Application of Network Pharmacology, Molecular Docking, and In Vitro Experimental Evaluation to Decipher the Anti-Inflammatory Mechanisms of Cirsium japonicum
Source abstract
Abstract
Cirsium japonicum, a traditional herb, exhibits significant anti-inflammatory activity. However, the main components and potential mechanisms of C. japonicum remain unclear. The aim of this study is to investigate the anti-inflammatory mechanism of Cirsium japonicum through network pharmacology and cellular experiments. The effective components of and potential targets for the anti-inflammatory activity of C. japonicum were identified using a traditional Chinese medicine systematic pharmacology database, the TCMSP analysis platform, and the GeneCards database. The drug–component–target–disease network diagram was constructed using Cytoscape 3.8.0 software, while the protein interaction network diagram was created using the STRING database and Cytoscape 3.8.0 software. Gene ontology (GO) enrichment and KEGG pathway enrichment analysis were carried out using the DAVID database. Molecular docking between key targets and active components was constructed with AutoDock 4.2.6 software to determine the best binding target. The results revealed that 14 active components of C. japonicum targeted 171 anti-inflammatory proteins. GO function enrichment analysis yielded 173 items, while KEGG pathway enrichment analysis identified 48 signaling pathways related to inflammation regulation. Molecular docking showed a strong affinity of sitosterol, stigmasterol, and other components with key targets such as peroxisome proliferator-activated receptor α recombinant protein (PPARA) and cyclooxygenase-2 (PTGS2). Vanillin, one active ingredient of C. japonicum, inhibited the release of lipopolysaccharide (LPS)-induced inflammatory factors in RAW264.7 cells. These findings suggest that C. japonicum may exert its anti-inflammatory effects by modulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal pathway (PI3K-Akt) and apoptin signal pathway, highlighting the multi-component, multi-target, and multi-channel molecular mechanism underlying its anti-inflammatory properties. Finally, the anti-inflammatory effect of vanillin, an effective component of C. japonicum, was verified by cell experiments. This study provides a new understanding of the pharmacological mechanisms of C. japonicum in the treatment of inflammatory conditions.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Silymarin and Mushroom Poisoning · Synthesis and bioactivity of alkaloids · Healthcare and Venom Research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
College of Grassland Agriculture, Northwest A&F University, Xianyang 712100, China
Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Beijing 100081, China
Funding
Third Xinjiang Scientific Expedition Program
References (75)
Show source-provided references
1. Anticancer Activity and Quantitative Analysis of Flavone of Cirsium japonicum DC10.1080/14786410701494686 ↗
2. Discusses the Anti-inflammatory Effect of Stigmasterol Based on Network Pharmacology and Cell Experiments
3. Beneficial Effects of a Medicinal Herb, Cirsium japonicum var. Maackii, Extract and its Major Component, Cirsimaritin on Breast Cancer Metastasis in MDA-MB-231 Breast Cancer Cells. Bioorg10.1016/j.bmcl.2017.07.070 ↗
4. In Renal Hypertension, Cirsium japonicum Strengthens Cardiac Function via the Intermedin/Nitric Oxide Pathway10.1016/j.biopha.2018.02.126 ↗
5. Wagle, A., Seong, S.H., Shrestha, S., Jung, H.A., and Choi, J.S. (2019). Korean Thistle (Cirsium japonicum Var. Maackii (Maxim.) Matsum.): A Potential Dietary Supplement Against Diabetes and Alzheimer’s Disease. Molecules, 24.10.3390/molecules24030649 ↗
6. Yoon, S., Kim, M., Shin, S., Woo, J., Son, D., Ryu, D., Yoo, J., Park, D., and Jung, E. (2022). Effect of Cirsium japonicum Flower Extract on Skin Aging Induced by Glycation. Molecules, 27.10.3390/molecules27072093 ↗
