Robust mitochondrial respiration provides energy to support physical performance and physiological well-being, whereas mitochondrial malfunction is associated with various pathologies and reduced longevity. In the current study, we tested whether myricetin, a natural flavonol with diverse biological activities, may impact mitochondrial function and longevity. The mice were orally administered myricetin (50 mg/kg/day) for 3 weeks. Myricetin significantly potentiated aerobic capacity in mice, as evidenced by their increased running time and distance. The elevated mitochondrial function was associated with induction of genes for oxidative phosphorylation and mitochondrial biogenesis in metabolically active tissues. Importantly, myricetin treatment led to decreased PGC-1α acetylation through SIRT1 activation. Furthermore, myricetin significantly improved the healthspan and lifespan of wild-type, but not Sir-2.1-deficient, C. elegans. These results demonstrate that myricetin enhances mitochondrial activity, possibly by activating PGC-1α and SIRT1, to improve physical endurance, strongly suggesting myricetin as a mitochondria-activating agent.

Polymethoxyflavanoids (PMFs) have exhibited a vast array of therapeutic biological properties. 5-O-Demethylnobiletin (5-DN) is one such PMF having anti-inflammatory activity, yet its role in hepatoprotection has not been studied before. Results from in vitro study revealed that 5-DN did not exert a high level of cytotoxicity on HepG2 cells at 40 μM, and it was able to rescue HepG2 cell death induced by carbon tetrachloride (CCl4). Subsequently, we investigated acute liver injury on BALB/c mice induced by CCl4 through the intraperitoneal injection of 1 mL/kg CCl4 and co-administration of 5-DN at (1 and 2 mg/kg) by oral gavage for 15 days. The results illustrated that treatment with 5-DN attenuated CCl4-induced elevated serum aminotransferase (AST)/alanine aminotransferase (ALT) ratio and significantly ameliorated severe hepatic damage such as inflammation and fibrosis evidenced through lesser aberrations in the liver histology of 5-DN dose groups. Additionally, 5-DN efficiently counteracted and equilibrated the production of ROS accelerated by CCl4 and dramatically downregulated the expression of CYP2E1 vitally involved in converting CCl4 to toxic free radicals and also enhanced the antioxidant enzymes. 5-DN treatment also inhibited cell proliferation and inflammatory pathway abnormally regulated by CCl4 treatment. Furthermore, the apoptotic response induced by CCl4 treatment was remarkably reduced by enhanced Bcl-2 expression and noticeable reduction in Bax, Bid, cleaved caspase 3, caspase 9, and apaf-1 expression. 5-DN treatment also induced the conversion of LC3 and promoted the autophagic flux. Conclusively, 5-DN exhibited hepatoprotective effects in vitro and in vivo and prevented liver fibrosis induced by CCl4.

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1Using Ar/Air mixture microwave plasma, we investigated the effects of air and gas temperature on the generation of electrons, ozone (O 3 ), and nitric oxide (NO) through experiments and chemical kinetics simulation. The global model (GM) chemical kinetics simulation was used to validate and complement experimental observations. As the air percentages in Ar plasma increase, electrons are mainly generated by reactive oxygen species (ROS), but electron densities decrease. This is why plasma jet length becomes shorter with the mixture of air to Ar plasma at the same power. The profile of O 3 densities has a maximum point because these are affected by oxygen (O 2 ) molecules and gas temperature. O 3 densities increase because these are generated via recombination of atomic oxygen (O) and O 2 radicals as the air percentages increase. As the gas temperature increases, O 3 densities decrease and O 3 radicals are mainly destroyed by ROS such as O 2 À , excited O 2 , and O, although air percentages increase. NO radicals increase continually with the addition of air mixture and increase in gas temperature. With respect to biomedical applications, in the case of Ar/Air plasma treatment, it takes just 2 d, which has reduced the wound area to 30% because of faster scab formation over the wound and mRNA activation. Abundant NO radicals with ROS in Ar/aAir plasma strongly enhance IL-6 and TGF-b1, which facilitate collagen remodeling and wound recovery effectively.