Oak and sumac gallnut polyphenol extracts attenuate aluminum-induced inflammation and oxidative stress in a human intestinal cell model

Chronic intestinal inflammation associated with inflammatory bowel diseases arises from dysregulated immune signaling, epithelial barrier dysfunction, oxidative stress, and sensitivity to environmental toxicants. Polyphenol-rich natural extracts represent promising modulators of these processes, yet their mechanisms of action remain incompletely characterized. Following an initial screening of multiple natural extracts, two polyphenol-rich candidates, oak gallnut extract (OGNE) and sumac gallnut extract (SGNE), were selected for further investigation using in vitro and in vivo models. OGNE and SGNE decreased NF-κB activation and downregulated key components of the TLR/NF-κB signaling axis, including TLR2, Dectin-1, and MyD88. This was accompanied by reduced expression and secretion of pro-inflammatory cytokines and chemokines and increased PPAR-γ expression. Both extracts attenuated reactive oxygen species accumulation and preserved epithelial barrier integrity in dextran sulfate sodium-treated intestinal Caco-2 cells, with OGNE displaying cytokine modulation. Chemical profiling revealed polyphenolic signatures dominated by glycosylated gallates (OGNE) or pentagalloylglucose (SGNE). Both extracts reduced intracellular aluminum accumulation and mitigated aluminum- and LPS-induced oxidative stress. In vivo, treatment with OGNE or SGNE improved nematode survival during C. albicans infection, reduced pathogen burden, and induced the antimicrobial gene lys-1.These findings highlight the complementary anti-inflammatory, antioxidant, and aluminum-detoxifying activities of OGNE and SGNE.