Possible Molecular Mechanisms of Dachengqi Decoction for Improving Subjective Symptoms of Degenerative Lumbar Spinal Stenosis: a Network Pharmacology Study

doi:10.19803/j.1672-8629.20240536

Abstract

Abstract: Objective To explore the molecular mechanisms of Dachengqi decoction in the treatment of degenerative lumbar spinal stenosis (DLSS) using a network pharmacology approach. Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was searched to retrieve information on the chemical components and genes related to Dachengqi decoction as of July 10, 2024. For compounds not covered by TCMSP or without target gene information, the molecular formulas were obtained from the PubChem database, and SwissADME was used for screening. Target prediction for eligible compounds was performed using the SwissTargetPrediction database, and gene names were standardized using the UniProt database. On the same day, the GenCards, OMIM, and DrugBank databases were searched to collect information on DLSS-related disease genes, which was then mapped to the drug targets. Common genes were imported into the STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database to construct a protein-protein interaction (PPI) network, followed by pathway enrichment analysis using the Metascape database. Cytoscape 3.10.2 software was used to create a “drug-compound-target” network, and NetworkAnalyzer was applied for topological analysis of key compounds and targets. Results Ten key active compounds, including rutin, 5,7,4'-trimethylapigenin, and eucalyptol, as well as ten key targets, including prostaglandin-endoperoxide synthase 2 (PTGS2) and heat shock protein β (HSPCB), were identified. Pathway enrichment analysis suggested that Dachengqi decoction could improve the subjective symptoms of DLSS patients through the PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, neurodegeneration pathway, and various cellular activities. Conclusion Dachengqi decoction can not only alleviate constipation and related symptom exacerbation in DLSS patients, but also modulate inflammation, oxidative stress, and nerve cell tissue repair through its active compounds, targets, and pathways.

Key words: Dachengqi Decoction, Rutin, 5,7,4'-trimethylapigenin, Eucalyptol, Degenerative Lumbar Spinal Stenosis, Network Pharmacology

CLC Number:

R943
R994.11

GAN Yena, HAN Sheng, YUAN Yi, XUE Lijuan, HUANG Haowen, LI Huanxin, ZHANG Xinci, KUI Siyi, MENG Bofei, LI Qifei, ANARGUL Tudi, LIU Zhifeng, QIN Lingling, LI Duoduo. Possible Molecular Mechanisms of Dachengqi Decoction for Improving Subjective Symptoms of Degenerative Lumbar Spinal Stenosis: a Network Pharmacology Study[J]. Chinese Journal of Pharmacovigilance, 2025, 22(2): 162-168.