7. Cirsium Japonicum Var. Maackii and Apigenin Block Hif-2α-induced Osteoarthritic Cartilage Destruction10.1111/jcmm.14418 ↗
8. Taoufiq, B., Imane, J., Rokia, G., Nasreddine, E.O., Kaoutar, H., Khalil, H., Maksim, R., Ali, S.M., Mohammad, M.S., and Jesus, S.C. (2022). The Current State of Knowledge in Biological Properties of Cirsimaritin. Antioxidants, 11.10.3390/antiox11091842 ↗
9. Predicting the Mechanism of Cirsium japonicum in Treating Hypertension Based on Network Pharmacology
10. Ethanol Extract of Cirsium japonicum var. ussuriense Kitamura Exhibits the Activation of Nuclear Factor Erythroid 2-Related Factor 2-dependent Antioxidant Response Element and Protects Human Keratinocyte HaCaT Cells Against Oxidative DNA Damage10.15430/JCP.2016.21.1.66 ↗
11. Ameliorative effects of Cirsium japonicum Extract and Main Component Cirsimaritin in Mice Model of High-Fat Diet-Induced Metabolic Dysfunction-Associated Fatty Liver Disease10.1002/fsn3.2548 ↗
12. Artichoke Extracts: Physiological Effects, Use in Obstetric Practice
13. Anti-inflammatory Effects and Corresponding Mechanisms of Cirsimaritin Extracted from Cirsium japonicum var. maackii Maxim10.1016/j.bmcl.2017.05.051 ↗
14. Comparative Antitumor and Anti-inflammatory Effects of Flavonoids, Saponins, Polysaccharides, Essential Oil, Coumarin and Alkaloids from Cirsium japonicum DC10.1016/j.fct.2019.01.020 ↗
15. Kong, F., Fang, Z.G., Cui, B., Gao, J.S., Sun, C.H., and Zhang, S.T. (2024). Study on the Compositional Analysis, Extraction Process, and Hemostatic and Anti-Inflammatory Activities of Cirsium japonicum Fisch. ex DC.—Cirsium setosum (Willd.) MB Extracts. Molecules, 29.10.3390/molecules29091918 ↗
16. KiKwang, O., Md, A., and DongHa, C. (2021). Network Pharmacology-Based Study to Uncover Potential Pharmacological Mechanisms of Korean Thistle (Cirsium japonicum var. maackii (Maxim.) Matsum.) Flower against Cancer. Molecules, 26.10.3390/molecules26195904 ↗
17. PI3K/AKT Pathway as A Key Link Modulates the Multidrug Resistance of Cancers10.1038/s41419-020-02998-6 ↗
18. A Network pharmacology10.1038/nbt1007-1110 ↗
19. Integrated Metabolomics and Network Pharmacology to Reveal the Mechanisms of Hydroxysafflor Yellow A Against Acute Traumatic Brain Injury10.1016/j.csbj.2021.01.033 ↗
20. Mechanism of Sijunzi Decoction in the Treatment of Colorectal Cancer Based on Network Pharmacology and Experimental Validation10.1016/j.jep.2022.115876 ↗
21. Zhang, P., Zhang, D.F., Zhou, W.A., Wang, L., Wang, B.Y., Zhang, T.Y., and Li, S. (2023). Network Pharmacology: Towards the Artificial Intelligence-based Precision Traditional Chinese Medicine. Brief Bioinform., 25.10.1093/bib/bbad518 ↗
22. Network Pharmacology, A Promising Approach to Reveal the Pharmacology Mechanism of Chinese Medicine Formula10.1016/j.jep.2023.116306 ↗
23. Network Pharmacology Approaches for Research of Traditional Chinese Medicines
24. Exploring Pharmacological Mechanisms of Xuefu Zhuyu Decoction in the Treatment of Traumatic Brain Injury via a Network Pharmacology Approach10.1155/2018/8916938 ↗
25. Network Pharmacology and Bioinformatics Approach Reveals the Therapeutic Mechanism of Action of Baicalein in Hepatocellular Carcinoma10.1155/2019/7518374 ↗
26. Ma, Q.Y., Liu, Y.C., Zhang, Q., Yi, W.D., Sun, Y., Gao, X.D., Zhao, X., Wang, H.W., Lei, K., and Luo, W.J. (2024). Integrating Network Pharmacology, Molecular Docking and Experimental Verification to Reveal the Mechanism of Artesunate in Inhibiting Choroidal Melanoma. Front. Pharmacol., 15.10.3389/fphar.2024.1448381 ↗
27. Ye, J.H., Li, L., and Hu, Z.X. (2021). Exploring the Molecular Mechanism of Action of Yinchen Wuling Powder for the Treatment of Hyperlipidemia, Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation. BioMed Res. Int., 21.10.1155/2021/9965906 ↗
28. Progress and Prospects of Research Ideas and Methods in the Network Pharmacology of Traditional Chinese Medicine10.18433/jpps32911 ↗
