Euphorbia factor L3 ameliorates rheumatoid arthritis by suppressing the inflammatory response by targeting Rac family small GTPase 1

References

• Bottini N, Firestein GS. Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. Nat Rev Rheumatol. 2013;9(1):24–33.
   PubMed Web of Science ®Google Scholar
• Nygaard G, Firestein GS. Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes. Nat Rev Rheumatol. 2020;16(6):316–333.
   PubMed Web of Science ®Google Scholar
• Massalska M, Maslinski W, Ciechomska M. Small molecule inhibitors in the treatment of rheumatoid arthritis and beyond: latest updates and potential strategy for fighting COVID-19. Cells. 2020;9(8):1876.
   PubMed Web of Science ®Google Scholar
• Ilchovska DD, Barrow DM. An overview of the NF-kB mechanism of pathophysiology in rheumatoid arthritis, investigation of the NF-kB ligand RANKL and related nutritional interventions. Autoimmun Rev. 2021;20(2):102741.
   PubMed Web of Science ®Google Scholar
• Zhu A, Zhang T, Wang Q. The phytochemistry, pharmacokinetics, pharmacology and toxicity of Euphorbia semen. J Ethnopharmacol. 2018;227:41–55.
   PubMed Web of Science ®Google Scholar
• Wang W, Wu Y, Li C, et al. Synthesis of new lathyrane diterpenoid derivatives from euphorbia lathyris and evaluation of their anti-inflammatory activities. Chem Biodivers. 2020;17(2):e1900531.
   PubMed Web of Science ®Google Scholar
• Chaea HJ, Kim H, Kang Y, et al. Heme oxygenase-1 induction by (S)-enantiomer of YS-51 (YS-51S), a synthetic isoquinoline alkaloid, inhibits nitric oxide production and nuclear factor-kappaB translocation in ROS 17/2.8 cells activated with inflammatory stimulants. Int Immunopharmacol. 2007;7(12):1559–1568.
   PubMed Web of Science ®Google Scholar
• Shao XT, Feng L, Yao H-P, et al. [Effect of Triptolide on TNFalpha-induced activation of NF-kappaB and expression of COX-2 and iNOS in human rheumatoid arthritis synovial fibroblasts]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2004;33(2):160–165.
   PubMedGoogle Scholar
• Bell RD, Slattery PN, Wu EK, et al. iNOS dependent and independent phases of lymph node expansion in mice with TNF-induced inflammatory-erosive arthritis. Arthritis Res Ther. 2019;21(1):240.
   PubMed Web of Science ®Google Scholar
• Dinarello CA. The IL-1 family and inflammatory diseases. Clin Exp Rheumatol. 2002;20(5 Suppl 27):S1–13.
   PubMed Web of Science ®Google Scholar
• Miyasaka N, Hirata Y. Nitric oxide and inflammatory arthritides. Life Sci. 1997;61(21):2073–2081.
   PubMed Web of Science ®Google Scholar
• Xin W, Huang C, Zhang X, et al. Evaluation of the new anti-inflammatory compound ethyl salicylate 2-O-β-D-glucoside and its possible mechanism of action. Int Immunopharmacol. 2013;15(2):303–308.
   PubMed Web of Science ®Google Scholar
• Song G, Feng T, Zhao R, et al. CD109 regulates the inflammatory response and is required for the pathogenesis of rheumatoid arthritis. Ann Rheum Dis. 2019;78(12):1632–1641.
   PubMed Web of Science ®Google Scholar
• Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25(4):402–408.
   PubMed Web of Science ®Google Scholar
• Kibble M, Saarinen N, Tang J, et al. Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products. Nat Prod Rep. 2015;32(8):1249–1266.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Ge L, Song G, et al. Azithromycin alleviates the severity of rheumatoid arthritis by targeting the unfolded protein response component of glucose-regulated protein 78 (GRP78). Br J Pharmacol. 2022;179(6):1201–1219.
   PubMed Web of Science ®Google Scholar
• Wang L, Dong H, Song G, et al. TXNDC5 synergizes with HSC70 to exacerbate the inflammatory phenotype of synovial fibroblasts in rheumatoid arthritis through NF-κB signaling. Cell Mol Immunol. 2018;15(7):685–696.
   PubMed Web of Science ®Google Scholar
• Goehring A, Lee C-H, Wang KH, et al. Screening and large-scale expression of membrane proteins in mammalian cells for structural studies. Nat Protoc. 2014;9(11):2574–2585.
   PubMed Web of Science ®Google Scholar
• Sawano A, Miyawaki A. Directed evolution of green fluorescent protein by a new versatile PCR strategy for site-directed and semi-random mutagenesis. Nucleic Acids Res. 2000;28(16):E78.
   PubMedGoogle Scholar
• Brand DD, Latham KA, Rosloniec EF. Collagen-induced arthritis. Nat Protoc. 2007;2(5):1269–1275.
