Interference by luteolin,quercetin, and taxifolin with chloroplast-mediated electron transport and phosphorylation

Summary The effects of luteolin, quercetin, and taxifolin on light induced phosphorylation and electron transport in isolated, greenhouse-grown, spinach (Spinacia oleracea L.) thylakoids were investigated. Luteolin and quercetin interacted with components associated with both the ATP-generating pathway and the electron-transport pathway. However, the action of taxifolin involved only the phosphorylation pathway. Interference with the phosphorylation pathway was evidenced by the greater sensitivity of phosphorylation than oxygen uptake in coupled whole-chain electron transport, inhibition of the light-activated Mg²⁺-ATPase, and inhibition of the Ca²⁺-ATPase associated with CF₁. The following order of decreasing inhibitory effectiveness was exhibited: luteolin > quercetin >>> taxifolin. On the electron-transport pathway, luteolin and quercetin interfered with the activity of the Q_B-protein complex as evidenced by inhibition of the partial reaction with diphenylcarbazide as the electron donor and 2,6-dichlorophenolindophenol as electron acceptor; alteration of the chlorophyll fluorescence transients; and competitive displacement of radiolabeled atrazine [2-chloro-4-(ethylamino)-6-(isopropylamino)-s-triazine].     

A homogeneous cell-based assay for measurement of endogenous paraoxonase 1 activity

Paraoxonase 1 (PON1) is a high-density lipoprotein-associated enzyme that plays an important role in organophosphate detoxification and prevention of atherosclerosis. Thus, there is significant interest in identifying nutritional and pharmacological enhancers of PON1 activity. To identify such compounds, we developed a rapid homogeneous assay to detect endogenous cell-associated PON1 activity. PON1 activity was measured by the simple addition of fluorigenic PON1 substrate DEPFMU to live Huh7 cells in medium and monitoring change in fluorescence. A specific PON1 inhibitor, 2-hydroxyquinoline, was used to confirm that the observed activity was due to PON1. The assay was optimized and characterized with regard to time course, substrate and sodium chloride concentration, number of cells, and tolerance to dimethyl sulfoxide and serum. Aspirin, quercetin, and simvastatin are compounds reported to increase PON1 expression. Consistent with the literature and Western blot data, these compounds enhanced PON1 activity in this assay with comparable efficacies and potencies. A known toxic compound did not increase assay signal. This assay method also detected PON1 activity in normal hepatocytes. Thus, a novel homogeneous assay for detection of endogenous PON1 expression has been developed and is amenable to high-throughput screening for the identification of small molecules that enhance PON1 expression.     

Quercetin prevents myocardial infarction adverse remodeling in rats by attenuating TGF-β1/Smad3 signaling: Different mechanisms of action

This study investigated the anti-remodeling and anti-fibrotic and effect of quercetin (QUR) in the remote non-infarcted of rats after myocardial infarction (MI). Rats were divided as control, control + QUR, MI, and MI + QUR. MI was introduced to the rats by ligating the eft anterior descending (LAD) coronary artery. All treatments were given for 30 days, daily. QUR persevered the LV hemodynamic parameters and prevented remote myocardium damage and fibrosis. Also, QUR supressed the generation of ROS, increased the nuclear levels of Nrf2, and enhanced SOD and GSH levels in the LVs of the control and MI model rats. It also reduced angiotensin II, nuclear level/activity of the nuclear factor NF-κβ p65, and protein expression of TGF-β1, α-SMA, and total/phospho-smad3 in the LVs of both groups. Concomitantly, QUR upregulated LV smad7 and BMP7. In conclusion, QUR prevents MI-induced LV remodeling by antioxidant, anti-inflammatory, and anti-fibroticα effects mediated by ROS scavenging, suppressing NF-κβ, and stimulating Nrf-2, Smad7, and BMP7.     

Design,synthesis and α-amylase inhibitory activity of novel chromone derivatives

Quercetin is one of the naturally occurring polyphenol flavonoid predominantly known for antidiabetic activity. In the present study, by considering the structural requirements, twenty two novel chromone derivatives (5–26) as α-amylase inhibitor were designed and subsequently in silico evaluated for drug likeness behavior. Designed compounds were synthesized, characterized by spectral analysis and finally evaluated for the inhibition of α-amylase activity by in vitro assay. Tested compounds exhibited significant to weak activity with IC₅₀ range of 12–125 µM. Among the tested compounds, analogues 5, 8, 12, 13, 15, 17 and 22 exhibited significant human α-amylase inhibitory activity with IC₅₀ values <25 µM, which can be further explored as anti-hyperglycemic agents. Putative binding mode of the significant and least active α-amylase inhibitors with the target enzyme was also explored by the docking studies.