五味子含药血清中木脂素类成分的UPLC-MS/MS分析北大核心CSCD

目的分析五味子含药血清中的木脂素类成分。方法 UPLC-MS/MS检测,经与五味子提取物、空白血清总离子流色谱图比较,发现含药血清中的药源性成分;经与对照品的保留时间和质谱数据相比对,对部分原形成分进行鉴定;经与提取物相同保留时间色谱峰质谱数据比较并参考相关文献,对部分原形成分进行推测。结果大鼠灌胃给予五味子提取物后,含药血清中产生了药源性成分,包括代谢产物和原形成分。鉴定了其中4个原形成分:五味子醇甲、五味子醇乙、五味子甲素和五味子乙素;推测了另外10个原形成分:戈米辛D、巴豆酰戈米辛H、当归酰戈米辛H、当归酰戈米辛P、五味子酯乙、五味子酚、戈米辛O、戈米辛N、6-O-苯甲酰戈米辛O和五味子丙素,所有14个成分均为联苯环辛烯类木脂素。结论五味子含药血清中的药源性成分主要为联苯环辛烯类木脂素。     

UHPLC-DAD法同时测定五味子标准汤剂中4种木脂素类成分的含量

目的建立五味子标准汤剂中4种木脂素类成分的超高效液相色谱含量测定方法。方法应用UHPLC-DAD法,乙腈-水为流动相梯度洗脱,柱温30℃,流速0.45 mL·min~(-1),检测波长220 nm,同时测定不同批次五味子标准汤剂中五味子醇甲、五味子醇乙、当归酰戈米辛H和五味子甲素4种木脂素类成分的含量。结果 10批五味子标准汤剂中4种木脂素类成分的含量分别为:五味子醇甲0.195 9%～0.324 5%、五味子醇乙0.035 74%～0.071 54%、当归酰戈米辛H 0.027 02%～0.050 56%和五味子甲素0.016 29%～0.042 24%。结论建立了五味子标准汤剂中4种木脂素类成分的超高效液相色谱含量测定方法,该方法专属性强、准确度高、高效可靠,为五味子标准汤剂的质量评价提供了参考依据。     

碘甘油联合曲安奈德口腔软膏治疗口腔溃疡的临床研究

目的 建立同时测定枣仁安神胶囊中五味子醇甲、五味子醇乙、隐丹参酮、丹参酮I、丹参酮II_A、五味子乙素的方法,为枣仁安神胶囊的质量控制提供科学的方法。方法 采用HPLC法,选用Thermo 120Å-C₁₈色谱柱（250 mm×4.6 mm,5 μm）;以乙腈-0.1%冰醋酸水溶液为流动相梯度洗脱,对枣仁安神胶囊中6种主要指标性成分的含量进行同时分析测定;检测波长：五味子醇甲、五味子醇乙、五味子乙素为250 nm,隐丹参酮、丹参酮I、丹参酮II_A为270 nm;体积流量1.0 mL/min,柱温为30℃。结果 五味子醇甲在4.7～3 153.6 ng（r=0.999 9）、五味子醇乙在7.864～314.500 ng（r=0.999 9）,隐丹参酮在14.4～1 256.9 ng（r=0.999 9）、丹参酮I在15.1～1 103.8 ng（r=0.999 9）、丹参酮II_A在15.3～1 532.0 ng（r=0.999 9）、五味子乙素在6.134～204.500 ng（r=0.999 9）内呈良好的线性关系。平均加样回收率分别为五味子醇甲为100.4%、五味子醇乙为98.7%、隐丹参酮为99.4%、丹参酮I为100.0%、丹参酮II_A为99.3%、五味子乙素100.2%,RSD分别为1.4%、2.7%、2.2%、2.2%、2.5%、2.1%;8批样品中各指标成分的质量分数分别为五味子醇甲1.545 7～1.909 9 mg/g、五味子醇乙0.129 8～0.235 1 mg/g、隐丹参酮0.508 4～0.523 4 mg/g、丹参酮I 0.111 7～0.122 3 mg/g、丹参酮II_A 0.755 8～0.874 4 mg/g、五味子乙素0.120 2～0.190 1 mg/g。结论 建立的含量测定分析方法灵敏度高、专属性强,可很好地控制枣仁安神胶囊质量。     

