Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized
by the production of inflammatory factors. In order to overcome the side effects of currently used
anti‐inflammatory drugs, several attempts have been made to identify natural products capable of
relieving RA symptoms. In this work, a herbal preparation consisting of propolis, pomegranate
peel, and Aglianico grape pomace (PPP) extracts (4:1:1) was designed and evaluated for its effect on
a murine collagen‐induced arthritis (CIA) model. Firstly, the chemical contents of four different
Italian propolis collected in the Campania region (Italy) were here reported for the first time.
LC‐MS analyses showed the presence of 38 constituents, identified in all propolis extracts,
belonging to flavonoids and phenolic acids classes. The Pietradefusi extract was the richest one and
thus was selected to design the PPP preparation for the in vivo assay. Our results highlight the
impact of PPP on RA onset and progression. By using in vivo CIA models, the treatment with PPP
resulted in a delayed onset of the disease and alleviated the severity of the clinical symptoms.
Furthermore, we demonstrated that early PPP treatment was associated with a reduction in serum
levels of IL‐17, IL‐1b, and IL‐17–triggering cytokines