Search

Background: Programmed death ligand 1 (PD-L1) has been demonstrated to facilitate tumor progression and therapeutic resistance in an immune-independent manner. Nevertheless, the function and underlying signaling network(s) of cancer cell-intrinsic PD-L1 action remain largely unknown. Herein, we sought to better understand how ubiquitin-specific peptidase 51 (USP51)/PD-L1/integrin beta-1 (ITGB1) signaling performs a cell-intrinsic role in mediating chemotherapeutic resistance in non-small cell lung cancer (NSCLC)., Methods: Western blotting and flow cytometry were employed for PD-L1 detection in NSCLC cell lines. Coimmunoprecipitation and pulldown analyses, protein deubiquitination assay, tissue microarray, bioinformatic analysis and molecular biology methods were then used to determine the significance of PD-L1 in NSCLC chemoresistance and associated signaling pathways in several different cell lines, mouse models and patient tissue samples. Ubiquitin-7-amido-4-methylcoumarin (Ub-AMC)-based deubiquitinase activity, cellular thermal shift and surface plasmon resonance (SPR) analyses were performed to investigate the activity of USP51 inhibitors., Results: We provided evidence that cancer cell-intrinsic PD-L1 conferred the development of chemoresistance by directly binding to its membrane-bound receptor ITGB1 in NSCLC. At the molecular level, PD-L1/ITGB1 interaction subsequently activated the nuclear factor-kappa B (NF-κB) axis to elicit poor response to chemotherapy. We further determined USP51 as a bona fide deubiquitinase that targeted the deubiquitination and stabilization of the PD-L1 protein in chemoresistant NSCLC cells. Clinically, we found a significant direct relationship between the USP51, PD-L1 and ITGB1 contents in NSCLC patients with chemoresistant potency. The elevated USP51, PD-L1 and ITGB1 levels were strongly associated with worse patient prognosis. Of note, we identified that a flavonoid compound dihydromyricetin (DHM) acted as a potential USP51 inhibitor and rendered NSCLC cells more sensitive to chemotherapy by targeting USP51-dependent PD-L1 ubiquitination and degradation in vitro and in vivo., Conclusions: Together, our results demonstrated that the USP51/PD-L1/ITGB1 network potentially contributes to the malignant progression and therapeutic resistance in NSCLC. This knowledge is beneficial to the future design of advanced cancer therapy., (© 2023 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Deregulation of epidermal growth factor receptor (EGFR) signaling is frequently observed in non-small cell lung cancer (NSCLC). The present study aimed to determine the impact of dihydromyricetin (DHM) on NSCLC, a natural compound extracted from Ampelopsis grossedentata with various pharmacological activities. Results of the present study demonstrated that DHM may act as a promising antitumor agent for NSCLC therapy, inhibiting the growth of cancer cells in vitro and in vivo. Mechanistically, results of the present study demonstrated that exposure to DHM downregulated the activity of wild-type (WT) and mutant EGFRs (mutations, exon 19 deletion, and L858R/T790M mutation). Moreover, western blot analysis indicated that DHM induced cell apoptosis via suppression of the antiapoptotic protein, survivin. Results of the present study further demonstrated that depletion or activation of EGFR/Akt signaling may regulate survivin expression though modulating ubiquitination. Collectively, these results suggested that DHM may act as a potential EGFR inhibitor, and may provide a novel choice of treatment strategy for patients with NSCLC., (© 2023 Wiley Periodicals LLC.)

Conocarpus lancifolius Engl. (Combretaceae) has several potential health-promoting effects, such as antidiabetic, antimicrobial, antioxidant, and cytotoxic effects. Phytochemical study of the ethyl acetate fraction of the leaf extract of this plant led to the isolation and identification of eight compounds viz. , gallic acid ( 1 ), dihydromyricetin ( 2) , myricetin ( 3 ), daucosterol ( 4 ), syringetin 3- O -β-D-glucopyranoside ( 5 ), quercetin 3- O -β-D-glucoside ( 6 ), gallocatechin ( 7 ), and (-)-epigallocatechin-3- O -gallate ( 8 ). Their acetylcholinesterase (AChE) in vitro and in silico inhibitory activities were evaluated. Daucosterol ( 4 ) showed the highest activity (IC 50 0.316 μM) which was further validated by the superimposed docking orientation with the co-crystallized inhibitor, donepezil.

A previously unreported gallocatechin glycoside, (2  R ,3 S ) 4'- O -methyl-gallocatechin-3- O -α-ʟ-rhamnopyranoside ( 1 ) and an unseparable mixture of two previously undescribed dihydromyricetin glycosides, (2  R ,3 R ) 4'- O -methyl-dihydromyricetin-3- O -α-ʟ-rhamnopyranoside ( 2a ) and (2  R ,3 S ) 4'- O -methyl-dihydromyricetin-3- O -α-ʟ-rhamnopyranoside ( 2 b ) along with three known compounds were isolated from the n -butanol soluble fraction of the stem bark of Olax subscorpioidea Oliv. Their structures were elucidated by detailed spectroscopic analyses, including 1 H NMR, 13 C NMR, 1 H- 1 H COSY, HSQC, HMBC, NOESY, HR-ESI-MS and chemical methods. The crude ethanol extract, the fractions, and some of the isolated compounds were screened for their antioxidant and antibacterial activities. They showed significant antioxidant activities with EC 50 ranging from 6.29 to 18.19 µg/mL in 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and EC 50 ranging from 85.77 to 86.39 mmol FeSO 4 /g in ferric reducing antioxidant power (FRAP) methods compared with 2.29 µg/mL and 3.52 mmol FeSO 4 /g for the positive control (ʟ-ascorbic acid). Nevertheless, no inhibition was observed against the tested bacterial strains at a MIC less than 256 μg/mL.

