谨防补骨脂掺入曼陀罗子

本院急诊科曾接诊一名患者，其症状表现为口干，灼热，面颊潮红，头痛、头晕，心悸、恶心，并伴有阵发性抽搐，谵语，意识不清。据称患者发病前曾服用过中药补骨脂，经我院主任中药师对其带来的中药补骨脂进行鉴定，发现其中掺有约1／3的曼佗罗子。     

HPLC法测定补骨脂中补骨脂定的含量

目的:建立HPLC法测定中药补骨脂中补骨脂定的含量。方法:采用Lichrospore C₁₈(250mm×4.6mm)色谱柱,甲醇-水-冰醋酸(78∶21∶1)作为流动相,流速1.0ml/min,检测波长347nm。结果:补骨脂定在2.5～20.0μg/ml线性关系良好,平均回收率为98.2%,RSD为1.3%,重现性好。结论:本法简便、快速,适用于评价中药补骨脂及其中药复方制剂的质量。     

HPLC法测定补骨脂中补骨脂定的含量

目的 :建立 HPL C法测定中药补骨脂中补骨脂定的含量。方法 :采用 L ichrospore C1 8(2 5 0 m m× 4 .6 mm )色谱柱 ,甲醇 -水 -冰醋酸 (78∶ 2 1∶ 1)作为流动相 ,流速 1.0 m l/ min,检测波长 347nm。结果 :补骨脂定在 2 .5～ 2 0 .0μg/ m l线性关系良好 ,平均回收率为 98.2 % ,RSD为 1.3% ,重现性好。结论 :本法简便、快速 ,适用于评价中药补骨脂及其中药复方制剂的质量     

补骨脂有效成分提取工艺的考察

目的：筛选并优化中药补骨脂提取工艺。方法：以补骨脂素、异补骨脂素含量为考察指标，采用浸提法、回流法、超声法、索氏法对中药补骨脂进行提取，应用高效液相色谱法进行含量测定，得到最适提取方法，并以补骨脂素、异补骨脂素、补骨脂素和异补骨脂素总含量以及出膏率为考察指标，对其最适提取方法进行优化。结果：应用回流法提取时补骨脂素、异补骨脂素含量较高，溶剂浓度和提取时问对实验结果影响较大。结论：回流法为提取补骨脂素与异补骨脂素的最佳方法；4倍量乙醇，提取2h，乙醇浓度为80％为最佳提取条件，且回流提取工尹操作简单．提取效率高．     

临床药师参与中药补骨脂致肝损害的药学监护

目的:探讨临床药师如何在药物性肝损伤的临床治疗中发挥作用。方法:采用查阅文献并与临床实际相结合的方法,分析临床药师在参与1例中药补骨脂致药物性肝损害患者的治疗过程中,针对患者病情变化提出合理化用药建议的过程。结果:在本例药物性肝损害的治疗中,临床药师参与用药计划制订和药学监护,并对患者进行用药教育,对缩短疾病病程起到了一定作用。结论:临床药师通过对患者实施药学监护,充分发挥自身的药学专长,可在临床治疗过程中起到积极的作用。     

中药五味子治疗药物性肝损伤的研究进展

摘 要中药五味子主要成分为五味子乙素、五味子脂甲、五味子甲素、五味子脂乙、五味子醇乙等。五味子中含有多种有效生物活性成分,在临床上主要用于与其他药物的联合治疗。目前临床上所使用的药物很多会引起药物性肝损伤(DILI),药物性肝损伤是药品不良反应的主要类型之一,因此临床上用药致肝脏损害的预防和治疗显得尤为重要。本文对五味子的有效成分及其对药物性肝损伤的相关治疗作用进行了综述。     

