Piceatannol is a stilbene similar to resveratrol that is found in limited levels in some of the same foods. They share many properties, and while piceatannol may be a possible alternative there is not enough evidence to suggest it is better than resveratrol.
Our evidence based analysis features 113 unique references to scientific papers.
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Table of Contents:
- 1 Sources and Structure
- 2 Molecular Targets
- 3 Pharmacology
- 4 Neurology
- 5 Cardiovascular Health
- 6 Inflammation and Immunology
Interactions with Hormones
- 7.1 Estrogen
Peripheral Organ Systems
- 8.1 Eyes
- 9 Interactions with Cancer Metabolism
Interactions with Aesthetics
- 10.1 Skin
Interactions with Medical Conditions
- 11.1 Alzheimer's Disease
Piceatannol is one of the major dietary stillbenes, a class of naturally occurring organic compounds with purported health benefits that includes pterostilbene and resveratrol. Piceatannol is sometimes referred to as astringin, although this technically refers to the glycoside of piceatannol (piceatannol-3'-O-β-d-glucopyranoside). While it shares many properties with resveratrol due to its structural similarity, small differences in chemical structure may alter piceatannol function in such a way that may have unique properties, including increased potency or health benefits.
Piceatannol is structurally related to resveratrol except for one small modification, and is found in plants alongside resveratrol and other related stilbenes. It is investigated for its health properties due to the research on resveratrol, which has caused a general increase in research on stillbenes.
Common dietary foods that contain piceatannol include:
Generally absent or at minute quantities in grapes (Vitus genera), but can be increased (by 50-100%) with postharvest irradiation similar to resveratrol and has been detected in Vitis vinifera cv. Cabernet Sauvignon at up to 52ng/g fresh weight; other red wines have had variable concentrations of piceatannol in the range of 0.54-5.22mg/L or have failed to find appreciable piceatannol
Almonds, identified in blanched water (collectively with oxyresveratrol) at 0.19-2.55μg/100g almond weight
Black tea (fermented camellia sinensis) at 14-53µg/g (trans-resveratrol at 51-56µg/g) and due to green tea (unfermented camellia sinensis) having 14-53µg/g it is unlikely fermentation influences the stilbene content
Plant sources of piceatannol appear to always contain resveratrol. (Conversely, most sources of resveratrol also contain piceatannol, although to a lesser extent). Piceatannol content can vary more than resveratrol content when assessing one batch of foods relative to the next, suggesting that piceatannol may be a more volatile food component.
With dietary supplements or plants not common in the diet comprising:
Supplements that have resveratrol also tend to also contain traces of piceatannol. There are not currently any known supplements or plants that are exceptionally good sources of piceatannol however, either alone or in combination with other stilbenes such as resveratrol.
The berries which contain piceatannol tend to contain undetectable quantities of pterostilbene and vice versa, meaning some variants (rabbiteye blueberry) have pterostilbene without picetannaol and others (highbush blueberry) being the opposite; some (deerberry) have different batches containing one or the other but not both. This relationship appears to exist between those two yet not resveratrol (present in all berries).
The structure of piceatannol is highly similar to resveratrol, as piceatannol (3,5,4',3'-tetrahydroxystilbene) has a single hydroxyl group at the 3'-carbon differing from resveratrol (3,5,4'-trihydroxystilbene). The glycoside of piceatannol is astringin, or piceatannol-3'-O-β-d-glucopyranoside.
Piceatannol is an off-white powder with a slightly lower melting point (226–223°C) than resveratrol (253–255°C) and a slightly higher molecular weight of 244.24 (resveratrol at 228.24). Both are soluble in ethanol and DMSO but not water, and similar to resveratrol piceatannol can be found in either a cis or trans form with the majority of instances referring to the more chemically stable trans-piceatannol molecule.