Objective: To investigate the effect and potential mechanism of dihydromyricetin (Dmy) on H9C2 cell proliferation, apoptosis, and autophagy., Methods: H9C2 cells were randomly divided into 7 groups, namely control, model, EV (empty pCDH-CMV-MCS-EF1-CopGFP-T2A-Puro vector), IV (circHIPK3 interference), Dmy (50 µ mol/L), Dmy+IV, and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry, respectivley. Western blot was used to evaluate the levels of light chain 3 II/I (LC3II/I), phospho-phosphoinositide 3-kinase (p-PI3K), protein kinase B (p-AKT), and phospho-mammalian target of rapamycin (p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells., Results: Compared to H9C2 cells, the expression of circHIPK in H9C2 hypoxia model cells increased significantly (P<0.05). Compared to the control group, the cell apoptosis and autophagosomes increased, cell proliferation rate decreased significantly, and the expression of LC3 II/I significantly increased (all P<0.05). Compared to the model group, the rate of apoptosis and autophagosomes in IV, Dmy, and Dmy+IV group decreased, the cell proliferation rate increased, and the expression of LC3 II/I decreased significantly (all P<0.05). Compared to the control group, the expressions of p-PI3K, p-AKT, and p-mTOR in the model group significantly reduced (P<0.05), whereas after treatment with Dmy and sh-circHIPK3, the above situation was reversed (P<0.05)., Conclusion: Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy, and the mechanism may be related to PI3K/AKT/mTOR pathway., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Microwave-assisted extraction (MAE) technique in combination with multi-stage countercurrent extraction (MCE), namely microwave multi-stage countercurrent extraction (MMCE), was evaluated for the extraction of dihydromyricetin (DMY) from Ampelopsis grossedentata. Ethanol, methanol and water were used as extract solvents in the MMCE method. Of the three solvents used, water was found to be the best in extracting DMY from Ampelopsis grossedentata because it had a good extraction yield and is inexpensive, non-toxic and environmentally friendly. The optimal conditions of MMCE for the extraction of DMY can be determined to be the ratio of the extraction solvent to plant material of 30:1, the extraction time of 5 min, the extraction temperature of 110 °C and the microwave power of 600 W. In addition, the extraction efficiency of the MMCE method was compared with that of the microwave static batch extraction (MSBE) under the optimum extraction conditions. It was found that the MMCE method offered higher extraction efficiency than the MSBE method. Thus, the study suggests that the MMCE method provides an alternative technique in terms of both cost and efficiency.

Substantial evidence has demonstrated that the decreased osteogenic differentiation of bone mesenchymal stem cells ( BMSCs) is closely related to bone metabolic diseases. Thus, it is very important to develop several potentially useful therapeutic agents to enhance BMSC osteogenesis. Flavonoids show promise in enhancing bone mass. Dihydromyricetin ( DMY), a type of flavonoid, has not yet been investigated regarding its effects on BMSC osteogenesis. To investigate the effects of DMY on osteogenesis, human BMSCs were induced with or without DMY. We found that DMY (0.1-50 μ m) exhibited no cytotoxic effect on proliferation, but increased alkaline phosphatase activity, osteoblast-specific gene expression, and mineral deposition. It also enhanced active β-catenin expression and reduced dickkopf-1(DKK1) and sclerostin expression. The Wnt/β-catenin signaling pathway inhibitor (DKK1 and β-catenin-specific si RNA) decreased the enhanced bone mineral formation caused by DMY. Taken together, these findings reveal that DMY enhances osteogenic differentiation of human BMSCs partly through Wnt/β-catenin in vitro. [ABSTRACT FROM AUTHOR]

Inadequate oxygen availability-for instance at high altitudes-leads to hippocampal neurodegeneration and memory impairment. Although oxidative stress is one factor, the mechanism underlying the effects of hypobaric hypoxia (HH) are unclear, and effective strategies for preventing the resultant damage to the brain are limited. In the present study, we demonstrate that ingesting dihydromyricetin (DM) protects against memory impairment in adult rats subjected to HH for 7 days, equivalent to an altitude of 5000 m above sea level. Moreover, DM treatment stimulated mitochondrial biogenesis and improved mitochondrial morphology and function, suppressed the generation of reactive oxygen species, and reduced lipid peroxidation in the hippocampus. In HT-22 cells exposed to hypoxic conditions, the neuroprotective effects of DM were shown to be exerted via attenuation of oxidative stress through sirtuin 3-induced forkhead box O3 deacetylation. [ABSTRACT FROM AUTHOR]

Reperfusion therapy is widely used to treat acute myocardial infarction (AMI). However, further injury to the heart induced by rapidly initiating reperfusion is often encountered in clinical practice. A lack of pharmacological strategies in clinics limits the prognosis of patients with myocardial ischemia-reperfusion injury (MIRI). Dihydromyricetin (DMY) is one of the most abundant components in vine tea, commonly known as the tender stems and leaves of Ampelopsis grossedentata. The aim of this study was to evaluate the cardioprotection of DMY against myocardial ischemia-reperfusion (I/R) injury and to further investigate the underlying mechanism. An I/R injury was induced by left anterior descending coronary artery occlusion in adult male rats in vivo and a hypoxia-reoxygenation (H/R) injury in H9c2 cardiomyocytes in vitro. We found that DMY pretreatment provided significant protection against I/R-induced injury, including enhanced antioxidant capacity and inhibited apoptosis in vivo and in vitro. This effect correlated with the activation of the PI3K/Akt and HIF-1α signaling pathways. Conversely, blocking Akt activation with the PI3K inhibitor LY294002 effectively suppressed the protective effects of DMY against I/R-induced injury. In addition, the PI3K inhibitor partially blocked the effects of DMY on the upregulation of Bcl-2, Bcl-xl, procaspase-3, -8, and -9 protein expression and the downregulation of HIF-1α, Bnip3, Bax, Cyt-c, cleaved caspase-3, -8, and -9 protein expression. Collectively, these results showed that DMY decreased the apoptosis and necrosis by I/R treatment, and PI3K/Akt and HIF-1α plays a crucial role in protection during this process. These observations indicate that DMY has the potential to exert cardioprotective effects against I/R injury and the results might be important for the clinical efficacy of AMI treatment. [ABSTRACT FROM AUTHOR]

Experiments have been carried out to compare the stabilization effect of two flavonoid type natural antioxidants, dihydromyricetin (DHM) and quercetin (Q) in polyethylene (PE). Additive concentrations changed between 0 and 500 ppm in several steps and 1000 ppm Sandostab PEPQ phosphorus containing secondary stabilizer was also added to each compound. Both antioxidants are very efficient stabilizers for PE, sufficient melt stability was achieved already at 50 ppm DHM content. At small concentrations dihydromyricetin proved to be more efficient melt stabilizer and it protected the secondary antioxidant better than quercetin. In spite of its better efficiency in melt stabilization, polymers containing DHM had the same residual stability as those prepared with quercetin. Accordingly, the larger efficiency does not result from the larger number of active phenolic hydroxyls in the molecule, but from interactions with the phosphorous secondary stabilizer that is stronger or at least different for DHM than quercetin. In spite that DHM is a white powder, it gave the polymer a brownish color which became deeper with increasing number of extrusions and additive content. Nevertheless, both natural antioxidants can be used efficiently for the stabilization of polymers in applications in which color is of secondary importance. [ABSTRACT FROM AUTHOR]

