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Published in: Inflammation 5/2020

01-10-2020 | Rheumatoid Arthritis | Original Article

Cinnamaldehyde Attenuates the Progression of Rheumatoid Arthritis through Down-Regulation of PI3K/AKT Signaling Pathway

Authors: Xiang Li, Yue Wang

Published in: Inflammation | Issue 5/2020

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Abstract

Cinnamaldehyde (CA), as an active compound isolated from the bark of Cinnamomum cassia, has been reported to possess the anti-fungal, anti-bacterial, anti-inflammatory, anti-mutagenic, and anti-oxidant properties. However, the possible effects and underlying mechanisms of CA on rheumatoid arthritis (RA) have not been revealed yet. In the present study, we found that CA obviously improved the type II collagen-induced RA in rats, accompanied with decreasing pro-inflammatory factors, proliferation and metastasis. In addition, CA decreased the expression levels of TNF-α, IL-1β, and IL-6 in RA-FLSs. Besides, CA remarkably inhibited the proliferation, downregulated the EdU-positive cells, and promoted apoptosis of RA-FLSs by CCK-8, EdU and flow cytometry analysis. Moreover, the results of wound healing, transwell migration and invasion assays showed that CA inhibited the migration and invasion of RA-FLSs. Further, western blot experiment showed CA inhibited the activation of PI3K/AKT signaling pathway in RA-FLSs. Finally, 740Y-P, the PI3K/AKT signaling pathway activator, could reverse the effects of CA on the proliferation and metastasis in RA-FLSs. In conclusion, we confirmed that CA exhibited potential therapeutic properties against RA via suppressing proliferation and metastasis of RA-FLSs by blockage of PI3K/AKT signaling pathway. Therefore, our study provides evidence that CA may emerge as a therapeutic option for RA treatment.
Literature
1.
go back to reference Scott, D.L., F. Wolfe, and T.W. Huizinga. 2010. Rheumatoid arthritis. Lancet 376 (9746): 1094–1108.PubMed Scott, D.L., F. Wolfe, and T.W. Huizinga. 2010. Rheumatoid arthritis. Lancet 376 (9746): 1094–1108.PubMed
2.
go back to reference Wasserman, A.M. 2011. Diagnosis and management of rheumatoid arthritis. Am Fam Physician 84 (11): 1245–1252.PubMed Wasserman, A.M. 2011. Diagnosis and management of rheumatoid arthritis. Am Fam Physician 84 (11): 1245–1252.PubMed
3.
go back to reference Fautrel, B., M. Belhassen, C. Hudry, et al. 2019. Predictive factors of tumour necrosis inhibitor treatment persistence for rheumatoid arthritis: an observational study in 8052 patients. Jt Bone Spine 24: 30151–30154. Fautrel, B., M. Belhassen, C. Hudry, et al. 2019. Predictive factors of tumour necrosis inhibitor treatment persistence for rheumatoid arthritis: an observational study in 8052 patients. Jt Bone Spine 24: 30151–30154.
4.
go back to reference Allard-Chamard, H., and G. Boire. 2019. Serologic diagnosis of rheumatoid arthritis. Clin Lab Med 39 (4): 525–537.PubMed Allard-Chamard, H., and G. Boire. 2019. Serologic diagnosis of rheumatoid arthritis. Clin Lab Med 39 (4): 525–537.PubMed
5.
go back to reference Mian, A., F. Ibrahim, and D.L. Scott. 2019. A systematic review of guidelines for managing rheumatoid arthritis. BMC Rheumatol 3: 42.PubMedPubMedCentral Mian, A., F. Ibrahim, and D.L. Scott. 2019. A systematic review of guidelines for managing rheumatoid arthritis. BMC Rheumatol 3: 42.PubMedPubMedCentral
6.
go back to reference Bustamante, M.F., R. Garcia-Carbonell, K.D. Whisenant, and M. Guma. 2017. Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis. Arthritis Res Ther 19 (1): 110.PubMedPubMedCentral Bustamante, M.F., R. Garcia-Carbonell, K.D. Whisenant, and M. Guma. 2017. Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis. Arthritis Res Ther 19 (1): 110.PubMedPubMedCentral
7.