Piceatannol was recently found to be a potent suppressor of PI3K signaling, suppressing PI3K-dependent migration and proliferation in human aortic smooth muscle cells (HASMCs). While resveratrol had a similar, although less robust effect, the ability of piceatannol to potently suppress PI3K signaling appears to be unique to this stilbene; piceatannol suppressed PI3K signaling in HASMCs in the 10-20μM range while resveratrol failed to have a notable effect at concentrations up to 20μM.  Notably, piceatannol suppressed PI3K signaling in vitro as well as ex-vivo with greater potency than LY294002, a well-known small-molecule PI3K inhibitor. Piceatannol appears to inhibit PI3K signaling by directly competing with ATP for the PI3K ATP-binding site. 
Piceatannol is a potent inhibitor of PI3K signaling. While resveratrol also inhibits PI3K, piceatannol appears to be much more potent. This has not been evaluated in vivo, however.
Piceatannol is known to inhibit spleen tyrosine kinase (Syk) signalling in vitro in PDGF-BB induced endothelial cell proliferation, Syk being required for proliferation of cells to occur from PDGF-BB.) Piceatannol's inhibition of Syk has been shown to have anti-allergic properties in vitro and in an animal model. Piceatannol inhibits Syk by binding directly to Syk at the protein/peptide binding site which inhibits its p40 kinase abilities.
Piceatannol appears to be a selective Syk inhibitor, which underlies its usagage in numerous studies which are researching Syk function
While resveratrol is known to be a COX-2 inhibitor with an IC50 of 530nM, piceatannol is both a more potent inhibitor and more selective for COX-2; it has an IC50 of 11nM in inhibiting COX-2 and is 417-fold more selective for COX-2 relative to COX-1. This is slightly less selective than celecoxib, which prefers COX-2 546 times more than COX-1 with an IC50 of 34nM, and significantly more selective than resveratrol which was essentially nonselective. Piceatannol directly docks at Arg120, Ser530, and Tyr385 of COX-2 while the binding site associated with selectivity of COX2 inhibitors (its subpocket) was not interacted with.
Piceatannol appears to be a selective COX-2 inhibitor, and its selectivity for COX-2 and overall potency are significantly better than resveratrol in vitro and comparable with celecoxib. Due to the significant differences between piceatannol and resveratrol, benefits related to COX-2 inhibition may be significantly different between the two supplements
Piceatannol has been noted to be a mixed-type inhibitor of ATPase, notably F-ATPase (the ATPase in the inner mitochondrial membrane) and the F1-ATPase subunit specifically. The F1 catalytic unit is comprised of several subunits (α3, β3, γ1, δ1, and ε1) while the F0 subunit anchors the F1 to the membrane and translocates protons.  Picetannol binds to the γ-subunit (at least in bovine ATPase) to inhibit the function of ATPase; this is similar to both resveratrol and quercetin, although another study using bacterial (Escherichia coli) ATPase noted inhibition of the interaction between the γ and β subunits.
Piceatannol may have the ability to inhibit ATPase similar to resveratrol, but potency and practical relevance of this information is not currently known
Piceatannol is absorbed when fed to rats. When 2-hydroxypropyl-β-cyclodextrin was used as a vehicle for piceatannol, te bioavailability of piceatannol was 50.7+/-15.0%; this is higher than resveratrol yet lower than pterostilbene.
Piceatannol appears to be absorbed from the intestines following oral ingestion in rats
Oral ingestion of piceatannol results in peak serum concentrations of of 710+/-219ng/mL within 45-120 minutes after ingestion.
Piceatannol appears to be detectable in rat plasma 12 hours after an IV injection of 10mg/kg at a concentration of 19+/-2ng/mL and after oral ingestion of 10mg/kg at a concentration of 28+/-3ng/mL. The overall AUC after 10mg/kg oral ingestion of piceatannol appears to be greater than that of an infusion of 4mg/kg. The decrease in concentration from peak to 12 hours appears to be linear.
Piceatannol appears to reach rat plasma with a peak concentration in the high nanomolar range, but possibly exerts longer (12 hour) benefits in the low nanomolar range
Piceatannol has been noted to dock onto transthyretin (TTR) similar to resveratrol at the thyroxine binding site, and as TTR is a transportation protein for small molecules in the serum and brain it is thought that this is how piceatannol is transported since it is poorly soluble in water.
