超临界CO2提取的百合挥发油化学成分的GC-MS分析

目的 研究百合挥发油化学成分。方法 采用超临界CO₂提取方法,GC-MS联用技术鉴定百合挥发油成分,并用峰面积归一化法测定各成分的相对百分含量。结果 超临界CO₂流体萃取法提取的挥发油共鉴定出50种成分,占挥发油总成分的72.96%。结论 超临界提取百合挥发油成分多、效率高,与水蒸气蒸馏提取出的挥发油成分有差异。     

超临界CO2萃取温郁金和温莪术药材挥发油及其成分分析比较

目的:采用超临界流体萃取技术分别提取温郁金和温莪术的挥发油,并用 GC-MS 对挥发油进行化学成分分析对比。方法:用正交实验法确定超临界 CO_2流体萃取温郁金和温莪术挥发油的最佳条件,考察萃取压力、温度、动态萃取时间及 CO_2流量对挥发油收率的影响;利用 GC-MS 分析最佳萃取条件下所得挥发油的化学成分,面积归一化法测定其百分含量,并对两者挥发油的的化学成分进行对比。结果:温郁金超临界 CO_2萃取最佳条件为:萃取压力30 MPa,温度50℃,萃取时间1 h,CO_2流量5 L·min~(-1);挥发油的得率0.62%,从中鉴定出了21个化合物,其含量占出峰物质总量的96.83%。温莪术超临界CO_2萃取最佳条件为:萃取压力24 MPa,温度60℃,萃取时间2 h,CO_2流量15 L·min~(-1);挥发油的得率4.46%,从中鉴定出了22个化合物,其含量占出峰物质总量的74.63%。结论:温郁金和温莪术挥发油中富含酮、环氧化合物、萜类化合物、酯等组分,两者主要成分相同,但各有特殊成分。     

超临界CO_2萃取紫苏叶挥发油及其成分分析

目的:采用超临界流体萃取技术提取紫苏叶挥发油,并用GC-MS对挥发油进行化学成分分析。方法:通过单因素实验和正交实验法确定超临界CO2流体萃取紫苏叶挥发油的最佳条件,考察萃取压力、温度、动态萃取时间及CO2流量对挥发油得率的影响;利用GC-MS分析最佳萃取条件下所得挥发油的化学成分,面积归一化法测定其百分含量。结果:紫苏叶超临界CO2萃取最佳条件为:萃取压力20 MPa,温度35℃,萃取时间150 min,CO2流量10 kg.h-1;挥发油的得率3.2%,从中鉴定出了16个化合物,其含量占出峰物质总量的97.68%。结论:紫苏叶挥发油中富含醚、萜类化合物、酯、酮和醇等组分。     

超临界CO_2萃取法提取迷迭香油工艺及其化学组分研究

目的:优化超临界CO2萃取迷迭香油工艺,并分析其主要化学组分。方法:采用正交试验优化超临界CO2萃取迷迭香油工艺的参数,将提取物的化学成分经气相色谱-质谱联用法(GC-MS)进行分离鉴定,并计算各组分的相对百分含量。结果:优化的最佳工艺为萃取压力20MPa,萃取温度45℃,分离压力6MPa,萃取时间120min。迷迭香油中鉴定出21种化学组分,占挥发油总量的97.99%。迷迭香挥发油中含量较高的成分是1,8-桉叶素(27.23%)、α-蒎烯(19.43%)、樟脑(14.26%)、莰烯(11.52%)等。结论:超临界CO2萃取迷迭香油具有提取时间短、提取率高等优点;浙江产迷迭香与西班牙型较为接近。     

GC-MS方法分析肠激安方中的挥发性成分

目的采用GC-MS方法分析肠激安方中超临界CO2萃取物中挥发性成分。方法取萃取的挥发油用GC-MS法进行分析,结合计算机检索技术通过标准图谱对分离的化合物进行结构鉴定,应用色谱峰面积归一化法计算各成分的相对百分含量。结果超临界CO2萃取物挥发性成分各组分均得到较好分离,共分离出21个成分,鉴定了10个化合物。结论用GC-MS法测定肠激安方中超临界CO2萃取物挥发性成分的方法可行。     

