https://doi.org/10.4081/ejh.2021.3202
New bitongling (NBTL) ameliorates rheumatoid arthritis in rats through inhibiting JAK2/STAT3 signaling pathway
Submitted: 19 November 2020
Accepted: 12 January 2021
Published: 17 February 2021
Accepted: 12 January 2021
Abstract Views: 1066
PDF: 590
HTML: 16
HTML: 16
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Authors
Rheumatoid arthritis (RA) is featured by a variety of physical symptoms and fibroblast-like synoviocytes (FLSs) abnormal proliferation. Increasing evidence has demonstrated that traditional Chinese medicine exerts an important role in RA treatment. New bitongling (NBTL) as one of the traditional Chinese medicine has been reported to be involved in the progression of RA, but the exact mechanism is unclear. In our study, we intended to investigate the effect of NBTL on RA to identify the mechanisms related to JAK2/STAT3 signaling pathway. Extracts of Tripterygium wilfordii (TW), a traditional Chinese herbal medicine, have been widely used for treating RA in China for several decades, so, TW was used as a positive control drug for TBNL. RA rats were constructed by immunization with collagen type II to evaluate the action of NBTL in vivo. Body weight and arthritic index were evaluated. Hematoxylin and Eosin staining was performed to analysis the morphological changes of ankle joints tissue. TUNEL and flow cytometry were performed to examine cell apoptosis, while CCK8 and Ethynyl-2′-deoxyuridine (EdU) were performed to examine cell proliferation. In addition, the markers of inflammation were detected by Western blot, ELISA, and RT-qPCR. Firstly, we find that rats treated with NBTL or TW not only reduced swelling degree and bone destruction, but also repressed IL-1 β and IL-6 levels. In addition, NBTL and TW could increase the weight of rats, and promote the level of IL-10 and IL-4 in vivo. Furthermore, NBTL inhibited inflammation of FLS, induced cell apoptosis and hindered cell proliferation, which was reversed by dipeptidyl peptidase (DPP), a JAK2/STAT3 pathway activator. Taken together, NBTL potentially retarded RA via JAK2/STAT3 pathway, highlighting novel mechanisms associated with RA.
Smolen JS, Aletaha D, Barton A, Burmester GR, Emery P, Firestein GS, et al. Rheumatoid arthritis. Nat Rev Dis Primers 2018;4:18001.
DOI: https://doi.org/10.1038/nrdp.2018.1
Safiri S, Kolahi AA, Hoy D, Smith E, Bettampadi D, Mansournia MA, et al. Global, regional and national burden of rheumatoid arthritis 1990-2017: a systematic analysis of the Global Burden of Disease study 2017. Ann Rheum Dis 2019;78:1463-71.
DOI: https://doi.org/10.1136/annrheumdis-2019-215920
Rutherford AI, Patarata E, Subesinghe S, Hyrich KL, Galloway JB. Opportunistic infections in rheumatoid arthritis patients exposed to biologic therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Rheumatology (Oxford) 2018;57:997-1001.
DOI: https://doi.org/10.1093/rheumatology/key023
Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev 2010;233:233-55.
DOI: https://doi.org/10.1111/j.0105-2896.2009.00859.x
de Oliveira PG, Farinon M, Sanchez-Lopez E, Miyamoto S, Guma M. Fibroblast-like synoviocytes glucose metabolism as a therapeutic target in rheumatoid arthritis. Front Immunol 2019;10:1743.
DOI: https://doi.org/10.3389/fimmu.2019.01743
Bi X, Guo XH, Mo BY, Wang ML, Luo XQ, Chen YX, et al. LncRNA PICSAR promotes cell proliferation, migration and invasion of fibroblast-like synoviocytes by sponging miRNA-4701-5p in rheumatoid arthritis. EBioMedicine 2019;50:408-20.
DOI: https://doi.org/10.1016/j.ebiom.2019.11.024
Li S, Wang H, Sun Q, Liu B, Chang X. Therapeutic effect of Xuebijing, a traditional Chinese medicine injection, on rheumatoid arthritis. Evid Based Complement Alternat Med 2020;2020:2710782.
DOI: https://doi.org/10.1155/2020/2710782
Jing R, Wang Y. The modernization research on new bitongling compound. Jilin J Tradit Chinese Med 2014;34:225-7.
Yuan-Qing G, Yue W. [Clinical study on effect of bitongling granule on treating 30 cases of stagnancy of cold-dampness in the meridian and joints of RA].[Article in Chinese]. Chinese J Inform TCM 2004.