基于细胞膜色谱技术的人参皂苷及五味子木脂素与血管内皮生长因子受体的作用分析

目的 运用细胞膜色谱（CMC）技术检测分析人参皂苷与五味子木脂素中15种成分与血管内皮生长因子（VEGF）受体的作用。方法 运用Western blotting法检测筛选VEGF受体高表达细胞株;构建VEGF受体CMC,并建立ECV304/CMC online-LC检测方法,以索拉菲尼作为阳性药,对人参皂苷Rb₁、Rb₂、Rb₃、Rc、Rd、Rg₁、Rg₂、Rg₃、Rh₁、Ro、F₂,五味子甲素,五味子乙素,五味子醇甲,五味子醇乙进行VEGF受体结合强度的检测分析;CCK-8法检测筛选出的成分（5、10 μg/mL）对ECV304细胞的促增殖作用。结果 Western blotting结果显示,ECV304细胞中VEGF受体高表达;人参皂苷Rb₁、Rb₂、Rb₃、Rc、Rd、Rg₃、Rh₁、F₂、五味子甲素、五味子乙素与VEGF受体CMC柱有结合作用;CCK-8法检测以上成分对ECV304细胞的活力影响发现,人参皂苷Rb₂能促进细胞的增殖。结论 人参皂苷Rb₂能与VEGF受体结合,且显著促进ECV304细胞增殖。     

一测多评法测定安神宁中4个木脂素含量

目的 建立测定安神宁中4个木脂素含量的一测多评方法(QAMS)。方法 采用高效液相色谱（HPLC）外标法,同时测定安神宁中五味子醇甲、五味子醇乙、五味子甲素、五味子乙素含量,并以五味子醇甲为内参物,建立一测多评法同时测定四个成分含量。结果 五味子醇甲、五味子醇乙、五味子甲素、五味子乙素分别在0.020 7～1.657 6 μg（r=0.999 9）、0.009 8～0.784 6 μg（r=0.999 9）、0.008 2～0.652 2 μg（r=0.999 9）、0.008 1～0.645 8 μg（r=0.999 9）范围内线性关系良好,平均回收率为98.52%、103.43%、109.69%、107.92%,校正因子重现性良好,校正因子法与外标法测定值之间无显著差异。结论 该方法准确、可靠,重复性好,一测多评法可用于安神宁的质量控制。     

正交试验法优化五味子总木脂素的提取工艺

摘 要 目的：优化五味子总木脂素提取工艺。方法: 采用正交试验法,以五味子醇甲、甲素及乙素的含量为五味子总木脂素的含量,与浸膏含量综合加权评分,考察乙醇浓度、提取时间、乙醇倍数、提取次数对五味子总木脂素的影响;采用HPLC法：华普Unitary C18柱（250 mm×4.6 mm,5 μm）,流动相为甲醇（A） 水（B）,梯度洗脱（0～10 min,A为70%;10～13 min,A为70%～85%;13～30 min,A为85%）;检测波长：217 nm;柱温：30℃;流速：1.0 ml·min^-1 ,进样量：10μl。结果: 五味子总木脂素提取的最佳工艺条件为：14倍量的85%乙醇提取3次,每次2.5 h,五味子总木脂素提取率为1.10%,浸膏量为22.99%。结论: 五味子总木脂素提取工艺稳定可靠,为生脉分散片新剂型改革提供了科学基础。     

高效液相色谱法测定内南五味子的木脂素含量

本文采用高效液相色谱法对药用植物内南五味子中的８种主要活性木脂素：五味子醇甲、五味子醇乙、戈米辛Ｇ、内南五味子素、五味子酯丁、内南五味子酯乙、一味子甲素和南五味子宁的含量进行了测定，在Ｃ１８柱上以甲醇一水（７０：３０）为流动相，检测波长２５４ｎｍ，８种木脂素的加样中嘏率９１．６－１００．９％，相对标准偏差小于４．３２％。内南五味子木脂素类成分的种类、含量因采收时间、雌雄、药用部位不同而有很大差别。     

