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Apoptosis effects of imperatorin on synoviocytes in rheumatoid arthritis through mitochondrial/caspase-mediated pathways


Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease associated with potential imbalance between growth and death of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). Imperatorin (IPT) is a naturally occurring furanocoumarin found in umbelliferous vegetables, citrus fruits, and some herbs. Effects of IPT on the proliferation and apoptosis of RA-FLSs and its potential underlying mechanisms remained unclear. RA-FLSs obtained from RA patients were induced by interleukin-1β (IL-1β) and treated with IPT. Cell viability was determined by MTT assay. Apoptotic cell death was analyzed by Annexin V-FITC/PI double staining and Hoechst 33342 staining. The loss in mitochondrial membrane potential (ΔΨm) was visualized on the basis of JC-1 staining via fluorescence microscopy, protein expression changes were assessed by Western blotting; whereas in vivo studies were conducted in male wistar rats followed by histopathological assessment via TUNEL assay and HE staining of tissues. Results showed that IPT significantly reduced cell viability, accelerated cell apoptosis and decreased matrix metalloproteinases-1/-3 expression in IL-1β-induced RA-FLSs. Furthermore, IPT exposure was found to disrupt the ΔΨm compared to the IL-1β-induced treatment. Moreover, IPT increased the release of mitochondrial cytochrome C, the ratio of Bax/Bcl-2, as well as the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase. In vivo studies showed that IPT not only significantly reduced the collagen induced arthritis by reducing synovial hyperplasia, pannus formation but also enhanced the apoptotic index of ankle joint cells. Conclusively, our findings suggest that IPT inhibits cell proliferation and induces apoptosis in RA-FLSs that may be associated with mitochondrial/caspase-mediated signalling pathways.

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Publication details

The article was received on 06 Nov 2017, accepted on 20 Feb 2018 and first published on 21 Feb 2018

Article type: Paper
DOI: 10.1039/C7FO01748K
Citation: Food Funct., 2018, Accepted Manuscript
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    Apoptosis effects of imperatorin on synoviocytes in rheumatoid arthritis through mitochondrial/caspase-mediated pathways

    K. Zhai, H. Duan, Y. Chen, G. J. Khan, W. Cao, G. Gao, L. Shan and Z. Wei, Food Funct., 2018, Accepted Manuscript , DOI: 10.1039/C7FO01748K

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