Wu S, Wang Y, Xia W. Effect of bitongling granule on VEGF mRNA expression in synovial tissue of collagen-induced rheumatoid arthritis rats. J New Chinese Med 2009;41:98-100.
Guo H, Wang Y, Ding W. [Effect of bitongling granule on the expression of serum soluble intercellular adhesion molecule-1 in the C57BL mice induced by inflammation].[Article in Chinese]. Hebei J Tradit Chin Medi 2006;12.
Fan R, Wang Y, XU J, Sang F, Song Y, Jiang L. Effect on expression of IL-17mRNA in synovial membrane of collagen induction arthritis by rheumatism painful spirit (bitongling) pellet].[Article in Chinese]. China J Chin Med 2011;5.
Feng-Lin Z, Gang W, Fan P, Yan L, Rong-Yue J, Yun-Ke G, et al. [Anti-inflammatory effect of new bitongling compound and its mechanism.[Article in Chinese]. Chin J Experim Tradit Med Formulae 2015.
Yan L, Gang W, Fenglin Z, Yunke G, Fang P, Rongyue J, et al. [Xinbitongling on mice immune function].[Article in Chinese]. J Changchun Univ Chinese Med 2015.
Shi-Hua Q. [Effects of bitongling particles on IL-2 of serum and tissue in rats with collagen-induced arthritis].[Article in Chinese]. West J Tradit Chinese Med 2011.
Zhou YZ, Zhao LD, Chen H, Zhang Y, Wang DF, Huang LF, et al. Comparison of the impact of Tripterygium wilfordii Hook F and Methotrexate treatment on radiological progression in active rheumatoid arthritis: 2-year follow up of a randomized, non-blinded, controlled study. Arthritis Res Ther 2018;20:70.
DOI: https://doi.org/10.1186/s13075-018-1563-6
Chen ZZ, Zhang XD, Chen Y, Wu YB. The role of circulating miR-146a in patients with rheumatoid arthritis treated by Tripterygium wilfordii Hook F. Medicine (Baltimore) 2017;96:e6775.
DOI: https://doi.org/10.1097/MD.0000000000006775
Ahmad Khan M, Sarwar A, Rahat R, Ahmed RS, Umar S. Stigmasterol protects rats from collagen induced arthritis by inhibiting proinflammatory cytokines. Int Immunopharmacol 2020;85:106642.
DOI: https://doi.org/10.1016/j.intimp.2020.106642
Wang M, Li H, Wang Y, Hao Y, Huang Y, Wang X, et al. Anti-rheumatic properties of gentiopicroside are associated with suppression of ROS-NF-kappaB-NLRP3 axis in fibroblast-like synoviocytes and NF-kappaB pathway in adjuvant-induced arthritis. Front Pharmacol 2020;11:515.
DOI: https://doi.org/10.3389/fphar.2020.00515
Xiang Y, Yang Y, Lin C, Wu J, Zhang X. MiR-23a-3p promoted G1/S cell cycle transition by targeting protocadherin17 in hepatocellular carcinoma. J Physiol Biochem 2020;76:123-34.
DOI: https://doi.org/10.1007/s13105-020-00726-4
Chen HY, Tang NH, Lin N, Chen ZX, Wang XZ. Hepatitis B virus X protein induces apoptosis and cell cycle deregulation through interfering with DNA repair and checkpoint responses. Hepatol Res 2008;38:174-82.
Wu S, Huang D, Su X, Yan H, Wu J, Sun Z. Oral exposure to low-dose bisphenol A induces hyperplasia of dorsolateral prostate and upregulates EGFR expression in adult Sprague-Dawley rats. Toxicol Ind Health 2019;35:647-59.
DOI: https://doi.org/10.1177/0748233719885565
He M, Wang L, Chen Y, Zhang T, Guo J. Effect of Wuziyanzong pill on levels of sex hormones, and expressions of nuclear- associated antigen Ki-67 and androgen receptor in testes of young rats. J Tradit Chin Med 2016;36:743-8.
DOI: https://doi.org/10.1016/S0254-6272(17)30009-2
Li GQ, Fang YX, Liu Y, Meng FR, Wu X, Zhang CW, et al. MALAT1-driven inhibition of Wnt signal impedes proliferation and inflammation in fibroblast-like synoviocytes through CTNNB1 promoter methylation in rheumatoid arthritis. Hum Gene Ther 2019;30:1008-22.
