Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats

BackgroundSilymarin, a known hepatoprotectant, owing to its poor oral bioavailability, has limited pharmacological effects. The present study was designed to improve its in vitro and in vivo hepatoprotection and increase its oral bioavailability against alcohol intoxication by formulating it in four different liposomal formulations namely conventional, dicetyl phosphate, stearyl amine and PEGylated liposomes.MethodThe liposomes were prepared using phosphatidylcholine, cholesterol, and silymarin in addition to dicetyl phosphate, stearyl amine and DSPE mPEG 2000 by film hydration method with 5% sucrose as a cryo-protectant. The optimized formulations were studied for their release profile at pH 1.2 and 6.8. Liposomes were studied for in vitro protection on Chang liver cells and efficacious liposomes were selected for in vivo hepatoprotection study. Further, conventional liposomes were studied for bioavailability in alcohol intoxicated Wistar rats.ResultsThe conventional liposomes increased in vitro release profile at pH 1.2 and 6.8 and also showed better in vitro protection compared to silymarin alone. Conventional and PEGylated liposomes showed better improvement in liver function, better efficacy in combating inflammatory conditions, better improvement in antioxidant levels and reversal of histological changes compared to silymarin alone. Conventional also showed an almost fourfold increase in area under the curve compared to silymarin suspension.ConclusionConventional and PEGylated liposomes of silymarin were found to be more efficacious as hepatoprotective against alcohol-induced hepatotoxicity by its free radical scavenging and anti-inflammatory effects. Conventional liposomes showed enhanced bioavailability compared to silymarin alone.     

Comb-shaped cardo poly(arylene ether nitrile sulfone) anion exchange membranes: significant impact of nitrile group content on morphology and properties

A series of comb-shaped cardo poly(arylene ether nitrile sulfone) (CCPENS-x) materials were synthesized by varying the content of nitrile groups as anion exchange membranes (AEMs). The well-designed architecture of cardo-based main chains and comb-shaped C10 long alkyl side chains bearing imidazolium groups was responsible for the clear microphase-separated morphologies, as confirmed by atomic force microscopy. The ion exchange capacity (IEC) of the AEMs ranged from 1.56 to 1.65 meq. g⁻¹. With strong dipole interchain interactions, the effects of nitrile groups on the membrane morphology and properties were investigated. With the nitrile group content increasing from CCPENS-0.2 to CCPENS-0.8, CCPENS-x revealed larger and more interconnected ionic domains to form more efficient ion-transport channels, thus increasing the corresponding ionic conductivity from 25.8 to 39.5 mS cm⁻¹ at 30 °C and 58.6 to 83 mS cm⁻¹ at 80 °C. Furthermore, CCPENS-x with a higher content of nitrile groups also exhibited lower water uptake (WU) and swelling ratio (SR), and better mechanical properties and thermal stability. This work presents a promising strategy for enhancing the performance of AEMs.

A series of comb-shaped cardo poly(arylene ether nitrile sulfone) (CCPENS-x) materials were synthesized by varying the content of nitrile groups as anion exchange membranes (AEMs).     

Multimodality noninvasive imaging for assessing therapeutic effects of exogenously transplanted cell aggregates capable of angiogenesis on acute myocardial infarction

Although the induction of neovascularization by cell-based approaches has demonstrated substantial potential in treating myocardial infarction (MI), the process of cell-mediated angiogenesis and its correlation with therapeutic mechanisms of cardiac repair remain elusive. In this work, three-dimensional (3D) aggregates of human umbilical vein endothelial cells (HUVECs) and cord-blood mesenchymal stem cells (cbMSCs) are constructed using a methylcellulose hydrogel system. By maximizing cell–cell and cell–ECM communications and establishing a hypoxic microenvironment in their inner cores, these cell aggregates are capable of forming widespread tubular networks together with the angiogenic marker α_vβ₃ integrin; they secret multiple pro-angiogenic, pro-survival, and mobilizing factors when grown on Matrigel. The aggregates of HUVECs/cbMSCs are exogenously engrafted into the peri-infarct zones of rats with MI via direct local injection. Multimodality noninvasive imaging techniques, including positron emission tomography, single photon emission computed tomography, and echocardiography, are employed to monitor serially the beneficial effects of cell therapy on angiogenesis, blood perfusion, and global/regional ventricular function, respectively. The myocardial perfusion is correlated with ventricular contractility, demonstrating that the recovery of blood perfusion helps to restore regional cardiac function, leading to the improvement in global ventricular performance. These experimental data reveal the efficacy of the exogenous transplantation of 3D cell aggregates after MI and elucidate the mechanism of cell-mediated therapeutic angiogenesis for cardiac repair.     

