李芳菲, 梁晓龙, 等. IL-1、IL-1β、IL-6、IL-10基因多态性与糖尿病性牙周炎发生的关系分析[J]. 分子诊断与治疗杂志, 2024, 16(1): 55-58, 67. [Liu J, Li FF, Liang XL, et al. Relationship between IL-1, IL-1β, IL-6 and IL-10 gene polymorphisms and the occurrence of diabetic periodontitis[J]. Journal of Molecular Diagnostics and Therapy, 2024, 16(1): 55-58, 67.] DOI: 10.3969/j.issn.1674-6929.2024.01.013.
35.吴秀琴, 刘丽霞, 尹玉娇, 等. 有氧运动和茶多酚对2型糖尿病大鼠胰岛素抵抗和血清炎症因子的影响[J]. 福建师范大学学报(自然科学版), 2016, 32(5): 106-112. [Wu XQ, Liu LX, Ying YJ, et al. The Effect of aerobic exercise and tea polyphenols on insulin resistance and inflammation factors in rat with type 2 diabetes[J]. Journal of Fujian Normal University(Natural Science Edition), 2016, 32(5): 106-112.] https://d.wanfangdata.com.cn/periodical/fjsfdxxb201605017.
36.李子璇. 糖尿病合并抑郁患者hs-CRP、IL-2、TNF-α、HOMA-IR变化及临床意义[J]. 慢性病学杂志, 2023, 24(9): 1293-1297, 1301. [Li ZX. Changes and clinical significance of hs-CRP、IL-2、TNF-α、HOMA-IR in T2DM patients with depression[J]. Chronic Pathematology Journal, 2023, 24(9): 1293-1297, 1301.] DOI: 10.16440/J.CNKI.1674-8166.2023.09.03.
37.常柏, 李巧芬, 李春深, 等. 抵挡汤早期干预对2型糖尿病大鼠血清IL-4、IL-13水平及主动脉TNF-αmRNA表达的影响[J]. 四川中医, 2013, 31(3): 48-50. [Chang B, Li QF, Li CS, et al. Effect of Didang decoction medicated early to type 2 diabetic rats on serum IL-4 and IL-13 level and aorta TNF-αmRNA expression[J]. Journal of Sichuan of Traditional Chinese Medicine 2013, 31(3): 48-50.] https://qikan.cqvip.com/Qikan/Article/Detail?id=45229841.
38.吴坤荣, 李晓黎, 李妍. 白细胞介素-10与2型糖尿病发病风险的关联性[J]. 卫生研究, 2020, 49(2): 331-335.[Wu KR, Li XL, Li Y. Association between interleukin-10 and the risk of developing type 2 diabetes[J]. Journal of Hygiene Research, 2020, 49(2): 331-335.] DOI: 10.19813/j.cnki.weishengyanjiu. 2020.02.030.
39.Murphy SP, Tayade C, Ashkar AA, et al. Interferon gamma in successful pregnancies[J]. Biol Reprod, 2009, 80(5): 848-859.DOI: 10.1095/biolreprod.108.073353.
40.李莲花. 小剂量辛伐他汀对老年2型糖尿病患者血清GM-CSF、hs-CRP水平的影响[J]. 中西医结合心脑血管病杂志, 2015, 13(12): 1462-1464. [Li LH. Effect of low-dose simvastatin on serum levels of GM-CSF and hs-CRP in elderly patients with type 2 diabetes mellitus[J]. Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease, 2015, 13(12): 1462-1464.] https://www.cnki.com.cn/Article/CJFDTotal-ZYYY201512043.htm.
41.Cai J, Wang M, Zhu M, et al. N-methyl-N-nitro-N'-nitrosoguanidine induces the expression of CCR2 in human gastric epithelial cells promoting CCL2-mediated migration[J]. Mol Med Rep, 2016, 13(2): 1083-1090. DOI: 10.3892/mmr.2015.4650.
42.高德勐, 付钰涓, 蒲馨怡, 等. 基于网络药理学和分子对接技术的灵芝改善2型糖尿病作用机制[J]. 北华大学学报(自然科学版), 2024, 25(3): 339-345. [Gao DM, Fu YJ, Pu XY, et al. Ganoderma lucidum improving type 2 diabetes based on network pharmacology and molecular docking technology[J]. Journal of Beihua University (Natural Science), 2024, 25(3): 339-345.] DOI: 10.11713/j.issn.1009-4822. 2024. 03.010.
43.尹谢添, 赵诗超, 向楠, 等. 桂枝附子汤调控AGEs/RAGE/NF-κB信号通路对类风湿关节炎大鼠的影响[J]. 中成药, 2023, 45(6): 1809-1815. [Yin XT, Zhao SC, Xiang N, et al. Effects of Guizhi Fuzi decoction on rats with rheumatoid arthritis via AGEs/RAGE/NF-κB signaling pathway[J]. Chinese Traditional Patent Medicine, 2023, 45(6): 1809-1815.] DOI: 10.3969/j.issn.1001-1528.2023.06.011.
44.李坤梦, 许泽鹏, 田妮, 等. 滋肾健脾化瘀片通过抑制AGEs/RAGE/NF-κB通路改善糖尿病大鼠的视网膜病变[J]. 中药新药与临床药理, 2020, 31(10): 1147-1152. [Li KM, Xu ZP, Tian N, et al. Zishen Jianpi Huayu tablets improve retinopathy in diabetic rats by inhibiting AGEs/RAGE/NF-κB pathway[J]. Traditional Chinese Drug Research and Clinical Pharmacology, 2020, 31(10): 1147-1152.] DOI: 10.19378/j.issn.1003-9783. 2020.10.003.