川芎嗪对小鼠急性肝损伤性脂肪肝保护作用的研究

目的：研究川芎嗪对小鼠急性肝损伤性脂肪肝的保护作用。方法：用0.5%四氯化碳花生油溶液复制小鼠急性肝损伤性脂肪肝模型。造模前1h,川芎嗪高、中、低3个剂量组分别腹腔注射川芎嗪注射液50、25、12.5mg/kg,造模后每天给药两次,连续给药7d后,测定血清中谷丙、谷草转氨酶活性,肝脏中甘油三脂、游离脂肪酸、丙二醛含量及肝脂酶和超氧化物歧化酶活性,并作肝脏HE切片。结果：与模型组比较,川芎嗪组小鼠血清中谷丙、谷草转氨酶活性均降低（P〈0.05）,肝脏中游离脂肪酸、甘油三酯、丙二醛含量均降低（P〈0.05或P〈0.01）,肝脂酶和超氧化物歧化酶活性升高（P〈0.05）,肝脏脂肪变性明显减轻。结论：川芎嗪可改善急性肝损伤性脂肪肝中脂肪的堆积,对肝脏有较明显的保护作用。其保肝机制可能与降低甘油三酯,促进游离脂肪酸的β-氧化,抗脂质过氧化作用有关。     

基于生物信息学技术探讨补骨脂致肝损伤的作用机制

目的 基于生物信息学技术建立补骨脂成分-靶点-信号通路-肝损伤网络,探讨补骨脂导致肝损伤的作用机制。方法 通过TCMIP数据库收集补骨脂成分以及肝损伤有关的靶点,依据反向药效团匹配方法预测补骨脂成分的作用靶点;采用Cytoscape 构建补骨脂成分-靶点网络,对补骨脂作用靶点构建网络模型进行GO与KEGG富集分析。结果 补骨脂中有22个成分作用于31个肝损伤靶点蛋白,血清白蛋白（ALB）、谷胱甘肽S-转移酶P（GSTP1）、运甲状腺素蛋白（TTR）和过氧化物酶体增殖物激活受体γ（PPARG）可能是关键节点蛋白。KEGG分析遴选出化学物致癌、AMPK、PPAR信号、P450代谢和谷胱甘肽等信号通路。结论 补骨脂可能是作用于ALB、GSTP1、TTR与PPARG等靶点并调控五类信号通路导致肝损伤。     

三叶青总氨基酸对四氯化碳致小鼠肝损伤的保护作用

目的观察三叶青总氨基酸（TAART）对四氯化碳（CCl4）诱导的小鼠急性肝损伤的保护作用。方法选用CCl4致小鼠急性肝损伤模型，以测定小鼠血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）活性，肝脏系数，肝组织中超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量及对肝组织进行病理学检查等指标观察TAART对肝损伤的保护作用。结果TAART能明显降低CCl4致小鼠肝损伤血清ALT，AST值，降低肝脏系数及肝组织中MDA的含量，增加肝组织中SOD活性，减轻CCl4对肝脏细胞的病理损伤。结论三叶青总氨基酸对CCl4致小鼠急性肝损伤具有保护作用，其机制可能与其抗氧化作用相关。     

仙灵骨葆相关肝损伤的临床病例分析及拆方实验研究

仙灵骨葆为骨科常用药,临床疗效好,但近年来发现有致肝损伤风险。本研究通过对文献不良反应报告和重点医院病例进行分析,发现文献检索到的仙灵骨葆肝损伤病例存在较大比例的报告信息不完整,难以准确判断其因果关系。重点医院药物性肝损伤(DILI)病例中,筛选出仙灵骨葆相关肝损伤患者6例,其中2例经整合证据链法评价达到了“临床诊断”标准。进一步对区域全人群健康大数据进行分析,估算其粗发生率为0.034%,属于罕见水平,具有显著的个体差异和特异质属性,仙灵骨葆相关肝损伤总体发生水平低于其他骨病用药。基于免疫应激介导的特异质肝损伤模型,通过拆方研究发现,方中淫羊藿和补骨脂是引起肝损伤的相关药味,全方的肝损伤严重程度弱于淫羊藿和补骨脂,提示方中另外4味药(续断、知母、地黄、丹参)有减轻二者引起的肝损伤作用。进一步进行拆方研究,发现4味药均有减轻淫羊藿和补骨脂所致肝损伤作用,其中丹参的配伍减毒效果最好。综上,仙灵骨葆可能在极少数易感个体引起特异质肝损伤,但发生风险低于其他常用骨病药物。临床应用仙灵骨葆要注意避免在免疫应激患者应用。仙灵骨葆引起肝损伤的主要药味为补骨脂、淫羊藿,且丹参在全方中起到配伍减毒作用。本研究可为仙灵骨葆临床合理用药提供参考。     