29. Activity Prediction, Structure-based Drug Design, Molecular Docking, and Pharmacokinetic Studies of 1,4-dihydropyridines Derivatives as α-amylase inhibitors
30. Dong, Y.K., Tao, B., Xue, X., Feng, C.X., Ren, Y.T., Ma, H.Y., Zhang, J.L., Si, Y.F., Zhang, S.S., and Liu, S. (2021). Molecular Mechanism of Epicedium Treatment for Depression Based on Network Pharmacology and Molecular Docking Technology. BMC Complement Med., 21.10.1186/s12906-021-03389-w ↗
31. Study on the Mechanism of Action of RoucongrongTang in Treating Functional Constipation based on Network Pharmacology and Molecular Docking
32. Larisa, I., and Mati, K. (2022). The Impact of Software Used and the Type of Target Protein on Molecular Docking Accuracy. Molecules, 27.10.3390/molecules27249041 ↗
33. Molecular Docking Studies on Isocytosine Analogues as Xanthine Oxidase Inhibitors10.1055/s-0043-125210 ↗
34. Mechanism Research of Apatinib-treated Breast Cancer Based on Network Pharmacology
35. Studies on the Compatibility Mechanism and Material Basis of Danggui Buxue Decoction Against Anemia Mice Using Metabonomics and Network Pharmacology10.1093/jpp/rgab016 ↗
36. Study on the Potential Pharmacodynamic Substances of Jinhua Qinggan Granule for Prevention and Treatment of Novel Coronavirus Based on Network Pharmacology and Molecular Docking Technology
37. Research progress of plant extracts in the field of feed additives based on network pharmacology
38. Stigmasterol Attenuates Hepatic Steatosis in Rats by Strengthening the Intestinal Barrier and Improving Bile Acid Metabolism10.1038/s41538-022-00156-0 ↗
39. Network Pharmacology and Experimental Study of Jiawei Guizhi Fuling Pill in the Treatment of Benign Prostatic Hyperplasia
40. Kim, R., Islam, M.S., Yoo, Y.J., Shin, H.Y., Lee, J.H., Cho, J.H., Park, Y.G., Choi, J., Tae, H.J., and Park, B.Y. (2022). Anti-inflammatory Effects of the Aralia elata and Cirsium japonicum in Raw264.7 Cells and in Vivo Colitis Model in Mice and Dogs. J. Biomed. Pharmacother., 151.10.1016/j.biopha.2022.113186 ↗
41. Metabonomics Study of Cirsium japonicum Extract in Improving Hypercholesterolemia Model Mice
42. Flavonols and Flavones as Potential Anti-Inflammatory, Antioxidant, and Antibacterial Compounds10.1155/2022/9966750 ↗
43. The Influence of Harvest Time on Total Phenolic and Flavonoid Contents, Antioxidant, Antibacterial and Cytotoxicity of Rheum Khorasanicum Root Extract10.1016/j.pharma.2022.11.010 ↗
44. Luteolin, a Flavone Ingredient: Anticancer Mechanisms, Combined Medication Strategy, Pharmacokinetics, Clinical Trials, and Pharmaceutical Researches10.1002/ptr.8066 ↗
45. Flavone Analogues as Antimicrobial Agents10.2174/1872213X11666170119094702 ↗
46. Physiological Function of β-sitosterol and Its Application in Animal Production
47. Antioxidation Activity Enhancement by Intramolecular Hydrogen Bond and Non-Browning Mechanism of Active Ingredients in Rosemary: Carnosic Acid and Carnosol10.1021/acs.jpcb.4c02949 ↗
48. Liposomal Resveratrol Alleviates Platelet Storage Lesion via Antioxidation and the Physical Buffering Effect10.1021/acsami.3c09935 ↗
49. Fermentation of Robinia pseudoacacia Flower for Improving the Antioxidation: Optimized Conditions, Active Composition, Mechanism, and Biotransformation Process10.1080/10826068.2023.2185637 ↗
50. The Antioxidation of Different Fractions of Dill (Anethum graveolens) and Their Influences on Cytokines in Macrophages RAW264.710.5650/jos.ess18134 ↗
51. Zidan, K., Nikhil, N., Abdur, R., Emran, T.B., Saikat, M., Fahadul, I., Deepak, C., Jackie, B., Khandaker, M.U., and Idri, A.M. (2022). Multifunctional Roles and Pharmacological Potential of β-sitosterol: Emerging Evidence Toward Clinical Applications. J. Chem.-Biol. Interact., 365.10.1016/j.cbi.2022.110117 ↗
52. Long, B.Y. (2019). Effect of Oleic Acid on Lipopolysaccharide-Induced Inflammatory Response of Mouse Macrophages and Its Mechanism. [Ph.D. Thesis, University of South China].
