大黄炮制前后的化学成分变化及其减毒研究

目的：探究大黄炮制成熟后成分的变化规律及其降低肝毒性的作用机制。方法：分别采用紫外分光光度法、高效液相色谱法分析大黄炮制过程中鞣质、总蒽醌、游离蒽醌含量的变化情况,并采用斑马鱼急性毒性试验评价大黄炮制前后的肝毒性变化。结果：生大黄的鞣质、总蒽醌及游离蒽醌含量分别为3.59%、1.96%和1.03%,经过炮制后,熟大黄的鞣质、总蒽醌及游离蒽醌含量分别为0.33%、1.86%和1.27%,鞣质和结合蒽醌的含量显著降低,而游离蒽醌含量显著升高。3批大黄炮制前后对斑马鱼的半数致死浓度（LC50）分别为210.15 μg/mL、216.63 μg/mL、248.25 μg/mL、1 082.12 μg/mL、1 200.98 μg/mL和1 189.27 μg/mL,与生大黄比较,熟大黄水提物的LC50显著升高。与对照组比较,生大黄呈现不同程度的肝脏变性（肝脏萎缩、卵黄囊吸收延迟、肝脏细胞肿大及组织空泡化）,而相同浓度下的熟大黄给药组,仅在高浓度条件下呈现轻微的肝脏变性。结论：大黄经过炮制后成分发生明显变化,肝毒性显著降低。     

不同煎煮方法与煎煮时间对大黄煎液中蒽醌与鞣质含量的影响

目的：探讨不同煎煮方法与煎煮时间对大黄蒽醌及鞣质提出率的影响，以寻求较理想的提取方法。方法：分光光度法。结果：大黄入汤剂以后下煎煮20－60min为宜。     

大黄九蒸九晒对蒽醌和鞣质含量的影响

探讨了九蒸九晒对大黄中蒽醌和鞣质含量的影响,并与其他几种炮制品进行了比较。九蒸九晒可使总蒽醌下降72.0％,游离蒽醌下降61.8％,结合蒽醌下降82.9％,鞣质下降42.8％,蒽醌与鞣质的比例由1:6.7下降为1:13.7。热压蒸晒3次大黄结果与之相似。     

酒大黄中大黄酚等蒽醌成分的含量分析

酒大黄中大黄酚等蒽醌成分的含量分析徐韧柳李建晨冯丽(河北省药品检验所石家庄050011)酒大黄是大黄药材经加酒拌匀、闷透、文火炒干的炮制品。大黄中含有大黄酚、大黄素甲醚、大黄素等多种蒽醌成分,在炮制过程中有一定程度的损失[1]。为考察酒大黄的质量,收集样品10份,应用薄层扫描法对大黄酚、大黄素甲醚和大黄素3种成分的含量进行了测定。1仪器与试药CS930型薄层扫描仪(日本岛津公司);定量毛细管(美国Drummond公司);大黄酚....     

枝穗大黄化学成分研究

目的 :研究枝穗大黄的化学成分。方法 :柱色谱和薄层色谱分离 ;UV ,IR ,MS ,NMR等技术鉴定结构。结果 :分离鉴定了 6个化合物 ,为大黄酚 ,大黄素 ,没食子酸 ,蔗糖 ,大黄酚-1-O-β-D-葡萄糖苷 ,大黄素-1-O-β-D- 葡萄糖苷。结论 :均为首次从该植物中分离得到。     

大黄蒽醌类的研究概况

根据国内外文献检索，综述对大黄蒽醌类成分的药理活性及其作用机理研究。结果证实，大黄蒽醌类成分除了具有泻下作用外，还有抗菌消炎、抗病毒、抗癌、保肝利胆、促智、抗衰老和延缓肾衰进程等作用。这些研究对大黄资源的进一步开发和利用具有重要的价值。     

大黄鞣质治疗慢性肾功能衰竭的研究近况

慢性肾功能衰竭（CRF）是各种慢性肾实质性疾病发展至后期的一种临床综合征，它以肾功能减退，代谢产物潴留，水、电解质、酸碱平衡失调为主要表现。目前非替代疗法对慢性肾功能衰竭早期治疗及延缓其病程发展至最终的尿毒症尤为重要。自上世纪60年代中药大黄应用于治疗CRF以来，众多医疗机构对大黄治疗CRF的作用多集中在其蒽醌类衍生物，却忽视了其鞣质成分（Rhatannin）对于CRF的重要作用，鞣质主要有水解型和缩合型两类，而没食子酸和d-儿茶素则是鞣质的这两类单体。大黄生药中鞣质含量很高，一般达10％-30％。本文将就近年来大黄鞣质（Rhatannin）对CRF治疗作用的研究做一综述。     

