Mechanism of Xianglian Pills in improving dyslipidemia in obese mice induced by high-fat diet based on network pharmacology and intestinal flora / 中国中药杂志

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.

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 1.25×10-4 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 anti-inflammatory activities of methylhesperetin-7-alkyl ether analogues / 药学学报

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.