DOI: https://doi.org/10.1089/hum.2018.212
Zheng M, Kuang N, Zeng X, Wang J, Zou Y, Fu Y. Daphnetin induces apoptosis in fibroblast-like synoviocytes from collagen-induced arthritic rats mainly via the mitochondrial pathway. Cytokine 2020;133:155146.
DOI: https://doi.org/10.1016/j.cyto.2020.155146
Zhao J, Chen B, Peng X, Wang C, Wang K, Han F, et al. Quercetin suppresses migration and invasion by targeting miR-146a/GATA6 axis in fibroblast-like synoviocytes of rheumatoid arthritis. Immunopharmacol Immunotoxicol 2020;42:221-7.
DOI: https://doi.org/10.1080/08923973.2020.1742732
Wang Y, Jiao T, Fu W, Zhao S, Yang L, Xu N, et al. miR-410-3p regulates proliferation and apoptosis of fibroblast-like synoviocytes by targeting YY1 in rheumatoid arthritis. Biomed Pharmacother 2019;119:109426.
DOI: https://doi.org/10.1016/j.biopha.2019.109426
Bao Y, Sun YW, Ji J, Gan L, Zhang CF, Wang CZ, et al. Genkwanin ameliorates adjuvant-induced arthritis in rats through inhibiting JAK/STAT and NF-kappaB signaling pathways. Phytomedicine 2019;63:153036.
DOI: https://doi.org/10.1016/j.phymed.2019.153036
Myers LK, Rosloniec EF, Cremer MA, Kang AH. Collagen-induced arthritis, an animal model of autoimmunity. Life Sci 1997;61:1861-78.
DOI: https://doi.org/10.1016/S0024-3205(97)00480-3
Chen Z, Bozec A, Ramming A, Schett G. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. Nat Rev Rheumatol 2019;15:9-17.
DOI: https://doi.org/10.1038/s41584-018-0109-2
Siebert S, Tsoukas A, Robertson J, McInnes I. Cytokines as therapeutic targets in rheumatoid arthritis and other inflammatory diseases. Pharmacol Rev 2015;67:280-309.
DOI: https://doi.org/10.1124/pr.114.009639
Saleem A, Saleem M, Akhtar MF, Shahzad M, Jahan S. Polystichum braunii extracts inhibit Complete Freund's adjuvant-induced arthritis via upregulation of I-kappaB, IL-4, and IL-10, downregulation of COX-2, PGE2, IL-1beta, IL-6, NF-kappaB, and TNF-alpha, and subsiding oxidative stress. Inflammopharmacology 2020;28:1633-48.
DOI: https://doi.org/10.1007/s10787-020-00688-5
Wachsmann D, Sibilia J. Survival in the rheumatoid synovium. Joint Bone Spine 2011;78:435-7.
DOI: https://doi.org/10.1016/j.jbspin.2011.05.026
Kiener HP, Watts GF, Cui Y, Wright J, Thornhill TS, Skold M, et al. Synovial fibroblasts self-direct multicellular lining architecture and synthetic function in three-dimensional organ culture. Arthritis Rheum 2010;62:742-52.
DOI: https://doi.org/10.1002/art.27285
Bustamante MF, Garcia-Carbonell R, Whisenant KD, Guma M. Fibroblast-like synoviocyte metabolism in the pathogenesis of rheumatoid arthritis. Arthritis Res Ther 2017;19:110.
DOI: https://doi.org/10.1186/s13075-017-1303-3
Du H, Wang Y, Zeng Y, Huang X, Liu D, Ye L, et al. Tanshinone IIA suppresses proliferation and inflammatory cytokine production of synovial fibroblasts from rheumatoid arthritis patients induced by TNF-alpha and attenuates the inflammatory response in AIA mice. Front Pharmacol 2020;11:568.
DOI: https://doi.org/10.3389/fphar.2020.00568
Dong H, Jian P, Yu M, Wang L. Silencing of long noncoding RNA LEF1-AS1 prevents the progression of hepatocellular carcinoma via the crosstalk with microRNA-136-5p/WNK1. J Cell Physiol 2020;235:6548-62.
DOI: https://doi.org/10.1002/jcp.29503
O'Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity 2012;36:542-50.
DOI: https://doi.org/10.1016/j.immuni.2012.03.014
Li HW, Zeng HS. Regulation of JAK/STAT signal pathway by miR-21 in the pathogenesis of juvenile idiopathic arthritis. World J Pediatr 2020;16:502-13.
