[Protective effect of ginsenoside Rg1 again PC-12 cells in OGD injury through mTOR/Akt/FoxO3 signaling pathway].

OBJECTIVE: To investigate the protective effect of ginsenoside Rg1 on oxygen-glucose deprivation (OGD) in PC-12 cells, and preliminarily discuss the potential molecular mechanism of mTOR/Akt/FoxO3 signaling pathway. METHOD: The OGD PC-12 cell model was established. The cell viability was measured by MTT assay. After the pretreatment with Rg1 with the concentration of 10, 20, 40 micromol x L(-1) for 24 h, the cell viability was observed. Lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) ac- tivity and malondialdehyde (MDA) level were detected by colorimetry assay. mTOR, p-Akt(ser473), p-Akt(tjr308), Akt, p-FoxO3, FoxO3 in cytoplasm and nucleus, and total FoxO3 protein expression were detected by Western blot assay. RESULT: OGD could significantly in- hibit cell proliferation in 4-24 h in a time-dependent manner. After pretreatment for 24 h, Rg1 (20, 40 micromol x L(-1)) could notably elevate the cell viability and SOD viability and reduce the LDH release and MDA content. Besides, Rg1 also inhibited OGD-induced mTOR and p-Akt(ser473) decreases. After treatment for 6 h, OGD could reduce FoxO3 phosphorylation and promote FoxO3 in cytoplasm. This data suggested that Rg1 could protect PC-12 cell injury through mTOR/p-Akt/FoxO3 signaling pathway. CONCLUSION: Ginsenoside Rg1 could attenuate OGD-induced PC-12 cell injury. Its action mechanism may be closely related to activation of mTOR/p-Akt/FoxO3 signaling pathway.

Mechanism of enhanced oral absorption of hydrophilic drug incorporated in hydrophobic nanoparticles.

Hydroxysafflor yellow A (HSYA) is an effective ingredient of the Chinese herb Carthamus tinctorius L, which has high water solubility and low oral bioavailability. This research aims to develop a hydrophobic nanoparticle that can enhance the oral absorption of HSYA. Transmission electron microscopy and freeze-fracture replication transmission election microscopy showed that the HSYA nanoparticles have an irregular shape and a narrow size distribution. Zonula occludens 1 protein (ZO-1) labeling showed that the nanoparticles with different dilutions produced an opening in the tight junctions of Caco-2 cells without inducing cytotoxicity to the cells. Both enhanced uptake in Caco-2 cells monolayer and increased bioavailability in rats for HSYA nanoparticles indicated that the formulation could improve bioavailability of HSYA significantly after oral administration both in vitro and in vivo.

Enhanced absorption of hydroxysafflor yellow A using a self-double-emulsifying drug delivery system: in vitro and in vivo studies.

Hydroxysafflor yellow A (HSYA), the main active ingredient of the safflower plant (Carthamus tinctorius L.), is a hydrophilic drug with low oral bioavailability. Water-in-oil-in-water (w/o/w) double emulsions may enhance the oral absorption of HSYA. In this study, we prepared a self-double-emulsifying drug delivery system (SDEDDS) to improve the absorption of HSYA. SDEDDS consists of water in oil emulsions and hydrophilic surfactants that can self-emulsify into w/o/w double emulsions in the aqueous gastrointestinal environment. Confocal laser scanning micrographs showed that spherical droplets were uniformly distributed in the dispersion medium with narrow particle size distribution and could form fine w/o/w double emulsions upon dilution in dispersion medium with gentle stirring. The dispersed oil droplets contained small dispersed aqueous droplets consistent with the characteristics of double emulsions. Furthermore, in vitro cellular experiments were performed to study the mechanism of the absorption promoting effect of SDEDDS. The accumulation of rhodamine-123 in Caco-2 cells was used to evaluate the efflux transport of p-glycoprotein inhibitor. Histopathologic studies on the rat intestine showed that SDEDDS can cause mucosal damage to a certain degree of toxicity, however this was not serious. These results suggest that SDEDDS can greatly improve the oral absorption of HSYA. Given the toxicity demonstrated to the small intestine, the formulation prescription should be improved to enhance security in the future.

2-Cyano-N,N-dimethyl-acetamide.

In the crystal structure of the title compound, C(5)H(8)N(2)O, mol-ecules are linked by weak C-H⋯O hydrogen bonds, forming a three-dimensional network.