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Punicalagin is a naturally occurring ellagitannin, a polyphenolic compound found primarily in pomegranate (Punica granatum) peel, but also in other plants like Terminalia and Combretum species. It has a large molecular weight (C48H28O30, 1084.7 g/mol) and exists as alpha and beta isomers. Punicalagin exerts antioxidant, anti-inflammatory, antiproliferative, anti-atherosclerotic, hepatoprotective, antimicrobial, neuroprotective, anti-hyperlipidemic, antidiabetic, gastroprotective, and potential anticancer effects. Mechanistically, it is known to inhibit the NF-κB pathway, suppressing the production of pro-inflammatory cytokines (such as IL-1β, IL-6, IL-8, IL-17A, and TNF-α), matrix metalloproteinases (MMP-1, MMP-13), and limiting inflammation-related cell proliferation and migration. Additional anticancer mechanisms involve inducing apoptosis and autophagy, downregulating proteins like Annexin A1 in tumor cells, and modulating fibroblast activation markers. Punicalagin is not an approved pharmaceutical drug but is being researched for potential therapeutic effects in conditions such as rheumatoid arthritis, colorectal cancer, and is proposed as a natural supplement ingredient[1][3][4][6][7][8].
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