Piceatannol has been confirmed to bind to transportation proteins that exist in humans, suggesting that this is how it is transported around in the blood and cerebrospinal fluid
The volume of distribution of piceatannol in rats following injections appears to be 10.76+/-2.88L/kg; since this is a greater volume than total body water it suggests tissue deposition of piceatannol from serum.
Current evidence suggests that there is tissue deposition of piceatannol following its presence in serum
The human liver appears to be able to metabolize resveratrol into piceatannol via either CYP1B1 (three metabolites, of which piceatannol is produced alongisde 3,4,5,4′-tetrahydroxystilbene and 3,4,5,3′,4′-pentahydroxystilbene) and also via CYP1A (aromatase) enzymes.
This metabolism has been confirmed in vivo in a study on mice, where oral ingestion of 75mg/kg resveratrol (which reached skin, liver, and blood levels of 21.75+/-7.22μM, 73.04+/-35.61μM, and 28.37+/-32.63μM respectively after five minutes) also led to increases in piceatannol (skin, liver, and blood levels of 2.40+/-0.54nM, 11.50+/-6.68nM, and 5.26+/-0.99nM) at the same time period. Serum concentrations of piceatannol were less than 1% that of serum resveratrol at this time point, and resveratrol glucuronide was comparable to resveratrol.
Resveratrol can metabolize into piceatannol, but the conversion in living systems (based on the limited evidence available) does not appear to be a high yield one
Piceatannol itself does not appear to undergo further phase I modifications to its structure, but it is known to be sulfated either as a disulfate or one of two monosulfates. Both in rat serum and human liver microsomes, three individual monoglucuronides can be formed from piceatannol via UGT enzymes.
Glucuronidation has been noted when rats are administered 10mg/kg piceatannol intravenously.
The conjugation of piceatannol is highly similar to that of resveratrol as it is subject to both sulfation and glucuronidation and seems to be quite rapidly conjugated in vitro
Elimination of piceatannol appears to be primarily hepatic in rats following injection since the clearance rate (2.13+/-0.92 L/h/kg) and hepatic clearance rate (1.43 L/h/kg) approach the hepatic plasma flow rate (1.74 L/h/kg).
One of the enzymes that metabolizes resveratrol into piceatannol (CYP1A) is inhibited by both resveratrol and piceatannol (Ki of 5.33μM and 9.67μM respectively), and CYP2E1 does not appear to be inhibited by piceatannol in the concentration range of 1-100μM whereas resveratrol may (Ki of 2.1μM).
Piceatannol appears to interact with the quinone reductase 2 enzyme (NQO2) at the same site that resveratrol interacts with.
Piceatannol may have anti-inflammatory properties in microglial cells secondary to Syk inhibition. One study using a prion (PrP106-126, known to be neurotoxic secondary to microglia activation) noted that CD36 was a downstream mediator of PrP106-126 causing microglial activation (seen previously with PrP106-126 and other neurotoxic proteins such as the Alzheimer's protein Aβ1-42) and CD36 is known to require Syk in its signalling pathway; when incubating microglial cells with piceatannol and PrP106-126, it seems that the iNOS mRNA and inflammatory cytokine induction seen with microglial activation is prevented.
Piceatannol may reduce neuroinflammation by inhibiting Syk
Incubation of neuronal (HT-22) cells for at least six hours with piceatannol appears to confer time-dependent protection against glutamate toxicity at concentrations of 5-10µM but not at 1µM, and this protective effect is partly dependent on the antioxidant effects of heme-oxygenase 1 (HO-1) induction from Nrf2 which was observed with piceatannol.