go back to reference Doody, K.M., N. Bottini, and G.S. Firestein. 2017. Epigenetic alterations in rheumatoid arthritis fibroblast- like synoviocytes. Epigenomics 9 (4): 479–492.PubMedPubMedCentral Doody, K.M., N. Bottini, and G.S. Firestein. 2017. Epigenetic alterations in rheumatoid arthritis fibroblast- like synoviocytes. Epigenomics 9 (4): 479–492.PubMedPubMedCentral
8.
go back to reference Wen, H., Y. Liu, J. Li, D. Wei, D. Liu, and F. Zhao. 2018. Inhibitory effect and mechanism of 1,2,5-dihydroxy vitamin D3 on RANKL expression in fibroblast-like synoviocytes and osteoclast-like cell formation induced by IL-22 in rheumatoid arthritis. Clin Exp Rheumatol 36 (5): 798–805.PubMed Wen, H., Y. Liu, J. Li, D. Wei, D. Liu, and F. Zhao. 2018. Inhibitory effect and mechanism of 1,2,5-dihydroxy vitamin D3 on RANKL expression in fibroblast-like synoviocytes and osteoclast-like cell formation induced by IL-22 in rheumatoid arthritis. Clin Exp Rheumatol 36 (5): 798–805.PubMed
9.
go back to reference Wang, L., N. Wang, Q. Zhao, B. Zhang, and Y. Ding. 2019. Pectolinarin inhibits proliferation, induces apoptosis, and suppresses inflammation in rheumatoid arthritis fibroblast-like synoviocytes by inactivating the phosphatidylinositol 3 kinase/protein kinase B pathway. J Cell Biochem 120 (9): 15202–15210.PubMed Wang, L., N. Wang, Q. Zhao, B. Zhang, and Y. Ding. 2019. Pectolinarin inhibits proliferation, induces apoptosis, and suppresses inflammation in rheumatoid arthritis fibroblast-like synoviocytes by inactivating the phosphatidylinositol 3 kinase/protein kinase B pathway. J Cell Biochem 120 (9): 15202–15210.PubMed
10.
go back to reference Huang, Z., S. Xing, M. Liu, et al. 2019. MiR-26a-5p enhances cells proliferation, invasion, and apoptosis resistance of fibroblast-like synoviocytes in rheumatoid arthritis by regulating PTEN/PI3K/AKT pathway. Biosci Rep 39(7):BSR20182192. Huang, Z., S. Xing, M. Liu, et al. 2019. MiR-26a-5p enhances cells proliferation, invasion, and apoptosis resistance of fibroblast-like synoviocytes in rheumatoid arthritis by regulating PTEN/PI3K/AKT pathway. Biosci Rep 39(7):BSR20182192.
11.
go back to reference Song, B., X.F. Li, Y. Yao, Q.Q. Xu, X.M. Meng, C. Huang, and J. Li. 2019. BMP9 inhibits the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis via the PI3K/AKT signaling pathway. Int Immunopharmacol 74: 105685.PubMed Song, B., X.F. Li, Y. Yao, Q.Q. Xu, X.M. Meng, C. Huang, and J. Li. 2019. BMP9 inhibits the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis via the PI3K/AKT signaling pathway. Int Immunopharmacol 74: 105685.PubMed
12.
go back to reference Yang, B., Y. Ge, Y. Zhou, J. Wang, X. Xie, S. Li, M. Tang, L.C. Xu, and J. Tian. 2019. miR-124a inhibits the proliferation and inflammation in rheumatoid arthritis fibroblast-like synoviocytes via targeting PIK3/NF-κB pathway. Cell Biochem Funct 37 (4): 208–215.PubMed Yang, B., Y. Ge, Y. Zhou, J. Wang, X. Xie, S. Li, M. Tang, L.C. Xu, and J. Tian. 2019. miR-124a inhibits the proliferation and inflammation in rheumatoid arthritis fibroblast-like synoviocytes via targeting PIK3/NF-κB pathway. Cell Biochem Funct 37 (4): 208–215.PubMed
13.
go back to reference Zhu, X., Y. Song, R. Huo, J. Zhang, S. Sun, Y. He, H. Gao, M. Zhang, X. Sun, T. Zhai, H. Li, Y. Sun, Z. Zhou, B. Shen, L. Xiao, and N. Li. 2015. Cyr61 participates in the pathogenesis of rheumatoid arthritis by promoting proIL-1β production by fibroblast-like synoviocytes through an AKT-dependent NF-κB signaling pathway. Clin Immunol 157 (2): 187–197.PubMed Zhu, X., Y. Song, R. Huo, J. Zhang, S. Sun, Y. He, H. Gao, M. Zhang, X. Sun, T. Zhai, H. Li, Y. Sun, Z. Zhou, B. Shen, L. Xiao, and N. Li. 2015. Cyr61 participates in the pathogenesis of rheumatoid arthritis by promoting proIL-1β production by fibroblast-like synoviocytes through an AKT-dependent NF-κB signaling pathway. Clin Immunol 157 (2): 187–197.PubMed
14.