Ethanol extracts from Hemerocallis citrina attenuate the upregulation of proinflammatory cytokines and indoleamine 2,3-dioxygenase in rats

Ethnopharmacological relevance

Hemerocallis citrina, a traditional herbal medicine, has been used for the improvement of behavioral and emotional status in Eastern-Asia countries. Previous studies in our laboratory demonstrated that ethanol extracts from Hemerocallis citrina (HCE) enhanced monoamines and brain-derived neurotrophic factor (BDNF) in depression-like model of rodents.

Materials and methods

The present study extends earlier works on the role of anti-inflammation in regulating the antidepressant-like actions of HCE in rats exposed to chronic unpredictable mild stress (CUMS). Frontal cortex and hippocampal proinflammatory cytokines levels and indoleamine 2,3-dioxygenase (IDO) activity were measured after 4-week HCE treatment in the CUMS an control rats.

Results

Chronic administration of HCE reversed the decreased sucrose preference in sucrose preference test. In addition, we also found that HCE inhibited interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) expression, as well as IDO activity in frontal cortex and hippocampus, which were increased in rats exposed to CUMS.

Conclusions

Combining with our previous studies, our present finding suggests that the anti-inflammatory property of HCE might play a crucial role in its antidepressant-like effect through, at least in part, the restoration or improvement of monoaminergic and neurotrophin systems.     

Synthesis and antimicrobial activities of chitosan/polypropylene carbonate-based nanoparticles

Antibiotic resistance is an emerging threat to public health. The development of a new generation of antimicrobial compounds is therefore currently required. Here we report a novel antimicrobial polymer of chitosan/polypropylene carbonate nanoparticles (CS/PPC NPs). These were designed and synthesized from readily available chitosan and a reactive oligomer polypropylene carbonate (PPC)-derived epoxy intermediate. By employing a simple and efficient functionalized strategy, a series of micelle-like chitosan-graft-polypropylene carbonate (CS-g-PPC) polymers and chitosan–polypropylene carbonate (CS–PPC) microgels were prepared by reacting mono-/bis-epoxy capped PPC with chitosan. The chemical structure, particle size, and surface charge of the newly synthesized polymers were characterized by infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS), and zeta potential measurements. The antimicrobial activities of these nanoparticles were determined in both Gram-positive bacteria (S. aureus) and Gram-negative bacteria (E. coli). Minimum inhibitory concentration (MIC), the nanoparticle concentration needed to completely inhibit the bacterial growth, was found at 128 μg mL⁻¹ to 1024 μg mL⁻¹, strongly depending both on the nature of the epoxy-imine network formed from the functional groups (mono- or bis-capped epoxy groups reacting with amine groups) and the feed ratio of the functional groups (-epoxy/-NH₂) between the functionalized PPC and chitosan. No hemolysis was observed at concentrations well in excess of the effective bacteria-inhibiting concentrations. These findings provide a novel strategy to fabricate a new type of nanoantibiotic for antimicrobial applications.

Chitosan-graft-polypropylene carbonate polymers (M-type) and microgels (G-type) exhibit high antimicrobial activity against E. coli and S. aureus and display no hemolytic activity towards mouse red blood cells in neutral medium.     

Metal oxide/CeO2 nanocomposites derived from Ce-benzene tricarboxylate (Ce-BTC) adsorbing with metal acetylacetonate complexes for catalytic oxidation of carbon monoxide

Herein, a series of metal oxide/CeO₂ (M/CeO₂) nanocomposites derived from Ce-benzene tricarboxylate (Ce-BTC) adsorbing with different metal acetylacetonate complexes were prepared for CO oxidation under four different CO gas atmospheres. It was demonstrated that Cu/CeO₂ exhibited the highest catalytic activity and stability in CO oxidation. Remarkably, both O₂ selectivity and CO selectivity to CO₂ are 100% in most of the investigated conditions. Several analytical tools such as N₂ adsorption–desorption and powder X-ray diffraction, were employed to characterize the prepared catalysts. In addition, the excellent catalytic performance of Cu/CeO₂ in CO oxidation was revealed by H₂ temperature-program reduction experiment, X-ray photoelectron spectroscopy, and in situ diffuse reflectance infrared Fourier transform spectroscopy. The result showed that high oxygen vacancy and high CO adsorption capacity (Cu⁺–CO) caused by the electron exchanges of Cu²⁺/Cu⁺ and Ce³⁺/Ce⁴⁺ pairs (Ce⁴⁺ + Cu⁺ ⇆ Ce³⁺ + Cu²⁺) are two key factors contributing to the high oxidation performance of Cu/CeO₂ catalyst.

