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Peer-reviewedCC BY 4.0Frontiers in Pharmacology

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

  • Maria Laura Bellone1,2
  • Angela Carmelita Abate2
  • Paola Di Pietro2
  • Valentina Parisi1
  • Michele D’Angiolo3
  • Federica Prosperi4
  • Claudio Pisano4
  • Albino Carrizzo2,5
  • Alessandra Braca3,6
  • Fabrizio Dal Piaz2
  • Marinella De Leo3,6
  • Nunziatina De Tommasi1
6 affiliations
  1. 1Department of Pharmacy, University of Salerno
  2. 2Department of Medicine, Surgery and Dentistry, University of Salerno
  3. 3Department of Pharmacy, University of Pisa
  4. 4Animal Facility Unit, Biogem
  5. 5Vascular Physiopathology Unit, IRCCS Neuromed
  6. 6Center for Instrument Sharing University of Pisa (CISUP), University of Pisa
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{bellone2026mixture,
  title = {{A mixture of pomegranate peels and propolis extracts reduces inflammation associated with rheumatoid arthritis in vivo}},
  author = {Maria Laura Bellone and Angela Carmelita Abate and Paola Di Pietro and Valentina Parisi and Michele D’Angiolo and Federica Prosperi and Claudio Pisano and Albino Carrizzo and Alessandra Braca and Fabrizio Dal Piaz and Marinella De Leo and Nunziatina De Tommasi},
  journal = {Frontiers in Pharmacology},
  year = {2026},
  month = oct,
  doi = {10.3389/fphar.2026.1910652},
  url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1910652/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A mixture of pomegranate peels and propolis extracts reduces inflammation associated with rheumatoid arthritis in vivo
AU  - Maria Laura Bellone
AU  - Angela Carmelita Abate
AU  - Paola Di Pietro
AU  - Valentina Parisi
AU  - Michele D’Angiolo
AU  - Federica Prosperi
AU  - Claudio Pisano
AU  - Albino Carrizzo
AU  - Alessandra Braca
AU  - Fabrizio Dal Piaz
AU  - Marinella De Leo
AU  - Nunziatina De Tommasi
PY  - 2026
DA  - 2026/10/07
JO  - Frontiers in Pharmacology
DO  - 10.3389/fphar.2026.1910652
UR  - https://www.frontiersin.org/articles/10.3389/fphar.2026.1910652/full
AB  - 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.
SN  - 1663-9812
ER  -