Add to citation manager EndNote|Ris|BibTeX

URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20240536

https://zgywjj.magtechjournal.com/EN/Y2025/V22/I2/162

References

[1] ROUSING R, JENSEN R K, FRUENSGAARD S, et al.Danish National Clinical Guidelines for Surgical and Nonsurgical Treatment of Patients with Lumbar Spinal Stenosis[J]. Eur Spine J, 2019, 28(6): 1386-1396.
[2] WHO. Musculoskeletal health[EB/OL]. (2022-07-14)[2024-05-28]. https://www.who.int/news-room/fact-sheets/detail/musculoskeletal-conditions.
[3] HARTVIGSEN J, HANCOCK MJ, KONGSTED A, et al.What Low Back Pain is and Why We Need to Pay Attention[J]. Lancet, 2018, 391(10137): 2356-2367.
[4] HUANG H, WANG SY, ZENG LH, et al.Effects of Huoxue Tongdu Decoction Combined with Tendon Manipulation on Lumbar Extension Angle and Hemorheology in Patients with Degenerative Lumbar Spinal Stenosis of Kidney Deficiency and Blood Stasis Type[J]. Hebei Journal of Traditional Chinese Medicine(河北中医), 2024, 46(6): 907-910, 914.
[5] BURGSTALLER JM, STEURER J, GRAVESTOCK I, et al.Long-Term Results after Surgical or Nonsurgical Treatment in Patients with Degenerative Lumbar Spinal Stenosis: A Prospective Multicenter Study[J]. Spine (Phila Pa 1976), 2020, 45(15):1030-1038.
[6] FAN SJ.Effect of Huoxue Tongdu Decoction Combined with Posterior Decompression and Internal Fixation Surgery on Degenerative Lumbar Spinal Stenosis[J]. Henan Journal of Surgery(河南外科学杂志), 2020, 26(2): 62-64.
[7] LIU WB, HE LD, LI Y, et al.Diagnosis and Progress of Integrated Traditional Chinese and Western Medicine in the Treatment of Degenerative Lumbar Spinal Stenosis[J]. Jiangxi Journal of Traditional Chinese Medicine(江西中医药), 2024, 55(7): 76-80.
[8] PAN GT, LIU YH, SHANG LR, et al.Study on the Protective Mechanism of Dachengqi Decoction in Alleviating Apoptosis in Rats with Acute Lung Injury[J]. Lishizhen Medicine and Materia Medica Research(时珍国医国药), 2021, 32(8): 1825-1829.
[9] XU YP.Clinical Study on the Use of “Xiafa” for Treating Lumbar Disc Herniation[J]. Chinese Journal of Traditional Orthopedics(中国骨伤), 2005(3): 144-145.
[10] QIN XK, SUN K, XU WG, et al.Evidence-Based Guidelines for Traditional Chinese Medicine in the Treatment of Lumbar Disc Herniation[J]. Western Journal of Traditional Chinese Medicine(西部中医药), 2024, 37(5): 1-15.
[11] PARK YS, PAN GX, LI T, et al.The Experience of Master Lu Fang in Treating “Bi Syndrome” with Accumulation of Pathogenic Qi Using the “Xiafa” Method[J]. Shandong Journal of Traditional Chinese Medicine(山东中医杂志), 2020, 39(2): 161-163.
[12] CAI YF, ZHANG S.Observation on the Clinical Efficacy of Zhang Zhongjing's “Lixiaobian” Method in Treating Acute Lumbar Disc Herniation[J]. China Medicine and Science(中国医药科学), 2013, 3(13): 93-94.
[13] RU J, LI P, WANG J, et al.TCMSP: a Database of Systems Pharmacology for Drug Discovery from Herbal Medicines[J]. J Cheminform, 2014, 6: 13.
[14] SHEN M, TIAN S, LI Y, et al.Drug-Likeness Analysis of Traditional Chinese Medicines: Property Distributions of Drug-Like Compounds, Non-Drug-Like Compounds and Natural Compounds from Traditional Chinese Medicines[J]. J Cheminform, 2012, 4(1): 31.
[15] DAINA A, MICHIELIN O, ZOETE V.SwissADME: a Free Web Tool to Evaluate Pharmacokinetics, Drug-Likeness and Medicinal Chemistry Friendliness of Small Molecules[J]. Sci Rep, 2017, 7: 42717.
[16] DAINA A, MICHIELIN O, ZOETE V.SwissTarget Prediction: Updated Data and New Features for Efficient Prediction of Protein Targets of Small Molecules[J]. Nucleic Acids Res, 2019, 47(W1): W357-W364.
