Ginkgolide J protects human synovial cells SW982 via suppression of p38‑dependent production of pro‑inflammatory mediators

Zhao,Yujie; Chen,Yuan; Wang,Jiayi; Zhu,Xue; Wang,Ke; Li,Yue; Zhou,Fanfan

doi:10.3892/mmr.2021.12194

Ginkgolide J protects human synovial cells SW982 via suppression of p38‑dependent production of pro‑inflammatory mediators

Authors:
- Yujie Zhao
- Yuan Chen
- Jiayi Wang
- Xue Zhu
- Ke Wang
- Yue Li
- Fanfan Zhou
View Affiliations

Affiliations: NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, P.R. China, Department of Rheumatology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China, Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia
Published online on: June 2, 2021 https://doi.org/10.3892/mmr.2021.12194
Article Number: 555
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Fibroblast‑like synoviocytes (FLS) in the synovial lining play a key role in the pathological process of rheumatoid arthritis (RA), which produce pro‑inflammatory mediators to perpetuate inflammation and proteases to contribute to cartilage destruction. Ginkgolide J (GJ) is a subclass of ginkgolides (GGs) that exhibits anti‑inflammatory activity. In the present study, the protective effect of GJ on lipopolysaccharide (LPS)‑treated human synovial cells SW982 and its related mechanisms were investigated using various methods, including ELISA, Griess assay, western blotting, immunofluorescence analysis and p38 kinase activity assay. The results revealed that GJ pretreatment significantly attenuated LPS‑induced excess production of pro‑inflammatory mediators in SW982 cells via suppression of tumor necrosis factor‑α/interleukin (IL)‑1β/IL‑18/NF‑κB/NLR family pyrin domain containing 3, prostaglandin E2/cyclooxygenase‑2 and inducible nitric oxide synthase/nitric oxide signaling. Mechanistic studies revealed that p38 activation contributed to the LPS‑induced inflammatory response, and GJ pretreatment dose‑dependently attenuated p38 activation, indicating that the suppressive effect of GJ was achieved by targeting p38 signaling. These findings may contribute to the prevention and treatment of RA.

