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.     

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.     

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).     

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.     

续随子化学成分和药理活性研究进展

续随子为大戟科大戟属植物,在我国吉林、河北、河南、浙江、安徽、广西、云南、四川等地区均有广泛分布。作为我国传统中药材,民间多用于治疗水肿、痰饮、积滞胀满、二便不通、血瘀经闭、外治顽癣、疣赘等。现代研究表明,续随子中化学成分主要包括脂肪酸、二萜、黄酮、香豆素、挥发油、甾醇等。临床上对白血病、食道癌、皮肤癌等疾病疗效甚佳,极具药用开发价值。本文系统综述了1970年以来续随子化学成分、药理活性等方面的研究进展,以期为续随子的深入研究和开发利用提供参考。     

重组α-L-鼠李糖苷酶制备普鲁宁

目的 利用重组α-L-鼠李糖苷酶,以柚皮苷为底物,通过生物转化法制备普鲁宁。方法 以HPLC检测生物转化反应产物,通过DNS法对酶促反应过程进行动态分析,分析酶促反应动力学,优化普鲁宁制备工艺。结果 重组α-L-鼠李糖苷酶水解柚皮苷反应完全后,可得到反应产物普鲁宁和鼠李糖;生物转化法制备普鲁宁的最适反应温度为60 ℃、pH值为4.0、加酶量为12 U·mL^-1、底物浓度为2.0 g·L^-1,在此最优工艺条件下,94%的柚皮苷转化为普鲁宁;高浓度的Mn²⁺、Fe²⁺能够促进柚皮苷转化生成普鲁宁;重组酶对底物亲和力强,酶促反应的米氏常数K_m为1.02 μmol·mL^-1,V_max为0.19 μmol·mL^-1·min^-1。结论 利用重组α-L-鼠李糖苷酶生物转化法制备普鲁宁,转化率高、重现性好、产物易于分离,可为普鲁宁功能研究、开发利用及改性等提供重要依据。     

Berberine exerts antidepressant-like effects via regulating miR-34a-synaptotagmin1/Bcl-2 axis

Objective: Berberine, a cationic alkaloid first isolated in 1917, has been approved by the China Drug Administration for decades. Accumulating evidence demonstrated its antidepressant-like activities in vivo. Our previous study has shown that chronic stress leads to the upregulation of miR-34a in the hippocampus of mice. This study aims to evaluate the underlying miR-34a mediated mechanism of berberine in chronic stress-induced depression in mice.Methods: In the present study, mice were administered with berberine during chronic stress. Levels of miR-34a, dendritic density, mitochondrial morphology, and neurogenesis were assessed in the hippocampus. Subsequently, miR-34a agomir was used as a pharmacological intervention for the investigation of berberine.Results: The results showed that berberine reversed the decrease in sucrose preference and the increase in latency to feed without altering total food consumption. Furthermore, chronic stress-induced overexpression of miR-34a decreased synaptotagmin-1 and Bcl-2 levels, thereby impairing spinal morphology,mitochondria and neurogenesis. Berberine inhibited miR-34a expression, in turn restored synaptotagmin-1 and Bcl-2 levels, and thus improved spinal morphology, mitochondria and neurogenesis in the hippocampus. However, the improvements induced by berberine were totally blocked by the pretreatment of miR-34a agomir, which caused the elevation of miR-34a levels in the hippocampus.Conclusion: This finding demonstrated that miR-34a downregulation was involved in the antidepressantlike effects of berberine in mice exposed to chronic stress.     

海藻酸钙/壳聚糖磁性微胶囊的制备及研究

采用高压静电法制备磁性海藻酸钙/壳聚糖微胶囊,Minitab全因子实验考察不同制备条件对微胶囊形貌、粒径分布及破损率的影响。以超氧化物歧化酶（SOD）为模型药物,考察磁性微胶囊的包封率、载药量及体外释放性能,并初步研究磁性微胶囊的靶向性。