补骨脂不同提取部位大鼠给药3个月的毒性比较研究

目的 研究补骨脂不同提取部位大鼠长期ig给药的毒性反应。方法 按照一定的方法制备得到补骨脂不同部位提取物,即渗漉药渣、上层渗漉液和混合物。将SD大鼠98只,按体质量、性别随机分为7组,即对照组,补骨脂药渣高、低剂量组,补骨脂干膏高、低剂量组,补骨脂混合物高、低剂量组（高、低剂量均相当于生药6、3 g/kg）,每组14只。以1 mL/100 g剂量ig给药12周。每周称大鼠体质量,给药结束后,剖取脏器,计算脏器系数;取血,检测血清生化指标;取肝脏和肾脏组织进行组织病理学检查。结果 连续给药12周后,与对照组相比,混合物高剂量组以及干膏高剂量组雄性大鼠体质量显著降低（P<0.05、0.01）;与对照组相比,随给药时间的延长,干膏低剂量组雌性大鼠体质量显著降低（P<0.05）,其余给药组无显著差异。除干膏高、低剂量组外,其余各组雄性、雌性大鼠肝脏系数均显著高于对照组（P<0.01、0.001）。与对照组比较,雄性大鼠混合物高剂量组以及药渣高、低剂量组的丙氨酸氨基转换酶（ALT）、三酰甘油（TG）显著下降（P<0.05、0.01）,混合高剂量组和干膏高、低剂量组尿素氨（BUN）显著降低（P<0.05、0.01、0.001）。与对照组相比,雌性大鼠混合物高剂量组和干膏高剂量组总胆汁酸（TBA）显著升高（P<0.01）,混合物高剂量组和药渣高、低剂量组总胆红素（TBIL）显著升高（P<0.05、0.01）。结论 大鼠长期ig给予补骨脂不同提取物可造成一定的毒性反应,且具有一定的剂量相关性,主要表现为肝脏和肾脏功能损害,并且损伤程度存在雌雄差异。     

补骨脂水提药渣大鼠三个月长期毒性试验研究

目的 研究补骨脂水提药渣大鼠ig给药的长期毒性。方法 SD大鼠70只,按体质量、性别随机分为5组：对照组、补骨脂生药粉高、低剂量组,补骨脂水提药渣高、低剂量组（各组高、低剂量均相当于生药6、3 g/kg,分别为临床等效剂量的11.11、5.56倍）,每组14只,雌雄各半,每日ig给药1次,连续给药12周。每周称大鼠体质量,药结束后,取心脏、肝脏、脾脏、肾脏、胸腺,称质量并计算脏器系数;血细胞分析仪检测血液学指标;全自动生化仪血清生化学指标;试剂盒法检测大鼠肝脏中氧化应激指标;做肝脏和肾脏组织病理学检查。结果 与对照组比较,生药粉和药渣高剂量组雄性大鼠体质量均显著下降（P<0.05）,而药渣组雌性大鼠体质量随给药时间延长无显著性变化;补骨脂生药粉和水提药渣雌性、雄性大鼠的肝系数均显著升高（P<0.01）;雄性大鼠生药粉和药渣高剂量组、雌性大鼠生药粉组和药渣高剂量组肾系数显著升高（P<0.05、0.01、0.001）;雄性大鼠生药粉高剂量组血小板（PLT）水平,药渣低剂量组红细胞（RBC）水平显著升高,生药粉低剂量组和药渣低剂量组白细胞（WBC）水平,药渣高剂量组PLT水平显著下降,雌性大鼠各给药组PLT均显著下降（P<0.05）;雄性大鼠生药粉组碱性磷酸酶（ALP）和三酰甘油（TG）水平均显著下降,总蛋白（TP）水平显著升高,生药粉低剂量组尿素氨（BUN）水平显著下降（P<0.05、0.01、0.001）;药渣高剂量组TP和白蛋白（ALB）、药渣低剂量组天冬氨酸转氨酶（AST）显著升高,丙氨酸转氨酶（ALT）和ALP显著下降（P<0.05、0.01、0.001）;雄性大鼠生药粉高剂量组和药渣组丙二醛（MDA）显著升高（P<0.05）,雌性大鼠生药粉组MDA和总抗氧化能力（T-AOC）、药渣组MDA均显著下降（P<0.05、0.01）。结论 长时间给予大剂量补骨脂水提药渣,对大鼠肝脏和肾脏功能均造成一定损害。     