Piceatannol has been noted to induce relaxation of isolated phenylephdrine-precontracted aortic tissue with an EC50 of 2.4+/-0.4µM with 20% relaxation at concentrations of 1µM, which was a potency noted to be greater than other stilbenes (resveratrol and desoxyrhapontigenin, with EC50 values of 28.6µM and 18.5µM) and the distilbene ε-viniferin (EC50 of 8.4+/-1.7µM). Piceatannol induced relaxation in a manner associated with the endothelium, and it was blocked by L-NAME suggesting these effects were via nitric oxide production.
Piceatannol appears to cause relaxation of precontracted blood vessels in a concentration that is feasible following oral ingestion, and this appears to be associated with nitric oxide metabolism
Smooth muscle cells in the aorta are known to proliferate under the influence of platelet-derived growth factor (PDGF) in a manner dependent on both Syk and PI3K activation, both of which are direct targets of piceatannol. Due to smooth muscle cell proliferation being pathological in atherosclerosis (resulting from intimal thickening of the aorta), agents that reduce proliferation are thought to be therapeutic.
Piceatannol is thought to have anti-atherosclerotic properties by inhibiting aortic thickening, but this has not yet been demonstrated following oral supplementation of piceatannol
There is an enzyme known as arginase which degrades L-arginine into L-ornithine, and a particular variant (Arginase II, which exists outside of the liver while arginase I exists within the liver and macrophages) appears to be a novel therapeutic target for cardiovascular disease as it competes with endothelial nitric oxide synthase (eNOS) for arginine availability and its inhibition results in increased arginine availability and blood flow. The activity of this enzyme (Arginase II) is known to be increased by inflammatory (endotoxin), oxidative (oLDL) and reduced oxygen (hypoxia) stressors in the endothelium.
Astringin (the glycoside of piceatannol) has been noted to inhibit Arginase I (25-38% at 1-10µM in mouse liver cells, IC50 of 11.22µM) and Arginase II (25-47% at 1-10µM in mouse kidney cells, IC50 of 11.06µM) showing no selectivity. This was noted to increase nitric oxide bioavailability in vitro and ex vivo when using endothelium from ApoE-/- atherogenic mice. However, the lone study assessing the aglycone (piceatannol) failed to find any significant influence on arginase activity or expression in vitro.
Inhibition of arginase in the endothelium is thought to be therapeutic in preserving blood flow, but piceatannol may not be active in this regard at concentrations found in the blood. The glycoside of piceatannol, called astringin, may be, but it is highly plausible that astringin is merely metabolized to piceatannol after oral ingestion and thus does not accumulate to desired levels in the blood
Asymmetric dimethylarginine (ADMA) is an endogenous NOS inhibitor produced by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) and increased activity of this enzyme sometimes occurs in periods of oxidative stress resulting in inhibition of NOS and less nitric oxide signalling. Normalizing ADMA is thought to be a therapeutic target since it plays a pathological role.
In endothelial cells exposed to high glucose concentrations, piceatannol (1μM) has been shown to preserve DDAH activity in a manner independent of SIRT1 despite having no inherent effect (in normal glucose concentration), which resulted in normalization of ADMA concentrations. These observations were similar with resveratrol, although resveratrol required a 10-fold higher concentration (10μM) to be as effective. The independence of SIRT1 is notable since dehydroxylated analogues of resveratrol seem to work via SIRT1, and these results suggest that piceatannol is working via directly sequestering free radicals (as its antioxidative potency is correlated with hydroxyl groups, and is higher than resveratrol).
Although no studies assessing orally ingested piceatannol exist, it appears to reduce ADMA and may preserve blood flow in periods of high oxidative stress in the blood (e.g. hypertension and diabetes). Resveratrol can also do this, but piceatannol appears to be more effective. The mechanism may be through just being an antioxidant, and thus the benefits would be similar to any potent antioxidant compound
In isolated human endothelial cells (EA.hy926), incubation of 50μM piceatannol for up to nine hours was able to enhance eNOS mRNA and protein content while 20μM was effective albeit over the course of 48 hours. This increased eNOS expression was associated with a 30% increase in eNOS phosphorylation which is required (at Ser-1177) for the activity of the enzyme.