超临界CO_2萃取与水蒸气蒸馏法提取太子参挥发油化学成分气质联用研究

目的:分析比较采用超临界CO2流体萃取法与水蒸气蒸馏法提取的太子参提取物中挥发性化学成分的异同。方法:使用水蒸馏提取法和超临界CO2萃取技术从太子参中提取挥发性成分,用归一化法测定其百分含量。用气相色谱-质谱(GC-MS)计算机联用技术分离鉴定其中的化学组成。结果:太子参超临界CO2流体萃取物中初步鉴定了33种成分,主要成分为:亚油酸乙酯(28.70%)、n-十六酸(23.12%)、3-糠醇(5.51%)等;水蒸气蒸馏法提取挥发油初步鉴定了17种成分,主要成分为2-丙基呋喃(22.45%)、3-糠醇(19.78%)、3-乙基-3-甲基戊烷(19.47%)。结论:2种方法提取的挥发油化学成分差异较大,超临界CO2流体萃取法提取的挥发油能更真实、全面地反映太子参药材中的化学成分。     

气相色谱-质谱技术分析中药丁香挥发油成分

目的:应用气相色谱-质谱(GC-MS)分析出中药丁香挥发油中的化学成分。方法:利用水蒸气蒸馏的方法提取中药丁香挥发油,并结合GC-MS技术对其成分进行检测。结果:中药丁香挥发油中共检测出4种成分,其中主要成分是3-烯丙基-2-甲氧基苯酚,占总成分的69.77%。结论:中药丁香挥发油的主要成分是3-烯丙基-2-甲氧基苯酚。     

川芎药材超临界CO2萃取与水蒸气蒸馏提取挥发油比较研究

目的 通过对不同工艺下得到的川芎挥发油的比较,阐明提取工艺对其有效成分的影响。方法 分别采用超临界CO₂萃取和水蒸气蒸馏法提取川芎挥发油,再通过气相色谱-质谱(GC-MS)联用技术分析鉴定其中的主要化学成分及相对含量。结果 2种方法所得川芎挥发油样品中共鉴定18种共有成分,水蒸气蒸馏提取物中苯酞类成分约占61%,单萜类成分约占25%,倍半萜类成分约占10%;超临界CO₂萃取物中苯酞类成分约占97%,单萜类成分约占1%,倍半萜类成分约占0.4%。结论 水蒸气蒸馏法对川芎药材中挥发性较强的单萜和倍半萜类保留相对较强,超临界CO₂萃取法对苯酞类有效成分的提取率相对较高,因此在川芎挥发油入药的中药制剂工艺中,应根据制剂的功效充分考虑提取工艺对有效成分的影响。     

紫苏梗挥发油的GC-MS定性分析

目的:定性分析紫苏梗中的挥发油。方法:采用超临界流体CO2(SFE-CO2)萃取紫苏梗挥发油,用气相色谱-质谱(GC-MS)法分离鉴定,同时用化学计量学方法解析重叠色谱峰的二维色谱MS数据。结果:共分离解析出81种组分,其中26种组分在紫苏的相关GC-MS分析中未见报道。结论:紫苏梗挥发油SFE-CO2萃取物中有多个正构烷烃存在。GC-MS结合化学计量学方法分析紫苏梗挥发油可获取更多的信息。     

龙胆超临界CO_2萃取物的GC-MS分析

目的分析龙胆的超临界CO2流体萃取成分。方法用超临界CO2流体(SFE)萃取的方法对龙胆进行提取。用GC-MS技术分析超临界CO2萃取物的化学成分。结果从龙胆中确定了28个峰的成分,含量最高的为香樟醇,占总成分的40%以上。结论本方法稳定可行,是分析龙胆中低极性组分的有效手段。     

A longitudinal assessment of aflatoxin M1 excretion in breast milk of selected Egyptian mothers.

