Dihydromyricetin Improves Cognitive Impairments in d-Galactose-Induced Aging Mice through Regulating Oxidative Stress and Inhibition of Acetylcholinesterase.

SCOPE: Alzheimer's disease (AD) is a neurodegenerative disease with phenomena of cognitive impairments. Oxidative stress and cholinergic system dysfunction are two widely studied pathogenesis of AD. Dihydromyricetin (DMY) is a natural dihydroflavonol with many bioactivities. In this study, it is aimed to investigate the effects of DMY on cognitive impairment in d-galactose (d-gal) induced aging mice. METHODS AND RESULTS: Mice are intraperitoneally injected with d-gal for 16 weeks, and DMY is supplemented in drinking water. The results show that DMY significantly improves d-gal-induced cognitive impairments in novel object recognition and Y-maze studies. H&E and TUNEL staining show that DMY could improve histopathological changes and cell apoptosis in mice brain. DMY effectively induces the activities of catalase, superoxide dismutase and glutathione peroxidase, and reduces malondialdehyde level in mice brain and liver. Furthermore, DMY reduces cholinergic injury by inhibiting the activity of Acetylcholinesterase (AChE) in mice brain. In vitro studies show that DMY is a non-competitive inhibitor of AChE with IC50 value of 161.2 µg mL-1 . CONCLUSION: DMY alleviates the cognitive impairments in d-gal-induced aging mice partly through regulating oxidative stress and inhibition of acetylcholinesterase.

Physicochemical properties of dihydromyricetin and the effects of ascorbic acid on its stability and bioavailability.

BACKGROUND: Dihydromyricetin (DMY) is a natural dihydroflavonol with many bioactive effects. However, the physicochemical properties of DMY related to its bioavailability, especially its stability, are unclear. RESULTS: The effects of pH, temperature, metal ions and ascorbic acid (AA) on the stability of DMY were studied using high-performance liquid chromatography (HPLC). The bioavailability of DMY in the presence and absence of AA was compared. Dihydromyricetin was unstable in weak alkaline solutions, and the degradation was significantly accelerated in the presence of Cu2+ and Fe3+ . The degradation process followed the first-order kinetic model. The degradation rate constant (k) increased with increasing pH and temperature. The remaining DMY was only 49% of its initial concnentration after 4 h in simulated intestinal fluid (SIF) at 37 °C. However, by supplementing with AA, the degradation of DMY was rarely occured within 6 h. The solubility of DMY at pH 3-5 was about 750 µg mL-1 , slightly increasing to 853 µg mL-1 at pH 6. Pharmacokinetic studies showed that the bioavailability of DMY increased from 0.122% to 0.341% by supplementing with AA (10% of DMY). CONCLUSION: The degradation of DMY is one reason for its poor bioavailability. The presence of AA could significantly improve the stability of DMY, and further improve its bioavailability in rats. © 2020 Society of Chemical Industry.

Metabolism, Excretion, and Tissue Distribution of Astilbin-Zein Nanoparticles in Rats.

The excretion, tissue distribution, and metabolic profile of astilbin in rat were studied by HPLC and UPLC-QTOF-MS. Astilbin underwent isomerization in the small intestine, and its four isomers were found in feces. Besides, taxifolin, the aglycone of astilbin, and its further metabolites by gut microbes through hydrogenation, dehydration, and ring-fission were found. The total feces excretion of astilbin was about 14.4% of administration. The forming of zein-caseinate nanoparticles can significantly delay and reduce the feces excretion of astilbin. Astilbin and its isomers were absorbed in their intact form. The main metabolites found in plasma and tissues were the methylated products. Astilbin was rapidly distributed in various tissues including brain and maintained relatively high concentration in heart. Compared with other tissues, significantly higher concentration and longer duration of astilbin were found in the gastrointestinal tract. Astilbin and its isomers were excreted in their intact and methylated form in urine.