Alpha-asarone inhibits HMG-CoA reductase, lowers serum LDL-cholesterol levels and reduces biliary CSI in hypercholesterolemic rats.

Our results showed that alpha-asarone was an inhibitor of hepatic HMG-CoA reductase and that the administration of alpha-asarone at 80 mg/kg body wt. for 8 days decreased serum cholesterol by 38% (p < 0.001) in hypercholesterolemic rats. This alpha-asarone treatment affected mainly the serum LDL-cholesterol levels, leaving serum HDL-cholesterol lipoproteins unaffected, with a consequent decrease of 74% in the LDL/HDL ratio. In addition, alpha-asarone especially stimulated bile flow in hypercholesterolemic rats (60%), increasing the secretion of bile salts, phospholipids and bile cholesterol. The drug also reduced the cholesterol levels of gallbladder bile, whereas the concentration of phospholipids and bile salts increased only slightly, leading to a decrease in the cholesterol saturation index (CSI) of bile in the hypercholesterolemic rats. This CSI decrease and the increase in bile flow induced by alpha-asarone may account for the cholelitholytic effect of alpha-asarone. It seems that alpha-asarone induced clearance of cholesterol from the bloodstream and that the excess of hepatic cholesterol provided by LDL-cholesterol is diverted to bile sterol secretion via a bile choleresis process. The inhibition of HMG-CoA reductase and the increase in bile flow induced by alpha-asarone, as well as the decrease in the CSI, could then explain the hypocholesterolemic and cholelitholytic effects of alpha-asarone.     

2,4,5-trimethoxycinnamic acid: the major metabolite of alpha-asarone, retains most of the pharmacological properties of alpha-asarone

2,4,5-trimethoxycinnamic acid (TMC), the major and non toxic metabolite of alpha-asarone (2,4,5-trimethoxy-1-propenyl benzene), retains most of the pharmacological properties of alpha-asarone, since both substances, administered to hypercholesterolemic rats at 80 mg/kg body wt, decreased total serum cholesterol, lowered LDL-cholesterol levels and kept unaffected HDL-cholesterol levels. In addition, both substances increased bile flow, especially in hypercholesterolemic rats, by rising the secretion of bile salts, phospholipids and bile cholesterol. These drugs also reduced cholesterol levels of gallbladder bile, whereas phospholipids and bile salts concentrations were increased, decreasing the cholesterol saturation index (CSI). We also found that alpha-asarone was 20 times better inhibitor of HMG-CoA reductase than TMC. This effect on HMG-CoA reductase was the only property highly reduced in TMC in comparison with alpha-asarone, while the other pharmacological properties of alpha-asarone were retained by TMC. These experiments strongly suggest that TMC can be further studied as a possible hypocholesterolemic and cholelitholytic agent.     

Genotoxicity of alpha-asarone analogues

The role of cholesterol in the formation of atherosclerotic lesions during hypercholesterolemia has been confirmed. alpha-Asarone is a substance of a potent hypolipidemic activity which is isolated from plants. We previously described the synthesis of several alpha-asarone analogues exhibiting hypolipidemic and antiplatelet activity. Genotoxic activity of four selected alpha-asarone analogues was theoretically evaluated based on quantum-mechanical method for calculation of enthalpy of carbocations formation (DeltaH(R)) according to the Testa's method. In the present paper, we evaluated the mutagenic and genotoxic activity of alpha-asarone isomers 2-5 based on the reference Ames test and micronucleus test. Results obtained in the study show that tested isomers were non-mutagenic, however, they exhibited growing cytotoxic activity. Relationship between the heat of formation of their putative metabolic intermediates and mutagenic/genotoxic activity was not confirmed.     

alpha- 细辛脑注射液对哮喘患儿血清COX-2，IL-8 及IgE 水平的影响及其 临床疗效

目的：评价琢-细辛脑注射液辅助治疗对哮喘患儿血清中COX-2、IL-8、IgE 水平的影响及其临床疗效。方法：选取我院哮喘 患儿96 例,随机分为实验组和对照组,各48 例,对照组采用常规药物治疗,实验组在此基础上加用琢-细辛脑注射液,观察患儿的 临床症状并测量血清中COX-2、IL-8、IgE 含量的变化情况。结果：实验组有效率明显高于对照组,差异具有统计学意义（x2=5.352, P=0.0207）;实验组喘息、呼吸困难、胸闷、咳嗽及哮鸣音等临床症状的消失时间明显低于对照组,差异均具有统计学意义（P<0. 05）;实验组治疗后血清COX-2、IL-8 及IgE 因子含量显著低于对照组,差异均具有统计学意义（P<0.05）。结论：琢- 细辛脑注射液 辅助治疗哮喘的疗效显著,能够降低患儿血清COX-2、IL-8 及IgE水平。     

Sister-chromatid exchange induction produced by in vivo and in vitro exposure to alpha-asarone.