View Figures

View References

1	Pisetsky DS and Ward MM: Advances in the treatment of inflammatory arthritis. Best Pract Res Clin Rheumatol. 26:251–261. 2012. View Article : Google Scholar : PubMed/NCBI
2	Kim Y, Oh HC, Park JW, Kim IS, Kim JY, Kim KC, Chae DS, Jo WL and Song JH: Diagnosis and treatment of inflammatory joint disease. Hip Pelvis. 29:211–222. 2017. View Article : Google Scholar : PubMed/NCBI
3	Firestein GS and McInnes IB: Immunopathogenesis of rheumatoid arthritis. Immunity. 46:183–196. 2017. View Article : Google Scholar : PubMed/NCBI
4	Tak PP and Breedveld FC: Current perspectives on synovitis. Arthritis Res. 1:11–16. 1999. View Article : Google Scholar : PubMed/NCBI
5	Yoshitomi H: Regulation of immune responses and chronic inflammation by fibroblast-like synoviocytes. Front Immunol. 10:1395. 2019. View Article : Google Scholar : PubMed/NCBI
6	Zuo W, Yan F, Zhang B, Li J and Mei D: Advances in the studies of Ginkgo biloba leaves extract on aging-related diseases. Aging Dis. 8:812–826. 2017. View Article : Google Scholar : PubMed/NCBI
7	Nash KM and Shah ZA: Current perspectives on the beneficial role of Ginkgo biloba in neurological and cerebrovascular Disorders. Integr Med Insights. 10:1–9. 2015. View Article : Google Scholar : PubMed/NCBI
8	Le Bars PL and Kastelan J: Efficacy and safety of a Ginkgo biloba extract. Public Health Nutr. 3((4a)): 495–499. 2000. View Article : Google Scholar : PubMed/NCBI
9	Xiao G, Lyu M, Wang Y, He S, Liu X, Ni J, Li L, Fan G, Han J, Gao X, et al: Ginkgo flavonol glycosides or Ginkgolides tend to differentially protect myocardial or cerebral ischemia-reperfusion injury via regulation of TWEAK-Fn14 signaling in heart and brain. Front Pharmacol. 10:735. 2019. View Article : Google Scholar : PubMed/NCBI
10	Jaracz S, Malik S and Nakanishi K: Isolation of ginkgolides A, B, C, J and bilobalide from G. biloba extracts. Phytochemistry. 65:2897–2902. 2004. View Article : Google Scholar : PubMed/NCBI
11	Li Y, Wu Y, Yao X, Hao F, Yu C, Bao Y, Wu Y, Song Z, Sun Y, Zheng L, et al: Ginkgolide A Ameliorates LPS-induced inflammatory responses in vitro and in vivo. Int J Mol Sci. 18:7942017. View Article : Google Scholar : PubMed/NCBI
12	Li C, Liu K, Liu S, Aerqin Q and Wu X: Role of Ginkgolides in the inflammatory immune response of neurological diseases: A review of current literatures. Front Syst Neurosci. 14:452020. View Article : Google Scholar : PubMed/NCBI
13	Wu F, Shi W, Zhou G, Yao H, Xu C, Xiao W, Wu J and Wu X: Ginkgolide B functions as a determinant constituent of Ginkgolides in alleviating lipopolysaccharide-induced lung injury. Biomed Pharmacother. 81:71–78. 2016. View Article : Google Scholar : PubMed/NCBI
14	Zhang H, Shi Q, Nan W, Wang Y, Wang S, Yang F and Li G: Ginkgolide B and bilobalide promote the growth and increase β-catenin expression in hair follicle dermal papilla cells of American minks. Biofactors. 45:950–958. 2019. View Article : Google Scholar : PubMed/NCBI
15	Vitolo O, Gong B, Cao Z, Ishii H, Jaracz S, Nakanishi K, Arancio O, Dzyuba SV, Lefort R and Shelanski M: Protection against beta-amyloid induced abnormal synaptic function and cell death by Ginkgolide J. Neurobiol Aging. 30:257–265. 2009. View Article : Google Scholar : PubMed/NCBI
16	Yoshino S and Ohsawa M: The role of lipopolysaccharide injected systemically in the reactivation of collagen-induced arthritis in mice. Br J Pharmacol. 129:1309–1314. 2000. View Article : Google Scholar : PubMed/NCBI
17	Bertani B and Ruiz N: Function and Biogenesis of Lipopolysaccharides. EcoSal Plus. 8:10.1128/ecosalplus.ESP.0001-2018. 2018. View Article : Google Scholar : PubMed/NCBI
18	Chang CF, Chau YP, Kung HN and Lu KS: The lipopolysaccharide-induced pro-inflammatory response in RAW264.7 cells is attenuated by an unsaturated fatty acid-bovine serum albumin complex and enhanced by a saturated fatty acid-bovine serum albumin complex. Inflamm Res. 61:151–160. 2012. View Article : Google Scholar : PubMed/NCBI
19	Yücel G, Zhao Z, El-Battrawy I, Lan H, Lang S, Li X, Buljubasic F, Zimmermann WH, Cyganek L, Utikal J, et al: Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes. Sci Rep. 7:2935. 2017. View Article : Google Scholar
20	Cope PJ, Ourradi K, Li Y and Sharif M: Models of osteoarthritis: The good, the bad and the promising. Osteoarthritis Cartilage. 27:230–239. 2019. View Article : Google Scholar : PubMed/NCBI
21	Alsaleh G, Suffert G, Semaan N, Juncker T, Frenzel L, Gottenberg JE, Sibilia J, Pfeffer S and Wachsmann D: Bruton's tyrosine kinase is involved in miR-346-related regulation of IL-18 release by lipopolysaccharide-activated rheumatoid fibroblast-like synoviocytes. J Immunol. 182:5088–5097. 2009. View Article : Google Scholar : PubMed/NCBI
22	Jin XN, Yan EZ, Wang HM, Sui HJ, Liu Z, Gao W and Jin Y: Hyperoside exerts anti-inflammatory and anti-arthritic effects in LPS-stimulated human fibroblast-like synoviocytes in vitro and in mice with collagen-induced arthritis. Acta Pharmacol Sin. 37:674–686. 2016. View Article : Google Scholar : PubMed/NCBI
23	Grabowski PS, Wright PK, Van't Hof RJ, Helfrich MH, Ohshima H and Ralston SH: Immunolocalization of inducible nitric oxide synthase in synovium and cartilage in rheumatoid arthritis and osteoarthritis. Br J Rheumatol. 36:651–655. 1997. View Article : Google Scholar : PubMed/NCBI
24	Kawashima M, Ogura N, Akutsu M, Ito K and Kondoh T: The anti-inflammatory effect of cyclooxygenase inhibitors in fibroblast-like synoviocytes from the human temporomandibular joint results from the suppression of PGE2 production. J Oral Pathol Med. 42:499–506. 2013. View Article : Google Scholar : PubMed/NCBI
25	Fu Q, Gao Y, Zhao H, Wang Z and Wang J: Galangin protects human rheumatoid arthritis fibroblast like synoviocytes via suppression of the NF κB/NLRP3 pathway. Mol Med Rep. 18:3619–3624. 2018.PubMed/NCBI
26	Herlaar E and Brown Z: p38 MAPK signalling cascades in inflammatory disease. Mol Med Today. 5:439–447. 1999. View Article : Google Scholar : PubMed/NCBI
27	Schieven GL: The p38alpha kinase plays a central role in inflammation. Curr Top Med Chem. 9:1038–1048. 2009. View Article : Google Scholar : PubMed/NCBI
28	Yong HY, Koh MS and Moon A: The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer. Expert Opin Investig Drugs. 18:1893–1905. 2009. View Article : Google Scholar : PubMed/NCBI