3-indolepropionic acid 3-indolepropionic acid 3-indolepropionic acid (ipa), or indole-3-propionic acid, is a potent neuroprotective antioxidant, plant auxin, and natural product in humans that was being studied for therapeutic use in alzheimer's disease as of 2002. it is endogenously produced by human microbiota and has only been detected in vivo when the species clostridium sporogenes is present in the gastrointestinal tract. as of april 2016, c. sporogenes, which uses tryptophan to synthesize ipa, is the only species of bacteria known to synthesize ipa in vivo at levels which are subsequently detectable in the blood plasma of the host. 3-indolepropionic acidclinical datatrade namesoxigonother namesconjugate acid: • 1h-indole-3-propanoic acid • indole-3-propionic acidconjugate base: • indole-3-propionateatc codenonelegal statuslegal status us: unscheduled un: unscheduled identifiers iupac name 3-(1h-indol-3-yl)propanoic acid cas number830-96-6 y pubchem cid3744iuphar/bps4709chemspider3613 yuniijf49u1q7knchebichebi:43580 ycomptox dashboard (epa)dtxsid7061192 echa infocard100.011.455 chemical and physical dataformulac11h11no2molar mass189.214 g·mol−13d model (jsmol)interactive imagemelting point134 to 135 °c (273 to 275 °f) smiles c1=cc=c2c(=c1)c(=cn2)ccc(=o)o inchi inchi=1s/c11h11no2/c13-11(14)6-5-8-7-12-10-4-2-1-3-9(8)10/h1-4,7,12h,5-6h2,(h,13,14)key:golxrndwautykt-uhfffaoysa-n (verify) ipa is an even more potent scavenger of hydroxyl radicals than melatonin, the most potent scavenger of hydroxyl radicals that is synthesized by human enzymes. similar to melatonin but unlike other antioxidants, it scavenges radicals without subsequently generating reactive and pro-oxidant intermediate compounds. in 2017, elevated concentrations of ipa in human blood plasma were found to be correlated with a lower risk of type 2 diabetes and higher consumption of fiber-rich foods. biosynthesis in humans and cellular effects tryptophan metabolism by human gastrointestinal microbiota () tryptophan clostridiumsporogenes lacto-bacilli tryptophanase-expressingbacteria ipa i3a indole liver brain ipa i3a indole indoxylsulfate ast-120 ahr intestinalimmunecells intestinalepithelium pxr mucosal homeostasis:↓tnf-α↑junction protein-coding mrnas l cell glp-1 t j neuroprotectant:↓activation of glial cells and astrocytes↓4-hydroxy-2-nonenal levels↓dna damage–antioxidant–inhibits β-amyloid fibril formation maintains mucosal reactivity:↑il-22 production associated with vascular disease:↑oxidative stress↑smooth muscle cell proliferation↑aortic wall thickness and calcification associated with chronic kidney disease:↑renal dysfunction–uremic toxin kidneys this diagram shows the biosynthesis of bioactive compounds (indole and certain other derivatives) from tryptophan by bacteria in the gut. indole is produced from tryptophan by bacteria that express tryptophanase. clostridium sporogenes metabolizes tryptophan into indole and subsequently 3-indolepropionic acid (ipa), a highly potent neuroprotective antioxidant that scavenges hydroxyl radicals. ipa binds to the pregnane x receptor (pxr) in intestinal cells, thereby facilitating mucosal homeostasis and barrier function. following absorption from the intestine and distribution to the brain, ipa confers a neuroprotective effect against cerebral ischemia and alzheimer's disease. lactobacillus species metabolize tryptophan into indole-3-aldehyde (i3a) which acts on the aryl hydrocarbon receptor (ahr) in intestinal immune cells, in turn increasing interleukin-22 (il-22) production. indole itself triggers the secretion of glucagon-like peptide-1 (glp-1) in intestinal l cells and acts as a ligand for ahr. indole can also be metabolized by the liver into indoxyl sulfate, a compound that is toxic in high concentrations and associated with vascular disease and renal dysfunction. ast-120 (activated charcoal), an intestinal sorbent that is taken by mouth, adsorbs indole, in turn decreasing the concentration of indoxyl sulfate in blood plasma. metabolism ipa can be converted in the liver or kidneys to 3-indoleacrylic acid, which is subsequently conjugated with glycine, forming indolylacryloyl glycine. history the neuroprotective, antioxidant, and anti-amyloid properties of ipa were first reported by a group of investigators in july 1999, led by dr. pappolla and dr. poeggeler at the university of south alabama.