辽藁本化学成分的研究

从辽藁本(Ligusticum jeholense Nakai et Kitagawa)根及根茎的95%乙醇提取物的石油醚—乙醚(1∶1)及乙醚溶解部分用常压、低压柱层析及制备薄层层析法,共分离得到5个化合物,经光谱解析(IR,MS,¹HNMR,¹³CNMR,¹H-¹³CCOSY,¹H-¹HCOSY,DEPT,HMBC和NOE差谱)及标准品对照,确定其中一个为新化合物,命名为新藁本内酯(I)。另外4个已知化合物分别为藁本内酯(II),4-羟基-3-甲氧基-苯乙烯(III),阿魏酸(IV)和β-谷甾醇(V),并对II的¹³CNMR谱进行了重新归属,使之更为合理。     

RP-HPLC法测定田七痛经胶囊中阿魏酸、藁本内酯、欧当归内酯A

目的 建立高效液相色谱法测定田七痛经胶囊中阿魏酸、藁本内酯、欧当归内酯A的方法。方法 选用Thermo Acclaim C₁₈色谱柱,Thermo SCIENTIFICSyncronis C₁₈色谱柱;检测波长为321、280 nm;体积流量1.0 mL/min;柱温35℃结果 阿魏酸、藁本内酯、欧当归内酯A的质量浓度与峰面积分别在1.12～112.30、1.33～132.60、0.96～95.50 μg/mL呈良好的线性关系;回归方程分别为Y=46 335 540 X+44 186.71（r=0.998）,Y=14 514 060 X+8 715.27（r=0.999）,Y= 22 031 250 X+16 472.10（r=0.999）。结论 该方法准确,简便,灵敏,可作为田七痛经胶囊质量控制的方法。     

四种藁本药材挥发油的气相色谱—质谱分析比较

本文采用毛细管气相色谱—质谱—计算机联用方法,比较了辽藁本(Ligusticum jeholense)、藁本(Ligusticum sinense)及两种新疆藁本(Conioselium tataricum)药材挥发油中的化学成分,初步鉴定111个组分68个化合物。新疆藁本和辽藁本均含有α-水芹烯、藁本内酯、正丁烯基酞内酯及榄香脂素;藁本主要成分为新蛇床酞内酯、柠檬烯及蛇床酞内酯;四种藁本均含有肉豆蔻醚,蛇床酞内酯、α-派烯及异松油烯。其中肉豆蔻醚的含量以尼县新疆藁本为最高(44.25%),其次为辽藁本(9.08%),以察县新疆藁本(1.13%)及藁本(1.63%)为最低。     

藁本中两种活性成分的高效液相色谱法测定

目的：为中药藁本内在质量的评价提供科学依据,建立了藁本中两种活性成分:阿魏酸(ferulic acid)、藁本酚(ligustiphenol)的定量分析方法。方法：反相高效液相色谱法,采用 7μm Nucleosil-C₁₈键合相柱,流动相为MeOH—H₂O(40～60),以H₃PO₄调至pH 3.6,2-萘酚为内标,280 nm为检测波长。结果：阿魏酸与藁本酚可达基线分离,两者标准品的进样量分别为0.27～4.38 μg和0.55～8.80 μg,对样品峰面积与内标峰面积比呈良好线性关系。平均回收率为97.4%～100.9%。用此法对不同产地野生及市售中国藁本及辽藁本的根及根茎进行了分析,测得了阿魏酸及藁本酚的含量,不同产地的藁本药材中此两种活性成分的含量差别较大。结论：此法简便、快速,适用于药材分析,可作为证实地道药材的化学依据。     

复方藁本内酯微乳的制备和含量测定

目的:制备复方藁本内酯微乳并测定其主要成分藁本内酯和桂皮醛的含量.方法:制备复方藁本内酯微乳,HPLC法测定其主要成分含量.色谱柱为Inertsil ODS-3 (250 mm×4.6 mm,5μm).测定藁本内酯时流动相为乙腈∶甲醇∶水(10∶60∶30),柱温为5℃,检测波长为280 nm;测定桂皮醛时流动相为甲醇∶水(60∶ 40),柱温为25℃;检测波长为290 nm.流速均为1.0 ml·min-1.结果:藁本内酯在0.50 ～50.00 μg·ml-1(r =0.999 9),桂皮醛在1.30 ～130.18 μg· ml-1(r =0.999 8)范围内线性良好,藁本内酯的回收率为99.65％,RSD为0.97％(n=9);桂皮醛的回收率为99.81％,RSD为0.62％(n=9).结论:复方藁本内酯微乳制备简单,以HPLC方法测定其主成分含量快速,准确,可靠.     