go back to reference Li, H.H., H. Livneh, C.C. Yeh, H.R. Guo, N.S. Lai, M.C. Lu, and T.Y. Tsai. 2019. Association between use of Chinese herbal medicine and depression risk in patients with rheumatoid arthritis: A nationwide retrospective cohort study. Int J Rheum Dis 22 (6): 986–994.PubMed Li, H.H., H. Livneh, C.C. Yeh, H.R. Guo, N.S. Lai, M.C. Lu, and T.Y. Tsai. 2019. Association between use of Chinese herbal medicine and depression risk in patients with rheumatoid arthritis: A nationwide retrospective cohort study. Int J Rheum Dis 22 (6): 986–994.PubMed
15.
go back to reference Pan, X., M.A. Lopez-Olivo, J. Song, G. Pratt, and M.E. Suarez-Almazor. 2017. Systematic review of the methodological quality of controlled trials evaluating Chinese herbal medicine in patients with rheumatoid arthritis. BMJ Open 7 (3): e013242.PubMedPubMedCentral Pan, X., M.A. Lopez-Olivo, J. Song, G. Pratt, and M.E. Suarez-Almazor. 2017. Systematic review of the methodological quality of controlled trials evaluating Chinese herbal medicine in patients with rheumatoid arthritis. BMJ Open 7 (3): e013242.PubMedPubMedCentral
16.
go back to reference Zhao, M., X. Yuan, Y.H. Pei, H.Y. Ye, A.H. Peng, M.H. Tang, D.L. Guo, Y. Deng, and L.J. Chen. 2019. Anti-inflammatory Ellagitannins from Cleidion brevipetiolatum for the treatment of rheumatoid arthritis. J Nat Prod 82 (9): 2409–2418.PubMed Zhao, M., X. Yuan, Y.H. Pei, H.Y. Ye, A.H. Peng, M.H. Tang, D.L. Guo, Y. Deng, and L.J. Chen. 2019. Anti-inflammatory Ellagitannins from Cleidion brevipetiolatum for the treatment of rheumatoid arthritis. J Nat Prod 82 (9): 2409–2418.PubMed
17.
go back to reference Sun, Q., B. Shang, L. Wang, Z. Lu, and Y. Liu. 2016. Cinnamaldehyde inhibits fungal growth and aflatoxin B1 biosynthesis by modulating the oxidative stress response of Aspergillus flavus. Appl Microbiol Biotechnol 100 (3): 1355–1364.PubMed Sun, Q., B. Shang, L. Wang, Z. Lu, and Y. Liu. 2016. Cinnamaldehyde inhibits fungal growth and aflatoxin B1 biosynthesis by modulating the oxidative stress response of Aspergillus flavus. Appl Microbiol Biotechnol 100 (3): 1355–1364.PubMed
18.
go back to reference Friedman, M. 2017. Chemistry, antimicrobial mechanisms, and antibiotic activities of cinnamaldehyde against pathogenic bacteria in animal feeds and human foods. J Agric Food Chem 65 (48): 10406–10423.PubMed Friedman, M. 2017. Chemistry, antimicrobial mechanisms, and antibiotic activities of cinnamaldehyde against pathogenic bacteria in animal feeds and human foods. J Agric Food Chem 65 (48): 10406–10423.PubMed
19.
go back to reference Kiwamoto, R., D. Ploeg, I.M. Rietjens, et al. 2016. Dose-dependent DNA adduct formation by cinnamaldehyde and other food-borne α,β-unsaturated aldehydes predicted by physiologically based in silico modelling. Toxicol in Vitro 31: 114–125.PubMed Kiwamoto, R., D. Ploeg, I.M. Rietjens, et al. 2016. Dose-dependent DNA adduct formation by cinnamaldehyde and other food-borne α,β-unsaturated aldehydes predicted by physiologically based in silico modelling. Toxicol in Vitro 31: 114–125.PubMed
20.
