3,5-Di-C-β-D-glucopyranosyl phloroacetophenone, a major component of Melicope ptelefolia, suppresses fibroblast activation and alleviates arthritis in a mouse model: Potential therapeutics for rheumatoid arthritis

Kim,Hyun Jong; Choi,Ji Hyun; Hwang,Jung‑Hwan; Kim,Kyong‑Shim; Noh,Jung‑Ran; Choi,Dong‑Hee; Moon,Sung Je; Kim,Hyun‑Yong; Kim,Sang‑Woo; Choi,Sangho; Eum,Sang Mi; Bach,Tran The; Rho,Jaerang; Lee,Ju Yong; Park,Jung Geun; Oh,Sei‑Ryang; Lee,Chul‑Ho; Oh,Won Keun; Kim,Yong‑Hoon

doi:10.3892/ijmm.2018.3849

3,5-Di-C-β-D-glucopyranosyl phloroacetophenone, a major component of Melicope ptelefolia, suppresses fibroblast activation and alleviates arthritis in a mouse model: Potential therapeutics for rheumatoid arthritis

Authors:
- Hyun Jong Kim
- Ji Hyun Choi
- Jung‑Hwan Hwang
- Kyong‑Shim Kim
- Jung‑Ran Noh
- Dong‑Hee Choi
- Sung Je Moon
- Hyun‑Yong Kim
- Sang‑Woo Kim
- Sangho Choi
- Sang Mi Eum
- Tran The Bach
- Jaerang Rho
- Ju Yong Lee
- Jung Geun Park
- Sei‑Ryang Oh
- Chul‑Ho Lee
- Won Keun Oh
- Yong‑Hoon Kim
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Affiliations: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea, Laboratory Animal Center, Osong Medical Innovation Foundation, Cheongju, Chungcheongbuk‑do 28160, Republic of Korea, International Biological Material Research Center, Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea, Institute of Ecology and Biological Resources, Vietnam Academy of Science and Technology, Hanoi, Vietnam, Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 34134, Republic of Korea, Korea Bioactive Natural Material Bank, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea, University of Science and Technology, Daejeon 34113, Republic of Korea
Published online on: August 30, 2018 https://doi.org/10.3892/ijmm.2018.3849
Pages: 2763-2775
Copyright: © Kim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Melicope ptelefolia has been traditionally used to treat rheumatism and fever. The present study aimed to investigate the therapeutic effect of 3,5‑di‑C‑β‑D‑glucopyranosyl phloroacetophenone (βGP), a main component of M. ptelefolia, on rheumatoid arthritis (RA). A model of collagen‑induced arthritis (CIA) was established in mice using the RAW 264.7 murine macrophage cell line and mouse embryonic fibroblasts (MEFs). The clinical scores of arthritis, swelling, histopathological findings, and micro‑computed tomography in CIA mouse paws were assessed. The levels of anti‑type II collagen antibody and cytokines were determined in the plasma and cell culture supernatant, respectively. Protein and gene expression levels were analyzed by western blot and reverse transcription‑quantitative polymerase chain reaction analyses. βGP significantly decreased the gross arthritic scores of CIA mice and joint swelling, and decreased articular inflammation, cartilage degradation and bone erosion. However, βGP did not exert any effect on anti‑type II collagen immunoglobulin G plasma levels or inflammatory cytokine expression in macrophages. βGP significantly suppressed the expression of interleukin‑6 and leukemia inhibitory factor and decreased the phosphorylation of signal transducer and activator of transcription 3, and expression of receptor activator of nuclear factor‑κB ligand in tumor necrosis factor‑α‑stimulated MEFs and in CIA mouse paws. Osteoclast‑related gene expression was significantly reduced in CIA mouse paws. Taken together, βGP suppressed the development of RA by regulating the activation of synovial fibroblasts.