DOI: https://doi.org/10.1007/s12519-019-00268-w
Aravilli RK, Vikram SL, Kohila V. Phytochemicals as potential antidotes for targeting NF-kappaB in rheumatoid arthritis. 3 Biotech 2017;7:253.
DOI: https://doi.org/10.1007/s13205-017-0888-1
Zhu L, Zhang Z, Xia N, Zhang W, Wei Y, Huang J, et al. Anti-arthritic activity of ferulic acid in complete Freund's adjuvant (CFA)-induced arthritis in rats: JAK2 inhibition. Inflammopharmacology 2020;28:463-73.
DOI: https://doi.org/10.1007/s10787-019-00642-0
Malemud CJ. The role of the JAK/STAT signal pathway in rheumatoid arthritis. Ther Adv Musculoskelet Dis 2018;10:117-27.
DOI: https://doi.org/10.1177/1759720X18776224
How to Cite
Li, X., Xie, Y., Kang, A., & Wang, Y. (2021). New bitongling (NBTL) ameliorates rheumatoid arthritis in rats through inhibiting JAK2/STAT3 signaling pathway. European Journal of Histochemistry, 65(1). https://doi.org/10.4081/ejh.2021.3202
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.
Similar Articles
- C. Pellicciari, Histochemistry through the years, browsing a long-established journal: novelties in traditional subjects , European Journal of Histochemistry: Vol. 54 No. 4 (2010)
- S. Huang, S. Guo, F. Guo, Q. Yang, X. Xiao, M. Murata, S. Ohnishi, S. Kawanishi, N. Ma, CD44v6 expression in human skin keratinocytes as a possible mechanism for carcinogenesis associated with chronic arsenic exposure , European Journal of Histochemistry: Vol. 57 No. 1 (2013)
- F. Aredia, M. Malatesta, P. Veneroni, M.G. Bottone, Analysis of ERK3 intracellular localization: dynamic distribution during mitosis and apoptosis , European Journal of Histochemistry: Vol. 59 No. 4 (2015)
- Zbigniew Kmiec, Jacek Kieżun, Bartlomiej E. Krazinski, Przemyslaw Kwiatkowski, Janusz Godlewski, The role of galanin in the progression and prognosis of colorectal cancer: the unfinished story , European Journal of Histochemistry: Vol. 68 No. 1 (2024): 1954-2024: 70 Years of Histochemical Research
- M.G. Bottone, G. Santin, C. Soldani, P. Veneroni, A.I. Scovassi, C. Alpini, Intracellular distribution of Tankyrases as detected by multicolor immunofluorescence techniques , European Journal of Histochemistry: Vol. 56 No. 1 (2012)
- E. Tarantola, V. Bertone, G. Milanesi, C. Gruppi, A. Ferrigno, M. Vairetti, S. Barni, I. Freitas, Dipeptidylpeptidase-IV activity and expression reveal decreased damage to the intrahepatic biliary tree in fatty livers submitted to subnormothermic machine-perfusion respect to conventional cold storage , European Journal of Histochemistry: Vol. 58 No. 3 (2014)
- A. Bonetti, A. Bonifacio, A. Della Mora, U. Livi, M. Marchini, F. Ortolani, Carotenoids co-localize with hydroxyapatite, cholesterol, and other lipids in calcified stenotic aortic valves. Ex vivo Raman maps compared to histological patterns , European Journal of Histochemistry: Vol. 59 No. 2 (2015)
- J. Knabl, A. Vattai, R. Hüttenbrenner, S. Hutter, M. Karsten, U. Jeschke, RXRα is upregulated in first trimester endometrial glands of spontaneous abortions unlike LXR and PPARγ , European Journal of Histochemistry: Vol. 60 No. 4 (2016)
- C. Di Nisio, V.L. Zizzari, S. Zara, M. Falconi, G. Teti, G. Tetè, A. Nori, V. Zavaglia, A. Cataldi, RANK/RANKL/OPG signaling pathways in necrotic jaw bone from bisphosphonate-treated subjects , European Journal of Histochemistry: Vol. 59 No. 1 (2015)
- A. Busato, P. Fumene Feruglio, P.P. Parnigotto, P. Marzola, A. Sbarbati, In vivo imaging techniques: a new era for histochemical analysis , European Journal of Histochemistry: Vol. 60 No. 4 (2016)
You may also start an advanced similarity search for this article.