The effect of alpha-asarone, a chemical with hypocholesterolemic properties extracted from Guatteria gaumeri, on SCE induction was studied both in human lymphocytes in vitro and in murine bone marrow cells in vivo. A slight but consistent increase in SCE was observed in both biological systems.     

3D QSAR study of hypolipidemic asarones by comparative molecular surface analysis

Three-dimensional quantitative structure-activity relationship (3D QSAR) modeled for alpha-asarone derivatives using the comparative molecular surface analysis (CoMSA) allowed us to reveal a correlation between the activity of these compounds and the electrostatic potential at the molecular surface. The grid formalism (s-CoMSA) allowed us to indicate a pharmacophore that is of key importance for compound activity. The CoMSA formalism coupled with the iterative variable elimination method gives a highly predictive model.     

Fungicidal property of active component derived from Acorus gramineus rhizome against phytopathogenic fungi

The fungicidal property of Acorus gramineus rhizome-derived materials against Botrytis cineria, Erysiphe graminis, Phytophthora infestans, Puccinia recondita, Pyricularia grisea, and Rhizoctonia solani was tested using a whole plant method in vivo, and was compared with a synthetic fungicide and seven commercially available A. gramineus rhizome-derived components. The responses varied according to the plant pathogen tested. At 2000 mg/l, the hexane fraction of A. gramineus rhizomes showed strong fungicidal activities against R. solani and P. infestans. The results indicated at least one of the fungicidal actions of alpha-asarone and asaronaldehyde derived from A. gramineus rhizomes.     

石菖蒲及α-细辛醚对疲劳运动大鼠学习记忆的影响及其机制*

目的: 研究石菖蒲及其活性成分-α-细辛醚改善疲劳运动大鼠学习记忆的作用及其机制。方法: 80只SD大鼠随机分为正常对照组(A)、单纯运动组(B)、运动+α-细辛醚低、中、高剂量组(C、D、E)、运动+石菖蒲低、中、高剂量治疗组(F、G、H),每组10只。并在疲劳运动开始前2 h分别以0.10、0.50 和 1.00 mg α-细辛醚,灌胃C、D、E组,以0.12、1.20和4.80 g. kg^-1. wt^-1石菖蒲提取物,灌胃 F、G、H组。实验结束后采用水迷宫实验进行学习记忆检测,采用生化法检测SOD、NOS活性和MDA含量,免疫印迹法检测海马nNOS蛋白表达水平。结果: 实验后E和H组大鼠逃避潜伏期、海马脑组织MDA含量低于B、C、D、F和G组;穿越平台次数、海马脑组织SOD和NOS活性、nNOS蛋白表达高于B、C、D、F和G组,P均＜0.01。A、E、H组大鼠海马脑组织SOD活性依次为A＞E＞H组, 而MDA含量则相反,P均＜0.01;E组大海马脑组织NOS活性和nNOS蛋白表达低于A和H组,P＜0.01或P＜0.05,但A和H组,差异无显著性,P均＞0.05。A、E、H组大鼠逃避潜伏期和穿越平台次数,差异均无显著性,P均＞0.05。结论: 石菖蒲及α-细辛醚改善疲劳运动大鼠学习记忆的作用基本一致,其机制与纠正海马自由基代谢失衡和上调海马nNOS/NO信号有关。     

Protection of cultured rat cortical neurons from excitotoxicity by asarone,a major essential oil component in the rhizomes of Acorus gramineus

Previous reports have shown that the methanol extract and the essential oil from Acori graminei Rhizoma (AGR) inhibited excitotoxic neuronal cell death in primary cultured rat cortical cells. In the present study, an active principle was isolated from the methanol extract by biological activity-guided fractionations and identified as asarone. We evaluated neuroprotective actions and action mechanisms of the isolated asarone as well as the alpha- and the beta-asarone obtained commercially. The isolated asarone inhibited the excitotoxicity induced by the exposure of cortical cultures for 15 min to 300 microM NMDA in a concentration-dependent manner, with the IC50 of 56.1 microg/ml. The commercially obtained alpha- and beta-asarone exhibited more potent inhibitions of the NMDA-induced excitotoxicity than the isolated asarone. Their respective IC50 values were 18.2 and 26.5 microg/ml. The excitotoxicity induced by glutamate (Glu) was also inhibited, but with much less potency than the toxicity induced by NMDA. The IC50 values for the alpha-, beta-, and the isolated asarone were 89.7, 121.7, and 279.5 microg/ml, respectively. Based on the receptor-ligand binding studies using a use-dependent NMDA receptor-channel blocker [3H]MK-801, asarone inhibited the specific bindings in a concentration-dependent fashion. These results indicate that asarone, the major essential oil component in AGR, exhibits neuroprotective action against the NMDA- or Glu-induced excitotoxicity through the blockade of NMDA receptor function. The alpha-asarone was found to exhibit more potent inhibition of [3H]MK-801 bindings, which is consistent with its more potent neuroprotective action than the beta- or the isolated asarone.     