大黄蒽醌致泻作用及其机理的初步研究

目的比较大黄结合蒽醌、游离蒽醌致泻作用的强度并探讨其相关机制。方法通过灌服高浓度的奶粉溶液以营造高营养性环境,在此基础上考察了大黄结合蒽醌及游离蒽醌对小鼠的致泻作用;并运用析因设计分析了奶粉在这些致泻作用中的作用,同时还考察了大黄结合蒽醌及其游离蒽醌体外对胃蛋白酶活性的影响。结果大黄游离蒽醌500,1000mg/kg均可使小鼠胃内容物和小肠内容物显著增加;大黄结合蒽醌500,1000 mg/kg也可显著增加小鼠小肠内容的重量,但对小鼠胃内容重量的影响作用较弱;各药物组均可显著增加小鼠各肠段内的蛋白质浓度。析因设计的实验结果显示,无论是大黄游离蒽醌或是结合蒽醌均可显著增加正常小鼠(未加用奶粉)的胃、小肠及全胃肠道的内容物及蛋白质的含量,并可显著降低小鼠小肠、结肠Cl-浓度和升高小鼠结肠K 浓度;奶粉本身也具有与大黄蒽醌类似的作用,与之合用可增强大黄蒽醌的作用。体外实验结果显示,无论是大黄游离蒽醌或是结合型蒽醌对胃蛋白酶的活性均无明显影响。结论大黄游离蒽醌和结合蒽醌均具有显著的致泻作用;其机理可能是通过刺激胃肠道分泌、增加胃肠道内蛋白质浓度而产生容积性导泻。     

正交试验法研究水提与醇提对大黄蒽醌提取率的影响

考察以水和乙醇为溶剂对大黄蒽醌提取率的影响。方法：分别采用正交试验考察浸泡时间／乙醇浓度、提取时间、提取次数及溶剂量等因素对大黄总蒽醌、结合蒽醌和还原型蒽醌提取率的影响。结果：2种溶剂对大黄原配提取率的影响因素不尽相同，以水为溶剂，煎煮次数对总蒽醌具有显著性影响(P＜0．05)，浸泡时间及煎煮次数对结合原配有一定影响；以乙醇为溶剂，煎煮次数对总蒽醌有一定影响(0．05＜P＜0．1)，而乙醇浓度及煎煮时间对还原型蒽醌有显著性影响(P＜0．05)，加醇量有一定影响(0．05＜P＜0．1)。结论：水提组与醇提组比较，醇提组对3种蒽醌的提取效果明显优于水提组，醇提组中，以80％乙醇为优，且煎煮时间均不宜过长，控制在1h左右为宜。     

大黄煎熬过程的化学变化研究

目的:了解大黄煎熬过程的化学变化。方法:采用HPLC法对大黄煎熬前后生药、煎液及药渣中的各种蒽醌的含量进行监测。结果:生药煎煮后各种结合蒽醌和游离蒽醌的含量均发生了变化。结论:这种现象可能与结合蒽醌的水解,游离蒽醌的降解以及蒽醌间的相互转化有关。     

口服大黄芒硝在全消化道造影中的应用

对56例口服大黄、芒硝在全消化道造影应用效果与其它口服造影法作了比较和总结。本组56例中38例口服大黄、芒硝后120分钟钡剂充盈直肠。占67.85％.150分钟本组获全部结肠钡剂充盈像。     

大黄中蒽醌类成分配伍前后的量变规律

目的 :目的:研究大黄分别与甘草、黄芩、赤芍、当归、黄连、木香、栀子配伍前后蒽醌类成分的含量变化。 方法: 以大黄素、大黄酸、芦荟大黄素、大黄酚、大黄素甲醚为指标,采用HPLC法测定大黄配伍前后游离和结合蒽醌类成分的含量。 结果 :配伍后游离蒽醌和结合蒽醌的总量有不同程度的降低,其中以与黄连配伍降低幅度最大;且大黄经配伍用药后,各蒽醌类成分含量均发生规律性变化。 结论 :大黄经配伍用药后,蒽醌含量发生变化,推测对降低其毒副作用有一定的贡献,该研究为大黄临床合理运用提供一定的依据。     

