Network Pharmacology and Experimental Validation Explore the Pharmacological Mechanisms of Herb Pair for Treating Rheumatoid Arthritis

Overview

Journal Comb Chem High Throughput Screen

Publisher Bentham Science Publishers

Specialty Chemistry

Date 2024 Jan 12

PMID 38213142

Authors

Xi-Xi Xu

Hua Shao

Qiao-Xue Wang

Zi-Yuan Wang

Affiliations

Soon will be listed here.

Abstract

Objective: This study aimed to elucidate the multitarget mechanism of the Mori Ramulus - Taxilli Herba (MT) herb pair in treating rheumatoid arthritis (RA).

Methods: The targets of the herb pair and RA were predicted from databases and screened through cross-analysis. The core targets were obtained using protein-protein interaction (PPI) network analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Finally, animal experiments were conducted to validate the anti-RA effect and mechanism of this herb pair.

Results: This approach successfully identified 9 active compounds of MT that interacted with 6 core targets (AKT1, TNF, IL6, TP53, VEGFA, and IL1β). Pathway and functional enrichment analyses revealed that MT had significant effects on the TNF and IL-17 signaling pathways. The consistency of interactions between active components and targets in these pathways was confirmed through molecular docking. Moreover, the potential therapeutic effect of MT was verified in vivo, demonstrating its ability to effectively relieve inflammation by regulating these targeted genes and pathways.

Conclusion: The present work suggests that the therapeutic effect of MT herb pair on RA may be attributed to its ability to regulate the TNF signaling pathway and IL-17 signaling pathway.

Citing Articles

Metabolic effects of quercetin on inflammatory and autoimmune responses in rheumatoid arthritis are mediated through the inhibition of JAK1/STAT3/HIF-1α signaling.

Zhang F, Zhang Y, Zhou J, Cai Y, Li Z, Sun J Mol Med. 2024; 30(1):170.

PMID: 39390367 PMC: 11468292. DOI: 10.1186/s10020-024-00929-1.

References

Smith M, Berman J . What Is Rheumatoid Arthritis?. JAMA. 2022; 327(12):1194. DOI: 10.1001/jama.2022.0786. View

Gravallese E, Firestein G . Rheumatoid Arthritis - Common Origins, Divergent Mechanisms. N Engl J Med. 2023; 388(6):529-542. DOI: 10.1056/NEJMra2103726. View

Roberts-Thomson P, Jones M, Walker J, Macfarlane J, Smith M, Ahern M . Stochastic processes in the causation of rheumatic disease. J Rheumatol. 2002; 29(12):2628-34. View

Klareskog L, van der Heijde D, de Jager J, Gough A, Kalden J, Malaise M . Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004; 363(9410):675-81. DOI: 10.1016/S0140-6736(04)15640-7. View

Sanchez-Piedra C, Sueiro-Delgado D, Garcia-Gonzalez J, Ros-Vilamajo I, Prior-Espanol A, Moreno-Ramos M . Changes in the use patterns of bDMARDs in patients with rheumatic diseases over the past 13 years. Sci Rep. 2021; 11(1):15051. PMC: 8302725. DOI: 10.1038/s41598-021-94504-x. View

Pelechas E, Voulgari P, Drosos A . Golimumab for Rheumatoid Arthritis. J Clin Med. 2019; 8(3). PMC: 6463251. DOI: 10.3390/jcm8030387. View

Breedveld F, Weisman M, Kavanaugh A, Cohen S, Pavelka K, van Vollenhoven R . The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had.... Arthritis Rheum. 2005; 54(1):26-37. DOI: 10.1002/art.21519. View

Guo Q, Wang Y, Xu D, Nossent J, Pavlos N, Xu J . Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res. 2018; 6:15. PMC: 5920070. DOI: 10.1038/s41413-018-0016-9. View

Lin W, Lu Y, Huang B, Chuang C, Cheng Y, Chen I . Selective activation of pro-anti-IL-1β antibody enhances specificity for autoinflammatory disorder therapy. Sci Rep. 2021; 11(1):14846. PMC: 8295355. DOI: 10.1038/s41598-021-94298-y. View

10.

