Paeoniflorin inhibits IL‑1β‑induced expression of inflammatory mediators in human osteoarthritic chondrocyte

Zhao,Lin; Chang,Qi; Huang,Tao; Huang,Changlin

doi:10.3892/mmr.2017.8222

Paeoniflorin inhibits IL‑1β‑induced expression of inflammatory mediators in human osteoarthritic chondrocyte

Authors:
- Lin Zhao
- Qi Chang
- Tao Huang
- Changlin Huang
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Affiliations: Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Institute of Military Training Related Medical Sciences, The 150 Hospital of Chinese People's Liberation Army, Luoyang, Henan 471003, P.R. China, Institute of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: December 8, 2017 https://doi.org/10.3892/mmr.2017.8222
Pages: 3306-3311

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Abstract

Interleukin (IL)-1β serves an important role in the promotion of the growth of osteoarthritis (OA) lesions. Paeoniflorin (PF) has been identified to exert anti‑inflammatory and anti‑arthritic effects. However, it is uncertain whether PF may affect the expression levels of inflammatory mediators in OA chondrocytes. Therefore, the objective of the present study was to determine the effects of PF on the expression levels of inflammatory mediators in IL‑1β‑stimulated human OA chondrocytes. The results of the present study determined that PF inhibited the production of nitric oxide and prostaglandin E2 induced by IL‑1β, and the expression of inducible nitric oxide synthase and cyclooxygenase‑2 in chondrocytes. Additionally, PF significantly inhibited the IL‑1β‑stimulated production of metalloproteinase‑3 (MMP‑3) and MMP‑13 in chondrocytes. PF inhibited the expression of nuclear factor‑κB (NF‑κB), p65 and NF‑κB inhibitor α degradation was induced by IL‑1β in chondrocytes. The results of the present study suggest that PF may inhibit IL‑1β‑induced expression of inflammatory mediators in human OA chondrocytes by suppressing the activation of the NF‑κB signaling pathway. Therefore, PF may be a potential agent in the future treatment of OA.