go back to reference Mateen, S., S. Shahzad, S. Ahmad, S.S. Naeem, S. Khalid, K. Akhtar, W. Rizvi, and S. Moin. 2019. Cinnamaldehyde and eugenol attenuates collagen induced arthritis via reduction of free radicals and pro-inflammatory cytokines. Phytomedicine 53: 70–78.PubMed Mateen, S., S. Shahzad, S. Ahmad, S.S. Naeem, S. Khalid, K. Akhtar, W. Rizvi, and S. Moin. 2019. Cinnamaldehyde and eugenol attenuates collagen induced arthritis via reduction of free radicals and pro-inflammatory cytokines. Phytomedicine 53: 70–78.PubMed
21.
go back to reference Guo, L.X., H.Y. Wang, X.D. Liu, et al. 2019. Saponins from Clematis mandshurica Rupr. regulates gut microbiota and its metabolites during alleviation of collagen-induced arthritis in rats. Pharmacol Res 149: 104459.PubMed Guo, L.X., H.Y. Wang, X.D. Liu, et al. 2019. Saponins from Clematis mandshurica Rupr. regulates gut microbiota and its metabolites during alleviation of collagen-induced arthritis in rats. Pharmacol Res 149: 104459.PubMed
22.
go back to reference Wang, Y., T. Jiao, W. Fu, et al. 2019. miR-410-3p regulates proliferation and apoptosis of fibroblast-like synoviocytes by targeting YY1 in rheumatoid arthritis. Biomed Pharmacother 119: 109426.PubMed Wang, Y., T. Jiao, W. Fu, et al. 2019. miR-410-3p regulates proliferation and apoptosis of fibroblast-like synoviocytes by targeting YY1 in rheumatoid arthritis. Biomed Pharmacother 119: 109426.PubMed
23.
go back to reference Sun, J., W. Su, X. Zhao, et al. 2019. LncRNA PFAR contributes to fibrogenesis in lung fibroblasts through competitively binding to miR-15a. Biosci Rep 39(7):BSR20190280. Sun, J., W. Su, X. Zhao, et al. 2019. LncRNA PFAR contributes to fibrogenesis in lung fibroblasts through competitively binding to miR-15a. Biosci Rep 39(7):BSR20190280.
24.
go back to reference Sun, Y., X. Sun, Z. Liu, X. Wang, and Y. Li. 2018. MiR-338-5p suppresses rheumatoid arthritis synovial fibroblast proliferation and invasion by targeting ADAMTS-9. Clin Exp Rheumatol 36 (2): 195–202.PubMed Sun, Y., X. Sun, Z. Liu, X. Wang, and Y. Li. 2018. MiR-338-5p suppresses rheumatoid arthritis synovial fibroblast proliferation and invasion by targeting ADAMTS-9. Clin Exp Rheumatol 36 (2): 195–202.PubMed
25.
go back to reference Du, H., X. Zhang, Y. Zeng, et al. 2019. A novel phytochemical, DIM, inhibits proliferation, migration, Invasion and TNF-α Induced Inflammatory Cytokine Production of Synovial Fibroblasts From Rheumatoid Arthritis Patients by Targeting MAPK and AKT/mTOR Signal Pathway. Front Immunol 10: 1620.PubMedPubMedCentral Du, H., X. Zhang, Y. Zeng, et al. 2019. A novel phytochemical, DIM, inhibits proliferation, migration, Invasion and TNF-α Induced Inflammatory Cytokine Production of Synovial Fibroblasts From Rheumatoid Arthritis Patients by Targeting MAPK and AKT/mTOR Signal Pathway. Front Immunol 10: 1620.PubMedPubMedCentral
26.
go back to reference Liu, Y., and X. Yan. 2019. Eriodictyol inhibits survival and inflammatory responses and promotes apoptosis in rheumatoid arthritis fibroblast-like synoviocytes through AKT/FOXO1 signaling. J Cell Biochem 120 (9): 14628–14635.PubMed Liu, Y., and X. Yan. 2019. Eriodictyol inhibits survival and inflammatory responses and promotes apoptosis in rheumatoid arthritis fibroblast-like synoviocytes through AKT/FOXO1 signaling. J Cell Biochem 120 (9): 14628–14635.PubMed
27.
