Piperine Suppresses Inflammatory Fibroblast-like Synoviocytes Derived from Rheumatoid Arthritis Patients via NF-κB Inhibition

• Published in: Cellular immunology 2023-09, Vol.391-392, p.104752-104752, Article 104752
• Main Authors: Noel Baito, Qoyama, Jaafar, Halmat M., Ahmad Merza Mohammad, Talar
• Format: Article
• Language: English
• Subjects: Fibroblast-like Synoviocytes; NF-κB; Piperine; Rheumatoid Arthritis
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2023.104752

•Piperine induces the apoptosis and reduce the proliferation of RA-FLSs in vitro.•Piperine directly reduces the phosphorylation of NF-kB in FLSs.•Piperine decreases the expression of NF-κB target genes related to RA-FLSs proliferation, apoptosis inhibition and inflammation in vitro.•Piperine reduced the protein levels of cytokines and chemokines secreted by RA-FLSs. Rheumatoid Arthritis (RA) is a common autoimmune disease recognized by hyperplasia of synoviocytes and chronic joint inflammation. Activation of fibroblast-like synoviocytes (FLSs) is one of the main features of RA which can trigger inflammation leading to articular cartilage and joint destruction. Aberrant activation of NF-κB signaling cascade was found to be responsible for the high proliferation and defective apoptosis of FLSs and subsequent inflammation in RA. Piperine is a principal constituent of piper species frequently used as antitumor and anti-inflammatory natural compound. In this study we aimed to assess the anti-inflammatory effect of piperine on RA-FLS through NF-κB inhibition. FLSs were isolated from 68 RA patients and 30 healthy controls and were exposed to piperine. The main assays were MTT assay, flow cytometric analysis, PI staining, reverse transcription-PCR (RT-PCR), and ELISA. Results showed that piperine can induce the apoptosis and reduce the proliferation of RA-FLSs in vitro. Moreover, piperine directly reduced the phosphorylation of NF-kB and the expression of NF-κB target genes related to RA-FLSs proliferation (c-Myc and Cycline D1), apoptosis inhibition (Bcl2 and Bcl-xl) and inflammation (COX2, IL-1β, TNF-α,IL-6, CCL5 and CXCL10) while increasing the expression of apoptosis related ones (Bax) in vitro. Piperine also reduced the protein levels of cytokines and chemokines secreted by FLSs as a result of NF-κB inhibition. In conclusion, our results provide evidence for the anti-inflammatory capacity of piperine through inhibition of NF-κB pathway in FLSs proposing this compound as a suitable alternative for chemical treatment of RA.