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1	Buckwalter JA, Mankin HJ and Grodzinsky AJ: Articular cartilage and osteoarthritis. Instr Course Lect. 54:465–480. 2005.PubMed/NCBI
2	Jakobsson U and Hallberg IR: Pain and quality of life among older people with rheumatoid arthritis and/or osteoarthritis: A literature review. J Clin Nurs. 11:430–443. 2002. View Article : Google Scholar : PubMed/NCBI
3	Richette P, Latourte A and Frazier A: Safety and efficacy of paracetamol and NSAIDs in osteoarthritis: Which drug to recommend? Expert Opin Drug Saf. 14:1259–1268. 2015. View Article : Google Scholar : PubMed/NCBI
4	Loeser RF: Molecular mechanisms of cartilage destruction: Mechanics, inflammatory mediators, and aging collide. Arthritis Rheum. 54:1357–1360. 2006. View Article : Google Scholar : PubMed/NCBI
5	Zhou PH, Liu SQ and Peng H: The effect of hyaluronic acid on IL-1beta-induced chondrocyte apoptosis in a rat model of osteoarthritis. J Orthop Res. 26:1643–1648. 2008. View Article : Google Scholar : PubMed/NCBI
6	Goldring SR and Goldring MB: The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat. 427 Suppl:S27–S36. 2004. View Article : Google Scholar
7	Mengshol JA, Vincenti MP, Coon CI, Barchowsky A and Brinckerhoff CE: Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-jun N-terminal kinase and nuclear factor kappaB: Differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum. 43:801–811. 2000. View Article : Google Scholar : PubMed/NCBI
8	Chabane N, Zayed N, Afif H, Mfuna-Endam L, Benderdour M, Boileau C, Martel-Pelletier J, Pelletier JP, Duval N and Fahmi H: Histone deacetylase inhibitors suppress interleukin-1beta-induced nitric oxide and prostaglandin E2 production in human chondrocytes. Osteoarthritis Cartilage. 16:1267–1274. 2008. View Article : Google Scholar : PubMed/NCBI
9	Wang H, Zhou H, Wang CX, Li YS, Xie HY, Luo JD and Zhou Y: Paeoniflorin inhibits growth of human colorectal carcinoma HT 29 cells in vitro and in vivo. Food Chem Toxicol. 50:1560–1567. 2012. View Article : Google Scholar : PubMed/NCBI
10	Wankun X, Wenzhen Y, Min Z, Weiyan Z, Huan C, Wei D, Lvzhen H, Xu Y and Xiaoxin L: Protective effect of paeoniflorin against oxidative stress in human retinal pigment epithelium in vitro. Mol Vis. 17:3512–3522. 2011.PubMed/NCBI
11	Cao W, Zhang W, Liu J, Wang Y, Peng X, Lu D, Qi R, Wang Y and Wang H: Paeoniflorin improves survival in LPS-challenged mice through the suppression of TNF-α and IL-1β release and augmentation of IL-10 production. Int Immunopharmacol. 11:172–178. 2011. View Article : Google Scholar : PubMed/NCBI
12	Nizamutdinova IT, Jin YC, Kim JS, Yean MH, Kang SS, Kim YS, Lee JH, Seo HG, Kim HJ and Chang KC: Paeonol and paeoniflorin, the main active principles of Paeonia albiflora, protect the heart from myocardial ischemia/reperfusion injury in rats. Planta Med. 74:14–18. 2008. View Article : Google Scholar : PubMed/NCBI
13	Liu H, Wang J, Wang J, Wang P and Xue Y: Paeoniflorin attenuates Aβ1-42-induced inflammation and chemotaxis of microglia in vitro and inhibits NF-κB- and VEGF/Flt-1 signaling pathways. Brain Res. 1618:149–158. 2015. View Article : Google Scholar : PubMed/NCBI
14	Wu D, Chen J, Zhu H, Xiong XG, Liang QH, Zhang Y, Zhang Y, Wang Y, Yang B and Huang X: UPLC-PDA determination of paeoniflorin in rat plasma following the oral administration of Radix Paeoniae Alba and its effects on rats with collagen-induced arthritis. Exp Ther Med. 7:209–217. 2014. View Article : Google Scholar : PubMed/NCBI
15	Cheng AW, Stabler TV, Bolognesi M and Kraus VB: Selenomethionine inhibits IL-1β inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) expression in primary human chondrocytes. Osteoarthritis Cartilage. 19:118–125. 2011. View Article : Google Scholar : PubMed/NCBI
16	Marcu KB, Otero M, Olivotto E, Borzí RM and Goldring MB: NF-kappaB signaling: Multiple angles to target OA. Curr Drug Targets. 11:599–613. 2010. View Article : Google Scholar : PubMed/NCBI
17	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 : PubMed/NCBI
18	Salvatierra J, Escames G, Hernandez P, Cantero J, Crespo E, Leon J, Salvatierra D, Acuña-Castroviejo D and Vives F: Cartilage and serum levels of nitric oxide in patients with hip osteoarthritis. J Rheumatol. 26:2015–2017. 1999.PubMed/NCBI
19	Salvemini D, Misko TP, Masferrer JL, Seibert K, Currie MG and Needleman P: Nitric oxide activates cyclooxygenase enzymes. Proc Natl Acad Sci USA. 90:pp. 7240–7244. 1993; View Article : Google Scholar : PubMed/NCBI
20	Guo RB, Wang GF, Zhao AP, Gu J, Sun XL and Hu G: Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-κB-mediated inflammatory responses. PLoS One. 7:e497012012. View Article : Google Scholar : PubMed/NCBI
21	Tetlow LC, Adlam DJ and Woolley DE: Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: Associations with degenerative changes. Arthritis Rheum. 44:585–594. 2001. View Article : Google Scholar : PubMed/NCBI
22	Dean DD, Martel-Pelletier J, Pelletier JP, Howell DS and Woessner JF Jr: Evidence for metalloproteinase and metalloproteinase inhibitor imbalance in human osteoarthritic cartilage. J Clin Invest. 84:678–685. 1989. View Article : Google Scholar : PubMed/NCBI
23	Mahmoud RK, El-Ansary AK, El-Eishi HH, Kamal HM and El-Saeed NH: Matrix metalloproteinases MMP-3 and MMP-1 levels in sera and synovial fluids in patients with rheumatoid arthritis and osteoarthritis. Ital J Biochem. 54:248–257. 2005.PubMed/NCBI
24	Wu JJ, Lark MW, Chun LE and Eyre DR: Sites of stromelysin cleavage in collagen types II IX, X, and XI of cartilage. J Biol Chem. 266:5625–5628. 1991.PubMed/NCBI
25	Aigner T, Fundel K, Saas J, Gebhard PM, Haag J, Weiss T, Zien A, Obermayr F, Zimmer R and Bartnik E: Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis. Arthritis Rheum. 54:3533–3544. 2006. View Article : Google Scholar : PubMed/NCBI
26	Scanzello CR and Goldring SR: The role of synovitis in osteoarthritis pathogenesis. Bone. 51:249–257. 2012. View Article : Google Scholar : PubMed/NCBI
27	Roman-Blas JA and Jimenez SA: NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage. 14:839–848. 2006. View Article : Google Scholar : PubMed/NCBI
28	Newton R, Kuitert LM, Bergmann M, Adcock IM and Barnes PJ: Evidence for involvement of NF-kappaB in the transcriptional control of COX-2 gene expression by IL-1beta. Biochem Biophys Res Commun. 237:28–32. 1997. View Article : Google Scholar : PubMed/NCBI
29	Stuhlmeier KM: The anti-rheumatic gold salt aurothiomalate suppresses interleukin-1beta-induced hyaluronan accumulation by blocking HAS1 transcription and by acting as a COX-2 transcriptional repressor. J Biol Chem. 282:2250–2258. 2007. View Article : Google Scholar : PubMed/NCBI
30	Liacini A, Sylvester J, Li WQ and Zafarullah M: Inhibition of interleukin-1-stimulated MAP kinases, activating protein-1 (AP-1) and nuclear factor kappa B (NF-kappaB) transcription factors down-regulates matrix metalloproteinase gene expression in articular chondrocytes. Matrix Biol. 21:251–262. 2002. View Article : Google Scholar : PubMed/NCBI
31	Wu H, Li W, Wang T, Shu Y and Liu P: Paeoniflorin suppress NF-kappaB activation through modulation of IkappaB alpha and enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells. Biomed Pharmacother. 62:659–666. 2008. View Article : Google Scholar : PubMed/NCBI
32	Zhang J, Dou W, Zhang E, Sun A, Ding L, Wei X, Chou G, Mani S and Wang Z: Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway. Am J Physiol Gastrointest Liver Physiol. 306:G27–G36. 2014. View Article : Google Scholar : PubMed/NCBI