rhamnetin and 3-methylquercetin

Alzheimer's disease (AD) is marked by the presence of amyloid plaques, neurofibrillary tangles, oxidatively damaged neuronal macromolecules and redox sensitive ions. Reduction of amyloid plaques and oxidative stress emerge as a convincing treatment strategy. Plaque reduction is achieved by inhibition of BACE1, the rate limiting enzyme generating the prime constituent of plaques, Aβ, through proteolysis of the amyloid precursor protein. Here, we report a QSAR model with five descriptors, developed to screen natural compounds as potent BACE1 inhibitors. Seven compounds out of which five flavonols namely isorhamnetin, syringetin, galangin, tamarixetin, rhamnetin and two flavanonols namely dihydromyricetin, taxifolin were screened. The ability of these compounds were validated using the BACE1 activity assay. The antioxidant property were estimated by the DPPH and ABTS assay. Although inhibition assay implied syringetin to be a promising BACE1 inhibitor, its poor antioxidant activity leaves it less effective as a multitarget ligand. Exhibiting moderate dual ability, isorhamnetin and taxifolin qualified as multi-target scaffolds for AD therapeutics. Our study reveals the importance of 4'-OH in the B ring of flavonols and the lack of any effect of 5'-OH in flavanonols for BACE1 inhibition. In case of antioxidant activity favourable association of 3'-O-methylation derivatives was observed in flavonols.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Aspartic Acid Endopeptidases; Disaccharides; Flavonoids; Flavonols; Humans; Molecular Docking Simulation; Neurons; Oxidative Stress; Plaque, Amyloid; Protein Conformation; Quantitative Structure-Activity Relationship; Quercetin

This study is aimed at determining the relationship of flavonoid structures to their chemical and intracellular antioxidant activities. The antioxidant activities of 60 flavonoids were investigated by three different antioxidant assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, oxygen radical absorption capacity (ORAC), and cellular antioxidant activity (CAA) assays. The result showed 6 flavonoids as good cellular antioxidants evaluated for the first time. The cellular antioxidant activities of compounds 7-methoxy-quercetin, 3-

Topics: Antioxidants; Catalase; Cell Proliferation; Flavonoids; Hep G2 Cells; Humans; Kaempferols; Quercetin; Structure-Activity Relationship; Superoxide Dismutase; Up-Regulation

Three new flavonoid glycosides-soyaflavonosides A (1), B (2), and C (3)-together with 23 known ones were obtained from the 70% EtOH extract of Flos Sophorae (Sophora japonica, Leguminosae). Their structures were elucidated by chemical and spectroscopic methods. Among the known isolates, 14, 18, 20, 22, and 26 were isolated from the Sophora genus for the first time; 12, 19, 24, and 25 were obtained from the species firstly. Moreover, NMR data for compounds 18 and 26 are reported for the first time here. Meanwhile, compounds 4, 8-13, 15, 16, 19, 21, and 22 presented obvious inhibitory effects on TG accumulation in HepG2 cells. Analysis of the structure-activity relationship indicated that all of the quercetin glycosides examined in this study possess significant activity that is not significantly influenced by the amount of glycosyl present, whereas increasing the amount of glycosyl reduced the activities of isorhamnetin glycosides and orobol. In addition, a high dose (30 μmol/l) of kaempferol was found to inhibit HepG2 cell growth, while a low dose (10 μmol/l) was observed to decrease TG accumulation.

Topics: Cell Proliferation; Flavonoids; Flowers; Glycosides; Hep G2 Cells; Hormesis; Humans; Kaempferols; Plant Extracts; Quercetin; Rutin; Sophora; Structure-Activity Relationship; Triglycerides

The effects of isorhamnetin, rhamnetin and quercetin on the serum and liver cholesterol concentrations, liver lipoperoxide (thiobarbituric acid-reactive substances: TBARS) content, and antioxidative enzyme activities were examined with rats fed on cholesterol-enriched and cholesterol-free diets. The total serum cholesterol of those rats fed with the cholesterol-enriched diet was decreased by feeding each all these flavonoids. The total liver cholesterol concentration and TBARS content in the rats fed with the cholesterol-free diet were decreased by feeding isorhamnetin, rhamnetin and quercetin. The activities of liver superoxide dismutase and catalase were almost unaffected by feeding these flavonoids. These results, the in vitro antioxidative activities of isorhamnetin, rhamnetin and quercetin, and the activities of these flavonoids in suppressing the generation of the superoxide anion in vitro suggest the possibility that the lower liver TBARS content in those rats fed on the cholesterol-free diet with added flavonoids is ascribable in part to the direct antioxidative and superoxide anion generation-suppressing activities of flavonoids and/or their metabolites absorbed from the gastrointestinal tract.

Topics: Animals; Catalase; Cholesterol; Cholesterol, Dietary; Flavonols; Lipid Peroxides; Liver; Male; Quercetin; Rats; Rats, Wistar; Spectrophotometry, Ultraviolet; Superoxide Dismutase; Xanthine Oxidase

The alkylation of bacterial DNA by two flavonoids: rhamnetin and isorhamnetin was examined using of strains Escherichia coli K-12: AB1157 (ada+) and (ada3). Rhamnetin and isorhamnetin and their putative metabolites formed in the presence of the S9 mix did not alkylate DNA at 0-6 of guanine.

Topics: Alkylation; Biotransformation; DNA, Bacterial; Escherichia coli; Flavonols; Guanine; Liver; Mutagens; Quercetin; SOS Response, Genetics

Genotoxic activities of flavonoids (quercetin, rhamnetin, isorhamnetin, apigenin, luteolin) were investigated using two short-term bacterial assays. In the "repair test" in Salmonella typhimurium (strains TA1538 uvrB- and TA1978 uvrB+) the flavonoids studied did not introduce any damage into the DNA recognized by UvrABC nuclease (correndonuclease II). The results of the SOS-Chromotest in Escherichia coli K-12 strains PQ37 (tag+, alk+) and PQ243 (tagA, alkA) indicated that flavonoids only weakly induced the SOS system. The addition of a liver activation system (S9 mix) did not increase the mutagenic effect of the flavonoids tested. Two compounds: rhamnetin, isorhamnetin and their putative metabolites formed in the presence of the S9 mix did not alkylate DNA at N-3 of adenine.

Topics: Animals; Chamomile; DNA Damage; DNA Repair; Escherichia coli; Flavonoids; Flavonols; In Vitro Techniques; Luteolin; Male; Microsomes, Liver; Mutagenicity Tests; Mutagens; Oils, Volatile; Plants, Medicinal; Quercetin; Rats; Salmonella typhimurium; SOS Response, Genetics

Topics: 2-Acetylaminofluorene; Amines; Animals; Anthracenes; Chamomile; Flavonoids; Flavonols; Fluorenes; Luteolin; Microsomes, Liver; Mutagens; Oils, Volatile; Plants, Medicinal; Quercetin; Rats