An overview on traditional uses and pharmacological profile of Acorus calamus Linn. (Sweet flag) and other Acorus species

Acorus calamus (Sweet flag) has a long history of use and has numerous traditional and ethnomedicinal applications. Since ancient times, it has been used in various systems of medicines such as Ayurveda, Unani, Siddha, Chinese medicine, etc. for the treatment of various aliments like nervous disorders, appetite loss, bronchitis, chest pain, colic, cramps, diarrhea, digestive disorders, flatulence, gas, indigestion, rheumatism, sedative, cough, fever, bronchitis, inflammation, depression, tumors, hemorrhoids, skin diseases, numbness, general debility and vascular disorders. Various therapeutic potentials of this plant have been attributed to its rhizome. A number of active constituents from leaves, rhizomes and essential oils of A. calamus have been isolated and characterized. Of the constituents, alpha and beta-asarone are the predominant bioactive components. Various pharmacological activities of A. calamus rhizome such as sedative, CNS depressant, anticonvulsant, antispasmodic, cardiovascular, hypolipidemic, immunosuppressive, anti-inflammatory, cryoprotective, antioxidant, antidiarrheal, antimicrobial, anticancer and antidiabetic has been reported. Genotoxicity and mutagenecity of beta and alpha-asarone is reported, which limits their use at high dosage. Though A. calamus has been used since ancient times, many of its uses are yet to be scientifically validated. In the present review an attempt has been made to explore traditional uses and pharmacological properties of A. calamus.     

Argon laser treatment of port-wine stains: the patients' evaluations of the result.

The argon laser is now a well-established method of treating port-wine stains (PWS) in the face and neck areas. Satisfactory results are reported in 44 to 75 percent of cases, but criteria for that classification and the patients' perceptions of the result are seldom given. In the present paper, a sample of 58 patients was used to assess the patients' own perceptions of the degree of lightening and scarring. Three felt the results were excellent, 23 good, 18 fair, and 14 poor. The treatment was considered as unpleasant by 76 percent, and 55 percent of the patients asked for a new consultation. Scarring was noticed by 50 percent. The patients' perceptions of the results and physicians' rating were the same in 69 percent. The best results were obtained in older patients with small port-wine stains. Such lesions also can be treated surgically with good results.     

Intensification of the excretory flow of plutonium-239 from the body in the late stage of its metabolism

The paper deals with the effect of iron preparations on the excretion of plutonium 239 from a body at a later stage of the radionuclide metabolism. The experimental results show that oral administration of the iron preparation at a later stage of 239Pu metabolism enhances the radionuclide excretion both in urine and in faeces. On the basis of the results obtained the coefficients are calculated for 239Pu excretion in urine and faeces and for its content in the organs of deposition. This may be used for increasing the sensitivity of indirect dosimetry of plutonium-239 within the body.     

The influence of the material properties on the biomechanical behavior of the pelvic floor muscles during vaginal delivery

In this work, a finite element model intends to represent the effects that the passage of a fetal head can induce on the muscles of the pelvic floor, from a mechanical point of view.The finite element method is a valuable tool, that is contributing to the clarification of the mechanisms behind pelvic floor disorders related to vaginal deliveries, although some care is necessary in order to obtain correct results. The present work shows how the variation of the material parameters, used in the constitutive model, can affect the obtained results from a finite element simulation. The constitutive equation adopted in this work for the pelvic floor muscles is a modified form of the incompressible transversely isotropic hyperelastic model proposed earlier by Humphrey and Yin.Results for the pelvic floor strain and stresses obtained during the passage of the fetus head are presented. The results show the importance of the material parameters and the need for a correct constitutive model.     