UPLC-MS/MS法测定比格犬血浆中五味子醇甲的血药浓度

目的 建立UPLC-MS/MS测定比格犬血浆中的五味子醇甲血药浓度分析方法。方法 采用ACQUITY UPLC^® BEH C₁₈色谱柱（50 mm×2.1 mm,1.7 μm）,流动相为0.1%乙酸水-甲醇梯度洗脱,体积流量为0.4 mL/min。柱温40℃,进样量5 μL。采用电喷雾（ESI）正离子模式进行多反应（MRM）监测,五味子醇甲和利伐沙班（内标）的定量离子对分别为m/z 433.20→384.30、437.19→145.13。结果 五味子醇甲在0.2～100 ng/mL线性关系良好（r=0.999 6）,最低定量限为0.2 ng/mL,批内、批间精密度分别为2.04%～7.62%、3.72%～8.29%;基质效应及提取回收率分别为95.7%～103%、81.2%～106%;稳定性结果均符合生物样品检测指导原则。结论 建立的UPLC-MS/MS方法快速、简单、灵敏度高,能满足五味子醇甲血药浓度测定及其药动学研究。     

芥辛化痰通窍巴布剂的质量标准研究

目的 建立芥辛化痰通窍巴布剂的质量标准。方法 对芥辛化痰通窍巴布剂中白芥子、延胡索、甘遂和细辛采用TLC定性鉴别;采用HPLC对芥子碱硫氰酸盐、延胡索乙素和细辛脂素进行定量测定。结果 薄层色谱法鉴别斑点清晰,分离度好,阴性无干扰;芥子碱硫氰酸盐在20.2~202.0 μg·mL^-1（r=0.999 4）、延胡索乙素在1.312~20.992 μg·mL^-1（r=0.999 7）和细辛脂素在1.925~38.500 μg·mL^-1（r=0.999 4）内与峰面积的线性关系良好;芥子碱硫氰酸盐的平均回收率为99.06%,RSD=2.20%;延胡索乙素的平均回收率为98.66%,RSD=2.35%;细辛脂素的平均回收率为99.75%,RSD=1.74%。结论 该法简便、准确、重复性好,可用于芥辛化痰通窍巴布剂的质量控制。     

五味子乙醇提取物的UPLC MS/MS分析

目的分析五味子乙醇提取物中的主要成分。方法UPLC MS/MS检测,通过与对照品的保留时间和质谱数据相比对,鉴定部分成分;通过质谱数据分析,并与相关文献比对,推测部分化合物结构。结果鉴定了五味子醇甲、五味子醇乙、五味子酯甲、五味子甲素、五味子乙素,推测另外17种成分,所有22种成分均为联苯环辛烯类木脂素。结论五味子乙醇提取物中主要存在联苯环辛烯类木脂素成分。     

Syntheses,opioid binding affinities,and potencies of dynorphin A analogues substituted in positions 1, 6, 7, 8 and 10

