双氢杨梅素与G-四链体的相互作用研究

双氢杨梅素(DMY)是从药用植物——广西藤茶中提取出来的一种含量极高的二氢黄酮醇类化合物, 具有抗肿瘤、抗氧化、调节血糖等作用, 但其抗肿瘤机理尚不清楚. 本文利用T_m值和CD光谱对G-四链体进行了表征, 利用电子吸收光谱和竞争性结合实验研究了DMY与G-四链体的相互作用. 结果显示DMY是通过外部堆积结合到G-四链体, 并通过稳定G-四链体结构而抑制端粒酶活性, 起到抗肿瘤的作用.     

A Novel Dual Drug Approach That Combines Ivermectin and Dihydromyricetin (DHM) to Reduce Alcohol Drinking and Preference in Mice

Alcohol use disorder (AUD) affects over 18 million people in the US. Unfortunately, pharmacotherapies available for AUD have limited clinical success and are under prescribed. Previously, we established that avermectin compounds (ivermectin [IVM] and moxidectin) reduce alcohol (ethanol/EtOH) consumption in mice, but these effects are limited by P-glycoprotein (Pgp/ABCB1) efflux. The current study tested the hypothesis that dihydromyricetin (DHM), a natural product suggested to inhibit Pgp, will enhance IVM potency as measured by changes in EtOH consumption. Using a within-subjects study design and two-bottle choice study, we tested the combination of DHM (10 mg/kg; i.p.) and IVM (0.5–2.5 mg/kg; i.p.) on EtOH intake and preference in male and female C57BL/6J mice. We also conducted molecular modeling studies of DHM with the nucleotide-binding domain of human Pgp that identified key binding residues associated with Pgp inhibition. We found that DHM increased the potency of IVM in reducing EtOH consumption, resulting in significant effects at the 1.0 mg/kg dose. This combination supports our hypothesis that inhibiting Pgp improves the potency of IVM in reducing EtOH consumption. Collectively, we demonstrate the feasibility of this novel combinatorial approach in reducing EtOH consumption and illustrate the utility of DHM in a novel combinatorial approach.     

The Synergistic Effect of Triterpenoids and Flavonoids—New Approaches for Treating Bacterial Infections?

Currently, the pharmaceutical industry is well-developed, and a large number of chemotherapeutics are being produced. These include antibacterial substances, which can be used in treating humans and animals suffering from bacterial infections, and as animal growth promoters in the agricultural industry. As a result of the excessive use of antibiotics and emerging resistance amongst bacteria, new antimicrobial drugs are needed. Due to the increasing trend of using natural, ecological, and safe products, there is a special need for novel phytocompounds. The compounds analysed in the present study include two triterpenoids ursolic acid (UA) and oleanolic acid (OA) and the flavonoid dihydromyricetin (DHM). All the compounds displayed antimicrobial activity against Gram-positive (Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, and Listeria monocytogenes ATCC 19115) and Gram-negative bacteria (Escherichia coli ATCC 25922, Proteus hauseri ATCC 15442, and Campylobacter jejuni ATCC 33560) without adverse effects on eukaryotic cells. Both the triterpenoids showed the best antibacterial potential against the Gram-positive strains. They showed synergistic activity against all the tested microorganisms, and a bactericidal effect with the combination OA with UA against both Staphylococcus strains. In addition, the synergistic action of DHM, UA, and OA was reported for the first time in this study. Our results also showed that combination with triterpenoids enhanced the antimicrobial potential of DHM.     