A study of the suitability of gas chromatography-electron capture detection for the analysis of deoxynivalenol in cereals

A gas chromatographic-electron capture detection (GC-ECD) method for the analysis of deoxynivalenol (DON) in cereals was investigated. The sample was extracted with a mixture of acetonitrile-water and purified with a MycoSep #225 column. The silylation was performed with Tri-Sil-TBT reagent, followed by dilution with hexane and a washing step with buffer. By using Tri-Sil-TBT reagent no double peaks were observed for DON in the gas chromatograms, in comparison with two other silylation reagents TMSI and Tri-Sil-Z. The use of trichothecolone (TRI) as an internal standard for DON was studied in order to indicate possible problems in the derivatisation reaction. TRI proved to be a relatively good internal standard for DON in cereal samples, as well as 1,1-bis-(4-chlorophenyl)-2,2-dichloroethylene (DDE), which was used as a GC standard for ensuring the function of GC-ECD. During the study, a matrix effect was clearly observed between the cereal matrix-assisted calibration curve and the calibration curve prepared without cereal matrix. The results of spiked and reference material samples, quantified with the calibration curve prepared without and with matrix, demonstrated that the matrix affects the results. However, after recovery correction the results were comparable. The validation results demonstrated that the GC-ECD method for DON analysis in cereals is sufficiently reliable.     

Genetic analysis of the role of the drosophila fat facets gene in the ubiquitin pathway

The Drosophila fat facets gene encodes a deubiquitinating enzyme required during eye development to limit the number of photoreceptors in each facet to eight. Ubiquitin is a small polypeptide that targets proteins for degradation by the proteasome. Deubiquitinating enzymes cleave ubiquitin-protein bonds. In order to investigate the role of FAT FACETS in the ubiquitin pathway, genetic interactions between fat facets and the Drosophila UbcD1 gene were assessed. In addition, three yeast deubiquitinating enzyme genes were tested for their ability to substitute for fat facets in the developing Drosophila eye and for their effects on eye morphology. The results of these experiments support the hypothesis that FAT FACETS activity antagonizes that of the proteolytic machinery. The implications of these results for the specificity of FAF and yeast UBPs are discussed as well.     

Further Investigations on the Robustness of the Standardized Selection Difference

The robustness of the standardized selection difference is investigated for the family of central chi-squared-distributions. The results are compared with those for the uniform, a family of triangular distributions and the exponential distribution. Beside these exact results and some simulation results are considered.     

Results of cytogenetic studies of the consequences of the Chernobyl accident

The selected results of the cytogenetic studies of the Chernobyl accident consequences were summarised. The chromosomal aberrations were used as a method of biodosimetry for a dose assessment for victims during the initial period after the Chernobyl accident. A good correlation between doses calculated based on chromosomal aberrations (dicentrics) and severity of acute radiation syndrome observed in clinic was found. The biodosimetry based on conventional cytogenetic technique (dicentrics) has been unsuccessful for various groups (rehabilitation workers, evacuees, inhabitants of contaminated areas) sampled long time after the Chernobyl accident. The possible reasons of the failure are analysed. The original results of multiaberration cell yield observed in different cohorts of the Chernobyl victims are presented. The problems related to the phenomena are discussed.     

Effect of the normal component of the magnetic field on the kink instability of the Earth’s magnetospheric current sheet

The kink instability of a thin anisotropic current sheet is analyzed. It is shown that, for highly anisotropic current sheets, the instability growth rate is larger than that previously obtained using the Harris isotropic sheet model. The calculated oscillation period is a few minutes. The results of calculations are compared to the observed oscillations of the magnetotail current sheet. The results obtained indicate that kink instability can significantly contribute to large-scale variations in the structure of the Earth’s magnetotail current sheet.     

Optimised loads for the simulation of axial rotation in the lumbar spine

Simplified loading modes (pure moment, compressive force) are usually applied in the in vitro studies to simulate flexion-extension, lateral bending and axial rotation of the spine. The load magnitudes for axial rotation vary strongly in the literature. Therefore, the results of current investigations, e.g. intervertebral rotations, are hardly comparable and may involve unrealistic values. Thus, the question 'which in vitro applicable loading mode is the most realistic' remains open. A validated finite element model of the lumbar spine was employed in two sensitivity studies to estimate the ranges of results due to published load assumptions and to determine the input parameters (e.g. torsional moment), which mostly affect the spinal load and kinematics during axial rotation. In a subsequent optimisation study, the in vitro applicable loading mode was determined, which delivers results that fit best with available in vivo measurements. The calculated results varied widely for loads used in the literature with potential high deviations from in vivo measured values. The intradiscal pressure is mainly affected by the magnitude of the compressive force, while the torsional moment influences mainly the intervertebral rotations and facet joint forces. The best agreement with results measured in vivo were found for a compressive follower force of 720N and a pure moment of 5.5Nm applied to the unconstrained vertebra L1. The results reveal that in many studies the assumed loads do not realistically simulate axial rotation. The in vitro applicable simplified loads cannot perfectly mimic the in vivo situation. However, the optimised values lead to the best agreement with in vivo measured values. Their consequent application would lead to a better comparability of different investigations.