Structural, stereochemical, stereoelectronic and conformational requirements for biological activity of dynorphin A_1–11-NH₂ analogues at opioid receptors were explored by substitution of Tyr¹, Arg⁶, Arg⁷, Ile⁸ and Pro¹⁰ with other amino acid residues. Interestingly, substitution of Tyr¹ with N^α-Ac-Tyr^l, D-Tyr¹, Phe¹ or p-BrPhe¹ led to analogues that were quite potent at κ opioid receptors, and additional substitution of Ile⁸with D-Ala⁸ and/or Pro¹⁰ with D-Pro¹⁰ retained high potency in brain binding assay: [N^α-Ac-Tyr¹]- (1), [D-Tyr¹]- (2) [Phe¹]- (3), [Phe¹. D-Ala⁸]- (5), [p-BrPhe¹, D-Ala^s]- (6), [Phe¹, D-Pro¹⁰]- (7) and [Phe¹, D-Ala⁸, D-Pro¹⁰]-Dyn A_1–11-NH₂ (8) had IC₅₀(nM) binding affinities of 13.2, 18.6, 1.64, 1.26, 1.84, 2.44 and 1.62 nM, respectively. The D-Phe¹ analogue 4, however, was only weakly active (610 nM). All of the analogues except 4 were modestly selective for κ vs. μ guinea pig brain opioid receptor (11- to 88–fold) and quite selective for κ vs. δ receptors (65–576). However, all of the analogues appeared to have very low or essentially no activity in the guinea pig ileum and mouse vas deference functional bioassays, and one analogue, 5, appeared to have weak antagonist activities. On the other hand, if constrained amino acids such as β-methylphenylalanine or 1,2,3,4-tetrahydroisoquinoline carboxylic acid, and hydroxyproline were placed in the 1 position, inactive analogues or analogues with greatly reduced potency and biological activity were obtained (compounds 12–14). It had previously been suggested that the Arg⁶ and Arg⁷ residues were critical for biological activity. However, when we replace either one of these residues, [Nle⁶]Dyn A_1–11 (9) and [Nle⁷]Dyn A_1–11-NH₂ (10) were both highly potent binders in κ receptor binding studies (IC₅₀= 0.95 and 0.43 nM, respectively), and interestingly also were potent in μ and δ binding studies. Furthermore, both of the analogues were modestly potent in the GPI and MVD assays (94, 65 nM; 31, 81 nM, respectively). These results demonstrate that basic residues at positions 6 and 7 in dynorphin are not very important for binding to κ opioid receptors. Finally, many of the compounds reported here showed high selectivity for central vs. peripheral κ opioid receptors, with compound 4 being the most selective (63 000-fold).     

半合成糖肽类抗生素达巴万星前体A40926的生物合成

综述了继替考拉宁之后的第二代半合成糖肽类抗生素达巴万星前体A40926的研究进展,包括其结构、发酵生产、生物合成以及结构修饰.重点阐述了A40926的生物合成基因簇以及合成途径.达巴万星是A40926的半合成化合物,目前处于Ⅲ期临床研究,它具有比万古霉索和替考拉宁更强的生物活性.     

A.A., Constructivism,and Reflecting Teams

Numerous studies and clinical anecdotes reveal a relationship between attendance at A.A. meetings and/or degree of involvement in A.A. and maintenance of sobriety. Hypotheses as to how A.A. and/or the A.A. meeting is helpful to its members have ranged from a focus on factors common to all therapy groups, to aspects of A.A. “treatment” which are behavioral in nature. Presented here is another way of understanding A.A.'s effectiveness within the frame of more recent, constructivistic approaches to family therapy. In particular, the A.A. topic meeting is compared to the reflecting team concept of Tom Anderson.     

Hepatic CYP3A4, SULT2A1, and UGT1A1 synergistically mediate metabolic detoxification of genipin

In the present study, we aimed to ascertain the metabolic detoxification routes of genipin via CYP3A4, SULT2A1, and UGT1A1 in HepaRG cells. It was found that the hepatic CYP3A4, SULT2A1, and UGT1A1 synergistically mediated the metabolic detoxification of genipin, and the CYP3A4 was the limited enzyme. In detail, the pivotal detoxification pathway was CYP3A4-SULT2A1/UGT1A1, indicating that SULT2A1 and UGT1A1 further catalyzed the phase II detoxification metabolism followed by the genipin metabolization by CYP3A4 to the phase I metabolites with alleviated toxicity. Our findings provided valuable cues for future studies on the detoxification of genipin, even the compatibility detoxification of Zhi-zi. Moreover, these data facilitated the development and rational administration of genipin and Zhi-zi.     