大黄中蒽醌类成分薄层扫描测定

采用薄支析法对大黄中游离态和结合态蒽醌类成分进行分离,并用薄层扫描法测定其含量,同时考察了游离在成分在酸性水溶液中的稳定性以及不同酸度对结合蒽醌水解的影响。     

伍用大黄蒽醌对黄芩提取物中黄芩苷在大鼠体内吸收动力学影响的研究

目的观察伍用大黄蒽醌对黄芩提取物中黄芩苷在大鼠体内吸收动力学的影响。方法两组大鼠分别给予配伍药物和黄芩提取物,在不同时间点从门静脉中采集血浆样本,用HPLC法测定血浆中黄芩苷浓度的经时变化,用经典的房室模型和双部位吸收模型分别对浓度-时间数据进行药物动力学参数计算。结果实验建立的血浆中黄芩苷的HPLC测定方法准确、精密、可靠;黄芩苷在门静脉中的吸收模型符合双部位吸收模型。结论黄芩提取物配伍大黄蒽醌后可提高黄芩苷的吸收程度,延长吸收时程。     

胆乐化瘀片中大黄蒽醌含量的比色分析

目的：建立一种胆乐化瘀片中大黄蒽醌含量的测定方法。方法：采用TU-1221紫外分光光度计进行比色分析。结果：该法灵敏、简便、准确且稳定性好。结论：该法可作为胆乐化瘀片中大黄蒽醌含量限度的常规测定方法。     

大黄对无创通气治疗慢性阻塞性肺病的影响

目的：观察大黄对接受无创正压通气治疗慢性阻塞性肺病（COPD）患者的影响。方法：对照组在给予常规治疗的同时无创通气,治疗组加用大黄鼻饲;比较两组治疗前,治疗后8、24小时及3、7天时的动脉血气分析,并观察记录神志、呼吸、心率、呼吸困难等在各个治疗时期的变化。结果：治疗组患者均明显好转出院,对照组治疗后5例无改善而改用有创通气治疗,其余35例患者均好转出院;两组住院时间、机械通气时间、3、7天时呼吸困难计分比较差异有显著性（P〈0．05,P〈0．01）;动脉血气分析结果治疗组明显优于对照组（P〈0．05）;面部压伤、感染等不良反应治疗组明显减少。结论：大黄对无创通气治疗COPD能明显缩短患者住院和机械通气时间,降低不良反应发生率。     

Assessment of the renal protection and hepatotoxicity of rhubarb extract in rats

Aim of the study

Rhubarb is well used to treat chronic renal failure (CRF) in China and Japan, but recent studies reported that the anthraquinone derivatives contained in rhubarb had nephrotoxicity. In this investigation an attempt was made to assess the value and toxic potential of rhubarb to treat CRF.

Materials and methods

Histopathologic and biochemical tests combined with toxicokinetic analysis were performed to investigate the nephrotoxic potential and protective effect of rhubarb extract.

Results

In normal rat groups, no death was observed and no renal lesion was found after repetitive administration of rhubarb for 3 weeks. The survival rate, pathologic conditions and biochemical indexes of CRF rats treated with rhubarb at two dosages were all improved and significant amelioration was found in the low dosage group compared to the untreated CRF group. Rhein was the mainly absorbable anthraquinone derivative into systemic circulation after oral administration and the area under curve of rhein in CRF groups was lower than that in normal groups at same dosage.

Conclusions

After 3 weeks of administration of rhubarb extract, there was evidence of protective effect to CRF rats, while incidences of hepatotoxicity with minimal to mild hyaline droplets were also observed in normal rats.     

