ABSTRACT
Size and surface modification are the two key factors affecting the effect of macrophages polarization induced by superparamagnetic iron oxide nanoparticles (SPIONs). The smaller the particle size, the better the polarization effect of SPIONs. Besides, the reasonable SPIONs surface modification method can also be used to enhance the polarization effect. In this study, SPIONs was prepared by solvothermal method and optimized by Box-Benhnken center combination design and response surface method. Furthermore, astragalus polysaccharide-superparamagnetic iron oxide nanocomplex (APS-SPIONs) was successfully constructed by EDC/NHS esterification method. The structure of APS-SPIONs was confirmed by dynamic light scatter and infrared spectrometer, and the contents of iron and polysaccharide were characterized by spectrophotometry. The effect of APS-SPIONs on inducing mouse macrophages RAW264.7 polarization was investigated by flow cytometry. The RAW264.7 macrophages-HepG2 human hepatoma cancer cells Transwell co-culture system was established to investigate APS-SPIONs improve anti-tumor function of macrophages in vitro, and the proliferation activity of APS-SPIONs on RAW264.7 detected by cell counting kit-8 (CCK-8) method. The results showed that the average particle size and zeta potential of APS-SPIONs were (82.93 ± 1.47) nm and (-24.00 ± 0.47) mV. Polysaccharide and Fe content were 8.69% and 7.04%, respectively. APS-SPIONs effectively induced the polarization of RAW264.7 into M1 type in vitro, improving the anti-tumor ability of macrophages in a co-culture system, without effecting the proliferation of macrophages. Our study provides a drug development strategy and preliminary research results to educate macrophages and reshape the tumor immune microenvironment to achieve tumor-killing effects.
ABSTRACT
To illuminate the similarities and differences between wild and cultivated Sarcandra glabra (S. glabra), we performed a comprehensively study on 26 batches of cultivated S. glabra and 2 batches of wild S. glabra. Chemical constituents and distribution characteristics of roots, stems and leaves in both wild and cultivated S. glabra were investigated through UHPLC-TOF-MS method. The result revealed that there were significant differences between roots, stems and leaves in S. glabra. And the chemical contents in the root part were less or even absence than those in leaf and stem, which suggested the root organ could be excluded as medicine. Meanwhile, the chemical contents of stems and leaves in cultivated S. glabra was sightly higher than that of wild samples. Therefore, cultivated S. glabra may have a high potential for substitution of wild S. glabra without affecting its pharmaceutical properties. In summary, our study could provide important information to the molecular basis for quality control of S. glabra.
ABSTRACT
Bexarotene is a synthetic analogue of retinoic acid and exerts protective effects on the nervous system. However, low bioavailability and poor solubility of the crystal type I form severely limits the application of bexarotene in the clinic. A co-amorphous sample of bexarotene-PVP-K30 was prepared and the structure was characterized by X-ray diffraction and infrared spectroscopy. To determine the pharmacokinetics and tissue distribution of bexarotene, an LC-MS method was established to profile and quantify bexarotene in plasma and tissues of SD rats. In vitro dissolution indicated that the co-amorphous form improved the dissolution of bexarotene in pure water 4.17-fold. After rats were orally administered bexarotene or bexarotene-PVP-K30 co-amorphous (equivalent to 30 mg·kg-1 bexarotene) the AUC of bexarotene was 7 034.89 and 10 174.03 μg·L-1·h respectively, the peak time was advanced from 7.33 h to 0.9 h with the amorphous form, and Cmax was enhanced from 627.76 to 3 011.88 μg·L-1. The co-amorphous form yielded higher concentrations of bexarotene in various tissues, especially brain, liver and kidney. Animal welfare and experimental procedures complied with the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. The results indicate that bexarotene-PVP-K30 co-amorphous improves the pharmacokinetic characteristics of bexarotene and provides preclinical data in support of bexarotene-PVP-K30 for the treatment of brain diseases.
ABSTRACT
In this study, we used Ultra Performance Liquid Chromatography-Time-of-Flight Mass Spectrometry(UPLC-TOF-MS)to identify the chemical constituents in both ethanol and water extract of Polygonum capitatum. A Waters ACQUITY UPLC BEH C₁₈ column(2.1 mm×100 mm,1.7 μm) was used for separation. The mobile phase was consisted of(A) 0.10% formic acid in water and(B)0.10% formic acid in acetonitrile, and the flow rate was 0.35 mL•min⁻¹. ESI source in negative ion mode was used for MS detection. Structural identification was carried out according to the accurate mass and matching with database. The results showed that flavonoids, polyphenols and lignans were the main components in both extracts. However, the chemical compositions of both extracts were different, e.g. there are less hydrolyzable tannins, loss of ellagic acid and more anthocyanins in ethanol extract. In a conclusion, this study provides an important scientific basis for identifying the active ingredients in P. capitatum, which also help to reveal the pharmacological effect of P. capitatum.