Isolation and identification of metabolites from dihydromyricetin

Dihydromyricetin (DHM) is the major bioactive constituent of Rattan Tea, which is the tender stems and leaves of Ampelopsis grossendentata. Seven metabolites (2-8) of DHM (1) were obtained by the chromatographic method. The metabolites 2-5 were obtained from the urine of rats administered orally with DHM; and metabolites 6-8 were detected in the fecal specimens of rats, which were also produced by human intestinal bacteria (HIB) in vitro, and were separated from the cultured media of HIB containing DHM. Their structures were elucidated as 5,7,3',5'-tetrahydroxyflavanonol (2); 5,7,3',5'-tetrahydroxy-4'-methoxyflavanonol (3); 5,7,4',5'-tetrahydroxy-3'-methoxyflavanonol (4); and dihydromyricetin-O-5-beta-D-glucuronide (5); (2R,3S)-5,7,3',4',5'-pentahydroxyflavanonol (6); 3,4,5,7,3',4',5'-hepthydroxyflavan (7) and 5,7,3',4',5'-pentahydroxyflavanone (8) on the basis of UV, NMR and LC-MS/MS data. These seven metabolites were formed through familiar metabolic reactions. Dihydromyricetin-O-5-beta-D-glucuronide (5) is a new compound. The (13)C-NMR data of (2) and (4) are reported for the first time.     

Pro-Apoptotic Effect of Zeolitic Imidazolate Framework-8 (ZIF-8)-Loaded Dihydromyricetin on HepG2 Cells

Dihydromyricetin (DHM) has garnered attention due to its promising antitumor activity, but its low bioavailability restricts its clinical application. Thus, developing nano-drug delivery systems could enhance its antitumor activity. We prepared DHM@ZIF-8 nanoparticles using the zeolite imidazole framework-8 (ZIF-8) as a carrier loaded with dihydromyricetin. A series of characterizations were performed, including morphology, particle size, zeta potential, X-single crystal diffraction, ultraviolet spectroscopy, infrared spectroscopy, and Brunauer–Emmett–Teller (BET). The in vitro release characteristics of DHM@ZIF-8 under pH = 5.0 and pH = 7.4 were studied using membrane dialysis. The antitumor activity and pro-apoptotic mechanism of DHM@ZIF-8 were investigated through CCK-8 assay, reactive oxygen species (ROS), Annexin V/PI double-staining, transmission electron microscopy, and Western blot. The results depicted that DHM@ZIF-8 possessed a regular morphology with a particle size of 211.07 ± 9.65 nm (PDI: 0.19 ± 0.06) and a Zeta potential of −28.77 ± 0.67 mV. The 24 h drug releasing rate in PBS solution at pH = 7.4 was 32.08% and at pH = 5.0 was 85.52% in a simulated tumor micro acid environment. DHM@ZIF-8 could significantly enhance the killing effect on HepG2 cells compared to the prodrug. It can effectively remove ROS from the tumor cells, promote apoptosis, and significantly affect the expression of apoptosis-related proteins within tumor cells.     

Effect of Dihydromyricetin on the Stability of Polypropylene in Natural Weathering Tests

Effects of dihydromyricetin (DMY), extracted from Ampelopsis grossedentata, on the antioxidantive properties of polypropylene were evaluated by investigating differences in mechanical properties and melt flowability between pre- and post-natural weathering tests. For comparison purposes, the effects of a synthetic phenolic commercial antioxidant (Irganox 1010) were also analyzed. The results showed that reduction in mechanical properties and increment in melt flowability of polypropylene containing DMY were slower than that of unstabilized reference during the aging process, which implies that DMY exhibits high efficiency as a thermal antioxidant for polypropylene. On the other hand, samples that contained Irganox 1010 obtained further improved stability over the samples containing DMY during 105 days; however, the effectiveness of DMY lasted longer than that of Irganox 1010. DMY has a characteristic of being harmless and having high activity, good stability, and abundant resources to be a good natural antioxidant.     

Extracting myricetin and dihydromyricetin simultaneously from Hovenia acerba seed by Ultrasound-Assisted extraction on a lab and small Pilot-Scale

The flavonoids myricetin and dihydromyricetin are significant components of Hovenia acerba seed. In this work, myricetin and dihydromyricetin were extracted from Hovenia acerba seed using an ultrasound-assisted technique, and the extraction parameters were adjusted using the response surface design approach. HPLC was used to assess the yield of myricetin and dihydromyricetin. According to the data, myricetin and dihydromyricetin yields were 0.53 mg/g and 4.06 mg/g at a 60 % ethanol solution concentration, 180 W of ultrasonic irradiation power, a 20 mL/g ratio of liquid to solid, and a 40 °C optimal extraction temperature. The aforementioned findings are virtually in agreement with the experimental findings suggested by the model. The study mentioned above thus offers a means of separating and developing useful components of natural goods.