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1	Myasoedova E, Crowson CS, Kremers HM, Therneau TM and Gabriel SE: Is the incidence of rheumatoid arthritis rising? Results from olmsted county, minnesota, 1955–2007. Arthritis Rheum. 62:1576–1582. 2010. View Article : Google Scholar : PubMed/NCBI
2	Jiang SH, Ping LF, Sun FY, Wang XL and Sun ZJ: Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses in mice. Exp Ther Med. 12:4035–4040. 2016. View Article : Google Scholar
3	Xu H, Wang J, Wang C, Chang G, Lin Y, Zhang H, Zhang H, Li Q and Pang T: Therapeutic effects of micheliolide on a murine model of rheumatoid arthritis. Mol Med Rep. 11:489–493. 2015. View Article : Google Scholar
4	Choy E: Understanding the dynamics: Pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 5(Suppl 51): pp. v3–v11. 2012, View Article : Google Scholar
5	Shin JS, Yun CH, Chung KS, Bang MH, Baek NI, Chung HG, Cho YW and Lee KT: Standardized ethyl acetate fraction from the roots of brassica rapa attenuates the experimental arthritis by down regulating inflammatory responses and inhibiting NF-κB activation. Food Chem Toxicol. 66:96–106. 2014. View Article : Google Scholar : PubMed/NCBI
6	Song YW and Kang EH: Autoantibodies in rheumatoid arthritis: Rheumatoid factors and anticitrullinated protein antibodies. QJM. 103:139–146. 2010. View Article : Google Scholar :
7	Hashizume M, Hayakawa N and Mihara M: IL-6 trans-signalling directly induces RANKL on fibroblast-like synovial cells and is involved in RANKL induction by TNF-alpha and IL-17. Rheumatology (Oxford). 47. pp. 1635–1640. 2008, View Article : Google Scholar
8	Weitzmann MN: The role of inflammatory cytokines, the RANKL/OPG axis, and the immunoskeletal interface in physiological bone turnover and osteoporosis. Scientifica (Cairo). 2013:1257052013.
9	Srirangan S and Choy EH: The role of interleukin 6 in the pathophysiology of rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2:247–256. 2010. View Article : Google Scholar : PubMed/NCBI
10	Kwan Tat S, Padrines M, Théoleyre S, Heymann D and Fortun Y: IL-6, RANKL, TNF-alpha/IL-1: Interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 15:49–60. 2004. View Article : Google Scholar : PubMed/NCBI
11	Charles JF and Aliprantis AO: Osteoclasts: More than 'bone eaters'. Trends Mol Med. 20:449–459. 2014. View Article : Google Scholar : PubMed/NCBI
12	Kamperdick C, Van NH, Sung TV and Adam G: Benzopyrans from Melicope ptelefolia leaves. Phytochemistry. 45:1049–1056. 1997. View Article : Google Scholar
13	Hong Van N, Kamperdick C, Van Sung T and Adam G: Benzopyran dimers from Melicope ptelefolia. Phytochemistry. 48:1055–1057. 1998. View Article : Google Scholar
14	Nguyen NH, Ha TK, Choi S, Eum S, Lee CH, Bach TT, Chinh VT and Oh WK: Chemical constituents from Melicope pteleifolia leaves. Phytochemistry. 130:291–300. 2016. View Article : Google Scholar : PubMed/NCBI
15	Sulaiman MR, Mohd Padzil A, Shaari K, Khalid S, Shaik Mossadeq WM, Mohamad AS, Ahmad S, Akira A, Israf D and Lajis N: Antinociceptive activity of Melicope ptelefolia ethanolic extract in experimental animals. J Biomed Biotechnol. 2010:9376422010. View Article : Google Scholar
16	Loi DT: Nhung cay Thuoc va vi thuoc Viet Nam (Glossary of Vietnamese Medicinal Plants). Science and Technics Publication; Hanoi, Vietnam: 1977
