Toxicological and pharmacokinetic analysis at therapeutic dose of SRS27, an investigational anti-asthma agent.

SRS27, an andrographolide analogue, had been proven to have therapeutic properties at a dose of 3 mg/kg in both in vitro and in vivo asthma models of our previous study. The present study focuses on the pharmacokinetic and toxicity profile of this compound to provide further evidence for the development of this compound as an anti-asthma agent. A simple pharmacokinetic study was performed in female BALB/c mice to measure blood plasma concentration of the compound at therapeutic dose. At a single dose of 3 mg/kg, SRS27 had a relatively short half-life but was able to achieve a concentration range of 13-19 µM that is related to its in vitro bioactivities. With regard to toxicity profile, SRS27 appears to be safe, as no histopathological changes were observed in the liver, kidneys and ovaries of SRS27-treated female BALB/c mice. In addition, there was no significant change in the mean body weight and organ weight of the animals in the SRS27-treated groups compared with the vehicle-treated control group at the end of the treatment. This fully supports the absence of any significant changes in peripheral blood leukocyte counts of SRS27-treated mice. Rewardingly, this acute toxicity study also revealed that SRS27 has a wide therapeutic window as no toxicity symptoms were detected with a dose up to 60 mg/kg daily when tested for 14 days. These results provide strong justification for further investigation of SRS27 as a potential new anti-asthma agent.

A semisynthetic diterpenoid lactone inhibits NF-κB signalling to ameliorate inflammation and airway hyperresponsiveness in a mouse asthma model.

Andrographolide (AGP) and 14-deoxy-11,12-didehydroandrographolide (DDAG), two main diterpenoid constituents of Andrographis paniculata were previously shown to ameliorate asthmatic symptoms in a mouse model. However, due to inadequacies of both compounds in terms of drug-likeness, DDAG analogues were semisynthesised for assessment of their anti-asthma activity. A selected analogue, 3,19-diacetyl-14-deoxy-11,12-didehydroandrographolide (SRS27), was tested for inhibitory activity of NF-κB activation in TNF-α-induced A549 cells and was subsequently evaluated in a mouse model of ovalbumin (OVA)-induced asthma. Female BALB/c mice, 6-8weeks old were sensitized on days 0 and 14, and challenged on days 22, 23 and 24 with OVA. Compound or vehicle (3% dimethyl sulfoxide) was administered intraperitoneally 1h before and 11h after each OVA aerosol challenge. On day 25, pulmonary eosinophilia, airway hyperresponsiveness, mucus hypersecretion, inflammatory cytokines such as IL-4, -5 and -13 in BAL fluid, gene expression of inflammatory mediators such as 5-LOX, E-selectin, VCAM-1, CCL5, TNF-α, AMCase, Ym2, YKL-40, Muc5ac, CCL2 and iNOS in animal lung tissues, and serum IgE were determined. SRS27 at 30µM was found to suppress NF-κB nuclear translocation in A549 cells. In the ovalbumin-induced mouse asthma model, SRS27 at 3mg/kg displayed a substantial decrease in pulmonary eosinophilia, BAL fluid inflammatory cytokines level, serum IgE production, mucus hypersecretion and gene expression of inflammatory mediators in lung tissues. SRS27 is the first known DDAG analogue effective in ameliorating inflammation and airway hyperresponsiveness in the ovalbumin-induced mouse asthma model.

Amino modified mesostructured silica nanoparticles for efficient adsorption of methylene blue.

In this work, mesostructured silica nanoparticles (MSN(AP)) with high adsorptivity were prepared by a modification with 3-aminopropyl triethoxysilane (APTES) as a pore expander. The performance of the MSN(AP) was tested by the adsorption of MB in a batch system under varying pH (2-11), adsorbent dosage (0.1-0.5 g L(-1)), and initial MB concentration (5-60 mg L(-1)). The best conditions were achieved at pH 7 when using 0.1 g L(-1) MSN(AP) and 60 mg L(-1)MB to give a maximum monolayer adsorption capacity of 500.1 mg g(-1) at 303 K. The equilibrium data were evaluated using the Langmuir, Freundlich, Temkin, and Harkins-Jura isotherms and fit well to the Freundlich isotherm model. The adsorption kinetics was best described by the pseudo-second order model. The results indicate the potential for a new use of mesostructured materials as an effective adsorbent for MB.

Utilization of bivalve shell-treated Zea mays L. (maize) husk leaf as a low-cost biosorbent for enhanced adsorption of malachite green.

In this work, two low-cost wastes, bivalve shell (BS) and Zea mays L. husk leaf (ZHL), were investigated to adsorb malachite green (MG) from aqueous solutions. The ZHL was treated with calcined BS to give the BS-ZHL, and its ability to adsorb MG was compared with untreated ZHL, calcined BS and Ca(OH)(2)-treated ZHL under several different conditions: pH (2-8), adsorbent dosage (0.25-2.5 g L(-1)), contact time (10-30 min), initial MG concentration (10-200 mg L(-1)) and temperature (303-323 K). The equilibrium studies indicated that the experimental data were in agreement with the Langmuir isotherm model. The use of 2.5 g L(-1) BS-ZHL resulted in the nearly complete removal of 200 mg L(-1) of MG with a maximum adsorption capacity of 81.5 mg g(-1) after 30 min of contact time at pH 6 and 323 K. The results indicated that the BS-ZHL can be used to effectively remove MG from aqueous media.