基于数据挖掘探讨中药复方专利治疗急性阑尾炎的组方规律及机制

doi:10.5246/jcps.2025.06.043

摘要/Abstract

摘要：

本研究利用数据挖掘及网络药理学探讨中药治疗急性阑尾炎的组方规律及作用机制,目的是为该病的临床治疗和进一步研究提供科学依据。首先检索国家专利数据库用于治疗急性阑尾炎的中药复方, 然后运用频次分析、性味归经分析、关联规则分析、层次聚类分析等探究中药治疗急性阑尾炎的组方规律, 筛选出关键中药组合。其次, 基于中药质量标志物筛选关键中药的主要活性成分, 运用SwissTargetPrediction、SymMap、ETCM、STRING等数据库分析关键中药治疗急性阑尾炎的药理作用机制, 通过分子对接对关键活性成分和靶点进一步验证。共纳入129项专利, 涉及316味中药, 其中24味经常使用。研究结果显示, 治疗急性阑尾炎的中药多为清热、活血化瘀和泻下药, 且以性寒、味苦、归肝经、肺经为主。大黄-牡丹皮-金银花组合治疗急性阑尾炎的主要活性成分包括大黄素、丹皮酚、大黄素甲醚、绿原酸、大黄酚、大黄酸、芦荟大黄素, 这些成分靶向关键蛋白, 如ALB、TP53、BCL2、STAT3、IL-6、TNF, 参与细胞对脂多糖等的反应、细胞组成以及细胞因子介导的多种生物学过程, 作用于AGE-RAGE、TNF、IL-17和FoxO等信号通路。本研究基于专利数据分析了急性阑尾炎治疗的用药规律, 探讨了关键中药组合治疗急性阑尾炎的可能机制, 为该病的诊治提供了科学依据和新的观点。

关键词: 急性阑尾炎, 数据挖掘, 组方规律, 层次聚类, 分子对接

Abstract:

In the present study, data mining and network pharmacology were utilized to explore the principles and mechanisms of traditional Chinese medicine (TCM) in treating acute appendicitis. The goal was to provide a scientific basis for clinical treatment and further research on this disease. First, we searched the National Patent Database for Chinese herbal compound prescriptions used to treat acute appendicitis. We then applied frequency analysis, character and taste meridian analysis, association rule analysis, and hierarchical cluster analysis to identify the patterns of TCM treatment for acute appendicitis, selecting key combinations of Chinese medicines. Next, we screened the main active components of these key TCM based on quality markers. Using databases such as SwissTargetPrediction, SymMap, ETCM, and STRING, we analyzed the pharmacological mechanisms of these key TCM in treating acute appendicitis. Key active components and targets were further verified through molecular docking. We identified a total of 129 patents involving 316 Chinese medicines, with 24 being frequently used. The results indicated that most Chinese herbs used for acute appendicitis were heat-clearing drugs, blood-activating and stasis-removing drugs, and purging drugs. The primary active ingredients of the Rhubarb-cortex moutan-flos lonicerae combination for treating acute appendicitis included Emodin, Paeonol, Physcion, Chlorogenic acid, Chrysophanol, Rhein acid, and Aloe-emodin. These ingredients targeted key proteins such as ALB, TP53, BCL2, STAT3, IL-6, and TNF, and were involved in cellular responses to lipopolysaccharides, cell composition, and various cytokine-mediated biological processes. They also interacted with signaling pathways like AGE-RAGE, TNF, IL-17, and FoxO. Based on patent data, this study analyzed medication patterns in the treatment of acute appendicitis, discussed the possible mechanisms of key TCM combinations, and provided a scientific basis and new perspectives for the diagnosis and treatment of the disease.

Key words: Acute appendicitis, Data mining, Rule of composition, Hierarchical clustering, Molecular docking

Supporting:

李跃文, 张勤生, 胡素芹. 基于数据挖掘探讨中药复方专利治疗急性阑尾炎的组方规律及机制[J]. 中国药学(英文版), 2025, 34(6): 566-580.