go back to reference Chen, K., Z.W. Lin, S.M. He, C.Q. Wang, J.C. Yang, Y. Lu, X.B. Xie, and Q. Li. 2019. Metformin inhibits the proliferation of rheumatoid arthritis fibroblast-like synoviocytes through IGF-IR/PI3K/AKT/m-TOR pathway. Biomed Pharmacother 115: 108875.PubMed Chen, K., Z.W. Lin, S.M. He, C.Q. Wang, J.C. Yang, Y. Lu, X.B. Xie, and Q. Li. 2019. Metformin inhibits the proliferation of rheumatoid arthritis fibroblast-like synoviocytes through IGF-IR/PI3K/AKT/m-TOR pathway. Biomed Pharmacother 115: 108875.PubMed
28.
go back to reference Singh, J.A., R. Christensen, G.A. Wells, M.E. Suarez-Almazor, R. Buchbinder, M.A. Lopez-Olivo, E.T. Ghogomu, and P. Tugwell. 2010. Biologics for rheumatoid arthritis: An overview of Cochrane reviews. Sao Paulo Med J 128 (5): 309–410.PubMed Singh, J.A., R. Christensen, G.A. Wells, M.E. Suarez-Almazor, R. Buchbinder, M.A. Lopez-Olivo, E.T. Ghogomu, and P. Tugwell. 2010. Biologics for rheumatoid arthritis: An overview of Cochrane reviews. Sao Paulo Med J 128 (5): 309–410.PubMed
29.
go back to reference Dommasch, E.D., K. Abuabara, D.B. Shin, J. Nguyen, A.B. Troxel, and J.M. Gelfand. 2011. The risk of infection and malignancy with tumor necrosis factor antagonists in adults with psoriatic disease: A systematic review and meta-analysis of randomized controlled trials. J Am Acad Dermatol 64 (6): 1035–1050.PubMedPubMedCentral Dommasch, E.D., K. Abuabara, D.B. Shin, J. Nguyen, A.B. Troxel, and J.M. Gelfand. 2011. The risk of infection and malignancy with tumor necrosis factor antagonists in adults with psoriatic disease: A systematic review and meta-analysis of randomized controlled trials. J Am Acad Dermatol 64 (6): 1035–1050.PubMedPubMedCentral
30.
go back to reference Cao, Y.X., D. Huang, J. Liu, R.K. Zong, L. Wan, C.B. Huang, W.D. Zhang, and Y. Wang. 2019. A novel Chinese medicine, Xinfeng capsule, modulates proinflammatory cytokines via regulating the toll-like receptor 4 (TLR4)/mitogen-activated protein kinase (MAPK)/nuclear kappa B (NF-κB) signaling pathway in an adjuvant arthritis rat model. Med Sci Monit 25: 6767–6774.PubMedPubMedCentral Cao, Y.X., D. Huang, J. Liu, R.K. Zong, L. Wan, C.B. Huang, W.D. Zhang, and Y. Wang. 2019. A novel Chinese medicine, Xinfeng capsule, modulates proinflammatory cytokines via regulating the toll-like receptor 4 (TLR4)/mitogen-activated protein kinase (MAPK)/nuclear kappa B (NF-κB) signaling pathway in an adjuvant arthritis rat model. Med Sci Monit 25: 6767–6774.PubMedPubMedCentral
31.
go back to reference Shi, N., S. Zhang, G. Silverman, M. Li, J. Cai, and H. Niu. 2019. Protective effect of hydroxychloroquine on rheumatoid arthritis-associated atherosclerosis. Anim Model Exp Med 2 (2): 98–106. Shi, N., S. Zhang, G. Silverman, M. Li, J. Cai, and H. Niu. 2019. Protective effect of hydroxychloroquine on rheumatoid arthritis-associated atherosclerosis. Anim Model Exp Med 2 (2): 98–106.
32.
go back to reference Luo, J., W.J. Song, Y. Xu, G.Y. Chen, Q. Hu, and Q.W. Tao. 2019. Benefits and safety of Tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: An overview of systematic reviews. Chin J Integr Med 25 (9): 696–703.PubMed Luo, J., W.J. Song, Y. Xu, G.Y. Chen, Q. Hu, and Q.W. Tao. 2019. Benefits and safety of Tripterygium glycosides and total glucosides of paeony for rheumatoid arthritis: An overview of systematic reviews. Chin J Integr Med 25 (9): 696–703.PubMed
33.
