The amyloid- (A) peptide and tau protein are believed to play major neuropathogenic roles in Alzheimers disease (AD). attractive therapeutics against AD. Naturally happening molecules called polyphenols have been shown to significantly modulate the self-assembly of A and tau. This short article identifies such molecules and discusses the proposed mechanisms behind the inhibition of self-assembly. 2. Chemical Properties of Polyphenols of Relevance to This Review Polyphenols are small molecules that contain one or more phenolic rings. They may be classified into curcuminoids, flavonoids, lignans, phenolic acids, stilbenes, and tannins . Table 1 presents the chemical constructions and common sources of the polyphenols included in this review. Table 1 Structures, common water and sources solubility of polyphenols within this review. thead th align=”middle” valign=”middle” design=”border-top:solid slim;border-bottom:solid slim” rowspan=”1″ colspan=”1″ Molecule Common Source/s Solubility in H2O /th th align=”middle” valign=”middle” design=”border-top:solid slim;border-bottom:solid slim” rowspan=”1″ colspan=”1″ Chemical substance Structure /th /thead Resveratrol burgandy or merlot wine & crimson grapesC14H12O3sparingly soluble5-[( em E /em )-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol Rosmarinic acid solution rosemary, basil & sageC18H16O8soluble(2 em R /em )-3-(3,4-dihydroxyphenyl)-2-[( em E /em )-3-(3,4-dihydroxyphenyl)prop-2-enoyl]oxypropanoic acid solution Epigallocatechin-3-gallate green teaC22H18O11slightly soluble[(2 em R /em ,3 em R /em )-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2 em H /em -chromen-3-yl] 3,4,5-trihydroxybenzoate Curcumin turmericC21H20O6sparingly soluble(1 em E /em ,6 em E /em )-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione Gallic acid solution dark tea, fruits & nutsC7H6O5sparingly soluble3,4,5-trihydroxybenzoic acid solution Quercetin onions, spinach & soluble2-(3 applesC15H10O7sparingly,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-1 Open in another window Resveratrol (RES) is normally a stilbene which has anticancer , antioxidant  and neuroprotective  properties. RES provides two isomers, cis- and trans-resveratrol (Amount 1), however the latter is even BAY 11-7085 more responsible and steady for the properties from the polyphenol . RES is metabolized and for that reason provides low bioavailability  rapidly. non-etheless, both RES and its own major metabolites have the ability to mix the blood-brain barrier (BBB)  and thus, these molecules possess the potential to accumulate at pharmacologically relevant concentrations in the brain. Open in a separate window Number 1 Isomers of resveratrol. Trans-resveratrol is definitely more stable than cis-resveratrol and accounts for the beneficial effects of the polyphenol. Rosmarinic acid (RA), a phenolic acid, is an ester of caffeic acid and 3,4-dihydroxyphenyllactic acid. RA offers neuroprotective, antioxidant and anti-inflammatory effects, as discussed in a recent review . It is quite soluble in water, and thus organic solvents are not required for in vitro studies of the effects of the polyphenol (e.g., ). However, the high solubility of RA in aqueous solvents means that its ability to mix the BBB is definitely low. If true and if in vitro and in vivo studies indicate the potential of RA for the prevention and/or treatment of AD is definitely high, then dealing with the delivery of RA across the BBB will be important. Epigallocatechin-3-gallate BAY 11-7085 (EGCG) is definitely a flavonoid and is the most abundant catechin in green tea made from the leaves of em Camellia sinensis /em . A recent review shows the anticancer, anticardiovascular, neuroprotective, anti-oxidant, anti-obesity, antidiabetic and anti-allergic effects of EGCG . However, EGCG therefore offers low bioavailability and, initiatives are underway to build up nanoformulations of EGCG made to prevent the speedy metabolism from the molecule (e.g., ). EGCG is normally somewhat soluble in drinking water but becomes even more soluble in ethanol and very similar solvents. Under cell lifestyle conditions, EGCG goes through oxidation to create digallate dimers, theasinensin P2 and A, and epimerization to create gallocatechin-3-gallate (GCG) (Amount 2) . Response rates are influenced by focus of EGCG, pH, heat BAY 11-7085 range, and the incomplete pressure of O2. Hence, mechanistic research from the biological ramifications of EGCG should consider its stability. Open up in another window Amount 2 Under common experimental circumstances, Rabbit Polyclonal to TNF12 epigallocatechin-3-gallate (EGCG) forms gallocatechin-3-gallate (GCG) through epimerization, and theasinensin P2 and A through oxidation-induced dimerization. Curcumin (CUR) is normally a curcuminoid that possesses antioxidant, anti-inflammatory, anticarcinogenic and neuroprotective results as reviewed  recently. It really is a linear diphenylheptanoid filled with two o-methoxy phenolic bands linked with a seven-carbon BAY 11-7085 string (Desk 1). Since it is normally lipophilic, CUR can combination the BBB, as proven in a number of studies using laboratory rodents (e.g., ). At 37 C, CUR degrades in solutions with pH 7; however, in acidic pH, its half-life raises by two orders of magnitude . Gallic acid (GA), aka 3,4,5-trihydroxybenzoic acid, is definitely a phenolic acid that has strong anticancer properties . In humans, GA is definitely absorbed more compared to additional polyphenols . It really is changed into additional substances by glucuronidation and methylation mainly, with 4- em O /em -methylgallic acid being among the crucial methyl derivatives in the physical body . Quercetin (QUE), a flavonoid, can be a powerful antioxidant within many fruits, meals and vegetables items such.