[Preparation and quality evaluation of comet-shaped hydroxy camptothecin-loaded amphiphilic block copolymer].

In this study, we used Shirasu porous glass membrane(SPG) as a template and hydroxy camptothecin (HCPT) as a model drug to prepare the comet-shaped Me PEG [methoxyl poly(ethylene glycol)]- PLGA [poly(lactic-co-glycolic acid)-HCPT amphiphilic block copolymer. Our method was optimized by the orthogonal design method. The partical size, zeta potential, drug-loaded content, yield, shape and status of the obtained comet-shaped Me PEG-PLGA-HCPT particles were further characterized by dynamic light scattering(DLS), scanning electron microscopy(SEM)/transmission electron microscopy (TEM), X-ray diffraction(XRD) and differential scanning calorimetry (DSC) et al, respectively. In vitro release was preliminary evaluated. MTT assay to preliminary evaluate the cytotoxicity of particles against human liver BEL-7402 cells. Based on these experimental results, the optimal preparation conditions contain: weight ratio of HCPT to Me PEG-PLGA was 1:1, nitrogen pressure was 100 k Pa and SPG membrane pore size was 1.1 µm. The particles exhibited a comet-shaped shape, fairly uniform size and were well dispersed. The drug-loading content was 46.2%, with yield of 96.4%, and zeta-31.4 m V. The distribution of HCPT in particles was very uniform, and HCPT showed a amorphous state existed in particles. The release behavior in vitro showed sustained releasing, and with the drug loading content in proportion to the release of the drug. MTT test indicated that the HCPT-loaded comet-shaped particles had enhanced the cytotoxicity against human liver BEL-7402 cells relatively to the HCPT-loaded spherical particles in vitro. The results showed a promising potential application of the preparation in clinical treatment of tumor.

Platycodin D Ameliorates Cognitive Impairment in Type 2 Diabetes Mellitus Mice via Regulating PI3K/Akt/GSK3ß Signaling Pathway.

Objectives: The aim of this study was to investigate the ameliorative effect of platycodin D (PD) on cognitive dysfunction in type 2 diabetes mellitus (T2DM) and its potential molecular mechanisms of action in vivo and in vitro. Materials and methods: An animal model of cognitive impairment in T2DM was established using a single intraperitoneal injection of streptozotocin (100 mg/kg) after 8 weeks of feeding a high-fat diet to C57BL/6 mice. In vitro, immunofluorescence staining and Western blot were employed to analyze the effects of PD on glucose-induced neurotoxicity in mouse hippocampal neuronal cells (HT22). Results: PD (2.5 mg/kg) treatment for 4 weeks significantly suppressed the rise in fasting blood glucose in T2DM mice, improved insulin secretion deficiency, and reversed abnormalities in serum triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein levels. Meanwhile, PD ameliorated choline dysfunction in T2DM mice and inhibited the production of oxidative stress and apoptosis-related proteins of the caspase family. Notably, PD dose-dependently prevents the loss of mitochondrial membrane potential, promotes phosphorylation of phosphatidylinositol 3 kinase and protein kinase B (Akt) in vitro, activates glycogen synthase kinase 3ß (GSK3ß) expression at the Ser9 site, and inhibits Tau protein hyperphosphorylation. Conclusions: These findings clearly indicated that PD could alleviate the neurological damage caused by T2DM, and the phosphorylation of Akt at Ser473 may be the key to its effect.

Platycodin D stimulates AMPK activity to inhibit the neurodegeneration caused by reactive oxygen species-induced inflammation and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) was considered to be a neurodegenerative disease that caused cognitive impairment. Reactive Oxidative stress (ROS) was considered to be one of a major cause of the onset and progression of AD. Platycodin D (PD), a representative saponin from Platycodon grandiflorum, has conspicuous antioxidant activity. However, whether PD could protect nerve cell against oxidative injury remains unknown. AIM OF STUDY: This study investigated the regulatory effects of PD on neurodegeneration caused by ROS. To determine whether PD could play its own antioxidant role in neuronal protection. MATERIALS AND METHODS: First, PD(2.5, 5 mg/kg) ameliorated the memory impairment induced by AlCl3 (100 mg/kg) combined with D-galactose (D-Gal) (200 mg/kg) in mice, using the radial arm maze (RAM) test, and neuronal apoptosis in the hippocampus was evaluated by hematoxylin and eosin staining (HE). Next, the effects of PD (0.5, 1, and 2 µM) on okadaic-acid (OA) (40 nM) -induced apoptosis and inflammation of HT22 cells were investigated. Mitochondrial ROS production was measured by fluorescence staining. The potential signaling pathways were identified through Gene Ontology enrichment analysis. The role of PD in regulating AMP-activated protein kinase (AMPK) was assessed using siRNA silencing of genes and an ROS inhibitor. RESULTS: In vivo, PD improved memory in mice, and recovered the morphological changes of brain tissue and nissl bodies. In vitro experiment, PD increased cell viability (p < 0.01; p < 0.05;p < 0.001), decreased apoptosis (p < 0.01), reduced excessive ROS and MDA, rised SOD and CAT content(p < 0.01; p < 0.05). Morover, it can block the inflammatory response caused by ROS. Be important, PD strengthen antioxidant ability by elevating AMPK activation both in vivo and in vitro. Furthermore, molecular docking suggested a good likelihood of PD-AMPK binding. CONCLUSION: AMPK activity is vital for the neuroprotective effect of PD, suggesting that PD may be a potential pharmaceutical agent to treat ROS-induced neurodegeneration.

1-O-Actylbritannilactone Ameliorates Alcohol-Induced Hepatotoxicity through Regulation of ROS/Akt/NF-κB-Mediated Apoptosis and Inflammation.

1-O-Acetylbritannilactone (ABL) is a marker component of Inula britannica L. and is reported to exhibit multiple pharmacological activities, including antiaging, anti-inflammatory, and antidiabetic properties. Although the protective effect of Inula britannica L. on animal models of liver injury has been widely reported, the effect of ABL on alcohol-induced liver damage has not been confirmed. The present study was designed to investigate the protective effect of ABL against alcohol-induced LO2 human normal liver cell injury and to further clarify the underlying mechanism. Our results revealed that ABL at concentrations of 0.5, 1, and 2 µM could remarkably suppress the decreased viability of LO2 cells stimulated by alcohol. In addition, ABL pretreatment improved alcohol-induced oxidative damage by decreasing the level of reactive oxygen species (ROS) and the excessive consumption of glutathione peroxidase (GSH-Px), while increasing the level of catalase (CAT) in LO2 cells. Moreover, Western blotting analysis showed that ABL pretreatment activated protein kinase B (Akt) phosphorylation, increased downstream antiapoptotic protein Bcl-2 expression, and decreased the phosphorylation level of the caspase family including caspase 9 and caspase 3 proteins, thereby attenuating LO2 cell apoptosis. Importantly, we also found that ABL significantly inhibits the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by reducing the secretion of proinflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin (IL-1ß). In conclusion, the current research clearly suggests that the protective effect of ABL on alcohol-induced hepatotoxicity may be achieved in part through regulation of the ROS/Akt/NF-κB signaling pathway to inhibit inflammation and apoptosis in LO2 cells. (The article path map has not been seen.).