The effect of myricetin (MY) and dihydromyricetin (DMY) on the activity of pepsin was evaluated. The interaction between MY and DMY with pepsin was investigated using multispectroscopic and molecular docking methods. Binding constant, number of binding sites, and thermodynamic parameters at different temperatures were measured. MY and DMY have no significant effect on the activity of pepsin. The results of fluorescence quenching revealed that MY and DMY could strongly quench the intrinsic fluorescence of pepsin through a static quenching procedure. The thermodynamic parameters showed that hydrophobic interactions played main roles in the interaction of MY with pepsin, while the Van der Waals' interactions and hydrogen bonds were mainly interactions between DMY and pepsin. The analysis of UV absorption spectra and molecular docking showed that MY and DMY induced conformational changes of pepsin. The synchronous fluorescence spectra indicated that microenvironment around tyrosine and tryptophan residues of pepsin were not changed obviously. The energy transfer from pepsin molecules to MY or DMY occurs with high probability. Displacement experiments indicated that DMY and MY could bind to the same site of pepsin. [ABSTRACT FROM AUTHOR]

Nuclear factor-kappa B (NF-κB) has been reported to play a pivotal role in many physiological processes including inflammation, apoptosis, and angiogenesis. We discovered a potent natural NF-κB inhibitor, dihydromyricetin, from the traditional herb Ampelopsis grossedentata, which has a long history of use in food and medicine. In this study, we demonstrated the effect of dihydromyricetin on NF-κB activation in TNF-α-induced HeLa cells. Dihydromyricetin was found to markedly inhibit the phosphorylation and degradation of the inhibitor of NF-κB alpha (IκBα), and subsequent nuclear translocation of p65. Dihydromyricetin also has an impact on upstream signaling of IKK through the inhibition of expression of adaptor proteins, TNF receptor-associated factor 2 (TRAF2), and receptor-interacting protein 1 (RIP1). Furthermore, the current results reveal that dihydromyricetin led to the downregulation of target genes involved in inflammation, proliferation, as well as potentiation of TNF-α-induced apoptosis through suppressing the activation of NF-κB. In conclusion, our data indicate that dihydromyricetin may be a potentially useful therapeutic agent for inflammatory diseases. [ABSTRACT FROM AUTHOR]

The inhibitory effects of dihydromyricetin purified from Ampelopsis grossedentata on melanogenesis and its antioxidant characteristics were investigated. Assays of tyrosinase activities and melanin content in B16F10 mouse melanoma cells were carried out spectrophotometrically, and the expression of melanogenesis-related proteins was determined by Western blotting. The possible signaling pathways involved in dihydromyricetin-mediated depigmentation were also examined using specific protein kinase regulators. The results revealed that dihydromyricetin effectively suppresses intracellular tyrosinase activity and decreases melanin amount in cells. Dihydromyricetin also exhibits antioxidant properties and effectively decreases intracellular reactive oxygen species (ROS) and reactive species (RS) levels. Our results indicated that dihydromyricetin inhibits melanogenesis through its antioxidant properties and by downregulating protein kinase A (PKA), protein kinase C (PKC), and mitogen-activated protein kinases (MAPK) signaling pathways. The present study indicates that dihydromyricetin has the potential to be developed into a depigmentation skin care product. [ABSTRACT FROM AUTHOR]

UVA irradiation stimulates the production of reactive oxygen species (ROS), which results in oxidative stress, cellular damage, and ultimately, cell death by interacting with other intracellular molecules. In the present study, we explored the protective role of Dihydromyricetin (DHM,1.25–10 μM) against UVA-induced inflammation response and apoptosis in the human keratinocyte cell line (HaCaT cells) and the underlying mechanisms. DHM pre-treatment significantly increased HaCaT cell viability and suppressed UVA-induced production of inflammatory cytokines, as well as apoptosis of HaCaT cells. Moreover, DHM pre-treatment prohibited UVA-induced ROS generation, mitochondrial membrane potential decrease, and the phosphorylation of histone H2AX(γ-H2AX), a sensitive biomarker for DNA damage. Meanwhile, DHM could enhance GSH-Px activity and decrease the content of MDA in UVA ray treated HaCaT cells. Notably, the anti-apoptotic potential of DHM was correlated with an increased expression of anti-apoptotic proteins (Bcl-2 and Bcl-xl) and decreased expression of pro-apoptotic proteins (Bax), as well as the inhibition of caspase proteins activation. Additionally, DHM treatment also prevented the nuclear translocation of NF-κB/p65 and the phosphorylation of c-Jun. N-terminal kinase (JNK), which is an upstream modulator of NF-κB/p65. Therefore, DHM may be potentially useful in the prevention of UVA-induced skin damage. [ABSTRACT FROM AUTHOR]

Aims Dihydromyricetin (DMY), a flavonoid component isolated from Ampelopsis grossedentata , was recently reported to ameliorate nonalcoholic fatty liver disease (NAFLD) in patients. However, the underlying mechanisms of this action remain unknown. Here, we evaluate the effect of DMY on an in vitro model of NAFLD and investigate the signal transduction pathways underlying DMY treatment. Main methods Oleic acid (OA) induced hepatic steatosis was established in L02 and HepG2 cells as in vitro model of NAFLD. Cell apoptosis, lipid accumulation and oxide stress were evaluated by flow cytometry, oil red O staining, and cellular biochemical assays, respectively. Signaling pathways involved in lipid metabolism including PPARγ, AMPK, and AKT were investigated by Western blot and RT-qPCR. Key findings DMY protected cells against apoptosis and lipid accumulation induced by oleic acid. DMY decreased the levels of cellular triglycerides (TG), cholesterol (TC) and malondialdehyde (MDA), while at the same time increasing the level of superoxide dismutase (SOD). DMY suppressed the expression of PPARγ and the phosphorylation of AKT, and promoted the phosphorylation of AMPK. Significance Our study suggests that DMY ameliorates OA-induced hepatic steatosis by inhibiting cell apoptosis, lipid accumulation and oxide stress. Furthermore, the effect of DMY is likely associated with its role in the regulating of PPARγ, AMPK and AKT signaling pathways. [ABSTRACT FROM AUTHOR]