Aflatoxins are potent toxins and carcinogens which can be excreted in the milk of exposed lactating mothers mainly in the form of aflatoxin M(1) (AFM(1)). We previously evaluated the level and frequency of AFM(1) in breast milk in a group of Egyptian mothers attending the New El-Qalyub Hospital, Qalyubiyah governorate, Egypt. In this study, fifty of those women who were AFM(1) positive were revisited monthly for 12 months to assess the temporal variation in breast milk AFM(1). AFM(1) was detected in 248 of 443 (56%) samples. In a multilevel model of the data there was a highly significant (p<0.001) effect of month of sampling on the frequency of AFM(1) detection with summer months having the highest frequency (>80%) and winter months the lowest frequency (<20%) of detection. AFM(1) was observed most frequently in June [OR 63, 95% CI (7.6, 522)]. The level of AFM(1) detection also followed this seasonal pattern with highest mean level in July (64 pg/ml milk, range 6.3-497 pg/ml milk) and the lowest mean level in January (8 pg/ml milk, range 4.2-108 pg/ml milk). The duration of lactation [p=0.0035, OR=1.08, 95% CI (1.02, 1.13)], and peanut consumption [p=0.06, OR=1.69, 95% CI (0.9, 2.9)] also contributed to the model. The identification and understanding of factors determining the presence of toxicants in human milk is important and may provide a knowledge driven basis for controlling the transfer of chemicals to infants.     

Prediction of volume of distribution in preclinical species and humans: application of simplified physiologically based algorithms

1. The present study was aimed at developing simplified physiologically based semi-mechanistic algorithms to predict V_ss and interspecies scaling factors to predict tissue-K_ps which require minimum input parameters, diminish the computing complexity and have better predictability.

2. V_ss of 86 structurally diverse compounds in preclinical species and 27 compounds in humans were predicted using only lung- and muscle-K_p as inputs. Interspecies scaling factor (s) were developed based on fold-differences in individual tissue lipid contents, relative organ blood flow: relative organ weight ratio between two species. Tissue-K_ps were predicted for 34 compounds using the newly developed interspecies scaling factors.

3. The predicted-to-experimental V_ss values for all the 113 compounds was 1.3?±?0.9 with 83% values being within a factor of two. The tissue-K_ps in rat, dog and human were predicted using experimental tissue-K_p data in rodents and interspecies scaling factors and here also, 83% of tissue-K_ps were within two-fold of the experimental values.

4. In conclusion, simplified physiologically based algorithms have been developed to predict both volume of distribution and tissue-K_ps, in which required input parameters as well as computing complexity have been noticeably reduced.

     

Serotonergic approaches in the development of novel antipsychotics

Schizophrenia is a chronic, debilitating neuropsychological disease characterised by positive, negative, and cognitive deficits. In recent years, new pharmacological treatment strategies have been developed to treat the sequalae of schizophrenia based upon more selective receptor activity profiles in the hope that treatment efficacy can be increased without inducing the side-effect profiles seen with current available therapies. One such strategy involves the development of combined (partial) 5-HT_1A agonists and D₂ receptor (partial) antagonists such as bifeprunox, SLV313, F15063 and SSR-181507 in an attempt to increase therapeutic efficacy of all symptom domains whilst alleviating adverse side effects. Other novel drugs including SLV310 and SLV314 combine selective serotonin reuptake inhibition (SSRI) functionality with D₂ receptor antagonism in an attempt to not only improve schizophrenic symptoms, but to also relieve other affective disorders intricately linked with the disorder. The main scope of this review will evaluate the major preclinical and clinical pharmacological findings concerning the aforementioned strategies and pharmacological agents, and compare their therapeutic potential with currently available antipsychotics; however, recent developments at other emerging serotonergic targets such as 5-HT_2C, 5-HT₆ and 5-HT₇ receptors will also be considered.     

