甘草苷的提取纯化和药理作用研究进展

甘草是我国传统的中药材,含有多种生物活性成分,其中甘草苷是重要的黄酮类化合物,提取分离技术难度较大,总结发现甘草苷常用有机溶剂、加热回流、闪式提取、超声波辅助提取、微波辅助提取、高压脉冲电场法等方法提取,有机溶剂、大孔树脂、无机陶瓷超滤、超滤-络合萃取及反萃取技术进行分离纯化。与此同时,已有研究表明甘草苷具有抗抑郁、抗氧化、抗炎、抗病毒、解毒等药理作用,为进一步研究开发甘草苷提供了参考依据。     

甘草甜素抗炎及抗肿瘤机制研究进展

甘草甜素是中药甘草的主要成分,具有抗炎、抗病毒、抗肿瘤等作用,随着研究的不断深入,甘草甜素广泛地应用于银屑病、慢性肝病、艾滋病及肿瘤等疾病的治疗中。近年来,学者对其抗炎和抗肿瘤作用研究较为突出,其机制包括抑制炎症因子、抗氧化、免疫调节、抗血管生成等,为更好地指导临床应用,就目前甘草甜素抗炎和抗肿瘤机制作一综述。     

不同栽培龄期光果甘草不同部位总黄酮含量的分析

光果甘草(Glycyrrhiza glabra L.)为甘草属(Glycyrrhiza L.)多年生草本植物,是药用甘草的原植物之一[1].甘草属植物所含的黄酮类成分具有抗血栓、抗氧化、抗肿瘤、抗衰老、增加白细胞、抗动脉硬化、抗心律失常和抑制HIV等作用[2-5];光果甘草中的黄酮类成分光甘草定具有良好的抗氧化、抗炎及抗菌作用,应用前景广阔[6].目前关于光果甘草总黄酮含量已有一些报道[7-8],但有关生长年限对栽培光果甘草总黄酮含量的影响却很少报道[9-10],尤其是对不同栽培龄期光果甘草在不同采集时间各部位总黄酮含量的变化规律缺乏较全面的研究,致使光果甘草药材生产缺乏有力的理论指导依据.     

雷公藤甲素研究进展

雷公藤甲素作为雷公藤的主要活性成分,具有抗炎、免疫抑制、抗生育、抗囊肿和抗肿瘤等药理作用。本文就近期雷公藤甲素的药代动力学研究、药理作用研究以及减毒研究三个方面作一综述。     

水溶性甘草多糖的分离纯化、结构及生物活性研究进展

甘草是广泛使用的中药材之一.甘草中含有多种活性物质,甘草多糖作为主要的活性大分子,具有抗肿瘤、抗病毒、抗氧化、抗补体以及免疫调节等生物活性.本文对近年来水溶性甘草多糖的分离纯化、结构解析以及生物活性研究的最新进展进行综述.     

黑老虎木脂素化学成分及药理作用研究进展CSCD

黑老虎是一种具有药用、食用、观赏等多种价值的经济植物。黑老虎的化学成分及药理作用研究进展较快,目前已分离出200余种化合物,其中木脂素类化合物121种,具有抗炎、抗肿瘤、抗HIV、抗凝血、抗氧化、保肝等多种药理作用。现对黑老虎中木脂素类化学成分和药理作用进行综述,为黑老虎的深入开发利用提供参考。     

芍药甘草汤及其活性成分的脑保护作用机制研究概述

芍药甘草汤由东汉张仲景创立,仅有芍药和甘草两味药物组成,具有调和肝脾,缓急止痛的功效,是经典的止痛方剂,临床主要用于血虚津伤所导致的各种内脏疼痛,腓肠肌痉挛的治疗中。已经展开的基础研究主要集中解痉、止痛和抗炎方面的机理研究。近年逐步认识到芍药甘草汤及其活性成分在神经保护领域的作用,在脑卒中、帕金森病、阿尔海默氏症、癫痫等中枢神经系统疾病基础研究中,取得成果。文章研读近年来国内外相关文献,分别从芍药、甘草的活性成份以及芍药甘草汤方剂在脑保护领域进行的基础研究的进展做一综述,显示了芍药甘草汤及其活性成分可以抑制脑组织免疫炎症反应、抑制氧化反应、抗谷氨酸毒性,改善脑血流、抗细胞凋亡和保护神经元的作用,阐述了芍药甘草汤的多途径、多靶点的药理优势及在脑保护领域的应用前景。     

