Simultaneous determination of periplocin, periplocymarin, periplogenin, periplocoside M and periplocoside N of Cortex Periplocae in rat plasma and its application to a pharmacokinetic study.

A sensitive and specific ultra-performance liquid chromatographic-tandem mass spectrometric method was developed and validated to simultaneously determine periplocin, periplocymarin (PM), periplogenin (PG), periplocoside M (PSM) and periplocoside N (PSN) in rat plasma. Acetonitrile was employed to precipitate plasma with appropriate sensitivity and acceptable matrix effects. Chromatographic separation was performed using a Waters HSS T3 column with a gradient elution using water and acetonitrile both containing 0.1% formic acid and 0.1 mm ammonium formate within 8 min. Detection was performed in positive ionization mode using multiple reaction monitoring. The method was fully validated in terms of selectivity, linearity, accuracy, precision, recovery, matrix effects and stability. Using this method, the concentrations of periplocin, PM, PG, PSM and PSN were established after oral administration of Cortex Periplocae extract to rats, and the pharmacokinetic characteristics of periplocin, PM, PG, PSM and PSN were assessed. Generally, PM, PG, PSM and PSN were eliminated slowly and their half-lives were all >8 h. In addition, the systemic exposure of PSM showed significant differences between genders with more than 10 times higher area under the concentration-time curve in female rats than in male rats. The findings of this study provide useful information for further research on Cortex Periplocae.

miR-485 suppresses inflammation and proliferation of mesangial cells in an in vitro model of diabetic nephropathy by targeting NOX5.

Diabetic nephropathy (DN) is among the common complications of diabetes and is a major cause of end-stage kidney disease. Emerging data indicate that renal inflammation is involved in DN progression and aggravation. Still, the exact cellular mechanisms remain unclear. Dysregulated expression of microRNAs (miRNAs) is associated with multiple diseases, including DN. The relationship between miRNAs and inflammation in DN is also unexplored. Here, we evaluated the role of miR-485 in mediating the response of human mesangial cells (HMCs) to a high glucose (HG) concentration, and the potential underlying mechanism. We found that miR-485 expression is significantly decreased in HG-stimulated HMCs. Overexpression of miR-485 suppressed HG-induced proliferation of HMCs. Lower production of proinflammatory cytokines (i.e., TNF-α, IL-1ß, and IL-6) was observed in miR-485-overexpressing HMCs. Overexpression of miR-485 markedly suppressed the overexpression of extracellular-matrix proteins, e.g., collagen IV (Col IV) and fibronectin (FN), in HG-stimulated HMCs. Furthermore, miR-485 suppressed the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 5 (NOX5), restrained the HG-induced HMC proliferation, downregulated the expression of proinflammatory cytokines, and inhibited the production of extracellular-matrix proteins in HMCs. These results provide new insights into the involvement of the miR-485-NOX5 signaling pathway in DN progression.

MiR-455-3p suppresses renal fibrosis through repression of ROCK2 expression in diabetic nephropathy.

Emerging evidence has shown that microRNAs (miRNAs) play a mediatory role in the pathogenesis of diabetic nephropathy (DN), but the function of the involved miRNAs is still incomplete. Here, we found that miR-455-3p was down-regulated in the human mesangial cells (HMC) and human proximal tubule epithelial cells (HK-2) stimulated with high glucose (HG) or transforming growth factor beta 1 (TGF-ß1). Rho-associated coiled coil-containing protein kinase 2 (ROCK2) was identified as a directed target of miR-455-3p. Overexpression of ROCK2 significantly attenuated the inhibitory effects of miR-455-3p on cell proliferation, extracellular matrix (ECM) synthesis and epithelial-mesenchymal transition (EMT) in HG-treated cells. Furthermore, the DN model was prepared by using high-fat feeding combined with Streptozotocin (STZ) induced rats, and the DN group was treated by injecting miR-455-3p agomir. The results of periodic acid-Schiff (PAS) and Masson staining showed that miR-455-3p overexpression improved the pathological changes of glomerular hypertrophy, mesangial amplification, and renal fibrosis. Additionally, miR-455-3p overexpression decreased ROCK2, proliferating cell nuclear antigen (PCNA) and Collagen I levels, and also reduced inflammatory cytokines TNF-α, MCP-1 and IL-1ß levels in vivo. Altogether, these results suggest that miR-455-3p plays an essential role in the treatment of renal fibrosis through repressing ROCK2 expression; and miR-455-3p might be an effective therapy for DN.

Pharmacokinetics, Tissue Distribution, and Excretion Characteristics of a Radix Polygoni Multiflori Extract in Rats.

Although progress has been achieved in the pharmacological activity and toxicity of Radix Polygoni Multiflori (RPM), the chemical basis of its toxicity is still unclear. Here, we performed a multicompound pharmacokinetic analysis and investigated the tissue distribution and excretion characteristics of RPM components after oral administration in rats. The findings demonstrated that the active ingredients of the RPM extract were quickly absorbed after oral administration, with high exposure levels of emodin, 2,3,5,4'-teterahydroxystilbene-2-O-ß-D-glucoside (TSG), citreorosein, torachrysone-8-O-glucoside (TG), emodin-8-O-ß-D-glucoside (EG), and physcion-8-O-ß-D-glucoside (PG). The tissue distributions of emodin, TSG, TG, EG, and PG were high in the liver and kidney. These components were the key contributors to the effectiveness and toxicity of RPM on the liver and kidney. Most of the active ingredients were mainly excreted through feces and bile, while a few were converted into other products in the body and excreted through urine and feces.

In-situ synthesis of calcium aluminum layered double hydroxides for advanced treatment of leachate biochemical tail water.

In the leachate system, Ca-Al-LDH was synthesized in situ by adding calcium aluminum material (AC) and Ca (OH)2. In the process of synthesis, the removal efficiencies of UV254, COD and TOC in the leachate reached 85.51%, 73.85% and 74.71%, respectively, and the organic matter could be effectively removed. XRD (X-Ray Diffraction) characterization analysis displayed that when AC and Ca (OH)2 were added at a ratio of 3:1, Ca-Al-LDH could be synthesized efficiently. The effect of this method on the removal of pollutants in leachate was better than that of Ca-Al-LDH. EEM (Excitation Emission Matrix) and GC-MS (Gas Chromatography-Mass Spectrometer) characterization analysis showed that these results could be attributed to the coagulation of calcium aluminum material AC, LDH surface adsorption and ion exchange.

Utilization of calcium-based and aluminum-based materials for the treatment of stabilized landfill leachate: a comparative study.

This study explored the efficiencies and mechanisms of refractory organic matters removal in the stabilized landfill leachate by adding different reagents. Calcium-based and aluminum-based materials were added into the leachate as comparing experiments. XRD, FTIR, and EEM were adopted to analyze the solid products and leachate. As a result, the in situ synthesized CaAl-LDHs were more beneficial for refractory organic matters removal, especially for benzodiazepines. When CaAl-LDHs were formed, the removal efficiencies of COD, UV254, and TOC were best and achieved 58.48, 81.22, and 71.30%, respectively. For fluorescent substances, humic acid-like and fulvic acid-like compounds were efficiently removed by CaAl-LDHs. In particular, CaAl-LDHs had selective removal effects on fulvic acid-like compounds, which were characteristic of small molecular weight and major carboxyl groups.