雷公藤化学成分的研究 Ⅲ.两种新二萜内酯——雷酚内酯甲醚和雷酚新内酯的分离及结构

从福建产雷公藤(Tripterygium wilfordii Hook.f.)的根皮中分离到三种二萜内酯。(1)雷酚内酯(triptophenolide),C₂₀H₂₄O₃,熔点232～233℃。(2)雷酚内酯甲醚(triptophenolide methyl ether),C₂₁H₂₆O₃,熔点152～154℃。(3)雷酚新内酯(neotriptophenolide),C₂₁H₂₆O₄,熔点189～191℃。根据理化性质及UV、IR、¹HNMR、¹³CNMR、MS等光谱数据,推测化学结构分别为Ⅴ、Ⅵ及Ⅶ。Ⅵ与Ⅶ是二种新的二萜内酯化合物。     

复方根皮素乳膏中根皮素、藁本内酯体外透皮吸收研究

摘 要 目的：测定复方根皮素乳膏中根皮素、藁本内酯的离体大鼠透皮吸收率。方法: 以Franz智能透皮实验仪进行体外透皮吸收试验,取不同时间点接收液,以HPLC法测定根皮素、藁本内酯含量,计算累计释放量和累计透过量,进行透皮吸收行为评价。结果: 根皮素、藁本内酯分别在0.044 2~4.42 μg·mL^-1(r=0.999 9)和0.048 7~4.87 μg·mL^-1(r=0.999 9)范围内线性良好,平均回收率分别为99.85%、99.92%,RSD分别为0.67%、0.66%(n=9),根皮素、藁本内酯透过离体大鼠皮肤的皮肤渗透行为符合Higuchi方程,r值均大于0.9,即累积渗透量Qn与时间t呈良好线性关系。结论:复方根皮素乳膏具有良好的透皮性能。     

变色马兜铃中银袋内酯乙、丙的结构测定

从变色马兜铃(Aristolochia versicolar S M Hwang)的块根中分离到两个新倍半萜内酯,分别命名为银袋内酯乙(versicolactone B)和银袋内酯丙(versicolactone C)。前者分子式C₁₅H₂₀O₃,熔点135～136℃;后者分子式C₁₅H₂₂O₄,熔点181～182℃,[α]_D³⁶—11.4°(C,2.6,EtOH)。经光谱(UV,IR,¹H NMR,¹³SCNMR,MS)分析和化学方法证明,并经x-衍射证实,两者的结构分别为(Ⅰ)和(Ⅲ)。银袋内酯丙系一新型骨架的奠类倍半萜内酯。     

GC-FID法测定消癥丸中莪术酮、藁本内酯和α-香附酮

目的 建立气相色谱–氢火焰离子化检测器（GC-FID）法同时测定消癥丸中莪术酮、藁本内酯和α-香附酮的方法。方法 采用HP-5MS毛细管柱（30 m×0.25 mm×0.25 μm）,FID检测器：280℃,进样口温度240 ℃;程序恒温130 ℃,保持45 min;载气为N₂,柱体积流量1.5 mL/min,不分流模式;进样量：1 μL。结果 莪术酮、藁本内酯、α-香附酮分别在1.684～168.400、2.496～249.600、2.180～218.000 μg/mL线性关系良好;平均回收率分别为97.98%、99.76%、96.06%,RSD值分别为1.62%、0.89%、1.29%。结论 该方法操作简单、重复性好,可为评价消癥丸的质量控制提供依据。     