甘草有效成分的药理活性研究

甘草为豆科植物甘草属植物的根及根茎,被喻为国老,是我国重要的传统药材,《神农本草经》记载甘草具有主五脏六腑寒邪气,坚筋骨,长肌肉,倍气力,金疮肿,解毒之功效,现代药理表明甘草具有抗肿瘤、抗氧化、抗炎、保肝、降血糖等功效,本章节旨在综述近年来甘草的主要活性,进而为开发甘草新药提供理论依据。     

甘草次酸保肝功效的通路作用机制

甘草的活性成分包括甘草甜素(glycyrrhizin,GL)和甘草次酸(glycyrrhetinic acid,GA),而GA是甘草中的主要生物活性成分,是GL的主要代谢产物,部分GL通过细菌在肠内代谢为GA。在许多以往的研究中已经证实其具有多种药理学效果,例如抗炎、抗过敏、抗致癌、抗损伤和抗氧化特性以及肝脏保护。最近的研究表明,GA可以降低逆转录因子、二氧化钛纳米粒子和环磷酰胺诱导的肝毒性,并且可以保护免受四氯化碳诱导的肝损伤。已报道的GA的保肝作用机制主要归因于诱导抗氧化剂防御,抑制炎症反应和细胞色素P450表达,本文将对GA在不同信号通路中发挥保肝作用进行综述。     

甘草有效成分及其作用机制研究进展

甘草是一种常见中药，资源丰富且药用价值高，已作为一种重要药物用于疾病治疗之中。近年来，甘草中黄酮类、三萜皂苷类、多糖类等有效成分被证实具有多种良性药理活性。甘草具有良好的抗炎、抗肿瘤、保肝、增强免疫等作用。本文主要介绍了甘草的有效成分及其作用机制，旨在为甘草的推广及临床应用提供参考。     

甘草抗动脉粥样硬化机制的网络药理学研究

利用网络药理学方法探讨甘草在抗动脉粥样硬化中的分子机制。本研究利用中医药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)分析甘草中的有效活性成分,并获得有效成分的作用靶点。通过Cytoscape软件构建可视化靶点互相作用网络,对网络中的关键靶点进行基因本体(GO)富集分析和KEGG通路富集分析。结果显示甘草中40种有效活性成分的预测靶点共97个,47个靶点与动脉粥样硬化(AS)相关,其中18个是血管保护药物和脂质修饰药物的作用靶点,表明甘草可作为调控AS发展的药物。基于97个预测靶点的GO富集分析,发现甘草可参与多种生物学过程,尤其是应对外源性刺激,以及参与细胞凋亡等过程。通过构建甘草靶点与AS疾病靶点相互作用网络(PPI),确定了AKT1、MAPK3、MAPK1、JUN和CASP3等关键靶点,并对关键靶点进行KEGG富集分析,结果表明甘草主要影响调控细胞增殖、生存以及凋亡的细胞信号转导相关通路,并激活先天免疫相关信号通路,调节炎性细胞因子释放,从而发挥抗动脉粥样硬化作用。甘草具有多成分、多靶点、多途径的作用特点,主要通过PI3K-AKT信号途径、MAPK信号途径、NOD样受体信号通路调控细胞增殖和凋亡,同时发挥免疫调控作用,从而影响动脉粥样硬化的发展,由此可见,甘草可作为动脉粥样硬化疾病治疗的候选中草药。     

Glycyrrhizae Radix attenuates peroxynitrite-induced renal oxidative damage through inhibition of protein nitration