Pharmacological activity of Salvinorin A, the major component of Salvia divinorum

The hallucinogenic plant Salvia divinorum (i.e., "magic mint") is a member of the Sage family that has been historically used for divination and shamanism by the Mazatecs. Today, S. divinorum has become increasingly popular as a recreational drug for its hallucinogenic effects. The non-nitrogenous diterpene, salvinorin A, the major active component of S. divinorum, is responsible for the hallucinogenic effect of this plant. Here, we described the behavioral effects of salvinorin A in animals including the addictive, antinociception and antidepressant properties of the drug. The present paper also demonstrates the not well recognized (or unclear) mechanisms of action of salvinorin A. The last part of the paper presents information about the legal status of S. divinorum and its derivatives. Taking into account the increasing popularity and consumption of salvinorin A and S. divinorum today, it is important to collect all data on the pharmacological profile of this plant and its products.     

A new compound,brefeldin A formylate,from Penicillium sp. strain HLKG-44

A novel compound named as brefeldin A formylate (1), together with two known compounds, brefeldin A (2) and ergosterol (3), was isolated from the Penicillium sp. strain HLKG-44, which was isolated from polluted environment in Fujian Province. Their structures were identified based on the spectral and X-ray crystallographic analyses. The compound 1, brefeldin A formylate, exhibited moderate cytotoxic activity against the human lung cancer cell line A549 with IC₅₀ value of 18.9 μg/ml by the MTT assay protocol.     

Decrease of plasma vitamin A,albumin and zinc in cadmium-treated rats

Male rats of the Wistar strain were injected subcutaneously with a total dose of 4.5 mg cadmium (Cd) per kg body weight. The first group (Sc-1) was injected with 18 doses of 0.25 mg/kg, the second group (Sc-II) was injected with 9 doses of 0.50 mg/kg, and the third group (Sc-III) with 2 doses of 2.25 mg/kg. Another group was given water containing 75 ppm Cd for 68 days and 50 ppm for the ensuing 75 days.The plasma concentration of vitamin A (VA) was statistically decreased by the subcutaneous injections of Cd, but the liver concentration of VA was not altered. The fractionated injection of the total Cd apparently reduced the toxicity of Cd on VA metabolism. The decrease of plasma albumin was highly correlated with the decrease of plasma VA. The relative coefficient between them was calculated as 0.812 (n = 34, P < 0.01) with all of the groups. The relative coefficient between plasma VA and zinc (Zn) was lower than that between plasma VA and albumin but was statistically significant (r = 0.697, P < 0.01). These results may indicate the involvement of hepatic damage in Cd intoxications. The decrease of plasma VA, however, could not be explained by the Zn deficiency of the liver. To clarify the role of Zn in VA metabolism, the secretion mechanisms of them should be investigated in the liver.     

Urinary metabolic markers reflect on hepatic,not intestinal,CYP3A activity in healthy subjects

Intestinal cytochrome P450 3A (CYP3A) plays an important role in oral drug metabolism, but only endogenous metabolic markers for measuring hepatic CYP3A activity were identified. Our study evaluated whether hepatic CYP3A markers reflected intestinal CYP3A activity. An open-label, three-period, six-treatment, one-sequence clinical trial was performed in 16 healthy Korean males. In the control phase, all subjects received a single dose of intravenous (IV) and oral midazolam (1 mg and 5 mg, respectively). Clarithromycin (500 mg) was administered twice daily for 4 days to inhibit hepatic and intestinal CYP3A, and 500 mL of grapefruit juice was given to inhibit intestinal CYP3A. Clarithromycin significantly inhibited total CYP3A activity, and the clearance of IV and apparent clearance of oral midazolam decreased by 0.15- and 0.32-fold, respectively. Grapefruit juice only reduced the apparent clearance of oral midazolam by 0.84-fold, which indicates a slight inhibition of intestinal CYP3A activity. Urinary markers, including 6β–OH–cortisol/cortisol and 6β–OH–cortisone/cortisone, were significantly decreased 0.5-fold after clarithromycin administration but not after grapefruit juice. The fold changes in 6β–OH–cortisol/cortisol and 6β–OH–cortisone/cortisone did not correlate to changes in intestinal availability but did correlate to hepatic availability. In conclusion, endogenous metabolic markers are only useful to measure hepatic, but not intestinal, CYP3A activity.