Tenuigenin Prevents IL-1β-induced Inflammation in Human Osteoarthritis Chondrocytes by Suppressing PI3K/AKT/NF-κB Signaling Pathway

Overview

Journal Inflammation

Specialties Allergy & Immunology
Pathology

Date 2016 Feb 6

PMID 26846886

Citations 27

Authors

Chunlei Wang

Lihong Zeng

Tao Zhang

Jiakun Liu

Wenbo Wang

Affiliations

Soon will be listed here.

Abstract

Tenuigenin (TEN), the main active component of Polygala tenuifolia, has been reported to have anti-inflammatory effects. However, the effects of TEN on IL-1β-stimulated osteoarthritis chondrocytes have not been reported. The purpose of this study was to investigate the anti-inflammatory effects and mechanism of TEN on IL-1β-stimulated human osteoarthritis chondrocytes. Human osteoarthritis chondrocytes were pretreated with or without TEN for 1 h and then stimulated with IL-1β. The production of NO and PGE2 were detected by the Griess reagent and ELISA. The expression of NF-κB and MAPKs (p38, JNK, ERK) were measured by Western blot analysis. The production of MMP-1, MMP3, and MMP13 were measured by ELISA. The results showed that treatment of TEN significantly inhibited IL-1β-induced NO and PGE2 production. TEN also suppressed IL-1β-induced MMP-1, MMP3, and MMP13 expression. Furthermore, TEN was found to inhibit IL-1β-induced NF-κB activation, PI3K, and AKT phosphorylation. In conclusion, these results suggest that TEN inhibits IL-1β-induced inflammation in human osteoarthritis chondrocytes by inhibiting PI3K/AKT/NF-κB signaling pathway.

Citing Articles

Tenuigenin inhibits osteosarcoma growth via CIP2A/PP2A/NF-κB axis.

Yang S, Liu S, Dai Z Cancer Chemother Pharmacol. 2024; 95(1):15.

PMID: 39739023 DOI: 10.1007/s00280-024-04733-w.

Eriodictyol attenuates osteoarthritis progression through inhibiting inflammation via the PI3K/AKT/NF-κB signaling pathway.

Kang W, Xu Q, Dong H, Wang W, Huang G, Zhang J Sci Rep. 2024; 14(1):18853.

PMID: 39143134 PMC: 11324885. DOI: 10.1038/s41598-024-69028-9.

: review of metabolites, pharmacological activities and toxicology.

Liu M, Wang X, Gao D Front Pharmacol. 2024; 15:1420853.

PMID: 38873413 PMC: 11169621. DOI: 10.3389/fphar.2024.1420853.

TAK-242 (Resatorvid) inhibits proinflammatory cytokine production through the inhibition of NF-κB signaling pathway in fibroblast-like synoviocytes in osteoarthritis patients.

Khomeijani-Farahani M, Karami J, Farhadi E, Soltani S, Delbandi A, Shekarabi M Adv Rheumatol. 2024; 64(1):46.

PMID: 38849923 DOI: 10.1186/s42358-024-00385-9.

Sipeimine ameliorates osteoarthritis progression by suppression of NLRP3 inflammasome-mediated pyroptosis through inhibition of PI3K/AKT/NF-κB pathway: An in vitro and in vivo study.

Fang Y, Lou C, Lv J, Zhang C, Zhu Z, Hu W J Orthop Translat. 2024; 46:1-17.

PMID: 38765604 PMC: 11099199. DOI: 10.1016/j.jot.2024.04.004.

References

Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier J, Fahmi H . Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2010; 7(1):33-42. DOI: 10.1038/nrrheum.2010.196. View

Kobayashi M, Squires G, Mousa A, Tanzer M, Zukor D, Antoniou J . Role of interleukin-1 and tumor necrosis factor alpha in matrix degradation of human osteoarthritic cartilage. Arthritis Rheum. 2005; 52(1):128-35. DOI: 10.1002/art.20776. View

Futani H, Okayama A, Matsui K, Kashiwamura S, Sasaki T, Hada T . Relation between interleukin-18 and PGE2 in synovial fluid of osteoarthritis: a potential therapeutic target of cartilage degradation. J Immunother. 2002; 25 Suppl 1:S61-4. DOI: 10.1097/00002371-200203001-00009. View

