Pharmacokinetics and safety evaluation of intravenously administered Pseudomonas phage PA_LZ7 in a mouse model.

IMPORTANCE: Phage therapy is gaining traction as an alternative to antibiotics due to the rise of multi-drug-resistant (MDR) bacteria. This study assessed the pharmacokinetics and safety of PA_LZ7, a phage targeting MDR Pseudomonas aeruginosa, in mice. After intravenous administration, the phage showed an exponential decay in plasma and its concentration dropped significantly within 24 h for all dosage groups. Although there was a temporary increase in certain plasma cytokines and spleen weight at higher dosages, no significant toxicity was observed. Therefore, PA_LZ7 shows potential as an effective and safe candidate for future phage therapy against MDR P. aeruginosa infections.

[A new 9,19-cycloartane glycoside from Asplenium ruprechtii].

Chemical constituents of water extracts of Asplenium ruprechtii were investigated. Five compounds were isolated by silica gel, Sephadex LH-20 gel column chromatographies and preparative HPLC, and their structures were identified by various spectral analyses as aspleniumside G(1), trans-p-coumaric acid(2), trans-p-coumaric acid 4-O-ß-D-glucoside(3), cis-p-coumaric acid 4-O-ß-D-glucoside(4), and(E)-ferulic acid-4-O-ß-D-glucoside(5). Among them, compound 1 is a new 9,19-cycloartane glycoside.

Structural Determination of a New Cycloartane Glycoside from Asplenium ruprechtii.

We characterized a new cycloartane glycoside, herein known as aspleniumside F (1), along with five known compounds as kaempferol-3-O-[(6-O-(E)-feruloyl)-ß-D-glucopyranosyl]-(1→2)-ß-D-galacopyranoside (2), quercetin-3-O-[(6-O-(E)-feruloyl)-ß-D-glucopyranosyl]-(1→2)-ß-D-glucopyranoside (3), kaempferol-3-O-[(6-O-(E)-caffeoyl)-ß-D-glucopyranosyl]-(1→2)-ß-D-glucopyranoside (4), kaempferol-3-O-[(6-O-(E)-caffeoyl)-ß-D-glucopyranosyl]-(1→2)-ß-D-glucopyranosyl-7-O-ß-D-glucopyranoside (5), and kaempferol-3-O-[(6-O-p-coumaroyl)-ß-D-glucopyranosyl]-(1→2)-ß-D-glucopyranosyl-7-O-ß-D-glucopyranoside (6), from Asplenium ruprechtii Sa. Kurata, a folk medicine widely used to treat Thromboangiitis obliterans in China, Japan, and Korea. Based on spectroscopic, mainly 1D-, 2D-NMR and (+)-HR-ESI-MS, analyses as well as through comparisons with previous reports, its chemical structure was determined as 3ß,24,30-tri-ß-D-glucopyranosyl-23,25-dihydroxycycloartane (= (23R,24R)-3ß,24-bis-(ß-D-glucopyranosyloxy)-23,25-dihydroxy-9ß-9,19-cyclolanostan-29-yl ß-D-glucopyranoside). According to the 1 H coupling constant of anomeric protons and co-TLC of the acid hydrolysate with D-glucose, all three glycoside groups in 1 were revealed as ß-D-glucopyranosyl. Furthermore, SOD-like antioxidant activity evaluation via IC50 of 12.43, 6.78, 9.12, 6.94 and 4.85 µM revealed that compounds 2-6 had bioactivity.

Structural determination and in vitro tumor cytotoxicity evaluation of five new cycloartane glycosides from Asplenium ruprechtii Sa. Kurata.

Five new cycloartane glycosides, named aspleniumside A - E, were discovered and characterized by re-investigated the remaining extracts of the whole plant of Asplenium ruprechtii Sa. Kurata, a famous folk medicine for treating thromboangitis obliterans in China, Japan, and Korea. Compounds 3-5 possessed the 9,19-seco-cycloartane-9,11-en triterpene aglycone with 3,7(or 23),24,25,30-highly oxidized methylene, methylene or quaternary carbons, that was found in this species for the first time. The stereo-chemistry of all new compounds were fully discussed by extensive analysis of the 1D and 2D NMR data, and comparisons with those data of known compounds. 24R configuration was determined here which indicated the different growing areas of the same species could influence the secondary metabolic behavior, leading to the differences in chemical composition. All glycoside groups were determined as ß-d-glucopyranosyl by 1H coupling constant of anomeric protons and co-TLC of the acid hydrolysate with d-glucose. All the cycloartane glycosides were evaluated against HL-60 and HepG2 cells for cytotoxicity, compounds 1-3, showed potential cytotoxicity with the IC50 in range of 18-60 µM, while the standard sorafenib showed IC50 value of 10.61 ± 0.43 and 13.43 ± 1.12 µM against HL-60 and HepG2, respectively. The results attained in this study indicated that cycloartane glycosides should be the cytotoxicity substance in A. ruprechtii Sa. Kurata, and had the potential to be developed as tumor cytotoxicity agent applied in clinic.

An anti-inflammatory C-stiryl iridoid from Camptosorus sibiricus Rupr.

A new iridoid glycoside, named camptoside (1), together with three known compounds as dehydrodiconiferyl alcohol-9'-O-ß-d-glucopyranoside (2), aesculetin (3) and vajicoside (4), have been isolated from Camptosorus sibiricus Rupr. (Aspleniaceae). Their structures were established on the basis of spectroscopic analysis, especially 1D- and 2D-NMR data, and by comparison of their spectroscopic and physical data with those reported in the literature. Compounds 1-3 exhibited inhibitions of nitric oxide production in lipopolysaccharide-induced RAW 264.7 macrophages with IC50 values of 11.2, 8.3 and 9.4 µM, respectively.

Hg removal and the effects of coexisting metals in forward osmosis and membrane distillation.

In this study, we investigate the rejection of Hg, Cd, and Pb and the effect of coexisting metals on Hg removal through forward osmosis (FO) and membrane distillation (MD) in order to establish a more effective water treatment process. The results of our laboratory experiment indicate that more than 97% of the rejection for each metal is achieved through the FO system, and this rejection is the highest among previous studies using membrane filtrations. Moreover, we examine the matrix effect of the coexisting Cd and Pb on the rejection of Hg in the FO system. Hg2+ rejection increases with increase in the concentration of the coexisting metals. Furthermore, we study the effect of the Hg concentration and the water temperature on rejection of Hg2+. Indeed, the rejection of Hg2+ is achieved above 95% under any condition. However, approximately 1-10 ppb Hg from the feed solution remains in the draw solution due to permeation. Therefore, we use a FO-MD hybrid system. Approximately 100% rejection of Hg2+ and a stable water flux are achieved. Thus, the FO-MD hybrid system is considered an important alternative to previous studies using membrane filtration for heavy metals removal.