Yuewen Li, Qinsheng Zhang, Suqin Hu. Unveiling the prescription patterns and mechanisms of Chinese herbal compound patents in the management of acute appendicitis: A data mining investigation[J]. Journal of Chinese Pharmaceutical Sciences, 2025, 34(6): 566-580.

图/表 13

Figure 1. Diagram of syndrome analysis.

Table 1. Statistics of high-frequency TCM use.

Table 2. Efficacy analysis of high-frequency Chinese materia medica.

Figure 2. Distribution map of the meridian tropism.

Table 3. Association rule information (Top 15 items in support order).

Figure 3. Visualization of key association rules of TCM.

Figure 4. Cluster number analysis of NBCLUST function.

Figure 5. Visualization of cluster analysis.

Figure 6. PPI network display.

Figure 7. Bubble diagram of GO enrichment analysis.

Figure 8. KEGG enrichment bubble diagram.

Figure 9. The key active ingredient-target-pathway diagram of TCM.

Figure 10. Visualization of molecular docking.

参考文献 41

[1]	Shi, H.Z.; Shi, X.; Tang, W. Latest research progress on the characteristics of acute appendicitis. Modern Med. 2014, 42, 840–842.
[2]	Stringer, M.D. Acute appendicitis. J. Paediatr. Child Health. 2017, 53, 1071–1076.
[3]	Song, L.Z. Analysis of risk factors and preventive strategies for postoperative infection in patients with acute appendicitis. Anti Infect. Pharm. 2021, 18, 870–874.
[4]	Tan, D.M.; Li, B.; He, C.W.; Zhao, X.K.; Feng, Y. Research progress in traditional Chinese medicine treatment of acute appendicitis. Mod. Digest. Int. Diagn. Treat. 2021, 26, 912–915.
[5]	Zhang, X.; Wu, C.X.; Wang, B.L. Exploring dosage patterns of Chinese herbal medicine for recurrent headaches: a data mining analysis. J. Chin. Pharm. Sci. 2024, 33, 110–122.
[6]	Liu, C.X.; Chen, S.L.; Xiao, X.H.; Zhang, X.J.; Hou, W.B.; Liao, M.L. A new concept on quality marker of Chinese materia medica: Quality control for Chinese medicinal products. Chin. Herbal Med. 2016, 47, 1443–1457.
[7]	Hsin, K.Y.; Ghosh, S.; Kitano, H. Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology. PLoS One. 2013, 8, e83922.
[8]	Li, N.Q. National planning textbook. Integrated Traditional Chinese and Western Medicine Surgery. Beijing: China Press of Chinese Medicine, 2005, 534–535.
[9]	Liu, F.; Chen, Z.Z.; Xue, L.F. Clinical diagnosis and treatment standards of traditional Chinese medicine syndrome types for acute appendicitis. Clin. Res. Tradit. Chin. Med. 2018, 10, 85–87.
[10]	Dan, W.C.; Zhao, G.Z.; He, Q.Y.; Zhang, H.; Li, B.; Zhang, G.Z. Analysis and prospects of common problems in clinical data mining of traditional Chinese medicine prescriptions. China J. Tradit. Chin. Med. 2023, 48, 4812–4818.
[11]	Zhang, Q.; Chen, Y.Y.; Le, S.J.; Wang, W.X.; Zhang, L.; Tang, Y.P. Research progress on the historical evolution of rhubarb processing and its impact on chemical components and traditional pharmacological effects. China J. Tradit. Chin. Med. Pharm. 2021, 46, 539–551.