53. Conditional Deletion of Adrb2 in Mesenchymal Stem Cells Attenuates Osteoarthritis-like Defects in Temporomandibular Joint10.1016/j.bone.2020.115229 ↗
54. PTGS2 (Cyclooxygenase-2) Expression and Survival among Colorectal Cancer Patients: A Systematic Review10.1158/1055-9965.EPI-13-0263 ↗
55. Licofelone Attenuates LPS-induced Depressive-like Behavior in Mice: A Possible Role for Nitric Oxide
56. Atf3 Negatively Regulates Ptgs2/Cox2 Expression During Acute Inflammation10.1016/j.prostaglandins.2015.01.001 ↗
57. Wautier, J.L., and Wautier, M.P. (2023). Pro- and Anti-Inflammatory Prostaglandins and Cytokines in Humans: A Mini Review. Int. J. Mol. Sci., 24.10.3390/ijms24119647 ↗
58. Neto, A.B.L., Vasconcelos, N.B.R., Santos, T.R.D., Duarte, L.E.C., Assunção, M.L., Sales-Marques, C., and Silva Ferreira, H. (2021). Prevalence of IGFBP3, NOS3 and TCF7L2 Polymorphisms and Their Association with Hypertension: A Population-based Study with Brazilian Women of African Descent. BMC Res. Notes, 17.10.1186/s13104-021-05598-5 ↗
59. Association Between the Polymorphism of Glu298Asp in Exon 7 of the eNOS Gene with Foot Ulcer and Oxidative Stress in Adult Patients with Type 2 Diabetes10.1016/j.jcjd.2017.03.001 ↗
60. BDNF—A Key Transducer of Antidepressant Effects10.1016/j.neuropharm.2015.10.034 ↗
61. PM2.5 Exposure Exacerbates Mice Thoracic Aortic Aneurysm and Dissection by Inducing Smooth Muscle Cell Apoptosis via the MAPK Pathway10.1016/j.chemosphere.2022.137500 ↗
62. Jin, W. (2020). Regulation of BDNF-TrkB Signaling and Potential Therapeutic Strategies for Parkinson’s Disease. J. Clin. Med., 17.10.3390/jcm9010257 ↗
63. Angelica Polysaccharide Ameliorates Memory Impairment in Alzheimer’s Disease Rat Through Activating BDNF/TrkB/CREB Pathway10.1177/1535370219894558 ↗
64. Activation of Peroxisome Proliferator-activated Receptor Gamma is Crucial for Antitumoral Effects of 6-iodolactone
65. Experimental Study on Yiqi Huayu Zhiwei Recipe Relieving Chronic Atrophic Gastritis by Regulating PI3K/AKT Signaling Pathway
66. Modified Linggui Zhugan Decoction Ameliorates Glycolipid Metabolism and Inflammation via PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α Signaling Pathways in Obese Type 2 Diabetic Rats10.1007/s11655-020-3285-2 ↗
67. TLR4 and CD14 Trafficking and its Influence on LPS-induced Pro-inflammatory Signaling10.1007/s00018-020-03656-y ↗
68. Lipopolysaccharide Modification in Gram-negative Bacteria During Chronic Infection10.1093/femsre/fuw007 ↗
69. Macrophage Migration Inhibitory Factor-mediated Mast Cell Extracellular Traps Induce Inflammatory Responses Upon Fusobacterium Nucleatum Infection10.1016/j.bbrc.2023.06.060 ↗
70. Integration Strategy of Network Pharmacology in Traditional Chinese Medicine: A Narrative Review
71. Covalent Docking in Drug Discovery: Scope and Limitations10.2174/1381612824999201105164942 ↗
72. Chemical Constituents and Biological Activities of Cirsium leucopsis, C. sipyleum, and C. eriophorum10.5560/znc.2014-0071 ↗
73. Traditional Uses, Phytochemical Composition, Pharmacological Properties, and the Biodiscovery Potential of the Genus Cirsium10.3390/chemistry4040079 ↗
74. Data of Co-extraction of Inulin and Phenolic Compounds from Globe Artichoke Discards, Using Different Conditioning Conditions of the Samples and Extraction by Maceration10.1016/j.dib.2020.105986 ↗
75. Chemical Compositions and Antibacterial Activity of Extracts Obtained from the Inflorescences of Cirsium canum (L.) All10.1080/14786419.2015.1030341 ↗