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Antisecretory factor is a phylogenetically ancient, multifunctional endogenous protein (~41–43 kDa) expressed in most mammalian tissues. It plays a critical role in regulating fluid and electrolyte transport across epithelial barriers—most notably within the gastrointestinal tract—by inhibiting excessive secretion induced by bacterial toxins such as those from cholera, E. coli, Campylobacter, and Clostridium difficile. The biologically active region resides within an N-terminal peptide sequence; synthetic peptides based on this region have demonstrated potent antisecretory effects. AF also exhibits anti-inflammatory properties by modulating immune responses—including T cell proliferation—and may contribute to innate immunity. Its expression increases following exposure to enterotoxins or certain dietary components like specially processed cereals. Clinically, increased activity or supplementation with active forms of AF has shown benefit in conditions characterized by abnormal secretion/inflammation such as diarrheal diseases (in children/adults), inflammatory bowel disease, gastroenteritis, Ménière’s disease (where it helps regulate endolymphatic pressure), and even post-weaning diarrhea prevention in livestock. Therapeutic strategies focus on stimulating endogenous production through diet or administering preformed active peptides/proteins via functional foods rather than traditional pharmacological agents. No significant safety concerns have been identified with these approaches so far.
Peptides derived from AF inhibit toxin-induced secretion by modulating ion channels/transporters at the intestinal epithelium. Reduces inflammation by regulating immune responses. May act via nerve-mediated pathways to rapidly inhibit ion transport.
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