[12]	Deng, C.S.; Zhang, C.Y.; Wu, J.F.; Luo, J.; Cui, S.Y.; Liang, W.J.; Wang, S.H. Systematic review and Meta-analysis of Dahuang Mudanpi decoction on acute appendicitis. J. Yunnan Coll. Tradit. Chin. Med. 2019, 42, 31–38.
[13]	Gao, B.Y. Therapeutic effects of Dahuangmudan decoction combined with antibiotics conservative treatment on acute appendicitis. Hebei Med. 2019, 4, 588–591.
[14]	Zhong, G.S. Traditional Chinese Medicine. 10^th edition, Beijing: China Press of Chinese Medicine, 2016.
[15]	Chen, Z.T.; Li, M. Analysis of the clinical effect of integrated traditional Chinese and Western medicine in the treatment of appendiceal inflammatory mass. World Latest Med. Inform. Abstr. 2018, 18, 149.
[16]	Ren, Z.Y.; Pan, W.Q.; Xu, Q.L.; Wang, J.; Ma, S.N.; Zhang, M. Analysis of Zhang Zhongjing’s use of Magnolia officinalis and Citrus aurantium. Tradit. Chin. Med. Res. 2021, 34, 48–51.
[17]	Dou, D.; Wang, J.L.; Zhong, X.G. Viewing on ZHANG Zhong-jing’s treatment of carbuncle from the research of the usage and meaning of "Cheng". China J. Tradit. Chin. Med. Pharm., 2023, 38, 1485–1488.
[18]	Red Vine-The King of Treating Intestinal Carbuncle. Chin. Med. Modern Dis. Edu.China. 2013, 11, 136.
[19]	Hao, Z.; Jiang, M.M.; Lu, X.L.; Liao, W.B.; You, H.Y. Analysis of the efficacy of Hedyotis diffusa in the treatment of residual abdominal infection after appendicitis. Jiangxi Med. J. 2020, 55, 1458–1459, 1463.
[20]	Wu, H.; Wang, X.Q.; Zhao, S. Research progress in the treatment of chronic appendicitis with traditional Chinese medicine. Henan Tradit. Chin. Med. 2014, 34, 2065–2066.
[21]	Li, Z.H.; Zhang, Q.S.; Li, M.Y.; Yan, Z.B.; Li, Y.L.; Yang, G.G.; Li, B.; Liang, Z.T. The efficacy of endoscopic retrograde appendicitis irrigation with traditional Chinese medicine in the treatment of acute appendicitis and its impact on VAS scores and inflammatory indicators. Tradit. Chin. Med. Res. 2022, 35, 42–46.
[22]	Yang, L. Expression of IL-6 and TNF-α in serum of patients with different types of acute appendicitis. Qinghai Med. J. 2017, 47, 63–65.
[23]	Zhang, P.; Qi, S.Q.; Wei, D.C. Changes and diagnostic value of C-reactive protein/albumin, Toll-like receptor 4, procalcitonin, and soluble intercellular adhesion molecule 1 levels in children with complex appendicitis. China Med. Herald. 2022, 19, 99–102.
[24]	Hou, C. Changes in cytokines before and after acute appendicitis surgery. Electron. J. Clin. Med. Literat. 2016, 3, 821–822.
[25]	Yan, K.; Liu, X.C. Effect of emodin on lipopolysaccharide-induced inflammatory response of bile duct epithelial cells. Chin. J. Clin. Pharm. 2024, 40, 368–372.
[26]	Wang, G.; Sun, B.; Zhu, H.; Gao, Y.; Li, X.R.; Xue, D.B.; Jiang, H.C. Protective effects of emodin combined with danshensu on experimental severe acute pancreatitis. Inflamm. Res. 2010, 59, 479–488.
[27]	Yu, Y.J.; Ye, S.F.; Deng, Y.F.; Chen, Q.Z.; Ouyang, Y. Effect of physcion on autophagy and gap junction protein in LPS-induced intestinal epithelial cell injury model. Chin. J. Hospital Pharm. 2023, 43, 2032–2036.