It is uncertain whether this is relevant to oral supplementation, as although the above study noted benefits in the 20-50μM range and noted that resveratrol was less active resveratrol has been noted to be active at concentrations as low as 50nM in HUVEC cells via estrogen receptor signalling which piceatannol is also known to influence at these low concentrations and piceatannol has caused relaxation at a low concentration (1μM) in a manner inhibited by L-NAME.
Piceatannol possibly has similar properties to resveratrol in increasing eNOS activity secondary to estrogenic signalling, although it is not fully certain if this occurs in humans following oral ingestion. Based on the concentrations at which resveratrol is active, and the relative potency of these two stilbenes, it is plausible
Piceatannol has failed to show any inhibitory properties against collagen or arachidonic acid induced platelet aggregation up to 3,000µM despite methoxylated stilbenes (rhapontigenin and desoxyrhapontigenin) having relatively potent efficacy in concentration ranges of 20-100µM.
No significant interaction with platelets are known to occur with piceatannol
Piceatannol, in a model of macrophrage activation, appears to be more potent than resveratrol in reducing inflammation as assessed by TNF-α and IL-1β secretion. This appeared to correlated with induction of heme-oxygenase 1 (HO-1) in macrophages and correlated with the hydroxyl count on the molecule, since a resveratrol analogue with no hydroxyl groups failed to induce HO-1.
Piceatannol appears to inhibit FcϵR1 signalling in mast cells secondary to inhibiting the Syk protein which is one of two proteins (the other being Lyn) critical for this signalling pathway to work. Piceatannol works in a concentration dependent manner between 5-50µg/mL reaching near full suppression (serotonin release from an antigen) at 50µg/mL or 100µM (histamine release) and has been noted to reach statistical significance in reducing leukotriene and histamine release at 30µM with lower concentrations ineffective.
Piceatannol appears to be more potent than pterostilbene in suppressing PMA-induced neutrophil activation (assessed by PKC activation) in the range of 10-100µM, while being comparable in potency to resveratrol at the lower concentration. When assessing chemiluminescence as a measure of peroxyl radical formation, piceatannol appeared to be the most potent stilbene with an IC50 of 600nM (6.2% inhibition at 100nM, 66% at 1µM, and a maximum potency of 99.3% at 10µM).
Piceatannol has been noted to activate the alpha subset of the estrogen receptor (ERα) and can compete with estrogen at binding to this receptor, with agonism present at 10nM (potency comparable to Myricetin) and more affinity for ERα than ERβ.
Piceatannol is a phytoestrogen and at a concentration which likely applies to oral ingestion of the compound, but it is not clear if (in practical situations) it confers more of an estrogenic effect or an antiestrogenic effect via competing with estrogen binding
30mg/kg piceatannol injected into rats either two hours before an inflammatory insult (LPS injection) or an hour after has been noted to significantly suppress the inflammatory changes, and this is thought to reflect protection against uveitis (inflammatory eye disease).
Piceatannol is researched for its anticancer effects not only due to the possibility of supplementation, but due to it being a metabolite of resveratrol secondary to CYP1B1. CYP1B1 is known to be overexpressed in cancer cells relative to normal cells and prodrugs (subactive or inactive prior to metabolism) that are subject to CYP1B1 are thought to be potential anticancer drugs.
It is possible that piceatannol is a putative anti-cancer metabolite of resveratrol, and that the benefits listed in the followed sections not only apply to piceatannol but may indirectly reflect some of resveratrol's actions
Angiogenesis (production of new blood vessels) is a process involved in the growth of tumors, and it appears that angiogenesis induced by endogenous factors (angiotension, VEGF) is partially attenuated when Syk is abolished by siRNAs or blocked by piceatannol (5μM). The influence of these factors on the receptor (VEGFr1/Flt-1) was not prevented by piceatannol and Syk is known to be activated by VEGFr1 via p38/c-Src.