   PubMed Web of Science ®Google Scholar
• Duan W, Li H. Combination of NF-kB targeted siRNA and methotrexate in a hybrid nanocarrier towards the effective treatment in rheumatoid arthritis. J Nanobiotechnology. 2018;16(1):58.
   PubMedGoogle Scholar
• Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. 2010;233(1):233–255.
   PubMed Web of Science ®Google Scholar
• Bustamante MF, Garcia-Carbonell R, Whisenant KD, et al. Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis. Arthritis Res Ther. 2017;19(1):110.
   PubMedGoogle Scholar
• Bell RD, White RJ, Garcia‐Hernandez ML, et al. Tumor necrosis factor induces obliterative pulmonary vascular disease in a novel model of connective tissue disease-associated pulmonary arterial hypertension. Arthritis Rheumatol. 2020;72(10):1759–1770.
   PubMed Web of Science ®Google Scholar
• Hopkins AL. Network pharmacology. Nat Biotechnol. 2007;25(10):1110–1111.
   PubMed Web of Science ®Google Scholar
• Gastonguay A, Berg T, Hauser AD, et al. The role of Rac1 in the regulation of NF-κB activity, cell proliferation, and cell migration in non-small cell lung carcinoma. Cancer Biol Ther. 2012;13(8):647–656.
   PubMed Web of Science ®Google Scholar
• Nazemian V, Kalanaky S, Manaheji H, et al. Anti-hyperalgesia effect of nanchelating based nano particle, RAc1, can be mediated via liver hepcidin expression modulation during persistent inflammation. Int Immunopharmacol. 2019;69:337–346.
   PubMed Web of Science ®Google Scholar
• Wang X, Dou Z, Yuan Y, et al. On-line screening of matrix metalloproteinase inhibitors by capillary electrophoresis coupled to ESI mass spectrometry. Journal of Chromatography B Analytical Technologies in the Biomedical & Life ences. 2013; 930: 48–53.
   PubMed Web of Science ®Google Scholar
• Adam O, Frost G, Custodis F, et al. Role of Rac1 GTPase activation in atrial fibrillation. J Am Coll Cardiol. 2007;50(4):359–367.
   PubMed Web of Science ®Google Scholar
• Alpízar-Rodríguez D, Finckh A. Environmental factors and hormones in the development of rheumatoid arthritis. Semin Immunopathol. 2017;39(4):461–468.
   PubMed Web of Science ®Google Scholar
• Lechtenboehmer CA, Burkard T, Reichenbach S, et al. Increased radiographic progression of distal hand osteoarthritis occurring during biologic DMARD monotherapy for concomitant rheumatoid arthritis. Arthritis Res Ther. 2021;23(1):267.
   PubMed Web of Science ®Google Scholar
• Li P, Schwarz EM. The TNF-alpha transgenic mouse model of inflammatory arthritis. Springer Semin Immunopathol. 2003;25(1):19–33.
   PubMed Web of Science ®Google Scholar
• Han C, Yang Y, Sheng Y, et al. Glaucocalyxin B inhibits cartilage inflammatory injury in rheumatoid arthritis by regulating M1 polarization of synovial macrophages through NF-κB pathway. Aging (Albany NY). 2021;13(18):22544–22555.
   PubMedGoogle Scholar
• Ma J, Zhang Y, Sugai T, et al. Inhibition of cellular and animal inflammatory disease models by NF-κB inhibitor DHMEQ. Cells. 2021;10(9):2271.
   PubMed Web of Science ®Google Scholar
• Li CH, Ma -Z-Z, Jian -L-L, et al. Iguratimod inhibits osteoclastogenesis by modulating the RANKL and TNF-α signaling pathways. Int Immunopharmacol. 2021;90:107219.
   PubMed Web of Science ®Google Scholar
• Ishikawa K, Ishikawa J. Iguratimod, a synthetic disease modifying anti-rheumatic drug inhibiting the activation of NF-κB and production of RANKL: its efficacy, radiographic changes, safety and predictors over two years’ treatment for Japanese rheumatoid arthritis patients. Mod Rheumatol. 2019;29(3):418–429.
   PubMed Web of Science ®Google Scholar
• Xie S, Li S, Tian J, et al. Iguratimod as a new drug for rheumatoid arthritis: current landscape. Front Pharmacol. 2020;11:73.
   PubMed Web of Science ®Google Scholar
• Ramshekar A, Wang H, Hartnett ME. Regulation of Rac1 activation in choroidal endothelial cells: insights into mechanisms in age-related macular degeneration. Cells. 2021;10(9):2414.
   PubMed Web of Science ®Google Scholar
• Chen X. Rac1 regulates platelet microparticles formation and rheumatoid arthritis deterioration. Platelets. 2020;31(1):112–119.
   PubMed Web of Science ®Google Scholar
• Zhang T, Lu X, Beier F, et al. Rac1 activation induces tumour necrosis factor-α expression and cardiac dysfunction in endotoxemia. J Cell Mol Med. 2011;15(5):1109–1121.
   PubMed Web of Science ®Google Scholar