This work reports the purification of dihydromyricetin (abbreviation: DMY) by the recrystallization method, with a yield of secondary recrystallization of up to 77 %. The products were confirmed by element and spectral analysis. The results showed a sharp R-bond absorption peak located around the near-ultraviolet band, which is close to K-bond absorption, illustrating the occurrence of a large conjugation of carbonyl with adjacent phenol and hydroxyl. This was further confirmed by the infrared (IR) spectrum, i.e., the carbonyl stretching vibration peaks were red-shifted from 1700 to 1641 cm. The standard thermodynamic energy was determined to be Δ U[DMY(s), 298.15 K] = −(5437.44 ± 5.14) kJ mol by an oxygen bomb calorimeter. Furthermore, the standard molar enthalpy of combustion was calculated to be Δ H[DMY(s), 298.15 K] = −(5434.96 ± 5.14) kJ mol, and the standard molar formation enthalpy of DMY was estimated to be Δ H[DMY(s), 298.15 K] = −(2182.67 ± 5.33) kJ mol. [ABSTRACT FROM AUTHOR]

As a natural flavonoid in Ampelopsis grossedentata, dihydromyricetin (DHM, 2R,3R-3,5,7,3′,4′,5′-hexahydroxy-2,3-dihydroflavonol) was observed to increase the viability of •OH-treated mesenchymal stem cells using a MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl] assay and flow cytometry analysis. This protective effect indicates DHM may be a beneficial agent for cell transplantation therapy. Mechanistic chemistry studies indicated that compared with myricetin, DHM was less effective at ABTS+• (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical) scavenging and reducing Cu2+, and had higher •O2− and DPPH• (1,1-diphenyl-2-picrylhydrazyl radical) scavenging activities. Additionally, DHM could also chelate Fe2+ to give an absorption maximum at 589 nm. Hence, such protective effect of DHM may arise from its antioxidant activities which are thought to occur via direct radical-scavenging and Fe2+-chelation. Direct radical-scavenging involves an electron transfer (ET) pathway. The hydrogenation of the 2,3-double bond is hypothesized to reduce the ET process by blocking the formation of a larger π-π conjugative system. The glycosidation of the 3–OH in myricitrin is assumed to sterically hinder atom transfer in the •O2− and DPPH• radical-scavenging processes. In DHM, the Fe2+-chelating effect can actually be attributed to the 5,3′,4′,5′–OH and 4–C=O groups, and the 3–OH group itself can neither scavenge radicals nor chelate metal. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Objective To explore the effect of dihydromyricetin (DMY) on the cholesterol efflux in macrophage derived foam cells and analyze the possible mechanisms. Methods RAW 264.7 macrophages were incubated by oxidized low density lipoprotein (ox-LDL, 50 mg/L) for 48 h to induce foam cells. Subsequently, the foam cells were subdivided into control group (RPMI1640 media) and DMY 1-4 groups (10, 20, 40 and 80 μmol/L) and cultured for 24 h. Cholesterol efflux from foam cells was examined by [3H] labed cholesterol. The high performance liquid chromatography assay was used to test the cellular contents of free cholesterol (FC), cholesteryl ester (CE) and total cholesterol (TC). The expression of ATP-binding cassette transporter A1 (ABCA1) was measured by Western blot assay. Results Compared with control group, cholesterol efflux was significantly increased, the content of FC, TC CE and CE/TC ratio were significantly decreased and expression of ABCA1 was significantly up-regulated in dose dependent manner in DMY (20, 40 and 80 μmol/L) groups (P < 0.05). There were no significant differences in cholesterol efflux, the content of FC, TC and CE, and expression of ABCA1 between control group and DMY (10 μmol/L) group of foam cells (P > 0.05). Conclusion DMY promotes the cholesterol efflux in the macrophage derived foam cells, which may be related with the increase of ABCA1 induced by DMY. [ABSTRACT FROM AUTHOR]

Dihydromyricetin (DMY) is a well-known natural flavonoid antioxidant and bacteriostat. However, its practical application, e.g., as a preservative, is limited by poor bioavailability due to its low solubility. To overcome this limitation, a solid dispersion formulation of DMY (DMYSD) was prepared from polyvinylpyrrolidone (PVP) K30, and characterized using spectroscopic, thermoanalytical, antioxidant and bacteriostatic methods. The results showed that the enhanced solubility of DMYSD (64.51 mg/mL), which was more than 90 times that of DMY, could be attributed to reduced crystallinity of the DMY solid dispersion. Immersion of sturgeon fillets in DMYSD solution (5.12 mg/mL) demonstrated that the shelf life of the treated fish stored at 4 °C could be extended by more than 3 d compared with pure DMY. Bacterial enumeration and physicochemical analyses of the treated stored fish indicated that the increased shelf life was due to reduced protein and lipid oxidation, and suppression of bacterial growth, by the solid dispersion. • The solubility of dihydromyricetin in water was increased 90-fold via solid dispersion. • The bioactivity of dihydromyricetin was improved after the preparation of solid dispersions. • Sturgeon fillets treated with solid dispersion had a minimum 3-day shelf life extension. [ABSTRACT FROM AUTHOR]

We have previously reported social isolation induces anxiety-like behavior, cognitive decline, and reduction in brain ATP levels in mice. These changes were ameliorated by treatment with dihydromyricetin (DHM), a compound that positively modulates γ-aminobutyric A (GAB A A) receptor. To gain further insight into the subcellular mechanisms underlying these changes, we utilized a social isolation-induced anxiety mouse model and investigated changes in mitochondrial oxidative capacity via the electron transport chain. We found that 4 weeks of social isolation decreased ATP levels by 43% and succinate dehydrogenase capacity by 52% of the control, while daily DHM (2 mg/kg oral) administration restored succinate dehydrogenase capacity. These results suggest that social isolation decreased mitochondrial capacity to generate ATP. DHM can be developed to be a therapeutic against anxiety and mitochondrial stress. [ABSTRACT FROM AUTHOR]