Psoralea corylifolia extract induces vasodilation in rat arteries through both endothelium-dependent and -independent mechanisms involving inhibition of TRPC3 channel activity and elaboration of prostaglandin

Context: Fructus Psoralea, Psoralea corylifolia L. (Leguminosae), has been widely used in traditional medicines for the treatment of dermatitis, leukoderma, asthma and osteoporosis.

Objectives: In this study, we sought to study mechanisms underlying the vasoactive properties of Psoralea corylifolia extract (PCE) and its active ingredients.

Materials and methods: To study mechanisms underlying the vasoactive properties of PCE prepared by extracting dried seeds of Psoralea corylifolia with 70% ethanol, isometric tension recordings of rat aortic rings and the ionic currents through TRPC3 (transient receptor potential canonical 3) channels were measured with the cumulative concentration (10–600?μg/mL) of PCE or its constituents.

Results: Cumulative treatment with PCE caused the relaxation of pre-contracted aortic rings in the presence and absence of endothelium with EC₅₀ values of 61.27?±?3.11 and 211.13?±?18.74?μg/mL, respectively. Pretreatment with inhibitors of nitric oxide (NO) synthase, guanylate cyclase, or cyclooxygenase and pyrazole 3, a selective TRPC3 channel blocker, significantly decreased PCE-induced vasorelaxation (p?50 128.9, 4.5, 32.1 and 114.9?μg/mL, respectively).

Discussion and conclusions: Taken together, our data indicate that the vasodilatory actions of PCE are dependent on endothelial NO/cGMP and also involved in prostaglandin production. PCE and its active constituents, bakuchiol, isobavachalcone, isopsoralen and psoralen, caused dose-dependent inhibition of TRPC3 channels, indicating that those ingredients attenuate Phe-induced vasoconstriction.     

Induction of quinone reductase activity by psoralidin isolated from <Emphasis Type="Italic">Psoralea corylifolia</Emphasis> in mouse hepa 1c1c7 cells

Quinone reductase (QR) is a protective phase II enzyme against mutagens and carcinogens which is inducible by a number of chemical compounds in plants. This study was carried out to investigate effects of the fractions from the seeds of Psoralea corylifolia on the induction of QR with Hepa 1c1c7 murine hepatoma cell line. The ethyl acetate-soluble fraction of the methanolic extract from the seeds was found to induce QR and the concentration of 1.5 fold QR induction (1.5 FIC) was 1.2 μg/mL. We obtained as an active compound, psoralidin, isolated from the ethyl acetate-soluble fraction after further sequential fractionation with column chromatography and 1.5 FIC of psoralidin was 0.5 μg/mL. The seeds of Psoralea corylifolia and psoralidin might be a candidate for developing QR inducers.     

