A mixture of pomegranate peels and propolis extracts reduces inflammation associated with rheumatoid arthritis in vivo.

BACKGROUND

Rheumatoid arthritis (RA) is a chronic condition characterized by the infiltration of immune and inflammatory cells into the synovial membranes, which often leads to severe damage to cartilage and bone. In spite of their efficacy, drug-based therapies produce severe side effects. Therefore, there remains an unmet need for non-pharmacological treatments with a low toxicity profile and limited costs. Propolis has been used since ancient times for the treatment of wounds, ulcers, infections, eczemas, myalgia, and rheumatism. Similarly, the traditional use of all parts of pomegranate (Punica granatum L.) is documented across Egyptian, Persian, and Chinese cultures for the treatment of infections and inflammations.

PURPOSE: This study aimed at the development of preparations containing bioactive compounds derived from propolis and pomegranate peels, inspired by traditional recipes used in rural areas of southern Italy, to validate their efficacy in counteracting the inflammation associated with RA.

MATERIALS AND

METHODS

A preliminary screening led to the selection of the most promising preparation, composed by propolis and pomegranate peel extracts in a ratio 1:2 (Pp1:2). It underwent a complete chemical characterization by both qualitative and quantitative LC-MS analyses and was tested on a collagen-induced arthritis (CIA) mouse model.

RESULTS

In vitro tests showed that Pp1:2 treatment of M1 stimulated by LPS/IFNγ reduces cell polarization; furthermore, it reverts the pro-inflammatory effects induced by IL-1β on synoviocytes. In vivo experiments, conducted by administering Pp1:2 orally to a suitable murine model, confirmed the ability of the preparation to reduce sensibly RA-like inflammatory effects, as inferred by the change observed in mice paws volume and other RA-related parameters. Furthermore, histological analyses revealed a reduction in the number of M1 macrophages in mice paws following Pp1:2 treatment, and an attenuation of the pathological remodeling of collagen IV and of ICAM-1 expression, compared to untreated controls.