Herein, a series of metal oxide/CeO₂ (M/CeO₂) nanocomposites derived from Ce-benzene tricarboxylate (Ce-BTC) adsorbing with different metal acetylacetonate complexes were prepared for CO oxidation.     

Effect of hydrothermal aging temperature on a Cu-SSZ-13/H-SAPO-34 composite for the selective catalytic reduction of NOx by NH3

Cu-SSZ-13 suffers activity loss after hydrothermal treatment at high temperatures, particularly above 850 °C. The stability of Cu-SSZ-13 can be enhanced by compositing with H-SAPO-34. This work investigates the effect of aging temperature on the composites. For the structure, the extra-framework P in H-SAPO-34 migrates and interacts with the Al in Cu-SSZ-13, forming a new framework P–Al bond. This interaction is enhanced with the increment of the aging temperature. For the cupric sites, the aging at 750 °C results in the agglomeration of Cu²⁺ ions to CuO. However, the sample aged at 800 °C exhibits higher activities than that aged at 750 °C, which might be attributed to the increased formation of framework P–Al bonds promoting the redispersion of CuO to Cu²⁺ ions. The composite suffers severe deactivation due to the significant loss of Cu²⁺ ions after aging at 850 °C.

Effect of aging temperature on SSZ-SAPO composites.     

Antidepressant effect of helicid in chronic unpredictable mild stress model in rats

Helicid (4-formylphenyl-β-D-allopyranoside) is a bioactive constituent of Helicid nilgirica Bedd that has been used in Chinese traditional herbal medicine to treat headache, insomnia, and depression. However, the underlying mechanisms of these effects are unclear. We have now investigated the effect of helicid on depression-related behaviors in rats exposed to chronic unpredictable mild stress (CUMS) and have also explored possible underlying mechanisms that involve neurotrophin expression. After 6 weeks isolation, body weight and sucrose preference were significantly reduced in rats with CUMS-induced depression compared with controls. The CUMS rats also showed significant inhibition of locomotory parameters in open field tests (involving behavioral assays). Helicid significantly regulated levels of corticosterone (CORT), inflammatory cytokines and 5-hydroxytryptamine (5-HT). Helicid also reversed CUMS-induced decreases of 5-HT1A receptor expression and promoted brain derived neurotrophic factor (BDNF) expression in the hippocampus The significant reversal of depressive-like behaviors by helicid is similar to that achieved by fluoxetine. The antidepressive effects are likely attributable to the promotion of hippocampal neurotrophin expression through activation of the serotonergic system. Helicid thus has potential for treating depressive disorders.     

Contamination assessment,source apportionment and health risk assessment of heavy metals in paddy soils of Jiulong River Basin,Southeast China

To trace the sources and evaluate the health risks of heavy metals in paddy soils of Jiulong River Basin, seventy-one samples of paddy soils were collected in July 2017. The heavy metals contents were determined using inductively coupled plasma mass spectrometry (ICP-MS) and atomic fluorescence spectrophotometry (AFS). The geo-accumulation index (I_geo) and potential ecological risk index (RI) methods were applied to evaluate the contamination of heavy metals, principal component analysis (PCA) and absolute principal component scores-multiple linear regression (APCS-MLR) were applied to trace the sources, and dose–response model was applied to assess the health risks to the human body. The results indicated that the paddy soils were moderately to heavily polluted by Cd and slightly polluted by Hg, Pb, As and Zn. Heavy metals in paddy soils presented considerable to high potential ecological risk, mostly contributed by Cd and Hg with contribution rates of 59.4% and 26.2%, respectively. The heavy metals contaminating paddy soils were derived from natural sources, agricultural activities, industrial discharge, coal combustion and unidentified sources, with source contribution rates of 31.37%, 24.87%, 19.65%, 18.05% and 6.06%, respectively. The heavy metals in paddy soils presented carcinogenic risks which humans can tolerate and no non-carcinogenic risks. The total non-carcinogenic risks mainly derived from agricultural activities and coal combustion, with contribution rates of 62.16% and 20.21%, respectively, while the total carcinogenic risks mainly derived from natural sources and industrial discharge, with contribution rates of 51.17% and 18.98%, respectively.

APCS-MLR and dose–response model were combined to identify the sources and human health risks of heavy metals in paddy soils.