Albumin is widely used in clinics due to its demonstrated biological safety and functional flexibility. Hydrogels derived from natural albumin possess high moisture retention ability and good biodegradability, making albumin ideal biomaterials compared with synthetic polymers. Herein, by reducing disulfide bonds in bovine serum albumin molecules with glutathione and re-oxidizing the free thiols using dimethyl sulfoxide (DMSO) as additional oxidant, three-dimensional network was assembled, leading to the formation of hydrogel. Meanwhile, DMSO is also an excellent solvent for many drugs, and the hydrophobic drug dihydromyricetin (DMY) can be well dissolved in DMSO. During the crosslinking reaction, DMSO participated in fabricating a porous albumin hydrogel network. At the same time, increased loading of DMY and sustained release of DMY were achieved, improving bioavailability of hydrophobic drug DMY. Rheological test and cytotoxicity assay proved excellent elasticity and biocompatibility of the hydrogel. Self-healing property and narrow-needle injection provided potential application of the hydrogel as biomedical materials. This method for formation hydrogels and in situ loading of drugs may expand to preparing other drug loaded hydrogels and find wide applications. [Display omitted] • Disulfide bonds in bovine serum albumin molecules was reduced by glutathione. • The free thiols were re-oxidized using dimethyl sulfoxide (DMSO) as oxidant. • Three-dimensional network was assembled and hydrogel was formed. • Hydrophobic drug dihydromyricetin can be well dissolved in DMSO. • Increased loading of dihydromyricetin and sustained release of dihydromyricetin were achieved. [ABSTRACT FROM AUTHOR]

Dihydromyricetin (DHM) is a natural bioactive flavonoid extracted from Ampelopsis Grossedentata , a commonly used Chinese herbal medicine. It has multiple beneficial pharmacological effects including lowering blood glucose and lipid, as well as anti-inflammation, anti-oxidation and hepato-protection. In this study, we elucidated its actions on mitochondrial dynamics and browning of white adipose. In the experiments in vivo , six-week-old male C57BL/6 mice were fed with normal diet (ND), high-fat diet (HFD), or HFD with intragastric administration of DHM (250 mg/kg.d−1); in the experiments in vitro , 3T3-L1 and mouse primary preadipocytes were induced and treated with various concentrations of DHM. The mouse metabolic phenotype, lipid accumulation, the browning and mitochondrial dynamics of white adipocytes were examined. It was found that DHM treatment reduced body weight and fat mass, improved glucose tolerance, insulin resistance and cold tolerance in mice with obesity. DHM treatment increased the expressions of classical brown adipocyte markers (UCP-1, PGC-1α, PRDM16) and mitochondrial dynamics-related proteins (DRP1, FIS1, OPA1, MFN2) in adipose tissue. Likewise, DHM treatment induced the differentiation of mature 3T3-L1 cells into brown-like adipocytes and also enhanced the expressions of mitochondrial dynamics-related proteins in vitro. Moreover, the pro-browning effect of DHM can be abrogated by mitochondrial fission inhibitor Mdivi-1. These findings indicate that DHM treatment induces the browning-remodeling of white adipose by enhancing mitochondrial fission and manifests an anti-obesity property via pro-browning mediated by mitochondrial fission, which implies it may play important roles in prevention and therapy of obesity and related diseases. [Display omitted] • DHM reduces body weights and fat accumulation, improves the homeostasis of glycolipid metabolism and insulin resistance. • DHM promotes the browning of WAT both in vitro and in vivo. • DHM induces the browning-remodeling of WAT by enhancing the mitochondrial fission. [ABSTRACT FROM AUTHOR]

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been steadily increasing, and it has become one of the most prevalent chronic liver diseases worldwide. Recent studies have shown that dihydromyricetin (DHM) is influential in treating NAFLD. The purpose of this review was to describe how DHM prevents and treats NAFLD and its potential mechanisms through an in-depth summary of preclinical in vitro and in vivo studies. A brief overview of DHM's potential role in NAFLD involves regulation of lipid/glucose metabolism, possibly via anti-inflammatory or sirtuin-dependent mechanisms. For NAFLD, there is currently no effective and approved medication for therapy. DHM has the characteristics of liver protection, antioxidation, anti-inflammatory and apoptosis-regulatory benefits, which provides a new idea for the treatment of NAFLD. With the increasing interest in utilizing natural products to prevent and control liver diseases, our work aims to provide new ideas for the treatment of NAFLD and accelerate its translation from bench to bedside. [ABSTRACT FROM AUTHOR]

The anticancer drug methotrexate (MTX) is known to cause hepatotoxicity as a possibly fatal adverse effect that hinders its clinical application. Although the natural flavonoid, dihydromyricetin (DHM), has antioxidant and anti-inflammatory effects; its role against MTX-induced hepatotoxicity has not been explored yet. For this, rats were administrated DHM orally for two weeks at a dose of 300 mg/kg per day, with or without a single i.p. injection of 40 mg/kg MTX on the 9th day of the experiment. MTX caused deterioration in liver structure and function, depicted by an increase in liver enzymes; ALT and AST. Moreover, MTX induced oxidative stress, shown by increasing malondialdehyde and decreasing reduced glutathione and total antioxidant capacity, initiated the inflammatory response via upregulated expression of Toll-like receptor 4 (TLR4) and its downstream transcription factor, nuclear factor-kappa B (NF-κB p65). Consequent to TLR4 signaling cascade, Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammosome was activated and caused caspase 1 mediated transformation of proinflammatory cytokines interleukin 1β (IL-1β) and interleukin 18 (IL-18) into their active forms. Interestingly, administering DHM with MTX improved liver structure and function, as well as significantly decreased all oxidative stress and inflammatory signaling. Collectively, DHM possesses antioxidant and anti-inflammatory properties that can ameliorate MTX-induced hepatotoxicity, through down-regulation of liver TLR4/NF-κB and therefore prohibit activation of NLRP3/caspase 1 pathway. [Display omitted] • Hepatotoxicity is the major side effect of methotrexate chemotherapy that hinders its clinical application. • Dihydromyricetin is a natural flavonoid with antioxidant and anti-inflammatory effects. • Administration of dihydromyricetin with methotrexate attenuates induced liver toxicity via down-regulation of hepatic TLR4/NF-κB and NLRP3/caspase 1 signaling pathways. [ABSTRACT FROM AUTHOR]

