Ginsenoside Rg2 alleviates astrocyte inflammation and ameliorates the permeability of the Alzheimer's disease related blood-brain barrier.

BACKGROUND: Damage to the blood-brain barrier (BBB) is vital for the development of Alzheimer's disease (AD). Ginsenoside Rg2 (G-Rg2) has been shown to improve a variety of brain injuries, but whether G-Rg2 can improve the BBB leakage related to AD is still unclear. PURPOSE: Illuminate the effect and mechanism of G-Rg2 on AD-related BBB damage. To clarify the role of G-Rg2 in Toll-like receptor pathway and oxidative stress pathway and its effect on tight junction proteins (TJs) expression in vivo and in vitro experiments. METHODS AND RESULTS: In our research, the tightness of the BBB was improved and the inflammatory pathway was suppressed after 4 weeks of treatment with G-Rg2 (10 mg kg-1 and 20 mg kg-1) in aluminum trichloride (AlCl3) plus d-galactose (D-gal) caused AD mice (p < 0.05; p < 0.01). Concurrently, the stability of TJs in mouse brain endothelial cells (bEnd3) was improved after okadaic acid (OA) -induced AD model cells were pretreated with G-Rg2 (5 µM, 10 µM, and 20 µM) for 24 h (p < 0.05; p < 0.01). The oxidative stress pathway and Toll-like receptor pathway in mouse astrocyte-cerebellum (MA-c) were inhibited (p < 0.05; p < 0.01). Meanwhile, in vitro interaction model results showed that G-Rg2 reduced the activation of MA-c, thereby alleviating the degradation of TJs in bEnd3 (p < 0.05; p < 0.01). The co-culture system of MA-c and bEnd3 further clearly demonstrated that G-Rg2 (20 µM) could improve their interaction and enhance BBB tightness. CONCLUSION: This study suggests that G-Rg2 can inhibit the TLR4/MyD88/MMP9 inflammatory pathway by reducing the activation of MA-c and the binding of TLR4 to MyD88, thereby decreasing the secretion of inflammatory factors and matrix metalloproteinases (MMPs), hence maintaining the stability of TJs in bEnd3, which may be one of the mechanisms of G-Rg2 in reducing AD-related BBB damage.

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.

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.).

[Sequence analysis of the complete genome of papaya ringspot virus hainan isolate].

Total RNA was extracted from infected papaya (Carica papaya L.) leaves in Hainan Province, and the full-length sequences of papaya ringspot virus were amplified by RT-PCR and RACE, and its complete genomic sequence was assembled, named Hainan-P isolate. The RNA genome sequence of Hainan-P isolate was 10323 nucleotides (nts)in length,excluding the 3'-terminal poly(A) tail. And it was composed of a single open reading frame encoding a polyprotein of 3343 amino acids.. The result of homology analysis with twelve GenBank PRSV isolates showed that the polyprotein identity of Hainan-P ranged from 89. 8% to 93.2%, that was higher than the complete nt homology of 82.3% to 89.1%. The P1 amino acid was the least conserved (sharing homology only between 65.4% and 80.1%), whereas HC-Pro, CI and CP were the most conserved. Phylogenetic tree were constructed by the Neighbor-joining method in MEGA 3.1, which showed that PRSV isolates were obviously relevant to geographical origin, and it was impossible to delineate host-specific (P type and W type)evolution.

[Recent advances in plant virus vector systems].

Most plant viral genome is relatively small and easy for genetic manipulation and inoculation. Therefore, plant viral vectors are attractive tools for expression foreign genes in plants. This paper reviews two basic types of epitope presentation and polypeptide expression systems, and discusses the development and application prospect of plant virus vector.