[17] LI M, WANG B, TANG ZS, et al.Study on the Differences in Anti-Inflammatory, Analgesic and Laxative Effects of Mangxiao and Its Main Components[J]. Pharmacology and Clinics of Chinese Materia Medica(中药药理与临床), 2012, 28(5): 55-57.
[18] UniProt Consortium. UniProt: the Universal Protein Knowledgebase in 2023[J]. Nucleic Acids Res, 2023, 51(D1): D523-D531.
[19] 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: 1.30.1-1.31.1.
[20] WISHART DS, FEUNANG YD, GUO AC, et al.DrugBank 5.0: a Major Update to the DrugBank Database for 2018[J]. Nucleic Acids Res. 2018, 46(D1): D1074-D1082.
[21] SZKLARCZYK D, GABLE AL, NASTOU KC, et al.The STRING Database in 2021: Customizable Protein-Protein Networks, and Functional Characterization of User-Uploaded Gene/Measurement Sets[J]. Nucleic Acids Res, 2021, 49(D1): D605-D612.
[22] SHANNON P, MARKIEL A, OZIER O, et al.Cytoscape: a Software Environment for Integrated Models of Biomolecular Interaction Networks[J]. Genome Res, 2003, 13(11): 2498-2504.
[23] ZHOU Y, ZHOU B, PACHE L, et al.Metascape Provides a Biologist-Oriented Resource for the Analysis of Systems-Level Datasets[J]. Nat Commun, 2019, 10(1): 1523.
[24] LIU YD, WANG QD, GUO J.Clinical Observation of Yaobi Shujin Decoction Combined with Massage in the Treatment of Degenerative Lumbar Spinal Stenosis[J]. Journal of Practical Traditional Chinese Medicine(实用中医药杂志), 2024, 40(2):195-197.
[25] FU ZH, ZHAO LL, ZHOU L, et al.Study on the Mechanism and Key Target Pathways of Dachengqi Decoction in Treating Sepsis Based on Network Pharmacology[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2021, 46(20): 5351-5361.
[26] ZHANG T, YANG CC, ZHANG SH, et al.Network Pharmacology Study on the Treatment of Intestinal Obstruction with Jiawei Dachengqi Decoction Using Huoxue Gongxia Method[J]. Chinese Journal of Integrated Traditional and Western Medicine in Surgery(中国中西医结合外科杂志), 2020, 26(5): 838-849.
[27] YANG JY, WANG R, JIN T, et al.Network Pharmacology Study on the Material Basis and Molecular Mechanism of Dachengqi Decoction in the Treatment of Acute Pancreatitis[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2020, 45(6): 1423-1432.
[28] HUO L, LI Y, CUI WH, et al.Clinical Study on the Treatment of Lumbar Spinal Stenosis with Kidney Qi Deficiency Type Using Radiofrequency Target Thermocoagulation Expansion Combined with Zhuangyao Qiangdu Decoction[J]. Heilongjiang Medical Journal(黑龙江医学), 2024, 48(1): 27-30.
[29] DONG TB, LIAO CY, ZHAO GH, et al.Clinical Observation of Dielong Shuyao Decoction in the Treatment of Degenerative Lumbar Spinal Stenosis (Kidney Deficiency and Blood Stasis Type)[J]. Journal of Clinical Chinese Medicine(中医药临床杂志), 2024, 36(2): 338-342.
[30] WEN HB, LI LG, GAO CY, et al.Randomized Double-Blind Controlled Trial of Baizhu Zhuanyao Decoction in the Treatment of Degenerative Lumbar Spinal Stenosis with Spleen-Kidney Yang Deficiency and Phlegm-Stasis Obstruction Syndrome[J]. Chinese Journal of Integrated Traditional and Western Medicine(中国中西医结合杂志), 2024, 44(6): 670-676.
[31] ZHOU LJ, LIU Y, HU Y.Comparison of Non-Surgical and Surgical Treatments for Degenerative Lumbar Spinal Stenosis in the Elderly[J]. Jilin Medical Journal(吉林医学), 2022, 43(1): 25-27.
[32] TAN F, TAN JW, WANG CX, et al.Advances in the Application of Minimally Invasive Surgery in Degenerative Lumbar Spinal Stenosis[J]. Medical Review(医学综述), 2021, 27(5): 967-972.
[33] YAN JB, LIU BX, GUO JB, et al.Therapeutic Effect of Taohong Chengqi Decoction on Postoperative Lumbar Vertebra with Stagnation of Blood Stasis and Heat Syndrome[J]. Guangdong Medical Journal(广东医学), 2023, 44(7): 838-841.