go back to reference Gorlier, C., J.E. Gottenberg, L. Laurans, T. Simon, H. Ait-Oufella, and J. Sellam. 2019. Serum level of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a biomarker of synovitis in rheumatoid arthritis. Int J Rheum Dis 22 (9): 1616–1618.PubMed Gorlier, C., J.E. Gottenberg, L. Laurans, T. Simon, H. Ait-Oufella, and J. Sellam. 2019. Serum level of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) is a biomarker of synovitis in rheumatoid arthritis. Int J Rheum Dis 22 (9): 1616–1618.PubMed
34.
go back to reference Brusca, S.B., S.B. Abramson, and J.U. Scher. 2014. Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity. Curr Opin Rheumatol 26 (1): 101–107.PubMedPubMedCentral Brusca, S.B., S.B. Abramson, and J.U. Scher. 2014. Microbiome and mucosal inflammation as extra-articular triggers for rheumatoid arthritis and autoimmunity. Curr Opin Rheumatol 26 (1): 101–107.PubMedPubMedCentral
35.
go back to reference Falconer, J., A.N. Murphy, S.P. Young, A.R. Clark, S. Tiziani, M. Guma, and C.D. Buckley. 2018. Review: Synovial cell metabolism and chronic inflammation in rheumatoid arthritis. Arthritis Rhematol 70 (7): 984–999. Falconer, J., A.N. Murphy, S.P. Young, A.R. Clark, S. Tiziani, M. Guma, and C.D. Buckley. 2018. Review: Synovial cell metabolism and chronic inflammation in rheumatoid arthritis. Arthritis Rhematol 70 (7): 984–999.
36.
go back to reference Jang, J., D.S. Lim, Y.E. Choi, Y. Jeong, S.A. Yoo, W.U. Kim, and Y.S. Bae. 2006. MLN51 and GM-CSF involvement in the proliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis. Arthritis Res Ther 8 (6): R170.PubMedPubMedCentral Jang, J., D.S. Lim, Y.E. Choi, Y. Jeong, S.A. Yoo, W.U. Kim, and Y.S. Bae. 2006. MLN51 and GM-CSF involvement in the proliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis. Arthritis Res Ther 8 (6): R170.PubMedPubMedCentral
37.
go back to reference Kim, E.K., J.E. Kwon, S.Y. Lee, E.J. Lee, D.S. Kim, S.J. Moon, J. Lee, S.K. Kwok, S.H. Park, and M.L. Cho. 2017. IL-17-mediated mitochondrial dysfunction impairs apoptosis in rheumatoid arthritis synovial fibroblasts through activation of autophagy. Cell Death Dis 8 (1): e2565.PubMedPubMedCentral Kim, E.K., J.E. Kwon, S.Y. Lee, E.J. Lee, D.S. Kim, S.J. Moon, J. Lee, S.K. Kwok, S.H. Park, and M.L. Cho. 2017. IL-17-mediated mitochondrial dysfunction impairs apoptosis in rheumatoid arthritis synovial fibroblasts through activation of autophagy. Cell Death Dis 8 (1): e2565.PubMedPubMedCentral
38.
go back to reference Zhai, K.F., H. Duan, G.J. Khan, H. Xu, F.K. Han, W.G. Cao, G.Z. Gao, L.L. Shan, and Z.J. Wei. 2018. Salicin from Alangium chinense ameliorates rheumatoid arthritis by modulating the Nrf2-HO-1-ROS pathways. J Agric Food Chem 66 (24): 6073–6082.PubMed Zhai, K.F., H. Duan, G.J. Khan, H. Xu, F.K. Han, W.G. Cao, G.Z. Gao, L.L. Shan, and Z.J. Wei. 2018. Salicin from Alangium chinense ameliorates rheumatoid arthritis by modulating the Nrf2-HO-1-ROS pathways. J Agric Food Chem 66 (24): 6073–6082.PubMed
39.
go back to reference Mo, B.Y., X.H. Guo, M.R. Yang, F. Liu, X. Bi, Y. Liu, L.K. Fang, X.Q. Luo, J. Wang, J.A. Bellanti, Y.F. Pan, and S.G. Zheng. 2018. Long non-coding RNA GAPLINC promotes tumor-like biologic behaviors of fibroblast-like Synoviocytes as MicroRNA sponging in rheumatoid arthritis patients. Front Immunol 9: 702.PubMedPubMedCentral Mo, B.Y., X.H. Guo, M.R. Yang, F. Liu, X. Bi, Y. Liu, L.K. Fang, X.Q. Luo, J. Wang, J.A. Bellanti, Y.F. Pan, and S.G. Zheng. 2018. Long non-coding RNA GAPLINC promotes tumor-like biologic behaviors of fibroblast-like Synoviocytes as MicroRNA sponging in rheumatoid arthritis patients. Front Immunol 9: 702.PubMedPubMedCentral
40.