Bavachin and isobavachalcone, acyl-coenzyme A: Cholesterol acyltransferase inhibitors from Psoralea corylifolia

Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes cholesterol esterification and plays important roles in intestinal absorption of cholesterol, hepatic production of lipoproteins and accumulation of cholesteryl ester within macrophages and smooth muscle cells. Ethanol extract of Psoralea corylifolia showed a significant inhibition of ACAT enzyme. Via bioactivity-guided fractionation of the ethanol extract of Psoralea corylifolia, two prenylated flavonoids were isolated. Their structures were determined as bavachin (1) and isobavachalcone (2) by spectroscopic analysis (¹H-, ¹³C-NMR, 2DNMR, and ESI-MS). The IC₅₀ values were 86.0 (1) and 48.0 (2) μM in the ACAT assay system using rat liver microsome. Compound 2 also decreased cholesteryl ester formations in HepG2 cells. In addition, this compound showed a noncompetitive type of inhibition of ACAT.     

枸杞子及其有效成分的药理作用研究进展

枸杞子Lycium barbarum是食药同源中药材,具有滋阴兴阳、止消渴、补劳伤的功效,富含枸杞多糖、枸杞总黄酮、类胡萝卜素和氨基酸等多种有效成分。现代药理学的研究显示,枸杞子及其活性成分具有抗肿瘤、调节血糖血脂、保护视力、抗抑郁与焦虑、防治神经系统疾病、抗炎抑菌、抗氧化、保护肝肺肾等作用。对枸杞子及其有效成分的药理作用进行总结和归纳,以期为其进一步应用开发及新药研究提供依据。     

Pharmacokinetics,tissue distribution and excretion of coumarin components from <Emphasis Type="Italic">Psoralea corylifolia</Emphasis> L. in rats

Coumarin components from Psoralea corylifolia L. are novel drugs in which psoralen and isopsoralen are the active components. The pharmacokinetics, tissue distribution and excretion of the two compounds were studied by liquid chromatography-tandem mass spectrometry after intravenous administration to Wistar rats. The elimination half-lives of psoralen and isopsoralen were 4.88 and 5.35 h. After dosing, the area under the curves of the tissues decreased in the following order: liver > lung > heart > kidney > spleen > brain for psoralen; and kidney > lung > liver > heart > spleen > brain for isopsoralen. After dosing, 51.27% of psoralen and 56.25% of isopsoralen were excreted as prototype, and urine was the major excretion route. In addition, the pharmacokinetics of psoralen and isopsoralen after oral administration to Wistar rats were also studied. The elimination half-lives of psoralen and isopsoralen were 4.13 and 5.56 h, and their relative bioavailabilities were 61.45% and 70.35%. Overall, the results show that coumarin components from P. corylifolia L. have high oral bioavailability, they are rapidly and widely distributed into tissues after intravenous administration, but they are slowly cleared and excreted.     

Activation of Estrogen Receptor by Bavachin from Psoralea corylifolia

In this study, we examined the estrogenic activity of bavachin, a component of Psoralea corylifolia that has been used as a traditional medicine in Asia. Bavachin was purified from ethanolic extract of Psoralea corylifolia and characterized its estrogenic activity by ligand binding, reporter gene activation, and endogenous estrogen receptor (ER) target gene regulation. Bavachin showed ER ligand binding activity in competitive displacement of [³H] E₂ from recombinant ER. The estrogenic activity of bavachin was characterized in a transient transfection system using ERα or ERβ and estrogen-responsive luciferase plasmids in CV-1 cells with an EC₅₀ of 320 nM and 680 nM, respectively. Bavachin increased the mRNA levels of estrogen-responsive genes such as pS2 and PR, and decreased the protein level of ERα by proteasomal pathway. However, bavachin failed to activate the androgen receptor in CV-1 cells transiently transfected with the corresponding receptor and hormone responsive reporter plasmid. These data indicate that bavachin acts as a weak phytoestrogen by binding and activating the ER.