藁本内酯二聚体的合成工艺研究

目的:研究藁本内酯二聚体(化合物Ⅰ)的全合成工艺。方法:以邻苯二甲酸酐(化合物Ⅱ)为原料,经硼氢化钠还原得到苯酞(化合物Ⅲ)后经4步反应得到藁本内酯二聚体,经质谱、核磁共振氢谱(1H-NMR)和核磁共振碳谱(13C-NMR)进行表征。以催化剂、反应温度、反应时间为因素,收率为指标,采用正交试验优化第5步合成工艺,并进行验证。结果:第5步的最优合成工艺为在2%三氯化铝的催化下以温度150℃反应5 h。成功合成目标产物,验证试验平均收率为56.16%(RSD=1.23%,n=3);总的反应产率为24.4%,得到目标产物的纯度为99.4%。结论:成功合成藁本内酯二聚体,且本合成工艺稳定、质量可控。     

黄花夹竹桃中强心甙测定方法的研究

从黄花夹竹桃果仁中提出的黄夹甙为一混合强心甙,主要含有黄花夹竹桃次甙甲、黄花夹竹桃次甙乙、单乙酰黄花夹竹桃次甙乙及2～3种微量的其它强心甙。本文报道了用碱性苦味酸钠试剂比色测定其总甙含量及用高压液相层析分别测定各个组分含量的方法。高压液相层析是用YWG-CH填充柱(25cm×7.9mm i.d.),70%甲醇作流动相,几个组分能完全分离。若样品为果仁的强心甙提取物则需经硅胶柱净化后,再用高压液相层析测定。本法简便、快速、重现性好。曾用本法测定了一些不同来源的黄夹甙样品,并与生物检定结果比较,二者一致。     

18-甲基炔诺酮中间体的拆分

D-及L-18-甲基炔诺酮是以消旋19-去甲基13β-乙基-3β,17β-双羟基17α-乙炔基-4-雄甾烯(Ⅲ)为原料,经Ⅲ的丁二酸单醋与(+)α-甲基苯乙胺成盐,然后分离,分别水解,氧化即得D-左旋18-甲基炔诺酮(Ⅶa)和L-右旋18-甲基炔诺酮(Ⅶb)。如用(—)α-甲基苯乙胺,首先得L-构型的右旋18-甲基炔诺酮(Ⅶb),而母液中的D-左旋体未进行分离。     

独角莲化学成分的研究

从天南星科植物独角莲块茎中分得三种成分:(1)β一谷甾醇,C₂9H₅₀O,熔点137—138℃,[α]_D²³=-36.4°(CHCl3).(2)β-谷甾醇-D-葡萄糖甙,C₃₅H₆₀O₆,熔点277—279℃(分解),[α]_D²²=-44.5°(吡啶).(3)不活性肌醇,C₆H₁₂O₆,熔点223—225℃. 尚未肯定部分有:(1)酸性部分:由醚浸出液经碳酸氢钠提得部分,进行纸上层析,溶剂系梳为正丁醇:5M甲酸水溶液(90:55),在紫外线下有二个蓝色萤光点.R_f1值=0.78,R_f2值=0.90.如以正戊醇:5M甲酸水溶液作溶剂,则R(f1)值=0.73,R_f2)值=0.90.(2)溶血成分:由醇浸出液经铅盐法处理,由盐基性沉淀部分,分得具溶血及吸湿性的淡棕色粉末,未能测得熔点,可能为皂甙。     

Mechanism of chloroform nephrotoxicity : II. In vitro evidence for renal metabolism of chloroform in mice

Preincubation of renal cortical slices with chloroform (CHCl₃) from male, but not female, mice resulted in a subsequent decrease of the ability of the slices to accumulate the organic ions, p-aminohippurate (PAH) and tetraethylammonium (TEA). These sex-related differences, the time required for manifestation of this effect (60 to 90 min), and the concentration dependency (0 to 50 μmol, 0 to 4 μl CHCl₃) were similar to in vivo observations on CHCl₃ nephrotoxicity in mice. Furthermore, an equimolar concentration of deuterated CHCl₃ (CDCl₃) in vitro was less effective than CHCl₃ in decreasing PAH and TEA accumulation in male renal cortical slices. The effects of CHCl₃ on PAH and TEA accumulation could be diminished or blocked by preincubation with CHCl₃ in the presence of carbon monoxide or at 0°C, respectively. The nephrotoxicity of CHCl₃ in vitro was increased in renal cortical slices from male mice pretreated with diethyl maleate. Thus, this in vitro model with mouse renal cortical slices and the sex-related differences in CHCl₃ nephrotoxicity suggests that the kidney may metabolize CHCl₃ in situ to a nephrotoxic metabolite.     

