A Herbal Mixture from Propolis, Pomegranate, and Grape Pomace Endowed with Anti-Inflammatory Activity in an In Vivo Rheumatoid Arthritis Model

Abstract

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.

Immunomodulatory Properties of Pomegranate Peel Extract in a Model of Human Peripheral Blood Mononuclear Cell Culture

“…Moreover, punicalagin ameliorated experimental lupus nephritis by inhibiting protease-activated receptor-2 [94]. The treatment with propolis, pomegranate, and grape pomace extracts alleviated the severity of the clinical symptoms of RA, which was followed by a decrease in serum levels of IL-17, IL-1β, and IL-17-triggering cytokines [95].…”

Allergic Inflammation: Effect of Propolis and Its Flavonoids

“…The anti-inflammatory effects of propolis have been confirmed by numerous studies in the literature [ 70 , 71 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 ]. Several studies have shown that propolis (as an aqueous or ethanol preparation) can act as a strong anti-inflammatory agent against acute and chronic inflammations [ 70 , 71 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 ].…”

The Role of Natural Products in Rheumatoid Arthritis: Current Knowledge of Basic In Vitro and In Vivo Research

“…Thus the treatment groups differed in the time of the mixture introduction after CIA induction (namely, aside from the untreated group (Group 1: non-induced control group, treated with vehicle) and the positive control group (Group 2, CIA-induced, treated with 50 μL of bovine type II collagen emulsified in CFA on day +1 and +21), Group 3 received the mixture (propolis (100 mg/kg), pomegranate extract (25 mg/kg) and pomace extract (25 mg/kg)), right after CIA induction and Group 4 received it 3 weeks later). In this study, the early treatment appeared to be beneficial as it resulted in a delayed onset of the disease (CIA onset on day 35) and alleviated the severity of the clinical symptoms, while it was also associated with a reduction in serum levels of the proinflammatory cytocides IL-17-, IL-1b-, and IL-17-triggering cytokines, which are particularly implicated in the pathogenesis of RA [ 83 ].…”