Piperine, an alkaloid found in black pepper (Piper nigrum), has been investigated for its anti-inflammatory and immunomodulatory properties. Several preclinical studies have explored its potential utility in treating rheumatoid arthritis (RA), mainly using animal models. For instance, research published in peer-reviewed journals has demonstrated that piperine can suppress the expression of pro-inflammatory cytokines (such as TNF-α, IL-1β, and IL-6) and inhibit joint swelling and cartilage degradation in rat models of arthritis. Mechanistically, piperine appears to inhibit key signaling pathways involved in inflammation, including NF-κB and MAPK pathways.

However, to date, there are no robust clinical trials in humans confirming its efficacy or safety for RA treatment. Most evidence remains preclinical, and while animal and in vitro results are promising, they do not guarantee similar outcomes in humans. Piperine has not been established as a conventional therapy for RA and is not included in clinical guidelines for RA management. Its use in RA is supported by scientific interest and some experimental data, but lacks high-quality human evidence. Therefore, the evidence supporting piperine's use in RA is rated as low-to-moderate (2 out of 5), with further research needed before it can be recommended as a treatment.