[Mechanism of Xianglian Pills in improving dyslipidemia in obese mice induced by high-fat diet based on network pharmacology and intestinal flora].

The present study aimed to investigate the effect of Xianglian Pills(XLP) on lipid metabolism in obese mice and explore the underlying mechanism based on network pharmacology and intestinal flora. Firstly, network pharmacology was used to predict the possible effect of XLP on obesity. Secondly, an obese mouse model induced by a high-fat diet was established to observe changes in mouse body weight, adiposity index, liver and adipose tissue pathology. Lipid profiles, liver and kidney function markers, insulin content, and the expression of recombinant uncoupling protein 1(UCP-1) and PR structural domain protein 16(PRDM16) were measured. The 16S rRNA gene sequencing technology was used to analyze the changes in the intestinal flora. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that XLP mainly played a role in improving obesity by regulating lipolysis, type 2 diabetes mellitus, and insulin resistance. The results of animal experiments showed that XLP significantly reduced body weight, adiposity, blood lipid levels, and serum insulin levels in obese mice, while enhancing the expression of UCP-1 and PRDM16 in adipose tissue without causing damage to the liver or kidneys. The 16S rRNA gene sequencing results showed that XLP decreased the Firmicutes/Bacteroidetes(F/B) ratio at the phylum level, increased the relative abundance of Akkermansia and Bacteroides at the family and genus levels, and reduced the abundance of Allobaculum. Therefore, XLP can effectively improve lipid metabolism disorders in high-fat diet-induced obese mice, and the mechanism is related to the improvement of brown adipose function, the browning of white fat, the accelerated lipid metabolism, and the improvement of intestinal flora. However, its effect on promoting the conversion of white adipose to brown adipose still needs to be further studied.

Self-catalyzed metal organic chemical vapor deposition growth of vertical ß-Ga2O3 nanowire arrays.

Self-catalyzed metal organic chemical vapor deposition (MOCVD) growth of Ga2O3 nanowires on GaN layers prepared on a sapphire substrate has been studied. Nanowire orientations are found to be growth temperature dominated. The vertical yields over total (VOT) curve shows a maximum peak beyond 70% around 480 °C, based on scanning electron microscope observations. X-ray diffraction patterns revealed a primary ß-(-201) normal orientation of as grown nanowires all over the studied temperature interval. Further transmission electron microscopy characterization had confirmed ß-(-201) normal axial orientation of these vertical nanowires, which have well crystallinity. The ß-(010)//GaN(110) in-plane epitaxial relationship is consistent with reported Ga2O3 film/nanowire growth. Nanowires crystallized in ß-[001] axial orientation were considered to be the inclined ones. Based on contrast experiments, the temperature dominated growth behavior is considered a thermodynamic process. The two observed crystalline orientation might have distinguishable but similar system energy, which results in coexistence of multi orientation nanowires over a large temperature span and an optimum temperature window for vertical ß-(-201) normal orientation. The presented optimized ß-Ga2O3 nanowire arrays with highest VOT close to 90% should effectively promote development of reliable high performance devices based on Ga2O3 nanowires.

Oxyresveratrol prevents lipopolysaccharide/d-galactosamine-induced acute liver injury in mice.

Oxyresveratrol (Oxy) is a natural polyhydroxystilbene abundant in mulberry that has anti-inflammation and anti-oxidant activities. We evaluated the protective effect of Oxy in the context of the lipopolysaccharide and d-galactosamine (LPS/d-GalN) induced acute liver injury. Oxy restricted the development of histopathological changes, markedly reduced the activity of alanine transaminase (ALT) and aspartate transaminase (AST), which are indicators of impaired liver function. Oxy significantly regulated the contents of oxidative stress related enzymes and products, and inhibited expressions of inflammatory mediators and cytokines. Oxy treatment diminished the Toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway in liver, activated the Kelch-like ECH-associated protein 1(Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, and increased expressions of heme oxygenase 1 (HO-1) and quinine oxidoreductase 1(NQO1). Pretreatment with Oxy decreased LPS/d-GalN stimulated hepatocyte apoptosis by efficaciously raising the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X (Bax) ratio, inhibiting the expression and activation of caspases, and activating the phosphoinoside-3-kinase (PI3K)-Akt pathway. Our results demonstrate the hepatoprotective efficacy of Oxy. The protection is mainly due to the prevention of TLR4/NF-κB pathway activation, induced activation of Keap1-Nrf2 signaling pathway, and decreased hepatocyte apoptosis. Oxy warrants further study as a potential therapeutic agent candidate for the management of acute liver injury.

Diosmetin exerts anti-oxidative, anti-inflammatory and anti-apoptotic effects to protect against endotoxin-induced acute hepatic failure in mice.