17	Perry LM and Metzger J: Medicinal Plants of East and Southeast Asia: Attributed Properties and Uses. MIT Press; Cambridge, UK: 1980
18	Lee CH, Bae SJ and Kim M: Mucosa-associated lymphoid tissue lymphoma translocation 1 as a novel therapeutic target for rheumatoid arthritis. Sci Rep. 7:118892017. View Article : Google Scholar : PubMed/NCBI
19	Sun J, Jia Y, Li R, Guo J, Sun X, Liu Y, Li Y, Yao H, Liu X, Zhao J and Li Z: Altered influenza virus haemagglutinin (HA)-derived peptide is potent therapy for CIA by inducing Th1 to Th2 shift. Cell Mol Immunol. 8:348–358. 2011. View Article : Google Scholar : PubMed/NCBI
20	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
21	Schett G and Gravallese E: Bone erosion in rheumatoid arthritis: Mechanisms, diagnosis and treatment. Nat Rev Rheumatol. 8:656–664. 2012. View Article : Google Scholar : PubMed/NCBI
22	Schmitz N, Laverty S, Kraus VB and Aigner T: Basic methods in histopathology of joint tissues. Osteoarthritis Cartilage. 3(Suppl 18): S113–S116. 2010. View Article : Google Scholar
23	van Boekel MA, Vossenaar ER, van den Hoogen FH and van Venrooij WJ: Autoantibody systems in rheumatoid arthritis: Specificity, sensitivity and diagnostic value. Arthritis Res. 4:87–93. 2002. View Article : Google Scholar : PubMed/NCBI
24	Yanni G, Whelan A, Feighery C and Bresnihan B: Synovial tissue macrophages and joint erosion in rheumatoid arthritis. Ann Rheum Dis. 53:39–44. 1994. View Article : Google Scholar : PubMed/NCBI
25	Kinne RW, Bräuer R, Stuhlmüller B, Palombo-Kinne E and Burmester GR: Macrophages in rheumatoid arthritis. Arthritis Res. 2:189–202. 2000. View Article : Google Scholar : PubMed/NCBI
26	Davignon JL, Hayder M, Baron M, Boyer JF, Constantin A, Apparailly F, Poupot R and Cantagrel A: Targeting monocytes/macrophages in the treatment of rheumatoid arthritis. Rheumatology (Oxford). 52. pp. 590–598. 2013, View Article : Google Scholar
27	Baumann H and Kushner I: Production of interleukin-6 by synovial fibroblasts in rheumatoid arthritis. Am J Pathol. 152:641–644. 1998.PubMed/NCBI
28	Palmqvist P, Persson E, Conaway HH and Lerner UH: IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae. J Immunol. 169:3353–3362. 2002. View Article : Google Scholar : PubMed/NCBI
29	Ospelt C: Synovial fibroblasts in 2017. RMD Open. 3:e0004712017. View Article : Google Scholar : PubMed/NCBI
30	Durand M, Boire G, Komarova SV, Dixon SJ, Sims SM, Harrison RE, Nabavi N, Maria O, Manolson MF, Mizianty M, et al: The increased in vitro osteoclastogenesis in patients with rheumatoid arthritis is due to increased percentage of precursors and decreased apoptosis-the In vitro osteoclast differentiation in arthritis (IODA) study. Bone. 48:588–596. 2011. View Article : Google Scholar
31	Hikata T, Takaishi H, Takito J, Hakozaki A, Furukawa M, Uchikawa S, Kimura T, Okada Y, Matsumoto M, Yoshimura A, et al: PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblasts. Blood. 113:2202–2212. 2009. View Article : Google Scholar
32	Cope AP, Schulze-Koops H and Aringer M: The central role of T cells in rheumatoid arthritis. Clin Exp Rheumatol. 25(Suppl 46): S4–S11. 2007.PubMed/NCBI
33	Kaplan C, Valdez JC, Chandrasekaran R, Eibel H, Mikecz K, Glant TT and Finnegan A: Th1 and Th2 cytokines regulate proteoglycan-specific autoantibody isotypes and arthritis. Arthritis Res. 4:54–58. 2002. View Article : Google Scholar : PubMed/NCBI