5种大黄游离蒽醌大鼠在体肠吸收的单向灌流法研究

目的 研究5种大黄游离蒽醌混合物(FAM,芦荟大黄素、大黄酚、大黄素、大黄酸、大黄素甲醚)在大鼠各肠段的吸收状况.方法 运用大鼠在体单向灌流肠吸收模型,HPLC法测定灌流液中FAM的浓度,分别考察FAM中5种物质在十二指肠、空肠、回肠、结肠及胆汁引流十二指肠段的吸收速率常数(Ka)和药物表观吸收系数(Papp).结果 芦荟大黄素、大黄素和大黄酸主要吸收部位为十二指肠,大黄酚在十二指肠和结肠段的吸收均较大,大黄素甲醚主要吸收部位为结肠;各物质在回肠段的吸收速率均最低(P<0.05).结论 FAM作为肠灌流液时,各物质的吸收与肠道的酸碱内环境和物质本身的脂溶性有关,同时可能存在相互间吸收的竞争与拮抗作用.胆汁对FAM在十二指肠的吸收有抑制作用.单向肠灌流实验表明FAM在各肠段吸收良好,这与体循环血液中除大黄酸外各物质测定浓度较低存在矛质,推测这与相关物质的肠道代谢有关.     

Identification of the multiple bioactive derivatives and their endogenous molecular targets that may mediate the laxative effect of rhubarb in rats

ObjectiveTo determine the mechanism of the laxative effect of rhubarb (Rheum tanguticum Maxim. ex Balf.) in rats using a combined bioinformatic and in vivo approach.MethodsSubstances derived from rhubarb that are present in the colorectum were identified using high-performance liquid chromatography, coupled with linear ion-trap quadrupole Orbitrap high-resolution mass spectrometry. The targets with a potential laxative effect were identified from databases and the literature, then used with rhubarb-derived substances in molecular docking modeling. The expression of candidate endogenous target molecules that bound specific components of rhubarb was then measured in constipated rats that had or had not been administered rhubarb by western blotting. Finally, potentially bioactive compounds were traced back to their prototype components.ResultsWe identified 17 anthraquinones and 21 anthrones derived from rhubarb in the colorectum of rats. G-scoring identified three potential mediators of the laxative effect: c-kit, 5-hydroxytryptamine receptor 4 (5-HT4), and aquaporin-3 (AQP3). In addition, 10 rhubarb-derived components (aloe-emodin, emodin, rhein, chrysophanol, physcion, sennoside A, sennoside C, physcionanthrone, aloe-emodinanthrone, and rheinanthrone), which have strong binding affinities for more than one of the three potential targets, were selected as likely active compounds. Rhubarb extract increased the expression of c-kit and 5-HT4, and reduced the expression of AQP3 in the colon of constipated rats, which might mediate its laxative effect. We also found that a single prototype component may be metabolized into several active metabolites, and a single active ingredient can also be generated from various prototype compounds.ConclusionThe present study demonstrates that various anthraquinones and anthrones present in rhubarb may be metabolized to form bioactive compounds that have additive or synergistic effects to promote defecation via c-kit, 5-HT4 and/or AQP3.     

The diarrhoeogenic and antidiarrhoeal bidirectional effects of rhubarb and its potential mechanism

Aim of the study

The present study investigated the pharmacological effects of different extracts of rhubarb on intestinal function of mice, further to explore possible reasons for the adverse effects of long-term use of rhubarb as a purgative.

Materials and methods

The total extract of rhubarb (TR) was extracted with 60% ethanol and the total anthraquinones extract (TA), total tannins extract (TT) and remaining components extract (RC) of rhubarb were separated from TR using macroporous resin. The pharmacological effects of each extract on the intestinal function of mice were evaluated by defecation test and the antidiarrhoeal activity of rhubarb tannins as well as its mechanism was studied by different animal models and histopathological examination.

Results

Both TR and TA produced purgative activities, but the purgative activity of TA was stronger than that of TR. Successive administration of TT produced an antidiarrhoeal activity in a time- and dose-dependent manner. Besides, successive administration of RC showed no significant effect on the intestinal function of mice. The antidiarrhoeal activity of rhubarb tannins was confirmed directly for the first time and its mechanism was probable that rhubarb tannins generated protein-precipitating reaction to the gastrointestinal mucosa due to its protein-precipitating action.

Conclusions

The results confirmed that rhubarb had the diarrhoeogenic and antidiarrhoeal bidirectional effects due to the coexistence of anthraquinones and tannins. The bidirectional effects might be the reason or one of the reasons for the adverse effects of long-term use of rhubarb as a purgative.