Objective: Dihydromyricetin (DMY), also called Ampelopsin, which was extracted from Ampelopsis grossedentata, has been demonstrated to have a protective effect against cell oxidative injury and cell apoptosis in vitro. In the present study, we tried to study the role of DMY on apoptosis of vascular smooth muscle cells (VSMCs) induced by hydrogen peroxide (H 2 O 2 ) and explore the underlying mechanisms., Methods: Apoptotic cells were detected by Hematoxylin and Eosin (H.E.) staining, Hoechst 33342 staining, and Annexin V-fluorescein isothiocyanate binding assay. The intracellular reactive oxygen species (ROS) level was estimated through fluorescence assay. The mRNA and protein expression of Caspase-3, Caspase-9, Bcl-2, and Bax were determined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot., Results: The results showed that the pretreatment of VSMCs with DMY not only significantly increased cell viability, reduced intracellular ROS release, alleviated the morphological changes of apoptosis, and decreased the apoptosis rate, but also upregulated Bcl-2 expression and downregulated Caspase-3, Caspase-9, Bax expression, and ultimately attenuated the H 2 O 2 -stimulated apoptosis., Conclusion: The inhibition of DMY on VSMC apoptosis may be mediated by ROS scavenging and the activation of the mitochondrial apoptotic signaling pathway.

Multicomponent crystals of a chiral drug with non-chiral components have attracted increasing attention in the application of enantiomer purification and regulation of the physicochemical properties of crystalline materials. Crystalline solid solutions provide opportunities for fine-tuning material properties because of continuously adjustable component stoichiometry ratios. The synthesis, crystal structure, thermodynamics and solid-state enantioselectivity of a series of multicomponent crystals of chiral dihydromyricetin (DMY) with caffeine (CAF) or theophylline (THE) were investigated and the results reveal how the subtle change of molecular structure of the coformer dictates the enantiomer selectivity in multicomponent cocrystals. A series of multicomponent cocrystal solvates of chiral DMY with CAF and THE were synthesized by the slurry cocrystallization method in acetonitrile. Although most racemic mixtures crystallize as racemic compounds or conglomerates, both DMY-CAF and DMY-THE crystallize as chiral solid solutions, unveiled by pseudo-binary melt phase diagrams and pseudo-ternary solution phase diagrams. Crystal structures of Rac-DMY-CAF, R,R-DMY-CAF, Rac-DMY-THE and R,R-DMY-THE are reported for the first time via single-crystal X-ray diffraction, displaying two distinct types of solid solution differing in mixing scale of enantiomers spanning several orders of magnitude. Surprisingly, this remarkable impact on enantiomer discrimination was simply achieved by the reduction of a methyl group of CAF to the THE coformer, which was further rationalized from their crystal structures and intermolecular interactions. Collectively, this work has demonstrated that a subtle change in the molecular structure of a coformer can regulate enantioselectivity in crystalline materials, guiding the purification of chiral racemic compounds via the cocrystallization method and the design of solid-solution crystalline materials., (open access.)

Dihydromyricetin (DHM), a dihydroflavonoid compound, exhibits a variety of biological activities, including antitumor activity. However, the effects of DHM on mammalian reproductive processes, especially during early embryonic development, remain unclear. In this study, we added DHM to porcine zygotic medium to explore the influence and underlying mechanisms of DHM on the developmental competence of parthenogenetically activated porcine embryos. Supplementation with 5 μM DHM during in vitro culture (IVC) significantly improved blastocyst formation rate and increased the total number of cells in porcine embryos. Further, DHM supplementation also improved glutathione levels and mitochondrial membrane potential; reduced natural reactive oxygen species levels in blastomeres and apoptosis rate; upregulated Nanog, Oct4, SOD1, SOD2, Sirt1, and Bcl2 expression; and downregulated Beclin1, ATG12, and Bax expression. Collectively, DHM supplementation regulated oxidative stress during IVC and could act as a potential antioxidant during in vitro porcine oocytes maturation.

The solubility of dihydromyricetin in the binary system of ethanol and water was measured by using UV spectrophotometric method at the maximum absorption wavelength of 290 nm from 288.15 K to 323.15 K. The solubility increases with temperature and mole fraction of ethanol in the binary system. The calculated solubility data of dihydromyricetin were computed by using three models, the modified Apelblat equation, the Buchowski–Książczak λH equation, and the Jouyban–Acree equation. The modified Apelblat equation and λH equation are more suitable for correlating experimental solubility data of dihydromyricetin. The activity coefficients were calculated based on the results of thermal properties of DMY (obtained by DSC), presenting good consistency with the solubility behavior. In this study, the enthalpy and entropy of a solution were evaluated using the van't Hoff equation. The course of dihydromyricetin dissolving in the binary system in the experimental temperature range was endothermic. [ABSTRACT FROM AUTHOR]

Ampelopsis grossedentata (Hand.-Mazz.) W.T. Wang has long been used as a traditional Chinese medicinal herb among the indigenous people in the Yangtze River region of China. Dihydromyricetin (DMY) is the most abundant (approximately 30%) and bioactive constituent in A. grossedentata (Hand.-Mazz.) W.T. Wang, and recent studies have demonstrated its various pharmacological activities. In the present study, a first specific, sensitive, rapid and reliable LC–MS/MS method for the determination of DMY in rat plasma was developed and validated. The plasma samples were prepared with protein precipitation method, and chromatographic separation was performed on a Welch Ultimate XB-C18 column (50 × 2.1mm, 5 μm) using a gradient elution with water and acetonitrile. The mass spectrometry (MS) analysis was conducted in negative ionization mode with multiple reaction monitoring (MRM) transitions at m/z 319.1 → 192.8 for DMY and m/z 609.0 → 301.2 for rutin (IS). The plasma concentration profiles and pharmacokinetic parameters were analyzed after oral administration of dextroisomer and racemate DMY at the dose of 100 mg/kg in rats. The method validation was conducted over the calibration range of 10.0–5000 ng/ml with the intra- and inter-day precision and accuracy within 12.0% (RSD) and 5.6% (RE). The recoveries, matrix effect and stability under different conditions were all proved acceptable. The values of T max , AUC 0-∞ and Vd were significantly different between the groups of dextroisomer and racemate DMY ( P < 0.05), and pharmacokinetic results revealed their poor absorptions into blood, probably high tissue distributions and slow elimination processes. The present study will provide helpful information for the further studies and future clinical applications of DMY. [ABSTRACT FROM AUTHOR]

