Piceatannol

Piceatannol (3,3',4,5'-tetrahydroxy-trans-stilbene) is a naturally occurring polyphenolic stilbenoid compound with molecular formula C14H12O4 and molecular weight 244.24 g/mol. It is a hydroxylated analog of resveratrol, possessing an additional hydroxyl group at the 3' position on the B-ring, which significantly influences its bioactivity and antioxidant capacity. Primary natural sources include passion fruit (Passiflora edulis) seeds (~2.5–4.8 mg/g dry weight), Japanese knotweed (Polygonum cuspidatum), rhubarb (Rheum rhaponticum), grapes (Vitis vinifera, particularly skin and seeds at ~0.1–0.5 µg/g), berries (blueberries, bilberries in trace amounts), white tea, and certain tree barks (Picea species, from which it derives its name). It also occurs as a metabolite of resveratrol via cytochrome CYP1B1-mediated hydroxylation in vivo. Piceatannol contains no macronutrients (protein, fat, carbohydrate, fiber) as it is a single bioactive compound, not a food matrix. Key bioactive characteristics: ORAC antioxidant capacity significantly exceeds resveratrol (~2–3× greater radical scavenging due to the catechol moiety on the B-ring); acts as a potent Syk tyrosine kinase inhibitor (IC50 ~10 µM); SIRT1 activator with reported EC50 lower than resveratrol; AMPK pathway activator; inhibitor of NF-κB and COX-2 signaling. Bioavailability notes: Oral bioavailability is estimated at <5% in humans, similar to or slightly better than resveratrol, due to extensive phase II metabolism (glucuronidation and sulfation) primarily in the intestine and liver. Major circulating metabolites include piceatannol-3'-O-glucuronide and piceatannol-4'-O-sulfate. The catechol group enhances protein binding but also renders it susceptible to oxidative degradation. Absorption is improved when co-administered with lipid-based carriers or piperine (potential 1.5–2× increase in plasma AUC based on preclinical analogy with resveratrol). Peak plasma concentrations after oral dosing of ~20 mg in humans reach approximately 0.5–2.0 µM transiently (Tmax ~1–2 hours), with rapid clearance (t½ ~1–2 hours). Enterohepatic recirculation may contribute to a secondary plasma peak. Gut microbiota can further metabolize piceatannol to dihydroresveratrol and lunularin, which may retain partial bioactivity. Typical supplemental doses in clinical studies range from 20–40 mg/day, though passion fruit seed extract standardized to piceatannol content (often 5–10% w/w) is more commonly available commercially.