Ultra-High-Performance Liquid Chromatography-High-Definition Mass Spectrometry-Based Metabolomics to Reveal the Potential Anti-Arthritic Effects of in Cultured Fibroblast-like Synoviocytes Derived from Rheumatoid Arthritis

Overview

Journal Metabolites

Publisher MDPI

Date 2024 Oct 25

PMID 39452898

Authors

Mingzhen Qin

Lu Chen

Xiaoli Hou

Wuwei Wu

Yu Liu

Yu Pan

Mengli Zhang

Zhien Tan

Danna Huang

Affiliations

Soon will be listed here.

Abstract

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. The fruits of , which is a medicinal and edible resource, have been shown to have anti-inflammatory properties.

Methods: In this study, we investigated the effects of extracts (IVEs) on human RA fibroblasts-like synoviocytes (RA-FLS) by using a sensitive and selective ultra-high-performance liquid chromatography with high-definition mass spectrometry (UPLC-HDMS) method. We subsequently analyzed the metabolites produced after the incubation of cultured RA-FLS with IVEs.

Results: IVEs inhibited the proliferation and suppressed the migration of RA-FLS, and reduced the levels of inflammatory factors including TNF-α and IL-6. Twenty differential metabolites responsible for the effects of IVEs were screened and annotated based on the UPLC-HDMS data by using a cell metabolomics approach.

Discussion: Our findings suggest that treating RA-FLS with IVEs can regulate lipid and amino acid metabolism, indicating that this extract has the potential to modify the metabolic pathways that cause inflammation in RA.

Conclusions: This might lead to novel therapeutic strategies for managing patients with RA.

References

Bottini N, Firestein G . Duality of fibroblast-like synoviocytes in RA: passive responders and imprinted aggressors. Nat Rev Rheumatol. 2012; 9(1):24-33. PMC: 3970924. DOI: 10.1038/nrrheum.2012.190. View

Han X . Lipidomics for studying metabolism. Nat Rev Endocrinol. 2016; 12(11):668-679. DOI: 10.1038/nrendo.2016.98. View

McGrath C, Young S . Lipid and Metabolic Changes in Rheumatoid Arthritis. Curr Rheumatol Rep. 2015; 17(9):57. DOI: 10.1007/s11926-015-0534-z. View

Summers S, Chaurasia B, Holland W . Metabolic Messengers: ceramides. Nat Metab. 2020; 1(11):1051-1058. PMC: 7549391. DOI: 10.1038/s42255-019-0134-8. View

Kohler B, Gunther J, Kaudewitz D, Lorenz H . Current Therapeutic Options in the Treatment of Rheumatoid Arthritis. J Clin Med. 2019; 8(7). PMC: 6678427. DOI: 10.3390/jcm8070938. View

Li R, Guo L, Li Y, Chang W, Liu J, Liu L . Dose-response characteristics of Clematis triterpenoid saponins and clematichinenoside AR in rheumatoid arthritis rats by liquid chromatography/mass spectrometry-based serum and urine metabolomics. J Pharm Biomed Anal. 2017; 136:81-91. DOI: 10.1016/j.jpba.2016.12.037. View

Seal A, Hughes M, Wei F, Pugazhendhi A, Ngo C, Ruiz J . Sphingolipid-Induced Bone Regulation and Its Emerging Role in Dysfunction Due to Disease and Infection. Int J Mol Sci. 2024; 25(5). PMC: 10932382. DOI: 10.3390/ijms25053024. View

Ahn J, Kim S, Hwang J, Kim J, Kim K, Cha H . GC/TOF-MS-based metabolomic profiling in cultured fibroblast-like synoviocytes from rheumatoid arthritis. Joint Bone Spine. 2016; 83(6):707-713. DOI: 10.1016/j.jbspin.2015.11.009. View

Abdel-Khalek M, El-Barbary A, Essa S, Ghobashi A . Serum hepcidin: a direct link between anemia of inflammation and coronary artery atherosclerosis in patients with rheumatoid arthritis. J Rheumatol. 2011; 38(10):2153-9. DOI: 10.3899/jrheum.110339. View

10.

Perricone C, De Carolis C, Perricone R . Glutathione: a key player in autoimmunity. Autoimmun Rev. 2009; 8(8):697-701. DOI: 10.1016/j.autrev.2009.02.020. View

11.

Hannun Y, Obeid L . Sphingolipids and their metabolism in physiology and disease. Nat Rev Mol Cell Biol. 2017; 19(3):175-191. PMC: 5902181. DOI: 10.1038/nrm.2017.107. View

12.

Miltenberger-Miltenyi G, Cruz-Machado A, Saville J, Conceicao V, Calado A, Lopes I . Increased monohexosylceramide levels in the serum of established rheumatoid arthritis patients. Rheumatology (Oxford). 2019; 59(8):2085-2089. DOI: 10.1093/rheumatology/kez545. View

13.

Chaurasia B, Summers S . Ceramides in Metabolism: Key Lipotoxic Players. Annu Rev Physiol. 2020; 83:303-330. PMC: 7905841. DOI: 10.1146/annurev-physiol-031620-093815. View

14.

Dekkers K, Slieker R, Ioan-Facsinay A, van Iterson M, Ikram M, van Greevenbroek M . Lipid-induced transcriptomic changes in blood link to lipid metabolism and allergic response. Nat Commun. 2023; 14(1):544. PMC: 9892529. DOI: 10.1038/s41467-022-35663-x. View

15.

Falconer J, Murphy A, Young S, Clark A, Tiziani S, Guma M . Review: Synovial Cell Metabolism and Chronic Inflammation in Rheumatoid Arthritis. Arthritis Rheumatol. 2018; 70(7):984-999. PMC: 6019623. DOI: 10.1002/art.40504. View

16.

Maceyka M, Spiegel S . Sphingolipid metabolites in inflammatory disease. Nature. 2014; 510(7503):58-67. PMC: 4320971. DOI: 10.1038/nature13475. View

17.

Ritter A, Hernandes L, da Rocha B, Estevao-Silva C, Wisniewski-Rebecca E, Cezar J . Anethole reduces inflammation and joint damage in rats with adjuvant-induced arthritis. Inflamm Res. 2017; 66(8):725-737. DOI: 10.1007/s00011-017-1053-3. View

18.

Nemeth T, Nagy G, Pap T . Synovial fibroblasts as potential drug targets in rheumatoid arthritis, where do we stand and where shall we go?. Ann Rheum Dis. 2022; 81(8):1055-1064. PMC: 9279838. DOI: 10.1136/annrheumdis-2021-222021. View

19.

Solomon D, Glynn R, Karlson E, Lu F, Corrigan C, Colls J . Adverse Effects of Low-Dose Methotrexate: A Randomized Trial. Ann Intern Med. 2020; 172(6):369-380. PMC: 7229518. DOI: 10.7326/M19-3369. View

20.

Handa O, Naito Y, Fukui A, Omatsu T, Yoshikawa T . The impact of non-steroidal anti-inflammatory drugs on the small intestinal epithelium. J Clin Biochem Nutr. 2014; 54(1):2-6. PMC: 3882490. DOI: 10.3164/jcbn.13-84. View