To investigate the effects and mechanism of diosmetin on acute hepatic failure (AHF), an AHF murine model was established through administration of lipopolysaccharides/D-galactosamine (LPS/D-GalN). In vitro, diosmetin scavenged free radicals. In vivo, diosmetin decreased mortality among mice, blocked the development of histopathological changes and hepatic damage, and suppressed levels of inflammatory mediators and cytokines. In addition, diosmetin prevented the expression of phosphorylated IKK, IκBα, and NF-κB p65 in the NF-κB signaling pathway, and JNK and p38 in the MAPK signaling pathway. Diosmetin also inhibited hepatocyte apoptosis. Thus, diosmetin exerts protective effects against endotoxin-induced acute hepatic failure in mice. The underlying mechanisms are antioxidation, NF-κB signaling inhibition, inflammatory mediator/cytokine attenuation, and hepatocyte apoptosis suppression. Diosmetin is thus a potential drug candidate for use in the treatment of acute hepatic failure.

[Synthesis and anti-inflammatory activities of methylhesperetin-7-alkyl ether analogues].

To investigate the relationship between the structures of methylhesperetin-7-alkyl ether analogues and their anti-inflammatory activities, nine new compounds, methyl-hesperetin (2), methylhesperetin-7-ethyl ether (3), 7-n-butyl ether (4), 7-n-hexyl ether (5), 7-n-octyl ether (6), 7-n-decyl ether (7), 7-n-dodecyl ether (8), 7-n-tetradecyl ether (9) and 7-n-hexadecyl ether (10), were synthesized with the lead compound of methylhesperidin (1). Their structures were confirmed by UV, 1H NMR, MS and HR-MS spectral data. The in vivo antiinflammatory activities of these compounds were tested on mouse paw edema induced by Freund's complete adjuvant (FCA) and mouse capillary permeability induced by acetic acid with po dose of 300 mg x kg(-1) x d(-1). The result indicated that the anti-inflammatory activities of the synthetic compounds increased firstly and then decreased with the elongating of the length of alkyl chain. After 25-day oral administration of compounds 6, 7 and 8, the inhibitory rates on mouse paw edema of adjuvant arthritis (AA) were 31.9%, 38.5%, 39.1%, respectively. They showed the concentrations of COX-2 in serum of AA mice respectively were 79.3, 75.4, 73.9 ng x L(-1) and the concentrations of PGE2 were in correspondence with 275.4, 258.9, 242.6 ng x L(-1). The inhibitory rates of compounds 6 and 7 on mouse capillary permeability induced by acetic acid were, respectively, 42.4% and 41.5% after 5-day oral administration. Compared with the lead compound of methylhesperidin, the anti-inflammatory activities of compounds 6, 7 and 8 were increased and showed an effective inhibition on the symptom of adjuvant arthritis and capillary permeability in mice.

Effect of 8-alkylberberine homologues on erythrocyte membrane.

8-alkylberberine homologues (Ber-C8-n, where n indicates carbon atom number of gaseous normal alkyl at 8 position, n = 0, 2, 4, 6, 8, 10, 12, or 16) were synthesized and their effects on the hemolysis of rabbit erythrocyte, the fluidity of membrane and the fluorescence of membrane protein were investigated by fluorescence analysis technique. Ber-C8-n with mediate length alkyl (4 < n < 10) exhibited obvious hemolysis effect on rabbit erythrocyte when their concentration exceed 1.25 x10(-4) mol/L, and Ber-C8-8 displayed the highest hemolysis effect among all tested homologues. All of Ber-C8-n influenced the fluidity of erythrocyte membrane to different extents, which exhibited an obvious dose-effect relationship. The effect of Ber-C8-n on fluidity increased as the length of alkyl chain was elongated and decreased gradually when the alkyl carbon atoms exceeded 8. The fluorescence of erythrocyte membrane protein was quenched by Ber-C8-n, which showed a similar changing tendency on membrane fluidity. Experiments in vitro suggested that disturbing effects of Ber-C8-n on the conformation and function of membrane protein leaded to the changes of membrane fluidity and stability, and then the membrane was broken down.

Synthesis and antimicrobial activity of 3-octyloxy-8-alkyljatrorrhizine derivatives.

By introducing octyloxy to C-3 and alkyl groups to C-8 of jatrorrhizine, a series of 3-octyloxy-8-alkyljatrorrhizine derivatives were synthesized and their antimicrobial activities were evaluated in vitro. The results indicated that the derivatives exhibited high antimicrobial activities, especially against Gram-positive bacteria. The 3-octyloxy-8-butyljatrorrhizine displayed the highest antimicrobial activity in all compounds. Their structure-activity relationships were discussed.