[28]	Dong, L.L.; Du, H.L.; Zhang, M.Y.; Xu, H.T.; Pu, X.L.; Chen, Q.Y.; Luo, R.F.; Hu, Y.C.; Wang, Y.T.; Tu, H.; Zhang, J.M.; Gao, F. Anti-inflammatory effect of Rhein on ulcerative colitis via inhibiting PI3K/Akt/mTOR signaling pathway and regulating gut microbiota. Phytother. Res. 2022, 36, 2081–2094.
[29]	Hu, B.Y.; Zhang, H.; Meng, X.L.; Wang, F.; Wang, P. Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW_264.7 macrophages. J. Ethnopharmacol. 2014, 153, 846–853.
[30]	Jadaun, K.S.; Mehan, S.; Sharma, A.; Siddiqui, E.M.; Kumar, S.; Alsuhaymi, N. Neuroprotective effect of chrysophanol as a PI3K/AKT/mTOR signaling inhibitor in an experimental model of autologous blood-induced intracerebral hemorrhage. Curr. Med. Sci. 2022, 42, 249–266.
[31]	Sun, M.; Liu, Y.L.; Liu, K.; Liu, L.L.; Zhang, L.N.; Yan, G.M. Paeonol ameliorates hepatic inflammation and oxidative stress injury on murine with alcoholic liver injury by regulating JAK2/STAT3 signaling pathway. Chin. Pharm. Bull. 2023, 39, 1078–1084.
[32]	Yang, Y.; Xu, Y.; Zhao, Y.F. Chlorogenic acid regulates the miR-124/STAT3 axis to reduce ox-LDL-induced inflammatory damage of vascular endothelial cells. Chin. J. Immunol. 2023, 39, 709–714.
[33]	Gu, Z.Q.; Liang, W.H. Study on the in vitro antibacterial effect and mechanism of rhein against Gram-negative bacteria. Clin. Ration. Drug Use. 2023, 16, 32–34, 38.
[34]	Wang, L.B.; Zhang, Y.; Liu, Y.; Xu, M.X.; Yao, Z.C.; Zhang, X.D.; Sun, Y.; Zhou, T.L.; Shen, M. Effects of chlorogenic acid on antimicrobial, antivirulence, and anti-quorum sensing of carbapenem-resistant Klebsiella pneumoniae. Front. Microbiol. 2022, 13, 997310.
[35]	Xu, W.Y.; Zhang, X.C.; Wang, L.B.; Zeng, W.L.; Sun, Y.; Zhou, C.; Zhou, T.L.; Shen, M. Effect of chlorogenic acid on the quorum-sensing system of clinically isolated multidrug-resistant Pseudomonas aeruginosa. J. Appl. Microbiol. 2022, 132, 1008–1017.
[36]	Samreen, Abul Qais, F.; Ahmad, I. In silico screening and in vitro validation of phytocompounds as multidrug efflux pump inhibitor against E. coli. J. Biomol. Struct. Dyn. 2023, 41, 2189–2201.
[37]	Zhang, X.; Wang, Y.N.; Xiao, C.; Wei, Z.K.; Wang, J.J.; Yang, Z.T.; Fu, Y.H. Resveratrol inhibits LPS-induced mice mastitis through attenuating the MAPK and NF-κB signaling pathway. Microb. Pathog. 2017, 107, 462–467.
[38]	Noack, M.; Miossec, P. Selected cytokine pathways in rheumatoid arthritis. Semin. Immunopathol. 2017, 39, 365–383.
[39]	Du, J.; Wang, J.; Wang, S.; Song, C.F. Effects of laparoscopic surgery on immune function and serum interleukin-8 and tumor necrosis factor-α levels in patients with acute suppurative appendicitis. Chin. Contemp. Med. 2021, 28, 99–101.
[40]	Zhao, K.; Wang, X.L.; Zhang, X.D.; Ding, W.Y. The research progress on the mechanism of advanced glyclation end products in diabetic kidney disease pathogenesis. Chin. J. Diabetes. 2020, 28, 951–954.
[41]	Manigrasso, M.B.; Juranek, J.; Ramasamy, R.; Schmidt, A.M. Unlocking the biology of RAGE in diabetic microvascular complications. Trends Endocrinol. Metab. 2014, 25, 15–22.