生物样品中天麻素测定方法及药代动力学研究进展＊

天麻素是从兰科植物天麻的块茎中提取分离而得，现已人工合成。天麻素药理作用广泛，如镇痛、镇静安眠、促智、保护神经元、降血压、抗惊厥、抗癫痫、抗氧化、抗衰老、改善微循环等，且安全、无明显毒副作用，其相关制剂在临床上亦被广泛用于心脑血管及神经精神系统疾病，如头痛、冠心病、高血压、后循环缺血性眩晕、突发性耳聋、癫痫、神经衰弱及脑卒中等。考虑到天麻素临床治疗上述疾病常与其他药物或治疗方法联用，故其体内过程及其药代动力学性质不容忽视。目前，有关天麻素综述多集中于药理作用和临床应用方面，而其药代动力学综述鲜见报道。随着天麻素药代动力学研究日渐深入，本研究将从其样品前处理、测定方法、药物ADME过程及影响体内过程的因素等方面较系统全面地对天麻素近年来的药代动力学研究作一综述，以期对天麻素制剂工艺及临床联合配伍应用有所裨益。     

Protective effect of gastrodin on bile duct ligation-induced hepatic fibrosis in rats

Gastrodin has been showed to possess many beneficial physiological functions, including protection against inflammation and oxidation and apoptosis. Studies showed inflammation and oxidation play important roles in producing liver damage and initiating hepatic fibrogenesis. However, it has not been reported whether gastrodin has a protective effect against hepatic fibrosis or not. This is first ever made attempts to test gastrodin against liver fibrosis in bile duct ligation (BDL) rats. The aim of the present study is to evaluate the effect of gastrodin on BDL-induced hepatic fibrosis in rats. BDL rats were divided into two groups, BDL alone group, and BDL-gastrodin group treated with gastrodin (5 mg/ml in drinking water). The effects of gastrodin on BDL-induced hepatic injury and fibrosis in rats were estimated by assessing serum, urine, bile and liver tissue biochemistry followed by liver histopathology (using hematoxylin & eosin and sirius red stain) and hydroxyproline content measurement. The results showed that gastrodin treatment significantly reduced collagen content, bile duct proliferation and parenchymal necrosis after BDL. The serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) decreased with gastrodin treatment by 15.1 and 23.6 percent respectively in comparison to BDL group did not receive gastrodin. Gastrodin also significantly increased the level of serum high density lipoprotein (HDL) by 62.5 percent and down-regulated the elevated urine total bilirubin (TBIL) by 56.5 percent, but had no effect on total bile acid (TBA) in serum, bile and liver tissues. The immunohistochemical assay showed gastrodin remarkably reduced the expressions of CD68 and NF-κB in BDL rats. Hepatic SOD levels, depressed by BDL, were also increased by gastrodin by 8.4 percent. In addition, the increases of hepatic MDA and NO levels in BDL rats were attenuated by gastrodin by 31.3 and 38.7 percent separately. Our results indicate that gastrodin significantly attenuated the severity of BDL-induced hepatic injury and fibrosis by attenuating oxidative stress and inflammation. Taken together, these findings suggest that gastrodin might be an effective antifibrotic drug in cholestatic liver disease.     

Antioxidantive activities and gastrodin determination of extracts of endophytic fungi isolated from Gastrodia elata Bl.

Gastrodia elata Bl. is a traditional Chinese herbal medicine with special pharmacological effects on headache and numbness. However, its wild sources are now in short supply because of over-excavation. A total of 14 endophytic fungi were isolated from Gastrodia elata Bl collected from Yinjing, in which 10 strains were identified, including Neonectria, Ascomycota, Fusarium, Oidiodendron and Dothiorella. All crude extracts showed some degrees of antioxidant activities by T-AOC method and DPPH methods, especially those from Oidiodendron GeR6 and Ascomycota sp. GeR2, which might be attributed due to their high phenolic contents. However, only Oidiodendron GeR6 contained gastrodin (39.2 μg/g) as the host plant in the crude extracts. In conclusion, the notable activities of GeR6 indicated its medical use as a natural antioxidant agent, as well as substitutable use for Gastrodia elata Bl. in the future.     

天麻素联合黛力新治疗更年期焦虑状态疗效观察

目的探讨天麻素联合黛力新治疗更年期焦虑状态的治疗效果。方法采用汉密尔顿焦虑量表对前来就诊的更年期妇女（年龄45～55岁）进行测试。量表分值在14分以上的156例患者随机分成治疗组与对照组。治疗组使用天麻素联合黛力新治疗，对照组单用黛力新治疗。结果治疗组总有效率92．30％，对照组总有效率为64．10％，差异具有统计学意义，治疗组治疗后焦虑量表分值平均（7．10±2．02）分，对照组平均（12．94±1．69）分，差异具有统计学意义。结论天麻素对改善更年期焦虑状态有明显疗效。     

Preparation and evaluation of sustained-release solid dispersions co-loading gastrodin with borneol as an oral brain-targeting enhancer

