连翘挥发油化学成分、药理作用及其开发利用研究进展

连翘作为我国常用大宗中药材,具有清热解毒、消肿散结、疏散风热的功效。现代药理学研究表明,挥发油是连翘发挥药理作用的主要物质基础之一。连翘挥发油包含众多不同类型的化学成分,如萜类、烷烃类、烯烃类、醇类、醛类、酮类等,具有解热镇痛、抗炎、抗菌、抗病毒、抗氧化、抗肿瘤等广泛的药理活性。因此,连翘挥发油开发利用前景广阔,在医药、仓储防护、食品保鲜、化工及化妆品行业中均展现出较高的开发利用价值。基于对连翘挥发油研究进展的总结,对其化学成分、药理作用及开发利用现状等方面进行综述,并对其发展前景进行展望,以期为连翘质量控制及连翘挥发油的深入研究、开发和利用提供参考。     

Toxic effects of pristine and aged polystyrene microplastics on selective and continuous larval culture of acorn barnacle Amphibalanus amphitrite.

This study evaluates the toxicity of pristine (Unwashed) and aged, clean (Biofilm-) or fouled (Biofilm+), PS microspheres (3 µm,10 µm), using Washed particles as a reference material, on selective and continuous larval culture of Amphibalanus amphitrite. Exposure to 3 µm Unwashed and Biofilm+ particles for 24 h induced significant mortality (60 % and 57 % respectively) in stage II larvae. Stage II and VI nauplii showed greater uptake of 3 µm Biofilm- particles. Accumulative exposure to microplastics in continuous larval culture significantly affected the naupliar survival, particularly of stage III and IV. Cumulative mortality was > 70% after exposure to 3 µm Unwashed and 10 µm Biofilm+ particles. Unwashed particles with increasing concentration and aged particles with increasing size, delayed the development of nauplii to cyprids. Though,> 50% cyprids showed successful settlement however the highest concentration of 3 µm Biofilm+ microspheres inhibited the settlement and induced precocious metamorphosis in 9 % of the cyprids.     

Exposure to diesel engine exhaust and alterations to the Cys34/Lys525 adductome of human serum albumin

We investigated whether exposure to carcinogenic diesel engine exhaust (DEE) was associated with altered adduct levels in human serum albumin (HSA) residues. Nano-liquid chromatography-high resolution mass spectrometry (nLC-HRMS) was used to measure adducts of Cys34 and Lys525 residues in plasma samples from 54 diesel engine factory workers and 55 unexposed controls. An untargeted adductomics and bioinformatics pipeline was used to find signatures of Cys34/Lys525 adductome modifications. To identify adducts that were altered between DEE-exposed and unexposed participants, we used an ensemble feature selection approach that ranks and combines findings from linear regression and penalized logistic regression, then aggregates the important findings with those determined by random forest. We detected 40 Cys34 and 9 Lys525 adducts. Among these findings, we found evidence that 6 Cys34 adducts were altered between DEE-exposed and unexposed participants (i.e., 841.75, 851.76, 856.10, 860.77, 870.43, and 913.45). These adducts were biologically related to antioxidant activity.     

Prediction of embryotoxic potential using the ReProGlo stem cell-based Wnt reporter assay

The ReProGlo assay was developed in 2009 to predict embryotoxic potential of drugs and chemicals by use of a stem cell-based in vitro system. It utilizes a luciferase reporter to detect drug-induced alterations in the canonical Wnt/β-catenin signaling pathway, which is involved in regulation of early embryonic development. It allows the simultaneous determination of cell viability and luciferase reporter activity in a high throughput format. The present study was conducted within the framework of the EU ChemScreen-project. It (1) enlarges the original number of test-compounds from 17 to now 80, (2) introduces a new classification scheme and (3) anchors the results against a prediction scheme based on structural features of chemicals. The assay is applicable as stand-alone for priority setting or in a test battery.     

