Aucubin (
AU
) is the main active ingredient of
Aucuba japonica
which has showed many positive effects such as anti‐inflammation and liver protection. Non‐alcoholic fatty liver disease (
NAFLD
) is the most common cause of chronic liver disease. In this research, we explored the effects of
AU
on the tyloxapol‐induced
NAFLD
in mice and apolipoprotein C‐
III
(apoC‐
III
) induced‐3T3L1 cells. Tyloxapol (300 mg/kg) was injected to C57
BL
/6 mice with aucubin. The differentiated 3T3‐L1 cells were treated with or without aucubin after stimulation of apoC‐
III
(100 μg/mL). In results, aucubin inhibited hyperlipidaemia, oxidative stress and inflammation by influencing the content of total cholesterol (
TC
), triglyceride (
TG
), low density lipoprotein (
LDL
), very low density lipoprotein (
VLDL
), myeloperoxidase (
MPO
), superoxide dismutase (
SOD
), tumour necrosis factor receptor‐α (
TNF
‐α), interleukin‐1β (
IL
‐1β), and
IL
‐6 in blood.
AU
activated
NF
‐E2‐related factor 2 (Nrf2), peroxisome proliferator‐activated receptor α (
PPAR
α),
PPAR
γ and hemeoxygenase‐1 (
HO
‐1) and promoted the phosphorylation of adenosine 5′‐monophosphate‐activated protein kinase (
AMPK
α),
AMPK
β, acetyl‐CoA carboxylase (
ACC
) and protein kinase B (
AKT
). In conclusion,
AU
performed the function of hypolipidaemic by its obvious anti‐inflammation and antioxidant activity, which may become a kind of new drug targeting at
NAFLD
.
Chitosan (CS) has been extensively used as a protein drug and gene delivery carrier, but its delivery efficiency is unsatisfactory. In this study, a mannose ligand was used to modify CS, which could enhance the delivery efficiency of CS via mannose receptor-mediated endocytosis. A preventative anti-GRP DNA vaccine (pCR3.1-VS-HSP65-TP-GRP6-M2, pGRP) was condensed with mannosylated chitosan (MCS) to form MCS/pGRP nanoparticles. Nanoparticles were intranasally administered in a subcutaneous mice prostate carcinoma model to evaluate the efficacy on inhibition of the growth of tumor cells. The titers of anti-GRP IgG that lasted for 11 weeks were significantly higher than that for administration of CS/pGRP nanoparticles (p < 0.01) and intramuscular administration of a pGRP solution (p < 0.05) to mice. In addition, immunization with MCS/pGRP nanoparticles could suppress the growth of tumor cells. The average tumor weight (0.79 ± 0.30 g) was significantly lower than that in the CS/pGRP nanoparticle group (1.69 ± 0.15 g) (p < 0.01) or that in the pGRP group (1.12 ± 0.37 g) (p < 0.05). Cell binding and cellular uptake results indicated that MCS/pGRP nanoparticles bound with C-type lectin receptors on macrophages. MCS was an efficient targeting gene delivery carrier and could be used in antitumor immunotherapy.
Gene transfer mediated by mannosylated chitosan (MCS) is a safe and promising approach for gene and vaccine delivery. MCS nanoparticles based gene delivery system showed high in vivo delivery efficiency and elicited strong immune responses in mice. However, little knowledge about the cell binding, transfection efficiency and intracellular trafficking of MCS nanoparticles had been acquired. In this study, using gastrin-releasing peptide as a model plasmid (pGRP), the binding of MCS/pGRP nanoparticles to macrophages and the intracellular trafficking of MCS/pGRP nanoparticles in macrophages were investigated. MCS-mediated transfection efficiency in macrophages was also evaluated using pGL-3 as a reporter gene. The results showed that the binding and transfection efficiency of MCS nanoparticles in macrophages was higher than that of CS, which was attributed to the interaction between mannose ligands in MCS and mannose receptors on the surface of macrophages. Observation with a confocal laser scanning microscope indicated the cellular uptake of MCS/pGRP nanoparticles were more than that of CS/pGRP nanoparticles in macrophages. MCS/pGRP nanoparticles were taken up by macrophages and most of them were entrapped in endosomal/lysosomal compartments. After the nanoparticles escaping from endosomal/lysosomal compartments, naked pGRP entered the nucleus, and a few MCS might enter the nucleus in terms of nanoparticles. Overall, MCS has the potential to be an excellent macrophage-targeting gene delivery carrier.
A valid and encyclopaedic evaluation method for assessing the quality of Sanhuang Gypsum Soup (SGS) has been set up based on analysis of high-performance liquid chromatography (HPLC) fingerprint combined with the quantitative analysis of multicomponents by single marker (QAMS) method, hierarchical cluster analysis (HCA), and similarity analysis. 20 peaks of the common model were obtained and used for the similarity analysis and HCA analysis. Berberine was selected as an internal reference, and the relative correction factors of mangiferin, geniposide, liquiritin, epiberberine, coptisine, baicalin, palmatine, harpagosid, wogonoside, cinnamic acid, cinnamic aldehyde, baicalein, glycyrrhizic acid, and wogonin were established. The accuracy of quantitative analysis of multicomponents by the single-marker method was verified by comparing the contents of the fourteen components calculated by the external standard method with those of the quantitative analysis of multicomponents by the single-marker method. No significant difference was found in the quantitative results of the established quantitative analysis of multicomponents by a single-marker method and an external standard method. In summary, these methods were applied to evaluate the quality of SGS successfully. As a result, these evaluation methods have great potential to be widely used in the quality control of traditional Chinese medicines (TCM).
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