Cohen S, Dore R, Lane N, Ory P, Peterfy C, Sharp J . Denosumab treatment effects on structural damage, bone mineral density, and bone turnover in rheumatoid arthritis: a twelve-month, multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. Arthritis Rheum. 2008; 58(5):1299-309. DOI: 10.1002/art.23417. View

11.

Takeuchi T, Tanaka Y, Ishiguro N, Yamanaka H, Yoneda T, Ohira T . Effect of denosumab on Japanese patients with rheumatoid arthritis: a dose-response study of AMG 162 (Denosumab) in patients with RheumatoId arthritis on methotrexate to Validate inhibitory effect on bone Erosion (DRIVE)-a 12-month, multicentre,.... Ann Rheum Dis. 2015; 75(6):983-90. PMC: 4893103. DOI: 10.1136/annrheumdis-2015-208052. View

12.

George M, Baker J, Winthrop K, Hsu J, Wu Q, Chen L . Risk for Serious Infection With Low-Dose Glucocorticoids in Patients With Rheumatoid Arthritis : A Cohort Study. Ann Intern Med. 2020; 173(11):870-878. PMC: 8073808. DOI: 10.7326/M20-1594. View

13.

Chen Y, Hsieh F, Chang C, Chi N, Wu H, Chiou H . Effect on Risk of Stroke and Acute Myocardial Infarction of Nonselective Nonsteroidal Anti-Inflammatory Drugs in Patients With Rheumatoid Arthritis. Am J Cardiol. 2018; 121(10):1271-1277. DOI: 10.1016/j.amjcard.2018.01.044. View

14.

Bergstra S, Sepriano A, Kerschbaumer A, van der Heijde D, Caporali R, Edwards C . Efficacy, duration of use and safety of glucocorticoids: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2022; 82(1):81-94. DOI: 10.1136/ard-2022-223358. View

15.

He B, Li Y, Luo W, Cheng X, Xiang H, Zhang Q . The Risk of Adverse Effects of TNF-α Inhibitors in Patients With Rheumatoid Arthritis: A Network Meta-Analysis. Front Immunol. 2022; 13:814429. PMC: 8888889. DOI: 10.3389/fimmu.2022.814429. View

16.

Hoisnard L, Pina Vegas L, Dray-Spira R, Weill A, Zureik M, Sbidian E . Risk of major adverse cardiovascular and venous thromboembolism events in patients with rheumatoid arthritis exposed to JAK inhibitors versus adalimumab: a nationwide cohort study. Ann Rheum Dis. 2022; 82(2):182-188. DOI: 10.1136/ard-2022-222824. View

17.

Mirzaei A, Jahed S, Kadijani A, Zabihiyeganeh M . Risk of infection in postmenopausal women with rheumatoid arthritis and osteoporosis taking denosumab and bDMARDS. Med J Islam Repub Iran. 2021; 35:12. PMC: 8111619. DOI: 10.47176/mjiri.35.12. View

18.

Curtis J, Xie F, Yun H, Saag K, Chen L, Delzell E . Risk of hospitalized infection among rheumatoid arthritis patients concurrently treated with a biologic agent and denosumab. Arthritis Rheumatol. 2015; 67(6):1456-64. DOI: 10.1002/art.39075. View

19.

Wu S, Xu X, Shi Y, Chen Y, Li Y, Jiang S . System pharmacology analysis to decipher the effect and mechanism of active ingredients combination from herb couple on rheumatoid arthritis in rats. J Ethnopharmacol. 2022; 288:114969. DOI: 10.1016/j.jep.2022.114969. View

20.

Yue S, Liu J, Feng W, Zhang F, Chen J, Xin L . System Pharmacology-Based Dissection of the Synergistic Mechanism of Huangqi and Huanglian for Diabetes Mellitus. Front Pharmacol. 2017; 8:694. PMC: 5633780. DOI: 10.3389/fphar.2017.00694. View