Evaluation of Biological Activity of Turkish Plants. Rapid Screening for the Antimicrobial,Antioxidant, and Acetylcholinesterase Inhibitory Potential by TLC Bioautographic Methods

Using thin-layer chromatography (TLC) bioautography, a total of 58 extracts from various organs (aerial parts, leaves, flowers, fruits, roots) of 16 Turkish plants were tested for their antibacterial, antifungal, acetylcholinesterase inhibitory, antioxidant, and radical scavenging activities. The hexane, CHCl₃/CH₂Cl₂, water, and total MeOH extracts were used. No activity was observed against two Gram-negative bacteria (Escherichia coli and Pseudomonas aureginosa) and the yeast Candida albicans. However, 23 plant extracts, mostly the CHCl₃/CH₂Cl₂ and H₂O-solubles, inhibited the growth of all five Gram-positive bacteria tested, Micrococcus luteus, Bacillus subtilis, Bacillus cereus, Staphylococcus aureus, and Staphylococcus epidermidis. Of the active extracts, the CHCl₃-soluble of the roots of Putoria calabrica (L. fil) DC (Rubiaceae) displayed the highest antibacterial potential. The majority of the CHCl₃/CH₂Cl₂ crude extracts also appeared to inhibit acetylcholinesterase on TLC plates at 100 µg/spot concentration. Particularly active samples were the middle polarity extracts (CHCl₃/CH₂Cl₂) of the leaves of Rhododendron smirnovii Trautv., R. ponticum L., and R. ungernii Trautv. (Ericaceae). β-Carotene, β-carotene/linoleic acid mixture, and 2,2-diphenyl-l-pieryhydrazyl (DPPH) solutions sprayed onto TLC plates were used for detecting antioxidant and radical scavenging properties of the crude extracts. Antioxidant and radical scavenging activities were found to be predominant in highly polar extracts. The water-solubles of all Rhododendron (Ericaceae) and Phlomis (Lamiaceae) species presented the most significant activity.     

Role of biotransformation in the alterations of chloroform hepatotoxicity produced by Kepone and mirex

A previous report demonstrated that pretreatment of mice with Kepone resulted in marked potentiation of CHCl₃-induced hepatotoxicity whereas pretreatment with a structural analog, mirex, had no effect on the liver injury produced by a challenging dose of CHCl₃. To determine some of the possible mechanisms for this difference in potentiating ability, various parameters were studied. The hepatic content of mirex and Kepone was determined 42 hr after the oral administration of each agent to male Swiss-Webster mice. The concentration of mirex within the liver increased in a dose-related fashion. Following a single dose (50 mg/kg) of either mirex or Kepone, the hepatic content of each agent was approximately equal. Kepone (50 mg/kg, po) had no effect on mouse hepatic glutathione content at 18 hr. The relationship between the effects of mirex and Kepone on microsomal mixed function oxidase (MFO) activity and the in vivo and in vitro irreversible binding of ¹⁴CHCl₃ reactive metabolite(s) to hepatic constituents was assessed at 18 hr. Mirex pretreatment (10, 50, 250 mg/kg) resulted in a more profound effect on hepatic MFO activity than did pretreatment with Kepone (50 mg/kg). However, mirex pretreatment (50 mg/kg) did not alter either the in vivo or in vitro irreversible binding of ¹⁴CHCl₃-derived radioactivity to mouse hepatic constituents. In contrast, pretreatment of mice with Kepone (50 mg/kg) resulted in profound increases in both the in vivo and in vitro irreversible binding of ¹⁴CHCl₃ metabolites. Thus it appears that the disparate potentiating abilities of mirex and Kepone are related to a difference in the capacity of these agents to increase the activity of the CHCl₃ bioactivation system of the liver.     

