tannins and morin

Aβ(1-42) is the proteolytic cleavage product of cleavage of the amyloid precursor protein by β- and γ-secretases. The aggregation of Aβ(1-42) plays a causative role in the development of Alzheimer's disease. To lock Aβ(1-42) in a homogenous state, we embedded the Aβ(1-42) sequence in an unstructured region of Bcl-x(L). Both the N-terminus and the C-terminus of Aβ(1-42) were constrained in the disordered region, whereas the conjunction did not introduce any folding to Aβ(1-42) but maintained the sequence as a monomer in solution. With Bcl-x(L)-Aβ(42), we developed an enzyme-linked immunosorbent assay to compare the affinity of compounds for monomeric Aβ(1-42). Bcl-x(L)-Aβ(42) was coated on a microplate and this was followed by incubation with different concentrations of compounds. Compounds binding to Leu17-Val24 of Aβ(1-42) inhibited the interaction between Bcl-x(L)-Aβ(42) and antibody 4G8. The method can not only reproduce the activities of the reported Aβ(1-42) inhibitors such as dopamine, tannin, and morin but can also differentiate decoy compounds that do not bind to Aβ(1-42). Remarkably, using this method, we discovered a new inhibitor that binds to monomeric Aβ(1-42) and inhibits Aβ(1-42) fibril formation. As the structure of Bcl-x(L)-Aβ(42) monomer is stable in solution, the assay could be adapted for high-throughput screening with a series of antibodies that bind the different epitopes of Aβ(1-42). In addition, the monomeric form of the Aβ(1-42) sequence in Bcl-x(L)-Aβ(42) would also facilitate the identification of Aβ(1-42) binding partners by coimmunoprecipitation, cocrystallization, surface plasmon resonance technology, or the assay as described here.

Topics: Amyloid beta-Peptides; bcl-X Protein; Binding Sites; Crystallography, X-Ray; Dopamine; Enzyme-Linked Immunosorbent Assay; Flavonoids; Models, Molecular; Peptide Fragments; Salicylic Acid; Structure-Activity Relationship; Tannins

Zingiber officinale Roscoe. (Family Zingiberaceae) is well known in Asia. The plant is widely cultivated in village gardens in the tropics for its medicinal properties and as a marketable spice in Malaysia. Ginger varieties are rich in physiologically active phenolics and flavonoids with a range of pharmacological activities. Experiments were conducted to determine the feasibility of increasing levels of flavonoids (quercetin, rutin, catechin, epicatechin, kaempferol, naringenin, fisetin and morin) and phenolic acid (gallic acid, vanillic acid, ferulic acid, tannic acid, cinnamic acid and salicylic acid), and antioxidant activities in different parts of Malaysian young ginger varieties (Halia Bentong and Halia Bara) with CO(2) enrichment in a controlled environment system. Both varieties showed an increase in phenolic compounds and flavonoids in response to CO(2) enrichment from 400 to 800 µmol mol-1 CO(2). These increases were greater in rhizomes compared to leaves. High performance liquid chromatography (HPLC) results showed that quercetin and gallic acid were the most abundant flavonoid and phenolic acid in Malaysian young ginger varieties. Under elevated CO(2) conditions, kaempferol and fisetin were among the flavonoid compounds, and gallic acid and vanillic acid were among the phenolic compounds whose levels increased in both varieties. As CO(2) concentration was increased from 400 to 800 µmol mol-1, free radical scavenging power (DPPH) increased about 30% in Halia Bentong and 21.4% in Halia Bara; and the rhizomes exhibited more enhanced free radical scavenging power, with 44.9% in Halia Bentong and 46.2% in Halia Bara. Leaves of both varieties also displayed good levels of flavonoid compounds and antioxidant activities. These results indicate that the yield and pharmaceutical quality of Malaysian young ginger varieties can be enhanced by controlled environment production and CO(2) enrichment.

Topics: Antioxidants; Carbon Dioxide; Catechin; Chromatography, High Pressure Liquid; Cinnamates; Coumaric Acids; Flavanones; Flavonoids; Flavonols; Free Radical Scavengers; Gallic Acid; Hydroxybenzoates; Kaempferols; Malaysia; Phenols; Quercetin; Rutin; Salicylic Acid; Tannins; Vanillic Acid; Zingiber officinale