In praise of H2O2, the versatile ROS,and its vanadium complexes

Hydrogen peroxide (H₂O₂) is generated in mitochondria in aerobic cells as a minor product of electron transport, is inhibited selectively by phenolic acids (in animals) or salicylhydroxamate (in plants) and is regulated by hormones and environmental conditions. Failure to detect this activity is due to presence of H₂O₂-consuming reactions or inhibitors present in the reaction mixture. H₂O₂ has a role in metabolic regulation and signal transduction reactions. A number of enzymes and cellular activities are modified, mostly by oxidizing the protein-thiol groups, on adding H₂O₂ in mM concentrations. On complexing with vanadate, also occurring in traces, H₂O₂ forms diperoxovanadate (DPV), stable at physiological pH and resistant to degradation by catalase. DPV was found to substitute for H₂O₂ at concentrations orders of magnitude lower, and in presence of catalase, as a substrate for user reaction, horseradish peroxidase (HRP), and in inactivating glyceraldehyde-3-phosphate dehydrogenase. superoxide dismutase (SOD) -sensitive oxidation of NADH was found to operate as peroxovanadate cycle using traces of DPV and decameric vanadate (V₁₀) and reduces O₂ to peroxide (DPV in presence of free vanadate). This offers a model for respiratory burst. Diperoxovanadate reproduces several actions of H₂O₂ at low concentrations: enhances protein tyrosine phosphorylation, activates phospholipase D, produces smooth muscle contraction, and accelerates stress induced premature senescence (SIPS) and rounding in fibroblasts. Peroxovanadates can be useful tools in the studies on H₂O₂ in cellular activities and regulation.     

Mechanisms of butylated hydroxytoluene chemoprevention of aflatoxicosis--inhibition of aflatoxin B1 metabolism

Chemoprevention of toxicoses and/or cancer through the use of nutrients or pharmacologic compounds is the subject of intense study. Among the many compounds examined, food additives such as antioxidants are being considered due to their ability to reduce disease formation by either induction or inhibition of key enzyme systems. One such compound, butylated hydroxytoluene (BHT), has been found to protect against cancer formation caused by exposure to aflatoxin B₁ (AFB₁) in rodents. We have shown that dietary BHT protects against clinical signs of aflatoxicosis in turkeys, a species that is very susceptible to this mycotoxin. In this study, the effect of BHT on AFB₁ metabolism and other cytochrome P450 (CYP)-related enzyme activities in turkey liver microsomes was examined to discern possible mechanisms of BHT-mediated protection against aflatoxicosis. Ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), prototype activities for CYP1A1 and 1A2, respectively, were decreased in the BHT fed (4000 ppm) animals, while oxidation of nifedipine, a prototype activity for CYP3A4, was increased. However, BHT added to microsomal incubations inhibited these CYP activities in a concentration-related manner. Importantly, BHT inhibited conversion of AFB₁ to the reactive intermediate AFB₁-8,-9-epoxide (AFBO), exhibiting Michaelis-Menton competitive inhibition kinetics (Ki = 0.81 μM). Likewise, microsomes prepared from turkeys fed BHT were significantly less active in AFBO formation compared to those from control birds. When turkeys were fed BHT for up to 40 days, residual BHT was present in liver, breast meat, thigh meat and abdominal fat in concentrations substantially below U.S. FDA guidelines for this antioxidant, but in concentrations greater than the Ki, likely sufficient to inhibit bioactivation of AFB₁in vivo. BHT-induced hydropic degeneration in the livers of BHT fed animals was significantly greater in birds that remained on BHT treatment for up to 30 days, but this lesion diminished in animals fed for 40 days or when returned to a control diet. The data indicate that the observed chemopreventive properties of BHT in turkeys may be due, at least in part, to its ability to inhibit hepatic AFB₁ epoxidation and also that the BHT-induced hydropic degeneration is reversible and does not appear to cause long-term effects.     

Determination of the kinetic properties of platycodin D for the inhibition of pancreatic lipase using a 1,2-diglyceride-based colorimetric assay

A 1, 2-diglyceride-based multi-step colorimetric assay to measure the pancreatic lipase activity was applied for the determination of the kinetic profiles of the lipase inhibition with a slight modification and the validity verification. With this assay method, our study revealed that platycodin D, one of major constituents of Platycodi Radix, inhibits the pancreatic lipase activity in a competitive type, with the value ofK _l being 0.18±0.02 mM. In addition, PD has affected the values ofK _{m, app} andK _cat/K _m in a dose- dependent manner. The results shed a meaningful light on how PD mediates lipid metabolism in the intestinal tracts. On the other hand, since the revised assay is sensitive, rapid, and does not affect the accuracy to the kinetic properties, it is applicable not only to evaluation of the kinetic properties of the pancreatic lipase, but also to highthroughput screening of pancreatic lipase activity.     