[34] GAO MQ, MA X, JIANG ZL, et al.Clinical Efficacy of Dachengqi Decoction in the Treatment of Abdominal Distension and Constipation after Spinal Trauma[J]. System Medicine(系统医学), 2022, 7(5): 31-35.
[35] YANG SS, LIN L.Study on the Effect and Mechanism of Dachengqi Decoction on Microglia in Rats with Cerebral Hemorrhage Model[J]. Journal of Huazhong University of Science and Technology (Medical Edition)(华中科技大学学报医学版), 2021, 50(6):728-733, 749.
[36] LIU YH, ZHANG MX, GUAN B, et al.Dachengqi Decoction Improves Inflammatory Gastrointestinal Motility Disorders in Rats by Inhibiting Inflammatory Response[J]. Journal of Shanxi Medical University(山西医科大学学报), 2015, 46(5): 411-416.
[37] FAN MH, SHUAI RY, LI QY.Rhein Inhibits Breast Cancer Cell Proliferation and Induces Apoptosis by Regulating MiR-582-3p and MAP3K1 activity[J]. Zhejiang Journal of Integrated Traditional Chinese and Western Medicine(浙江中西医结合杂志), 2024, 34(5): 407-414.
[38] ZHAO JF, HU DS, WANG CY.Research Progress on Dachengqi Decoction Experimental Study[J]. Henan Traditional Chinese Medicine(河南中医), 2014, 34(1): 29-31.
[39] LI L, MA BL, HE B, et al.The Effect of Poria Acid on Ferroptosis of Endometrial Stromal Cells in Rats with Endometriosis by Regulating the AMPK/GSK-3β/Nrf2 Signaling Pathway[J]. Hunan Journal of Traditional Chinese Medicine(湖南中医杂志), 2024, 40(6): 175-182.
[40] JI Y, DENG YC, LI XH.The Role and Mechanism of Immune System Abnormalities in Atherosclerosis Induced by Inflammatory Stimulation during Pregnancy[J]. Chinese Journal of Pharmacology and Toxicology(中国药理学与毒理学杂志), 2019, 33(10): 810.
[41] ZHU DX, WU Z, HAO FX, et al. Study on the Mechanism of Polygonum Cuspidatum in Preventing and Treating Gosling Gout Based on Network Pharmacology, Molecular Docking,Animal Experiments[J]. Heilongjiang Animal Science and Veterinary Medicine (黑龙江畜牧兽医), 2024(13): 91-97, 113-114.
[42] MENG YN, HUANG WJ, GAO LX, et al.Expression of Ferroptosis-Related Genes in Diffuse Large B-Cell Lymphoma and Their Relationship with Immune Cells and Signaling Pathways[J]. Journal of Practical Oncology(实用肿瘤杂志), 2024, 39(1): 49-57.
[43] ZHU YL, QIU ZY, HE XB, et al.Research Progress on the Pathogenesis of Ulcerative Colitis and Chinese Medicine Intervention Based on PI3K/Akt Pathway[J]. Journal of Traditional Chinese Medicine(中医药学报), 2024, 8: 102-109.
[44] HONG XM, PENG Y, ZHANG C, et al.Preliminary Exploration of the Molecular Mechanism of Jingshui LiuJun Decoction Combined with Chemotherapy and Radiotherapy for Malignant Melanoma Based on Network Pharmacology and in vitro Experiments[J]. Journal of Shenyang Pharmaceutical University(沈阳药科大学学报), 2024, 41(3): 330-342.
[45] ZHU ZQ, QIN QQ, XIN XY, et al.Study on the Mechanism of Bupleurum-Paeoniae Decoction in the Treatment of High-Risk Human Papillomavirus Infection of the Cervix Based on Network Pharmacology[J]. China Journal of Hospital Pharmacy Evaluation and Analysis(中国医院用药评价与分析), 2024, 24(6): 662-666, 671.
[46] LUO XM, CAO B, CAO T, et al.The effect of Ganoderma Lucidum Phenol on Inflammation and Renal Fibrosis in Rats with Chronic Kidney Disease through the AGE/RAGE Signaling Pathway[J]. Progress in Modern Biomedicine(现代生物医学进展), 2024, 24(7): 1235-1239.
[47] CHANG B, MA BX, GUAN YL, et al.Research Progress on the Treatment of Lumbar Disc Herniation with Duhuo Jisheng Decoction[J]. Journal of Clinical Chinese Medicine(中医药临床杂志), 2022, 34(10): 1976-1979.
[48] XIA TW, ZHOU GW, LIU JZ, et al.Study on the Mechanism of Bushen Huoxue Decoction in the Treatment of Avascular Necrosis of the Femoral Head Based on Network Pharmacology[J]. Shandong Journal of Traditional Chinese Medicine(山东中医杂志), 2021, 40(1): 25-31.