BackgroundQuercetin is the most abundant flavonoid in fruit and vegetables and is believed to attenuate cardiovascular disease. We hypothesized that quercetin inhibits cardiac hypertrophy by blocking AP-1 (c-fos, c-jun) and activating PPAR-γ signaling pathways.Methodology/Principal FindingsThe aim of this study was to identify the mechanism underlying quercetin-mediated attenuation of cardiac hypertrophy. Quercetin therapy reduced blood pressure and markedly reduced the ratio of left ventricular to body weight (LVW/BW) (P<0.05, vs. spontaneously hypertensive rats (SHRs)). In vitro, quercetin also significantly attenuated Ang II-induced H9C2 cells hypertrophy, as indicated by its concentration dependent inhibitory effects on [3H]leucine incorporation into H9C2 cells (64% reduction) and by the reduced hypertrophic surface area in H9C2 cells compared with the Ang II group (P<0.01, vs. Ang II group). Concurrently, we found that PPAR-γ activity was significantly increased in the quercetin-treated group both in vivo and in vitro when analyzed using immunofluorescent or immunohistochemical assays (P<0.05, vs. SHRs or P<0.01, vs. the Ang II group). Conversely, in vivo, AP-1 (c-fos, s-jun) activation was suppressed in the quercetin-treated group, as was the downstream hypertrophy gene, including mRNA levels of ANP and BNP (P<0.05, vs. SHRs). Additionally, both western blotting and real time-PCR demonstrated that PPAR-γ protein and mRNA were increased in the myocardium and AP-1 protein and mRNA were significantly decreased in the quercetin-treated group (P<0.05, vs. SHRs). Furthermore, western blotting and real time-PCR analyses also showed that transfection with PPAR-γ siRNA significantly increased AP-1 signaling and reversed the effects of quercetin inhibition on mRNA expression levels of genes such as ANP and BNP in hypertrophic H9C2 cells.ConclusionsOur data indicate that quercetin may inhibit cardiac hypertrophy by enhancing PPAR-γ expression and by suppressing the AP-1 signaling pathway.

Background: Ticagrelor as a reversible P2Y12 receptor antagonist which plays an important role in the treatment of acute coronary syndrome (ACS). Dyspnea is one of the main adverse reactions of ticagrelor, however the mechanism is not clearly now. The aim of this study was to assess the possible relationship between ticagrelor-related dyspnea and some neurotransmitter in plasma which can contract the bronchial smooth muscle.Methods: The effects of ticagrelor on the plasma level of adrenaline, histamine, serotonin, and acetylcholine was studied in rats. Ticagrelor was administered at a loading dose of 24 mg/kg for the first time, and then maintenance dose 12 mg/kg, twice a day for 6 days. The plasma level of adrenaline, histamine, serotonin, and acetylcholine was determined by LC-MS/MS.Results: The plasma level of serotonin increased after ticagrelor administrating, especially at 1.5h ( p <0.05) reach the level of statistical significance. The level of serotonin in plasma was consistent with ticagrelor blood concentration. Meanwhile, ticagrelor can cause a decrease in the plasma concentration of histamine, and the change was statistically significant at time points of 1.5h, 3.5h and 10.5h respectively. The concentration of the adrenaline and acetylcholine had no change.Conclusions: The results of this study reveal that ticagrelor can increases blood serotonin levels and this may be a cause of dyspnea ticagrelor-related.

Plant-specialized secondary metabolites have ecological functions in mediating interactions between plants and their entophytes. Here, we aimed to reveal the interaction between flavonoid synthesis and endophytic bacterial communities in wild Ginkgo trees spanning 100-800 years. We found that flavonoids including quercetin, kaempferol and isorhamnetin decreased while the microbial diversity in leaves increased with the age of sampled trees. Older trees had more unique genera and shifted their endophytic bacterial community structure. Also, Mantel tests and correlation analysis indicated a generally significant (p < 0.05) negative correlation between endophytic bacterial communities and flavonoids. Additionally, both deterministic and stochastic processes could play roles in the assembly of endophytic bacterial communities in Ginkgo trees with a progressive increase in stochastic processes as flavonoid concentrations decreased. This study provides a mechanistic understanding of how flavonoids modulate the endophytic microbial community assembly.