Goldring M, Berenbaum F . The regulation of chondrocyte function by proinflammatory mediators: prostaglandins and nitric oxide. Clin Orthop Relat Res. 2004; (427 Suppl):S37-46. DOI: 10.1097/01.blo.0000144484.69656.e4. View

Baker R, Hayden M, Ghosh S . NF-κB, inflammation, and metabolic disease. Cell Metab. 2011; 13(1):11-22. PMC: 3040418. DOI: 10.1016/j.cmet.2010.12.008. View

Chen Y, Huang X, Chen W, Wang N, Li L . Tenuigenin promotes proliferation and differentiation of hippocampal neural stem cells. Neurochem Res. 2011; 37(4):771-7. DOI: 10.1007/s11064-011-0671-3. View

Silverstein F, Faich G, Goldstein J, Simon L, Pincus T, WHELTON A . Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA. 2000; 284(10):1247-55. DOI: 10.1001/jama.284.10.1247. View

Fukui N, Zhu Y, Maloney W, Clohisy J, Sandell L . Stimulation of BMP-2 expression by pro-inflammatory cytokines IL-1 and TNF-alpha in normal and osteoarthritic chondrocytes. J Bone Joint Surg Am. 2003; 85-A Suppl 3:59-66. DOI: 10.2106/00004623-200300003-00011. View

Daheshia M, Yao J . The interleukin 1beta pathway in the pathogenesis of osteoarthritis. J Rheumatol. 2008; 35(12):2306-12. DOI: 10.3899/jrheum.080346. View

10.

Burrage P, Mix K, Brinckerhoff C . Matrix metalloproteinases: role in arthritis. Front Biosci. 2005; 11:529-43. DOI: 10.2741/1817. View

11.

Koskinen A, Vuolteenaho K, Nieminen R, Moilanen T, Moilanen E . Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients. Clin Exp Rheumatol. 2011; 29(1):57-64. View

12.

Benito M, Veale D, FitzGerald O, van den Berg W, Bresnihan B . Synovial tissue inflammation in early and late osteoarthritis. Ann Rheum Dis. 2005; 64(9):1263-7. PMC: 1755629. DOI: 10.1136/ard.2004.025270. View

13.

Yang G, Im H, Wang J . Repetitive mechanical stretching modulates IL-1beta induced COX-2, MMP-1 expression, and PGE2 production in human patellar tendon fibroblasts. Gene. 2005; 363:166-72. PMC: 2901527. DOI: 10.1016/j.gene.2005.08.006. View

14.

Pelletier J, Martel-Pelletier J, Abramson S . Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets. Arthritis Rheum. 2001; 44(6):1237-47. DOI: 10.1002/1529-0131(200106)44:6<1237::AID-ART214>3.0.CO;2-F. View

15.

Studer R, Jaffurs D, Stefanovic-Racic M, Robbins P, Evans C . Nitric oxide in osteoarthritis. Osteoarthritis Cartilage. 1999; 7(4):377-9. DOI: 10.1053/joca.1998.0216. View

16.

Pelletier J, Mineau F, Ranger P, Tardif G, Martel-Pelletier J . The increased synthesis of inducible nitric oxide inhibits IL-1ra synthesis by human articular chondrocytes: possible role in osteoarthritic cartilage degradation. Osteoarthritis Cartilage. 1996; 4(1):77-84. DOI: 10.1016/s1063-4584(96)80009-4. View

17.

Karan A, Karan M, Vural P, Erten N, Tascioglu C, Aksoy C . Synovial fluid nitric oxide levels in patients with knee osteoarthritis. Clin Rheumatol. 2003; 22(6):397-9. DOI: 10.1007/s10067-003-0761-y. View

18.

Jacques C, Gosset M, Berenbaum F, Gabay C . The role of IL-1 and IL-1Ra in joint inflammation and cartilage degradation. Vitam Horm. 2006; 74:371-403. DOI: 10.1016/S0083-6729(06)74016-X. View

19.

Lawrence T, Fong C . The resolution of inflammation: anti-inflammatory roles for NF-kappaB. Int J Biochem Cell Biol. 2009; 42(4):519-23. DOI: 10.1016/j.biocel.2009.12.016. View

20.

Cheng A, Stabler T, Bolognesi M, Kraus V . Selenomethionine inhibits IL-1β inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) expression in primary human chondrocytes. Osteoarthritis Cartilage. 2010; 19(1):118-25. PMC: 3053078. DOI: 10.1016/j.joca.2010.10.019. View