Health risk assessment induced by chloroform content of the drinking water in Iran: systematic review

Long-term intake of water with high content of trihalomethanes (THMs) such as chloroform (CHCl₃) is hazardous for human health. Some studies have shown that clinical effects of THMs in drinking water may be yet observed to doses lower to standard limit. In our study, we performed a meta-analysis to assess both the mean concentration of CHCl₃ in Iranian drinking water and the relative health effects by long-term exposure to safe dose of CHCl₃ in the male and female age groups and in female categories. We applied the Target Hazard Quotient (THQ) for the evaluation of the noncarcinogenic risk of CHCl₃. Meta-analysis (14 studies) showed that the average concentration of CHCl₃ was 24?µg/l (95%CI:18.1–30.1?µg/l), I²?=?99.88, p?3 was related to Mashhad (3.5?±?0.5?µg/l) and Mazandaran (57.3?±?13.1?µg/l) province, respectively. The average concentration of CHCl₃ in the all studied provinces was lower than USEPA (70?µg/l) and national standard limits (200?µg/l). The minimum and maximum THQ was related to?<0.5 and 15–19?years age groups in both the males and females. The rank order of THQ in the female categories was females aging 15–44 (0.074)>?non-pregnant and non-lactating females age 4–15 (0.071)?>?pregnant (0.071)?>?lactating (0.043). The THQ in the females was higher than males, non-significantly (p?>.05). Except Mazandaran province, in other provinces both males and females, for all age groups, were not exposed to significant risks by non-carcinogenic exposure of CHCl₃ in drinking water (THQ <1).     

EVALUATION OF THE HEALTH RISK ASSOCIATED WITH EXPOSURE TO CHLOROFORM IN INDOOR SWIMMING POOLS

The exposure of swimmers to chloroform (CHCl₅) was investigated in indoor swimming pools of the Quebec City region along with the associated carcinogenic risk. Six training sessions involving 52 competition swimmers (11 to 20 yr old) were conducted in 3 different pools, while 12 adult leisure swimmers attended 5 sessions, each held in a different pool. For each session, water and ambient air CHCl₃ concentrations were measured and CHCl₃ levels in alveolar air samples (CHCl₃ALV) collected from swimmers prior to entering the swimming pool premises and after 15, 35, and 60 min of swimming. Mean water concentrations varied from 18 µg/L to 80 µg/L, while those in air ranged from 78 µg/m3 to 329 µg/m3. Multiple linear regression analyses revealed that CHCl₃ALV values in competition swimmers were strongly correlated to ambient air and water levels, and to a lesser degree to the intensity of training. Only ambient air concentration was positively correlated to CHCl₃ALV in the leisure group. Concentrations of CHCl₃ metabo lites bound to hepatic and renal macromolecules, estimated using a physiologically based pharmacokinetic (PBPK) model, were 1.6 and 1.9 times higher for the competition swimmers than for the leisure swimmers, respectively. The highest hepatic concentration predicted in competition swimmers, 0.22 µg CHCl equivalents/kg of tissue, was at least 10,000 times lower than the smallest no observed³effect level for liver tumors in animals. Data indicate that the safety margin is therefore very large, for competitive swimmers as well as for leisure swimmers.     

钩枝藤中生物碱的分离和鉴定

钩枝藤(Ancistrocladus tectorius)的总生物碱对大白鼠W-256有一定的抑制作用,从中分得三种带有萘环的四氢异喹啉生物碱结晶,晶1和晶2分别鉴定为ancistrocladine(Ⅰ)和hamatine(Ⅱ),晶3为新生物碱,命名为钩枝藤碱(ancistrocline),并推定其平面结构和部分立体关系如(Ⅲ)所示,总生物碱,晶1和晶2对小鼠肿瘤S-180和艾氏腹水瘤的抑制作用不明显,其他抗肿瘤试验还在进行中。