Ampelopsis grossedentata , a medicinal and edible plant, has been widely used in China for hundreds of years, and dihydromyricetin is the main active ingredient responsible for its various biological actions. We investigated the effects of dihydromyricetin on glucose and lipid metabolism, inflammatory mediators and several biomarkers in nonalcoholic fatty liver disease. In a double-blind clinical trial, sixty adult nonalcoholic fatty liver disease patients were randomly assigned to receive either two dihydromyricetin or two placebo capsules (150 mg) twice daily for three months. The serum levels of alanine, aspartate aminotransferase, γ-glutamyl transpeptidase, glucose, low-density lipoprotein-cholesterol and apolipoprotein B, and the homeostasis model assessment of insulin resistance (HOMA-IR) index were significantly decreased in the dihydromyricetin group compared with the placebo group. In the dihydromyricetin group, the serum levels of tumor necrosis factor-alpha, cytokeratin-18 fragment and fibroblast growth factor 21 were decreased, whereas the levels of serum adiponectin were increased at the end of the study. We conclude that dihydromyricetin supplementation improves glucose and lipid metabolism as well as various biochemical parameters in patients with nonalcoholic fatty liver disease, and the therapeutic effects of dihydromyricetin are likely attributable to improved insulin resistance and decreases in the serum levels of tumor necrosis factor-alpha, cytokeratin-18, and fibroblast growth factor 21. [ABSTRACT FROM AUTHOR]

Skeletal muscle insulin resistance (SMIR) plays an important role in the pathogenesis of type 2 diabetes. Dihydromyricetin (DHM), a natural flavonoid, exerts various bioactivities including anti-oxidative and hepatoprotective effects. Herein, we intended to determine the effect of DHM on SMIR and the underlying mechanisms. We found that DHM increased the expression of phosphorylated insulin receptor substrate-1, phosphorylated Akt and glucose uptake capacity in palmitate-treated L6 myotubes under insulin-stimulated conditions. The expression of light chain 3, Beclin 1, autophagy-related gene 5 (Atg5), the degradation of sequestosome 1 and the formation of autophagosomes were also upregulated by DHM. Suppression of autophagy by 3-methyladenine and bafilomycin A1 or Atg5 and Beclin1 siRNA abolished the favorable effects of DHM on SMIR. Furthermore, DHM increased the levels of phosphorylated AMP-activated protein kinase (AMPK) and Ulk1, and decreased phosphorylated mTOR levels. AMPK inhibitor compound C (CC) and AMPK siRNA abrogated DHM-induced autophagy, subsequently suppressed DHM-induced SMIR improvement. Additionally, DHM inhibited the activity of F1F0-ATPase thereby activating AMPK. Finally, the results of in vivo study conducted in high fat diet-fed rats were consistent with the findings of in vitro study. In conclusion, DHM improved SMIR by inducing autophagy via the activation of AMPK signaling pathway. [ABSTRACT FROM AUTHOR]

Three new compounds, (2 S ,3 S )-5-methyldihydromyricetin ( 1 ), (2 S ,3 S )-5-methyldihydromyricetin-3′- O -sulfate ( 2 ) and β- d -glucopyranoside, 3-methyl, but-3-en-1-yl 4- O -α- l -rhamnopyranosyl ( 3 ) have been isolated from the Limonium caspium , together with dihydromyricetin ( 4 ), dihydromyricetin-3′- O -sulfate ( 5 ), myricetin-3′- O -sulfate ( 6 ), 5-methylmyricetin ( 7 ), myricetin ( 8 ), myricetin-3- O -β-glucoside ( 9 ), as well as phloridzin ( 10 ), and tyramine ( 11 ). Compounds 5 and 6 were isolated for the first time as acids. This is the first report of all these compounds from this plant. Their structures were established by extensive NMR studies ( 1 H NMR, 13 C NMR, DEPT, 1 H– 1 H COSY, HSQC, HMBC) as well as HRESIMS. All isolated compounds were evaluated for their antibacterial, antifungal, antimalarial and antileishmanial activities. Compounds 7 , 8 and 9 exhibited good antifungal activity against Candida glabrata with IC 50 values of 6.79, 15.37 and 8.53 μg/mL, respectively. Compound 8 displayed significant antimalarial activity against resistant and sensitive strains of Plasmodium falciparum with IC 50 values of 1.82 and 1.51 μg/mL, respectively. Compounds 1 , 4 , 6 , 8 and 9 showed excellent activity against Trypanosoma brucei with IC 50 values of 6.93, 9.65, 8.52, 7.67 and 6.31 μg/mL, respectively. To date, this is the first report on the phytochemical and biological activity of secondary metabolites from L. caspium . [ABSTRACT FROM AUTHOR]

Heading aims Dihydromyricetin (DMY) is the most abundant ingredient in vine tea. Here, we investigated the cytoprotective effects and possible mechanisms of DMY on hydrogen peroxide (H 2 O 2 )-induced oxidative stress damage in human umbilical vein endothelial cells (HUVECs). Materials and methods The percentage of cell viability was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. We determined the antioxidant properties of DMY by measuring the activity of superoxide dismutase (SOD) and malondialdehyde (MDA). Flow cytometry was used to measure apoptosis in HUVECs that were double stained with Hoechst 33342 and propidium iodide (PI). The generation of intracellular reactive oxygen species (ROS) was measured in 2′,7′-dichlorofluorescin diacetate (DCFH-DA)-loaded HUVECs using a fluorescent microscope. Moreover, the expression of apoptosis-related proteins was determined by Western blotting. In addition, the release of nitric oxide (NO) was analyzed using a commercial kit. Key findings HUVECs treated with H 2 O 2 had a notable decrease in cell viability that was attenuated when cells were pretreated with DMY (37.5–300 μM). DMY pretreatment significantly attenuated H 2 O 2 -induced apoptosis in HUVECs and inhibited intracellular ROS overproduction. Finally, pretreatment of cells with DMY prior to H 2 O 2 exposure resulted in the inhibition of p53 activation, followed by the regulation of the expression of Bcl-2 and Bax, the release of cytochrome c, the cleavage (activation) of caspase-9 and caspase-3, and then the suppression of PARP cleavage in H 2 O 2 -induced HUVECs. Significance Our study is the first to report that DMY can protect HUVECs from oxidative stress damage, an effect that is mediated by the mitochondrial apoptotic pathways. [ABSTRACT FROM AUTHOR]