Borneol is a traditional Chinese medicine that can promote drug absorption from the gastrointestinal tract and distribution to the brain. However, stomach irritation may occur when high doses of borneol are used. In the present work, gastrodin, the main bioactive ingredient of the traditional Chinese drug “Tianma” (Rhizoma Gastrodiae) was used as a model drug to explore reasonable application of borneol. Sustained-release solid dispersions (SRSDs) for co-loading gastrodin and borneol were prepared using ethylcellulose as a sustained release matrix and hydroxy-propyl methylcellulose as a retarder. The dispersion state of drug within the SRSDs was analyzed by using scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffractometry. The results indicated that both gastrodin and borneol were molecularly dispersed in an amorphous form. Assay of in vitro drug release demonstrated that the dissolution profiles of gastrodin and borneol from the SRSDs both fitted the Higuchi model. Subsequently, gastric mucosa irritation and the brain targeting of the SRSDs were evaluated. Compared with the free mixture of gastrodin and borneol, brain targeting of SRSDs was slightly weaker (brain targeting index: 1.83 vs. 2.09), but stomach irritation obviously reduced. Sustained-release technology can be used to reduce stomach irritation caused by borneol while preserving sufficient transport capacity for oral brain-targeting drug delivery.KEY WORDS: Borneol, Gastrodin, Oral drug delivery, Brain-targeting, Gastric mucosa irritation, Sustained-release     

天麻苷对小鼠免疫功能的影响研究

目的 研究天麻苷对小白鼠免疫功能的影响。方法 通过在小白鼠日常饮水中加入不同剂量的天麻苷（低、中、高剂量分别是10、20、40 g /L）。采用脾脏重量和生长指数测定、腹腔巨噬细胞吞噬功能检测和体外抗体形成细胞检查法，检测天麻苷对小鼠外周免疫器官脾脏、抗体生成及吞噬细胞功能的影响。结果 天麻苷喂饲各组均未观察到任何中毒表现；在喂食的第14和21天，与阴性对照组比较，中、高剂量组小鼠的脾脏重量、生长指数、抗体生成及吞噬细胞功能均明显提高（P < 0.05），尤其是高剂量组更为显著（P < 0.01），且有一定剂量依赖性。结论 天麻苷可提高小鼠的免疫功能，增强抗感染能力。     

天麻素注射液联合盐酸氟西丁治疗卒中后抑郁的临床效果观察

目的 探讨天麻素注射液联合盐酸氟西丁治疗卒中后抑郁的临床效果及安全性.方法 对符合条件的102例卒中后抑郁患者随机分为两组,每组51例,天麻素注射液(600 mg,1次/d,静脉滴注,疗程14 d)联合盐酸氟西丁(20 mg,1次/d,口服,30 d)组为治疗组.单用盐酸氟西丁(20 mg,1次/d,口服,30 d)为对照组.观察两组患者的症状及体征变化以及汉密尔顿抑郁量表评分,评价疗效.结果 治疗组痊愈9.8％ (5/51),显著进步52.9％ (27/51),进步27.5％(14/51),无效9.8％ (5/51),总有效率90.2％ (46/51).对照组痊愈2.0％(1/51),显著进步11.7％ (6/51),进步66.7％ (34/51),无效19.6％(10/51),总有效率80.4％ (41/51).治疗组的疗效优于对照组,二者比较差异有统计学意义(x2=13.03,P＜0.05).治疗组不良反应发生率为3.92％ (2/51),对照组为25.5％(13/51),两组比较差异有统计学意义(x2=9.64,P＜0.01).结论 天麻素注射液联合盐酸氟西丁是治疗卒中后抑郁的一种疗效确切且副反应少的治疗方法.     

云南昭通不同产地天麻质控成分的含量测定

目的以天麻的质控成分天麻素(gastrodin,GAS)及对羟基苯甲醇(p-hydroxybenzyl alcohol,HBA)含量为指标对云南昭通不同产地的天麻进行考察,以确定其最佳产地。方法选取昭通境内彝良小草坝、镇雄盐源、威信水田3个产地的乌天麻,用95%乙醇进行回流提取,计算其提取率;采用HPLC分析方法测定天麻醇提取物中质控成分GAS及HBA的含量,进行天麻最佳产地的初步评价。结果彝良小草坝、镇雄盐源、威信水田的天麻醇提取物的提取率分别为:17.9、9.2、10.5%,所含质控成分的总量(GAS+HBA)分别为:0.8119、0.2478、0.2022%。结论通过分析,云南昭通境内的彝良小草坝产地的天麻醇提取物的提取率及质控成分总量均为三者中最高,可认为该地为天麻道地药材的最佳产地之一。     

天麻灵芝颗粒的质量标准研究

目的:建立天麻灵芝颗粒的质量标准。方法:采用TLC法对处方中天麻、淫羊藿、灵芝进行定性鉴别;采用HPLC法测定天麻素和淫羊藿苷的含量。结果:薄层色谱上样品与对照品显相同的斑点,分离效果好,阴性对照无干扰;天麻素在0.0502μg~0.3012μg、淫羊藿苷在8.4480μg~84.4800μg与峰面积具有良好的线性关系;平均回收率分别为99.85%和99.78%,RSD分别为0.33%和0.90%(N=9)。结论:该方法简单、可靠、准确,可以作为控制天麻灵芝颗粒的质量标准。     

天麻有效成分提取工艺研究

目的:考察不同条件下天麻素的提取情况。方法:采用正交试验法,以提取液中天麻素的含量为指标优选提取工艺条件。结果:提取的最佳条件为选用6倍药材量的600 ml/L乙醇提取3次,每次1.5 h。