Flavonoid intake and the risk of age-related cataract in China’s Heilongjiang Province

Background/Objectives: Epidemiological evidence suggests that diets rich in flavonoids may reduce the risk of developing age-related cataract (ARC). Flavonoids are widely distributed in foods of plant origin and the objective of this study was to evaluate retrospectively the association between the intakes of the five flavonoid subclasses and the risk of ARC.  Subjects/Methods: A population-based case-control study (249 cases and 66 controls) was carried out in Heilongjiang province, which is located in the Northeast of China, and where intakes and availability of fresh vegetables and fruits can be limited. Dietary data gathered by food-frequency questionnaire (FFQ) were used to calculate flavonoid intake. Adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated by logistic regression.  Results: No linear associations between risk of developing ARC and intakes of total dietary flavonoids, anthocyanidins, flavon-3-ol, flavanone, total flavones or total flavonols were found, but quercetin and isorhamnetin intake was inversely associated with ARC risk (OR 11.78, 95% CI: 1.62-85.84, P<0.05, and OR 6.99, 95% CI:1.12-43.44, P<0.05, quartile 4 vs quartile 1, respectively).  Conclusion: As quercetin is contained in many plant foods and isorhamnetin is only contained in very few foods, we concluded that higher quercetin intake may be an important dietary factor in the reduction of risk of age-related cataract

Microarray analysis revealed different gene expression patterns in HepG2 cells treated with low and high concentrations of the extracts of Anacardium occidentale shoots

In this study, the effects of low and high concentrations of the Anacardium occidentale shoot extracts on gene expression in liver HepG2 cells were investigated. From MTT assays, the concentration of the shoot extracts that maintained 50% cell viability (IC50) was 1.7 mg/ml. Cell viability was kept above 90% at both 0.4 mg/ml and 0.6 mg/ml of the extracts. The three concentrations were subsequently used for the gene expression analysis using Affymetrix Human Genome 1.0 S.T arrays. The microarray data were validated using real-time qRT–PCR. A total of 246, 696 and 4503 genes were significantly regulated (P < 0.01) by at least 1.5-fold in response to 0.4, 0.6 and 1.7 mg/ml of the extracts, respectively. Mutually regulated genes in response to the three concentrations included CDKN3, LOC100289612, DHFR, VRK1, CDC6, AURKB and GABRE. Genes like CYP24A1, BRCA1, AURKA, CDC2, CDK2, CDK4 and INSR were significantly regulated at 0.6 mg/ml and 1.7 mg but not at 0.4 mg/ml. However, the expression of genes including LGR5, IGFBP3, RB1, IDE, LDLR, MTTP, APOB, MTIX, SOD2 and SOD3 were exclusively regulated at the IC50 concentration. In conclusion, low concentrations of the extracts were able to significantly regulate a sizable number of genes. The type of genes that were expressed was highly dependent on the concentration of the extracts used

Identifying chondroprotective diet-derived bioactives and investigating their synergism

Osteoarthritis (OA) is a multifactorial disease and nutrition is a modifiable factor that may contribute to disease onset or progression. A detailed understanding of mechanisms through which diet-derived bioactive molecules function and interact in OA is needed. We profiled 96 diet-derived, mainly plant-based bioactives using an in vitro model in chondrocytes, selecting four candidates for further study. We aimed to determine synergistic interactions between bioactives that affected the expression of key genes in OA. Selected bioactives, sulforaphane, apigenin, isoliquiritigenin and luteolin, inhibited one or more interleukin-1-induced metalloproteinases implicated in OA (MMP1, MMP13, ADAMTS4, ADAMTS5). Isoliquiritigenin and luteolin showed reactive oxygen species scavenging activity in chondrocytes whereas sulforaphane had no effect and apigenin showed only a weak trend. Sulforaphane inhibited the IL-1/NFκB and Wnt3a/TCF/Lef pathways and increased TGFβ/Smad2/3 and BMP6/Smad1/5/8 signalling. Apigenin showed potent inhibition of the IL-1/NFκB and TGFβ/Smad2/3 pathways, whereas luteolin showed only weak inhibition of the IL-1/NFκB pathway. All four bioactives inhibited cytokine-induced aggrecan loss from cartilage tissue explants. The combination of sulforaphane and isoliquiritigenin was synergistic for inhibiting MMP13 gene expression in chondrocytes. We conclude that dietary-derived bioactives may be important modulators of cartilage homeostasis and synergistic relationships between bioactives may have an anti-inflammatory and chondroprotective role

A systems approach to identifying correlated gene targets for the loss of colour pigmentation in plants

<p>Abstract</p> <p>Background</p> <p>The numerous diverse metabolic pathways by which plant compounds can be produced make it difficult to predict how colour pigmentation is lost for different tissues and plants. This study employs mathematical and <it>in silico </it>methods to identify correlated gene targets for the loss of colour pigmentation in plants from a whole cell perspective based on the full metabolic network of <it>Arabidopsis</it>. This involves extracting a self-contained flavonoid subnetwork from the AraCyc database and calculating feasible metabolic routes or elementary modes (EMs) for it. Those EMs leading to anthocyanin compounds are taken to constitute the anthocyanin biosynthetic pathway (ABP) and their interplay with the rest of the EMs is used to study the minimal cut sets (MCSs), which are different combinations of reactions to block for eliminating colour pigmentation. By relating the reactions to their corresponding genes, the MCSs are used to explore the phenotypic roles of the ABP genes, their relevance to the ABP and the impact their eliminations would have on other processes in the cell.</p> <p>Results</p> <p>Simulation and prediction results of the effect of different MCSs for eliminating colour pigmentation correspond with existing experimental observations. Two examples are: i) two MCSs which require the simultaneous suppression of genes DFR and ANS to eliminate colour pigmentation, correspond to observational results of the same genes being co-regulated for eliminating floral pigmentation in <it>Aquilegia </it>and; ii) the impact of another MCS requiring CHS suppression, corresponds to findings where the suppression of the early gene CHS eliminated nearly all flavonoids but did not affect the production of volatile benzenoids responsible for floral scent.</p> <p>Conclusions</p> <p>From the various MCSs identified for eliminating colour pigmentation, several correlate to existing experimental observations, indicating that different MCSs are suitable for different plants, different cells, and different conditions and could also be related to regulatory genes. Being able to correlate the predictions with experimental results gives credence to the use of these mathematical and <it>in silico </it>analyses methods in the design of experiments. The methods could be used to prioritize target enzymes for different objectives to achieve desired outcomes, especially for less understood pathways.</p