go back to reference Wei, X.J., X.W. Li, J.L. Lu, Z.X. Long, J.Q. Liang, S.B. Wei, C.X. Lu, and W.Z. Lu. 2017. MiR-20a regulates fibroblast-like synoviocyte proliferation and apoptosis in rheumatoid arthritis. Eur Rev Med Pharmacol Sci 21 (17): 3886–3893.PubMed Wei, X.J., X.W. Li, J.L. Lu, Z.X. Long, J.Q. Liang, S.B. Wei, C.X. Lu, and W.Z. Lu. 2017. MiR-20a regulates fibroblast-like synoviocyte proliferation and apoptosis in rheumatoid arthritis. Eur Rev Med Pharmacol Sci 21 (17): 3886–3893.PubMed
41.
go back to reference Kaneshiro, K., Y. Sakai, K. Suzuki, K. Uchida, K. Tateishi, Y. Terashima, Y. Kawasaki, N. Shibanuma, K. Yoshida, and A. Hashiramoto. 2019. Interleukin-6 and tumour necrosis factor-α cooperatively promote cell cycle regulators and proliferate rheumatoid arthritis fibroblast-like synovial cells. Scand J Rheumatol 48 (5): 353–361.PubMed Kaneshiro, K., Y. Sakai, K. Suzuki, K. Uchida, K. Tateishi, Y. Terashima, Y. Kawasaki, N. Shibanuma, K. Yoshida, and A. Hashiramoto. 2019. Interleukin-6 and tumour necrosis factor-α cooperatively promote cell cycle regulators and proliferate rheumatoid arthritis fibroblast-like synovial cells. Scand J Rheumatol 48 (5): 353–361.PubMed
42.
go back to reference Xu, X., H. Chen, Q. Zhang, J. Xu, Q. Shi, and M. Wang. 2017. MiR-650 inhibits proliferation, migration and invasion of rheumatoid arthritis synovial fibroblasts by targeting AKT2. Biomed Pharmacother 88: 535–541.PubMed Xu, X., H. Chen, Q. Zhang, J. Xu, Q. Shi, and M. Wang. 2017. MiR-650 inhibits proliferation, migration and invasion of rheumatoid arthritis synovial fibroblasts by targeting AKT2. Biomed Pharmacother 88: 535–541.PubMed
43.
go back to reference Udalova, I.A., A. Mantovani, M. Feldmann, et al. 2016. Macrophage heterogeneity in the context of rheumatoid arthritis. Nat Rev Rheumatol 12 (8): 472–485.PubMed Udalova, I.A., A. Mantovani, M. Feldmann, et al. 2016. Macrophage heterogeneity in the context of rheumatoid arthritis. Nat Rev Rheumatol 12 (8): 472–485.PubMed
44.
go back to reference Yang, M., X. Feng, J. Ding, F. Chang, and X. Chen. 2017. Nanotherapeutics relieve rheumatoid arthritis. J Control Release 252: 108–124.PubMed Yang, M., X. Feng, J. Ding, F. Chang, and X. Chen. 2017. Nanotherapeutics relieve rheumatoid arthritis. J Control Release 252: 108–124.PubMed
45.
go back to reference Qu, Y., Y.P. Zhang, J. Wu, L.G. Jie, J.X. Deng, D.B. Zhao, and Q.H. Yu. 2019. Downregulated microRNA-135a ameliorates rheumatoid arthritis by inactivation of the phosphatidylinositol 3-kinase/AKT signaling pathway via phosphatidylinositol 3-kinase regulatory subunit 2. J Cell Physiol 234 (10): 17663–17676.PubMed Qu, Y., Y.P. Zhang, J. Wu, L.G. Jie, J.X. Deng, D.B. Zhao, and Q.H. Yu. 2019. Downregulated microRNA-135a ameliorates rheumatoid arthritis by inactivation of the phosphatidylinositol 3-kinase/AKT signaling pathway via phosphatidylinositol 3-kinase regulatory subunit 2. J Cell Physiol 234 (10): 17663–17676.PubMed
46.
