Piperine suppresses inflammatory fibroblast-like synoviocytes derived from rheumatoid arthritis patients Via NF-kappa B inhibition

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-kappa B 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-kappa B 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-kappa B target genes related to RA-FLSs proliferation (c-Myc and Cycline D1), apoptosis inhibition (Bcl2 and Bcl-xl) and inflammation (COX2, IL-1 beta, TNF-alpha,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-kappa B inhibition. In conclusion, our results provide evidence for the anti-inflammatory capacity of piperine through inhibition of NF-kappa B pathway in FLSs proposing this compound as a suitable alternative for chemical treatment of RA.

Automated summary

In this study, piperine was found to induce apoptosis and reduce proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) through inhibition of the NF-kappa B pathway. It also decreased the expression of genes related to RA-FLS proliferation, apoptosis inhibition, and inflammation, while increasing the expression of apoptosis-related genes. Moreover, piperine reduced the secretion of cytokines and chemokines by FLSs as a result of NF-kappa B inhibition.