The process of angiogenesis appears to be positively influenced by Syk activation, which occurs when the major receptor (VEGFr1) is activated. Inhibiting Syk with piceatannol can attenuate angiogenesis in experimental settings
An in vitro experiment in a human non-small cell lung cancer line found that piceatannol in concentrations from 2 to 50 µM decreased the IC50 of the anti-cancer drug gemcitabine over 100-fold (IC50 was 391 µM without piceatannol, and ranged from 0.071 to 0.132 at 2 to 50 µM piceatannol). Picetannol did not induce cell death in the cell line on its own; instead, it seemed to work by increasing the expression of the proapoptotic protein Bak, which move the cancer cells further along the apoptotic pathway, upon which gemcitabine then acted to actually induce apoptosis.
Piceatannol has shown anti-proliferative properties in prostatic cancer cells (CWR22Rv1) secondary to inducing NQO2 activity, and due to high expression of the enzyme that metabolizes resveratrol into piceatannol (CYP1B1) in tumor cells relative to normal cells it is thought that piceatannol could be a biologically active metabolite of resveratrol.
In vitro, piceatannol has been noted to inhibit LNCaP cell proliferation with an IC50 of 31.7µM which underperformed relative to both pterostilbene (22.9µM) and resveratrol (12.7µM); the synthetic 3-methoxyresveratrol was the most potent (2.5µM), and these anti-proliferative effects extended to Du145 and PC3M prostatic cancer cells.
The induction of NQO2 seen with piceatannol (thought to be secondary to Nrf2 activation) is thought to be therapeutic in prostate cancer
Oral ingestion of 50mg/kg piceatannol every other day for two weeks before tumor implantment (LNCaP prostatic tumor cells) and for another five weeks in mice reduced tumor growth and proliferation with a potency comparable to 50mg/kg resveratrol. Despite this efficacy, piceatannol was not detected in the serum nor the tumor at the end of the study (whereas a small resveratrol content was detected in both for the resveratrol group) but a reduction in serum IL-6 was noted.
Orally ingested piceatannol appears to act similarly to resveratrol in regards to suppressing prostatic tumor growth
Tumor necrosis factor alpha (TNF-α) is implicated in cancer metabolism from both a positive (cytotoxic to tumors) and negative (proinflammatory) manner, and its inhibition is thought to be therapeutic in some cancers associated with inflammation. TNF-α is known to exist in both a soluble and membrane bound form, and since the membrane bound form is a more potent activator of one of its receptors (TNFR2) and the 'shedding' of TNFα from the membrane to activate this receptor is mediated via a few proteins but most notably ADAM17.
In isolated U937 (leukemic) cells, piceatannol (1μM for 8-24 hours) has been noted to reduce TNF-α secretion and NF-kB activation. This seemingly antiinflammatory effect was dependent on a downregulation of ADAM17 (known to positively influence activation of the NF-kB pathway), which was directly due to an increase in β-TrCP protein levels causing degradation of Sp1 (intermediate in the link between ADAM17 and NF-kB); in other words, β-TrCP interruppted the ability of ADAM17 to induce NF-kB. The increase in β-TrCP was further linked back to a decrease in FOXp3 signalling (and its product, miR-183) due to inhibition of Akt/mTOR. β-TrCP mRNA was not actually affected much with piceatannol and the increased protein content was secondary to reduced miR-183 (known to degrade β-TrCP). Inhibition of NF-kB signalling (not necessarily linked back to Akt/mTOR) has also been observed in the KBM-5 leukemic cell line with 50μM piceatannol, and it may be related to the same mechanisms since using the JCaM-1 cell line that lacks Syk and p56Ick (other mechanisms of piceatannol) does not impair the actions of 50μM piceatannol.
Inhibition of Akt/mTOR signalling could either be linked back to direct inhibition of PI3K seen with piceatannol or simply due to ablating ADAM17. Piceatannol has also been noted to enhance TRAIL induced apoptosis and the efficacy of Cytarabine, in line with anti-survival mechanisms.
