6'-O-Caffeoylarbutin from Que Zui tea ameliorates acetaminophen-induced liver injury via enhancing antioxidant ability and regulating the PI3K signaling pathway.

Que Zui tea (QT), a traditional herbal tea in China, has a significant hepatoprotective effect. 6'-O-Caffeoylarbutin (CA) is the most abundant chemical compound in the QT. However, the hepatoprotective effect of CA has not been investigated. This study is aimed to evaluate the protective effect of CA on acetaminophen (APAP) induced hepatotoxicity in vivo and in vitro and its possible underlying mechanism. In APAP-induced HepG-2 cells, CA inhibited intracellular ROS accumulation and cell apoptosis, and improved the expression of antioxidants including SOD, CAT and GSH. In APAP-administrated mice, CA pretreatment remarkably ameliorated the histopathological damage and inflammatory response, and antioxidant enzyme activity in the serum and liver tissues. Moreover, the immunohistochemistry and immunofluorescence assay results revealed that the CA markedly reduced ROS production and apoptosis, and activated antioxidant transcription factor Nrf2 in the liver. Meanwhile, molecular docking results showed that the strong binding force of CA and PI3K was due to the higher number of hydrogen- and π-bonds with active site residues. Notably, CA pretreatment significantly regulated the expression of PI3K, Akt, Nrf2, NQO1, HO-1, Bcl-2, Bax, caspase-3, and caspase-9 proteins in APAP-treated liver tissues. These data demonstrated that CA had a protective effect against APAP-induced hepatotoxicity via regulating the PI3K/Akt and Nrf2 signaling pathway.

Anti-leukemic effect and molecular mechanism of 11-methoxytabersonine from Melodinus cochinchinensis via network pharmacology, ROS-mediated mitochondrial dysfunction and PI3K/Akt signaling pathway.

Melodinus cochinchinensis (Lour.) Merr. is a Yunnan endemic folk medicine. Our previous study showed that 11-methoxytabersonine (11-MT) isolated from M. cochinchinensis has strong cytotoxicity on human T-ALL cells, but its molecular mechanism has not been studied. In current study, the cytotoxicity and possible mechanism of 11-MT on T-cell acute lymphoblastic leukemia was explored using network pharmacology and molecular biology techniques. 11-MT significantly inhibited the cell proliferations on different four human T-ALL cells (MOLT-4, Jurkat, CCRF-CEM, and CEM/C1 cells). 11-MT triggered ROS accumulation, calcium concentration and cell apoptosis, and decreased the mitochondrial membrane potential (MMP) in human T-ALL cells, especially MOLT-4 cells. Western blot analysis showed that it can induce MOLT-4 cell apoptosis by up-regulating PI3K/Akt signaling pathway. Therefore, 11-MT induces human T-ALL cells apoptosis via up-regulation of ROS-mediated mitochondrial dysfunction and down-regulation of PI3K/Akt/mTOR signaling pathway.

Calcium effect on the metabolic pathway of phosphorus accumulating organisms in enhanced biological phosphorus removal systems.

Phosphorus accumulating organisms (PAOs) have been found to act as glycogen-accumulating organisms (GAOs) under certain conditions, thus, the deterioration in the performance of enhanced biological phosphorus removal systems is not always attributed to the proliferation of GAOs. In this work, the effects of calcium on the metabolic pathway of PAOs were explored. It was found that when the influent Ca(2+) concentration was elevated, the tendency and extent of extracellular calcium phosphate precipitation increased, and the intracellular inert Ca-bound polyphosphate was synthesized, while the microbial population remained almost unchanged. The changes in the ratios of phosphorus released/acetate uptaken, the glycogen degraded/acetate uptaken and the poly-ß-hydroxyalkanoates synthesized/acetate uptaken during the anaerobic period confirm that, as the influent Ca(2+) concentration was increased, the polyphosphate-accumulating metabolism was partially shifted to the glycogen-accumulating metabolism. At an influent Ca(2+) around 50 mg/L, in addition to the extracellular calcium phosphate precipitation, the intracellular inert Ca-bound polyphosphate synthesis might also be involved in the metabolic change of PAOs. The results of the present work would be beneficial to better understand the biochemical metabolism of PAOs in enhanced biological phosphorus removal systems.

Phosphorus removal in an enhanced biological phosphorus removal process: roles of extracellular polymeric substances.

Phosphorus-accumulating organisms are considered to be the key microorganisms in the enhanced biological phosphorus removal (EBPR) process. A large amount of phosphorus is found in the extracellular polymeric substances (EPS) matrix of these microorganisms. However, the roles of EPS in phosphorus removal have not been fully understood. In this study, the phosphorus in the EBPR sludge was fractionated and further analyzed using quantitative (31)P nuclear magnetic resonance spectroscopy. The amounts and forms of phosphorus in EPS as well as their changes in an anaerobic-aerobic process were also investigated. EPS could act as a reservoir for phosphorus in the anaerobic-aerobic process. About 5-9% of phosphorus in sludge was reserved in the EPS at the end of the aerobic phase and might further contribute to the phosphorus removal. The chain length of the intracellular long-chain polyphosphate (polyP) decreased in the anaerobic phase and then recovered under aerobic conditions. However, the polyP in the EPS had a much shorter chain length than the intracellular polyP in the whole cycle. The migration and transformation of various forms of phosphorus among microbial cells, EPS, and bulk liquid were also explored. On the basis of these results, a model with a consideration of the roles of EPS was proposed, which is beneficial to elucidate the mechanism of phosphorus removal in the EBPR system.

Species of phosphorus in the extracellular polymeric substances of EBPR sludge.

In this study, the species of extracellular phosphorus and their transformation during extracellular polymeric substances (EPS) extraction were explored by using (31)P nuclear magnetic resonance spectroscopy. Results show that the extraction methods had a substantial influence on the phosphorus species in the extracted EPS. Cation exchange resin method was more appropriate for extracting EPS from the enhanced biological phosphorus removal (EBPR) sludge. Orthophosphate, pyrophosphate and polyphosphate were the main species of phosphorus found to be present in the EPS, which together accounted for about 6.6-10.5% of the total phosphorus in the EBPR sludge. The high percentage of extracellular phosphorus and their diverse species might reveal a new insight into the characteristics of the phosphorus in EPS in EBPR system.