SuanZaoRen decoction amliorates mitochondrial dysfunction of APP/PS1 mice via activating AMPK/SIRT1/PGC-1α signaling pathway / 中国药理学通报

Aim To explore the effect of Suanzaoren decoction(SZRD) on mitochondrial dysfunction in AD model of APP/PS1 mice via AMPK/SIRT1/PGC-1α signaling pathway and to reveal the possible mechanism. Methods Thirty APP/PS1 mice were randomly divided into app /PS1 group, low-dose SZRD group(L-SZRD) and high-dose SZRD group(H-SZRD). Ten C57BL/6JNju mice were set as control group(WT). Morris water maze test was used to detect the learning and memory ability of mice. Thioflavin T staining was used to observe senile plaques hippocampus. Immunohistochemistry was performed to detect the expression level of Aβ in hippocampus. Transmission electron microscope was used to observe the mitochondrial morph hology in hippocampus. Kits were employed to detect the contents of ATP and ROS in hippocampus; Western blot was employed to detect the expression levels of AMPK, p-AMPKThrK172, SIRT1, PGC-1α, NRF1, NRF2 and TFAM in hippocampus. Results Compared to the APP/PS1 group, L-SZRD and H-SZRD induced mouse cognitive impairment, reduced the deposition of senile plaques, inhibited the expression of Aβ, improved the damage of mitochondrial structure, increased the content of ATP in the hippocampus, reduced the expression level of ROS in hippocampus and increased the expression of p-AMPK-ThrK172, SIRT1, PGC-1α, NRF1, NRF2, TFAM Conclusions SZRD could improve the cognitive impairment, senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Reduced the Deposition of Senile Plaques, Inhibited the Expression of Aβ, Improved The Damage of Mitochondric Structure, Increased the Content of At in TH. E hippocampus, Reduced the Expression level of Ros in Hippocampus and Increased The Expression of P-Ampk-Thrk172, SIRT1, SIRT1 PGC-1α, NRF1, NRF2, TFAM. Conclusions SZRD could improve the cognitive impairment, senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Reduced the Deposition of Senile Plaques, Inhibited the Expression of Aβ, Improved The Damage of Mitochondric Structure, Increased the Content of At in TH. E hippocampus, Reduced the Expression level of Ros in Hippocampus and Increased The Expression of P-Ampk-Thrk172, SIRT1, SIRT1 PGC-1α, NRF1, NRF2, TFAM. Conclusions SZRD could improve the cognitive impairment, senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.

A highly selective C-rhamnosyltransferase from Viola tricolor and insights into its mechanisms

C-Glycosides are important natural products with various bioactivities. In plant biosynthetic pathways, the C-glycosylation step is usually catalyzed by C-glycosyltransferases (CGTs), and most of them prefer to accept uridine 5'-diphosphate glucose (UDP-Glc) as sugar donor. No CGTs favoring UDP-rhamnose (UDP-Rha) as sugar donor has been reported, thus far. Herein, we report the first selective C-rhamnosyltransferase VtCGTc from the medicinal plant Viola tricolor. VtCGTc could efficiently catalyze C-rhamnosylation of 2-hydroxynaringenin 3-C-glucoside, and exhibited high selectivity towards UDP-Rha. Mechanisms for the sugar donor selectivity of VtCGTc were investigated by molecular dynamics (MD) simulations and molecular mechanics with generalized Born and surface area solvation (MM/GBSA) binding free energy calculations. Val144 played a vital role in recognizing UDP-Rha, and the V144T mutant could efficiently utilize UDP-Glc. This work provides a new and efficient approach to prepare flavonoid C-rhamnosides such as violanthin and iso-violanthin.

Interaction between tumor-associated macrophages (TAMs) and HUT-78 lymphoma cells / 中国实验血液学杂志

This study was aimed to explore the effects of lymphoma cells on the differentiation of monocytes from peripheral blood to tumor-associated macrophages (TAM) and the effect of TAM on proliferation of lymphoma cells in vitro, and investigate the difference between newly diagnosed lymphoma patients and healthy volunteers. Blood samples were obtained from 15 newly diagnosed lymphoma patients and 8 healthy volunteers. Monocytes from peripheral blood were isolated by Ficoll- Hypaque density gradient centrifugation and CD14 immuno-magnetic beads. Then monocytes were directly co-cultured with HUT-78 lymphoma cells by using Transwell apparatus in vitro. Expression of the markers of TAM (CD68 and CD163) were detected by flow cytometry to analyse the proportion of differentiated TAM. Growth curve of HUT-78 cells was made by direct cell count. The IL-10 and VEGF levels in the co-culture system were detected by ELISA. The detection results of newly diagnosed lymphoma patients were compared with that of healthy controls. The results showed that the proportion of CD68(+), CD163(+) and CD68+CD163 (+) cells were significantly up-regulated after co-cultured with HUT-78 lymphoma cells in both patients and healthy controls (P < 0.05). There was no statistical significance in the increasing degree between patients and healthy controls. TAM differentiated from peripheral blood monocytes showed no significant promotion or inhibition on the growth of co-cultured lymphoma cells. For patients, the IL-10 and VEGF levels in the co-culture group were significantly lower than those in two single culture groups (P < 0.05) . For healthy controls, there was no significant difference between these two. It is concluded that lymphoma cells can promote the differentiation of monocytes to macrophages with M2-like phenotype. There is no difference in the promoting degree between patients and healthy controls. TAM differentiated from patients' monocytes significantly down-regulate levels of IL-10 and VEGF in the co-culture system, exhibited functions more like M1 macrophages. In contrast, TAM differentiated from monocytes of healthy controls show no such effects on the co-culture system.