Urinary biomarkers of aflatoxin exposure in young children from Egypt and Guinea.

Aflatoxins are a major risk factor for hepatocellular carcinoma (HCC), and thus understanding the pattern of aflatoxin exposure in different regions is important in order to develop targeted intervention strategies. Given the early onset of HCC in many countries early life exposures may be important. This study investigated aflatoxin exposure in Egyptian children (n=50, aged 1-2.5 years) by assessing urinary aflatoxin metabolite (AFM(1), AFB(1), AFB(2), AFG(1), AFG(2)) levels. Samples from Guinean children (n=50, aged 2-4 years) were analyzed in parallel providing a comparison to a region of established frequent aflatoxin exposure. Aflatoxins were isolated from urine using C18-cartridges followed by immunoaffinity clean-up, and quantified by HPLC with fluorescence detection. Overall aflatoxins were less frequently present in Egyptian (38%) than Guinean urine samples (86%) (p<0.001), which was particularly related to differences in detection rates of AFM(1) (8% compared to 64%, respectively, (p<0.001)). For AFM(1) the geometric mean level in Guinea (16.3 pg/ml; 95% CI: 10.1, 26.6 pg/ml) was 6-fold higher (p<0.001) than in Egypt (2.7 pg/ml; 95% CI: 2.5, 2.8 pg/ml). Urinary aflatoxins from healthy children in these two regions have not previously been reported, and exposure appears modest in Egypt compared to Guinea. These data suggest that measures to reduce aflatoxin exposure in both regions are important, though particularly in Guinea.     

一例房颤合并冠心病患者初始抗栓治疗策略及文献复习

目的 探讨房颤伴急性冠脉综合征的抗栓治疗策略。方法 1例46岁房颤合并冠心病的男性患者,房颤卒中风险低危,入院期间未给予抗凝治疗,后出现急性脑梗塞。通过提阅部分指南及文献,分析CHA₂DS₂-VAS_c评分为1分,并伴急性冠脉综合征患者的不同抗栓治疗策略方案及其优劣。结果 文献提示,CHA₂DS₂-VAS_c评分为1分出血低危患者,建议尽早服用抗凝药。双联抗栓（华法林+氯吡格雷）能够有效抗栓并且降低患者出血风险,因此需根据患者的具体情况,尽快将三联调整为双联抗栓（1~3个月内）,保证患者疗效的情况下,降低患者出血风险。结论 临床上遇到相关患者需充分评估患者的出血及血栓风险,制定个体化的抗栓治疗策略。     

人参-黄芪药对治疗2型糖尿病作用机制的网络药理学研究

目的采用网络药理学方法研究人参–黄芪药对治疗2型糖尿病的作用机制。方法利用中药系统药理学技术平台(TCMSP)获取人参–黄芪药对的主要成分和对应靶点,通过UniProt和DrugBank数据库查询靶点对应的基因,运用Cytoscape3.6.1构建活性成分–靶点相互作用网络。然后通过TTD、DigSee、CTD多个数据库查询2型糖尿病的相关靶点,与人参-黄芪药对作用靶点取交集后获得人参–黄芪药对–T2DM疾病交集靶点。运用STRING在线数据库构建蛋白相互作用(PPI)网络,最后通过DAVID进行GO功能和KEGG通路富集分析。结果筛选得到41个活性化合物,对应靶点219个,关键靶点涉及PTGS2、PTGS1、ADRB2、NCOA2、SCN5A等。PPI网络包含36个蛋白,包括BCL2、CASP3、CASP8、TGFB1、NOS2、PPARG等。GO功能分析获得269个条目(P0.05),KEGG通路富集得到71条信号通路(P0.05),包括胰岛素抵抗通路、PI3K/Akt信号通路、脂肪细胞因子信号通路等。结论人参–黄芪药对治疗2型糖尿病是多成分、多靶点、多通路协同作用,主要参与炎症反应、细胞凋亡、氧化应激等发挥作用。