34	Edwards JC, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close DR, Stevens RM and Shaw T: Efficacy of B-Cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 350:2572–2281. 2004. View Article : Google Scholar : PubMed/NCBI
35	Brennan F and Foey A: Cytokine regulation in RA synovial tissue: Role of T cell/macrophage contact-dependent interactions. Arthritis Res. 3(Suppl 4): S177–S182. 2002. View Article : Google Scholar
36	Alves CH, Farrell E, Vis M, Colin EM and Lubberts E: Animal models of bone loss in inflammatory arthritis: From cytokines in the bench to novel treatments for bone loss in the bedside-a comprehensive review. Clin Rev Allergy Immunol. 51:27–47. 2016. View Article : Google Scholar
37	Siebert S, Tsoukas A, Robertson J and McInnes I: Cytokines as therapeutic targets in rheumatoid arthritis and other inflammatory diseases. Pharmacol Rev. 67:280–309. 2015. View Article : Google Scholar : PubMed/NCBI
38	St C: Interleukin 10 treatment for rheumatoid arthritis. Ann Rheum Dis. 58(Suppl 1): I99–I102. 1999. View Article : Google Scholar
39	Brzustewicz E and Bryl E: The role of cytokines in the pathogenesis of rheumatoid arthritis-practical and potential application of cytokines as biomarkers and targets of personalized therapy. Cytokine. 76:527–536. 2015. View Article : Google Scholar : PubMed/NCBI
40	Vane JR: Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 231:232–235. 1971. View Article : Google Scholar : PubMed/NCBI
41	Ogston NC, Karastergiou K, Hosseinzadeh-Attar MJ, Bhome R, Madani R, Stables M, Gilroy D, Flachs P, Hensler M, Kopecky J and Mohamed-Ali V: Low-dose acetylsalicylic acid inhibits the secretion of interleukin-6 from white adipose tissue. Int J Obes (Lond). 32:1807–1815. 2008. View Article : Google Scholar
42	Nakao S, Ogtata Y, Shimizu E, Yamazaki M, Furuyama S and Sugiya H: Tumor necrosis factor alpha (TNF-alpha)-induced prostaglandin E2 release is mediated by the activation of cyclooxygenase-2 (COX-2) transcription via NFkappaB in human gingival fibroblasts. Mol Cell Biochem. 238:11–18. 2002. View Article : Google Scholar : PubMed/NCBI
43	Jones DH, Kong YY and Penninger JM: Role of RANKL and RANK in bone loss and arthritis. Ann Rheum Dis. 2(Suppl 61): ii32–ii39. 2002. View Article : Google Scholar
44	Feng X: RANKing intracellular signaling in osteoclasts. IUBMB Life. 57:389–395. 2005. View Article : Google Scholar : PubMed/NCBI
45	Boyce BF and Xing L: Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 473:139–146. 2008. View Article : Google Scholar : PubMed/NCBI
46	Tawara K; Oxford JT; Jorcyk CL: Clinical significance of interleukin (IL)-6 in cancer metastasis to bone: Potential of anti-IL-6 therapies. Cancer Manag Res. 3:177–189. 2011.PubMed/NCBI
47	Miyamoto T, Mori T, Yoshimura A and Toyama T: STAT3 is critical to promote inflammatory cytokines and RANKL expression in inflammatory arthritis. Arthritis Res Ther. 14(Suppl 1): P432012. View Article : Google Scholar :
48	O'Brien CA, Gubrij I, Lin SC, Saylorsi RL and Manolagas SC: STAT3 activation in stromal/osteoblastic cells is required for induction of the receptor activator of NF-κB ligand and stimulation of osteoclastogenesis by gp130-utilizing cytokines or interleukin-1 but not 1,25-dihydroxyvitamin d3 or parathyroid hormone. J Biol Chem. 274:19301–19308. 1999. View Article : Google Scholar : PubMed/NCBI