go back to reference Kuuliala, K., A. Kuuliala, M. Hämäläinen, R. Koivuniemi, H. Kautiainen, E. Moilanen, H. Repo, and M. Leirisalo-Repo. 2017. Impaired Akt phosphorylation in monocytes of patients with rheumatoid arthritis. Scand J Immunol 85 (2): 155–161.PubMed Kuuliala, K., A. Kuuliala, M. Hämäläinen, R. Koivuniemi, H. Kautiainen, E. Moilanen, H. Repo, and M. Leirisalo-Repo. 2017. Impaired Akt phosphorylation in monocytes of patients with rheumatoid arthritis. Scand J Immunol 85 (2): 155–161.PubMed
47.
go back to reference Liu, Y., W. Wei, C. Hong, Y. Wang, X. Sun, J. Ma, and F. Zheng. 2019. Calreticulin induced endothelial ICAM-1 up-regulation associated with tristetraprolin expression alteration through PI3K/Akt/eNOS/p38 MAPK signaling pathway in rheumatoid arthritis. Mol Immunol 107: 10–20.PubMed Liu, Y., W. Wei, C. Hong, Y. Wang, X. Sun, J. Ma, and F. Zheng. 2019. Calreticulin induced endothelial ICAM-1 up-regulation associated with tristetraprolin expression alteration through PI3K/Akt/eNOS/p38 MAPK signaling pathway in rheumatoid arthritis. Mol Immunol 107: 10–20.PubMed
48.
go back to reference Yan, X., Y. Liu, X. Kong, J. Ji, H. Zhu, Z. Zhang, T. Fu, J. Yang, Z. Zhang, F. Liu, and Z. Gu. 2019. MicroRNA-21-5p are involved in apoptosis and invasion of fibroblast-like synoviocytes through PTEN/PI3K/AKT signal. Cytotechnology 71 (1): 317–328.PubMedPubMedCentral Yan, X., Y. Liu, X. Kong, J. Ji, H. Zhu, Z. Zhang, T. Fu, J. Yang, Z. Zhang, F. Liu, and Z. Gu. 2019. MicroRNA-21-5p are involved in apoptosis and invasion of fibroblast-like synoviocytes through PTEN/PI3K/AKT signal. Cytotechnology 71 (1): 317–328.PubMedPubMedCentral
49.
go back to reference Yu, Z., H. Xu, H. Wang, and Y. Wang. 2018. Foxc1 promotes the proliferation of fibroblast-like synoviocytes in rheumatoid arthritis via PI3K/AKT signalling pathway. Tissue Cell 53: 15–22.PubMed Yu, Z., H. Xu, H. Wang, and Y. Wang. 2018. Foxc1 promotes the proliferation of fibroblast-like synoviocytes in rheumatoid arthritis via PI3K/AKT signalling pathway. Tissue Cell 53: 15–22.PubMed
50.
go back to reference Meng, Q., X. Du, H. Wang, et al. 2017. Astragalus polysaccharides inhibits cell growth and pro-inflammatory response in IL-1β-stimulated fibroblast-like synoviocytes by enhancement of autophagy via PI3K/AKT/mTOR inhibition. Apoptosis 22 (9): 1138–1146.PubMed Meng, Q., X. Du, H. Wang, et al. 2017. Astragalus polysaccharides inhibits cell growth and pro-inflammatory response in IL-1β-stimulated fibroblast-like synoviocytes by enhancement of autophagy via PI3K/AKT/mTOR inhibition. Apoptosis 22 (9): 1138–1146.PubMed
51.
go back to reference Li, G.Q., Y. Zhang, D. Liu, Y.Y. Qian, H. Zhang, S.Y. Guo, M. Sunagawa, T. Hisamitsu, and Y.Q. Liu. 2013. PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial-mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis. Mol Cell Biochem 372 (1–2): 221–231.PubMed Li, G.Q., Y. Zhang, D. Liu, Y.Y. Qian, H. Zhang, S.Y. Guo, M. Sunagawa, T. Hisamitsu, and Y.Q. Liu. 2013. PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial-mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis. Mol Cell Biochem 372 (1–2): 221–231.PubMed
Metadata
Title
Cinnamaldehyde Attenuates the Progression of Rheumatoid Arthritis through Down-Regulation of PI3K/AKT Signaling Pathway
Authors
Xiang Li
Yue Wang
Publication date
01-10-2020
Publisher
Springer US
Published in
Inflammation / Issue 5/2020
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-020-01246-5

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