Absence of glutaredoxin1 increases lens susceptibility to oxidative stress induced by UVR-B

We investigated if the absence of glutaredoxin1, a critical protein thiol repair enzyme, increases lens susceptibility to oxidative stress caused by in vivo exposure to ultraviolet radiation type B (UVR-B). Glrx^−/− mice and Glrx^+/+ mice were unilaterally exposed in vivo to UVR-B for 15 min. Groups of 12 animals each received 4.3, 8.7, and 14.5 kJ/m² respectively. 48 h post UVR-B exposure, the induced cataract was quantified as forward lens light scattering. Cataract morphology was documented with darkfield illumination photography. Glutathione (GSH/GSSG) content was analyzed in Glrx^−/− and Glrx^+/+ lenses. UVR-B exposure induced anterior sub-capsular cataract (ASC) in Glrx^−/− and Glrx^+/+ mice. In Glrx^−/− lenses the opacities extended further towards the lens equator than in wild type animals (Glrx^+/+). Lens light scattering in Glrx^−/− mice was increased in all dose groups compared to lenses with normal glutaredoxin1 function. The difference was more pronounced with increasing exposure dose. Lens sensitivity for UVR-B induced damage was significantly higher in Glrx^−/− lenses compared to Glrx^+/+ lenses. The Glrx gene provides a 44% increase of protection against close to threshold UVR-B induced oxidative stress compared to the absence of the Glrx gene. In conclusion, the absence of glutaredoxin1 increases lens susceptibility to UVR-B induced oxidative stress in the mouse.     

定坤丹胶囊的药效学研究

目的探讨定坤丹胶囊的药效作用。方法采用皮下注入肾上腺素加冰水复制血瘀模型，测定全血黏度、血浆黏度和血细胞比容；采用塑料环和二甲苯法，测定肉芽肿和耳肿胀；采用腹腔注射醋酸法，测定小鼠扭体次数；采用小鼠断头法，测定鼠头存活时间；采用子宫称重法，测定小鼠子宫发育状态。结果定坤丹胶囊可显著降低全血黏度、血浆黏度和血细胞比容，减轻肉芽肿和耳肿胀程度，减少小鼠扭体次数，延长耐缺氧时间，对小鼠子宫发育有显著促进作用。结论定坤丹胶囊具有较好的活血化瘀、抗炎、止痛、抗缺氧和促进子宫发育的作用。     

A NEW BUTADIENE DERIVATIVE,T-686, INHIBITS PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 PRODUCTION IN VITRO BY CULTURED HUMAN VASCULAR ENDOTHELIAL CELLS AND DEVELOPMENT OF ATHEROSCLEROTIC LESIONS IN VIVO IN RABBITS

Plasminogen activator inhibitor-1 (PAI-1), the major physiologic inhibitor of tissue-type plasminogen activator and urokinase, is abundantly expressed in atherosclerotic vascular wall. To determine the role of PAI-1 in vascular wall, we have used a novel inhibitor of PAI-1, (3E, 4E)-3-benzylidene-4-(3,4,5-trimethoxy-benzylidene)-pyrrolidine-2,5-dione (T-686). T-686 was given to human vascular endothelial cells in vitro and to rabbits subjected to high cholesterol diet and mechanical injury in vivo. T-686 attenuated the augmentation of PAI-1 antigen accumulation induced by transforming growth factor β in conditioned medium from the human umbilical vein endothelial cells. In rabbits with aortic atherosclerosis induced by hypercholesterolemia and implantation of indwelling plastic tubing, oral administration of T-686 (30mg/kg body weight/day) for 8 weeks attenuated the increase in plasma PAI-1 activity induced by vascular injury without decreasing blood triglyceride and cholesterol. This was accompanied by the reduction in aortic PAI-1 mRNA expression and the inhibition of development of atherosclerosis lesions. Thus, T-686 not only decreased PAI-1 synthesis in vascular cells in vitro but also protected against the development of vascular lesions in vivo. This compound may be useful in defining the role of PAI-1 in atherothrombotic states. Copyright © 1997 Elsevier Science Ltd