Exploring Punica granatum L. peels from different southern Italian varieties for their potential healthy value

Punica granatum L. is a small deciduous shrub belonging to Lythraceae family, commonly called pomegranate. Already known since ancient times, pomegranate is nowadays widely cultivated throughout the Mediterranean region, as well Africa, Asia, and South America. Its attractive red-purple fruit is considered as one of the oldest edible fruit still consumed worldwide fresh or as a juice. Traditionally employed for the treatment of various ailments, pomegranate is included today among the richest fruits in health-promoting substances, including polyphenols as anthocyanins, phenolic acids, flavonoids, and both hydrolyzable and condensed tannins. As a by-product of the juice production, pomegranate peels are a bio-waste of environmental impact. On the other hand, pomegranate peels are attracting a great attention for their beneficial properties, still known in the traditional medicine and recently discovered due to scientific studies reporting anti-inflammatory, antimicrobial, wound‐healing, and antioxidant properties attributed due to their high content in polyphenols. The cultivation of pomegranate has a long tradition in the Southern Italian internal areas and recently is strongly encouraged to promote the rural and agricultural development of many depopulated internal villages. Taking into account all the benefits in promoting pomegranate products, the aim of this study was the exploration of fourteen pomegranate varieties from internal areas of South Italy, focusing the investigation on both the chemical composition and biological properties of the peels. The whole fruits were separated into arils and peels, thus the latter were extracted using ethanol-water (70% v/v) by ultrasound assisted extraction for 15 min. The dried extracts were subjected to an ultra-high performance liquid chromatography coupled to a high resolution electrospray ionization source mass spectrometer (UHPLC-HR-ESI-MS) for the chemical profiling. Furthermore, DPPH and ABTS+-based radical scavenger assay, MTT assay, and in vitro anti-inflammatory assay monitoring three typical markers of rheumatoid arthritis (IL-6, IL-1β, and TNF-α) were performed. Through LC-MS metabolomic fingerprint 55 compounds were identified, including ellagitannins, flavonoids and anthocyanins, evidencing superimposable profiles for most of the studied varieties. Quantitative estimation showed punicalagin as the major components in all extracts, followed by ellagic acid. Among anthocyanins cyanidin 3-O-glucoside was the most represented. All the extracts showed good antioxidant properties in both radical scavenger essays. No cytotoxicity was observed by MTT assay in all varieties. When the extracts were tested on THP-1 derived macrophage cells co-stimulated with lipopolysaccharide, modulation of IL-6 and IL-1β pro-inflammatory cytokines were observed; instead, TNF-α was slightly modulated by pomegranate treatment. Anyway, the different varieties showed a similar effect. In conclusion, the results of the present work confirmed that pomegranate peels, considered as a by-product of the juice production, are a rich source of different classes of phenolic compounds exerting antioxidant and anti-inflammatory properties with good chance in the management of rheumatoid arthritis.