A study on the efficiency of a flavonoid compound as an antioxidant stabilizer for polypropylene (PP) is reported. Dihydromyricetin (DMY), a 2,3-dihydroflavonol compound, was extracted from Ampelopsis grossedentata. Its stabilizing activity was compared with that of a commercial phenolic antioxidant. Thermogravimetric analysis and oxidation onset temperature measurements performed on samples, as well as a α,α-diphenyl-β-picrylhydrazyl radical assay on DMY, provided evidence for the effectiveness of the DMY. Based on our results, it could be used as an efficient and high value-added additive for PP. DMY was less toxic and highly effective as a good, natural antioxidant for PP. [ABSTRACT FROM AUTHOR]

Dihydromyricetin is the principle component of the Chinese herbal tea Teng-cha and a promising ingredient for functional food and nutraceuticals, but its low solubility limits its application potentials. This study explored enzymatic acylation of dihydromyricetin to improve its solubility in lipid systems. Acylation was achieved with several lipases with the synthesis of a major (>86%) product and a minor product. Isolation and purification of the products by preparative HPLC followed by LC–MS, 13 C NMR, 1 H NMR and 2 D-HSQC NMR analyses showed that the major product was a dihydromyricetin monoester with the acylation site at the 3-OH group of C ring. Quantum chemical calculations revealed that the 3-OH had the lowest antioxidant activity, and therefore acylation at this site was expected to have minimum impact on the antioxidant activity. Several factors, including solvent, acyl donor, enzyme origin, molar ratio of substrates and reaction temperature and time, exhibited significant effects on the initial rate, conversion yield and regioselectivity of the reaction. Acylation occurred only with vinyl acetate as the acyl donor, and highest conversion yields were achieved with immobilized Penicillium expansum lipase and Novozyme 435 with DMSO and acetonitrile being the best solvents. In general, the acylation results were found to be superior to previous reports on acylation of aglycone flavonoids with respects to conversion yield and regioselectivity. [ABSTRACT FROM AUTHOR]

Dihydromyricetin (DHM) is a flavonoid compound which possesses potent antitumor activity. In the present study, it was demonstrated that DHM significantly inhibited proliferation and induced apoptosis in mouse hepatocellular carcinoma Hepal-6 cells. Transforming growth factor β (TGF-β) is recognized as a major profibrogenic cytokine and is therefore a common target for drugs in the treatment of liver disease. The present study aimed to investigate whether TGF-β was involved in DHM-triggered cell-viability inhibition and apoptosis induction. An MTT assay was used to evaluate the viability of Hepal-6 cells following DHM treatment. TGF-β signalling is mediated by Smads and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is a crucial regulator of reactive oxygen species ROS production. TGF-β, Smad3, phosphorylated (p)-Smad2/3 and NOX4 protein expression levels were evaluated by western blot analysis. TGF-β and NOX4 gene expression levels were determined by quantitative polymerase chain reaction. The results indicated that DHM downregulated TGF-β, Smad3, p-Smad2/3 and NOX4 in a concentration-dependent manner. A cell counting assay indicated that DHM also inhibited Hepal-6 cell growth in a concentration-dependent manner. TGF-β expression was significantly decreased following DHM treatment. In conclusion, the results of the present study defined and supported a novel function for DHM, indicating that it induced cell apoptosis by downregulating ROS production via the TGF-β/Smad3 signaling pathway in mouse hepatocellular carcinoma Hepal-6 cells. [ABSTRACT FROM AUTHOR]

In this paper, the molecular geometry of dihydromyricetin was optimized based on density functional theory (DFT) using B3LYP functional combined with 6-31G group, based on which the active sites of dihydromyricetin molecules were calculated using water as solvent and the infrared spectra was analyzed. The electrostatic potential results showed that the nucleophilic active site of dihydromyricetin is located near the phenolic hydroxyl atom (H23); while the electrophilic active site is located in and near the oxygen atom (032). The results of frontline molecular orbital studies indicate that the highest occupied orbitals (HOMO) of dihydromyricetin molecules are located near ketone oxygen (032) and hydroxyl oxygen (020), indicating that these sites are susceptible to reaction with electrophilic reagents. And the lowest occupied orbitals (LUMO) are located in the carbon atom (C12, C13, C14) region, indicating that these regions can react with nucleophilic reagents. The results of the simplified Fukui function (f) confirm that the electrophilic activity of the f value of the oxygen atom reagents. The results of the simplified Fukui function (f) confirm that the electrophilic activity of the f value of the oxygen atom located in the C-OC bond is larger than those of the oxygen atom in other sites; while the f value of the carbon atom located in C8 is larger, so the nucleophilic activity is stronger in this site. The infrared spectral data of dihydromyricetin obtained by theoretical calculations do not differ much from those obtained experimentally, which indicates that the theoretical calculations may be reliable. Thus, it provides some theoretical reference for the experimental and theoretical studies of the relationship between the structure and properties of dihydromyricetin. [ABSTRACT FROM AUTHOR]

• TPGS-QS-SMEDDS is designed to enhance the absorptivity of DMY. • The DMY-S can regulate the increase of body weight, serum and hepatic TG. • The DMY-S can decrease the ratio of Firmicutes to Bacteroidetes. • The DMY-S could inhibit sphingomyelin, CoA, nicotinate acid, and pyruvate expressions. The present study aims to design a self-microemulsion delivery system (d-α-tocopheryl polyethylene glycol 1000 succinate - quillaja saponin) to enhance the absorptivity of dihydromyricetin (DMY-S), and to investigate its dietary intervention effect on high-fat-diet (HFD) fed mice. We find DMY-S can inhibit the increase of body weight and fat mass, preventing non-alcoholic fatty liver disease. Compared to the model group, the abundance of mice intestinal flora is mainly changed in certain bacterial genera of Firmicutes and Bacteroides, including norank_f_Muribaculaceae and Blautia. The result of metabolism analysis indicated that the expression levels of cincassiol B, creatine, pantothenic acid and aminobutyric acid in the liver tissues of mice treated with DMY-S showed a down-regulation. The DMY-S prevented hyperlipidemia in HFD mice mainly by affecting different pathways including glycerophospholipid metabolism, sphingolipid metabolism and pantothenate and CoA biosynthesis. [ABSTRACT FROM AUTHOR]