Piceatannol appears to be associated with anti-survival mechanisms in a leukemic cell, which is due to reducing the amount of TNF-α released from the cell membrane and thus reducing its ability to act on its receptor (mostly TNRF2) and ultimately influence the survival signalling (NF-kB). This appears to be traced back to inhibition of Akt/mTOR signalling, although the mechanisms further beyond this (be it ADAM17 or PI3K inhibition) are not fleshed out.
The above mechanisms (ADAM17 mediated Akt pathways) is known to induce apoptosis of the U937 cell line and elsewhere piceatannol has been noted to increase Sp1 activity (different from the aforementioned Sp2) and ERK activity resulting in increased DR5 receptor expression and enhancing TRAIL-induced apoptosis (THP-1 cells); elsewhere and in U937 cells, piceatannol (5μM) has noted to actually inactivate ERK (opposing the effects seen in THP-1 cells) but still induced apoptosis via increasing Fas and FasL mRNA and protein levels (secondary to signalling via MEK and p38 MAPKs, which influence c-Jun and ATF-2) which are another class of death receptors alongside DR5 and TRNF1 that mediate apoptosis.
Piceatannol has been confirmed to, at concentrations of 5μM, reduce cell viability of leukemic cells to 48% of control after 24 hours of incubation.
Alterations in certain death receptors (DR5 and Fas) appear to enhance the cytotoxicity of agents that would signal through these receptors, which are also in line with an antisurvival effect of piceatannol. Piceatannol appears to reduce viability of these cancer cells by itself, suggesting enhanced sensitivity to endogenous agents (produced by the cancer cell to limit its own growth) as well
At this moment in time there are no studies in living models testing the efficacy of piceatannol on leukemia
Isolated piceatannol appears to concentration dependently inhibit melanogenesis starting at 4.5μM in MNT-1 cells (less than 20% inhibition) increasing to near 30% inhibition above 20μM; piceatannol was more potent than resveratrol at low concentrations (as resveratrol was inactive, yet piceatannol has an IC50 of 1.53) and while one study noted that they were similarly potent at 20μM another suggested the IC50 value of piceatannol was 41-fold lower. The inhibition of melanogenesis appears to be associated with the antioxidant properties and increase in glutathione seen with piceatannol.
5μM piceatannol has increased collagen synthesis (around 30%) with a potency greater than resveratrol, although the two were comparable at 10μM reaching 50% and ineffective at 20μM.
Appears to have a max potency comparable to resveratrol in regards to promoting collagen synthesis and inhibiting melanogenesis (involved in skin tanning), but is active at lower concentrations when resveratrol is not
In regards to UV radiation, piceatannol (and scirpusin B; a picetannol:resveratrol heterodimer) appeared to mediate the protective effects of passionfruit seeds by increasing glutathione concentrations in a concentration dependent manner (0.25-2µg/mL with piceatannol reaching a higher induction at 2µg/mL) which reduced oxidation from UVB damage (0.5-2µg/mL). The induction of glutathione, as well as a reduction in MMP-1 concentrations, occurred regardless of whether UVB was present (but the reduction in oxidation dependent on UVB causing it).
Appears to protect skin cells from radiation at concentrations which are probably relevant to oral ingestion of the compound, but oral ingestion has not yet been tested
Piceatannol is thought to have properties similar to resveratrol in Alzheimer's disease as both molecules bind to the transport protein transthyretin (TTR) at the thyroxine binding site. TTR is a transport protein that normally exists as a tetramer (quadrants) but it can be dissociated into monomers (singles) which can then contribute to the production of protein aggregates (amyloid). Any small molecule that binds to the tetramer can stabilize it and prevent degeneration into monomers which is thought to be therapeutic.
Beyond that, TTR itself (regardless of what it is carrying) can bind to amyloid peptides to prevent larger aggregates from being formed and both resveratrol and piceatannol (as well as other phenolics like the green tea catechins) are implicated in increasing TTR via acting on a common receptor in the nanomolar range.
Piceatannol is thought to confer some protection against the development of Alzheimer's Disease when ingested daily due to its interactions with transthyretin
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