We investigated the protective effects of Glycyrrhizae Radix extract against peroxynitrite (ONOO^-)-induced oxidative stress under in vivo as well as in vitro conditions. The extract showed strong ONOO^- and nitric oxide (NO) scavenging effects under in vitro system, in particular higher activity against ONOO^-. Furthermore, elevations of plasma 3-nitrotyrosine levels, indicative of in vivo ONOO^- generation and NO production, were shown using a rat in vivo ONOO^--generation model of lipopolysaccharide injection plus ischemia-reperfusion. The administration of Glycyrrhizae Radix extract at doses of 30 and 60 mg/kg body weight/day for 30 days significantly reduced the concentrations of 3-nitrotyrosine and NO and decreased inducible NO synthase activity. In addition, the nitrated tyrosine protein level and myeloperoxidase activity in the kidney were significantly lower in rats given Glycyrrhizae Radix extract than in control rats. However, the administration of Glycyrrhizae Radix extract did not result in either significant elevation of glutathione levels or reduction of lipid peroxidation in renal mitochondria. Moreover, the in vivo ONOO^- generation system resulted in renal functional impairment, reflected by increased plasma levels of urea nitrogen and creatinine, whereas the administration of Glycyrrhizae Radix extract reduced these levels significantly, implying that the renal dysfunction induced by ONOO^- was ameliorated. The present study suggests that Glycyrrhizae Radix extract could protect the kidneys against ONOO^- through scavenging ONOO^- and/or its precursor NO, inhibiting protein nitration and improving renal dysfunction caused by ONOO^-.     

The constituents of licorice (Glycyrrhiza uralensis) differentially suppress nitric oxide production in interleukin-1β-treated hepatocytes

Licorice (Glycyrrhizae radix) is the roots and stolons of Glycyrrhiza uralensis Fischer or Glycyrrhiza glabra Linnaeus in the Japanese Pharmacopoeia. Glycyrrhizae radix has been widely used as a sweetener and a traditional medicine. A Glycyrrhizae radix extract contains many constituents and has antispasmodic, antitussive, anti-ulcer, and anti-inflammatory effects. However, reports comparing the anti-inflammatory effects of these constituents are very few. Here, we purified several constituents from the roots and stolons of G. uralensis and examined and compared their anti-inflammatory effects by monitoring the levels of the inflammatory mediator, nitric oxide (NO), in interleukin (IL)-1β-treated rat hepatocytes. From the G. uralensis extract, we purified the main constituent glycyrrhizin and the constituents that are characteristic of G. uralensis (chalcones and flavanones). These constituents suppressed NO production in IL-1β-treated rat hepatocytes, and isoliquiritigenin showed the greatest suppression activity. Isoliquiritigenin, isoliquiritin, and liquiritigenin significantly decreased both protein and mRNA for the inducible nitric oxide synthase. These constituents reduced the levels of mRNAs encoding tumor necrosis factor α and IL-6. In contrast, although glycyrrhizin is abundant, it showed a 100-fold lower potency in NO suppression. Therefore, both glycyrrhizin and the minor constituents (isoliquiritigenin, isoliquiritin, and liquiritigenin) may be responsible for the anti-inflammatory effects of G. uralensis. It is also implied that these constituents may have a therapeutic potential for inflammatory hepatic disorders.     

Changes in Components,Glycyrrhizin and Glycyrrhetinic Acid,in Raw Glycyrrhiza uralensis Fisch,Modify Insulin Sensitizing and Insulinotropic Actions

We hypothesized that roasted Glycyrrhizae Radix (Glycyrrhizin Radix Praeparata, GRP) might modify anti-diabetic action due to compositional changes. Then we examined the anti-diabetic effect and mechanism of raw Glycyrrhizae Radix (GR) and GRP extracts and their major respective components, glycyrrhizin and glycyrrhetinic acid. In partial pancreatectomized (Px) diabetic mice, both GR and GRP improved glucose tolerance, but only GRP enhanced glucose-stimulated insulin secretion as much as exendin-4. Both GR and GRP extracts enhanced insulin-stimulated glucose uptake through peroxisome proliferation-activated receptor (PPAR)-γ activation in 3T3-L1 adipocytes. Consistently with the results of the mice study, only GRP and glycyrrhetinic acid enhanced glucose-stimulated insulin secretion in isolated islets. In addition, they induced mRNA levels of insulin receptor substrate-2, pancreas duodenum homeobox-1, and glucokinase in the islets, which contributed to improving β-cell viability. In conclusion, GRP extract containing glycyrrhetinic acid improved glucose tolerance better than GR extract by enhancing insulinotropic action. Thus, GRP had better anti-diabetic action than GR.     

Changes in components, glycyrrhizin and glycyrrhetinic acid, in raw Glycyrrhiza uralensis Fisch, modify insulin sensitizing and insulinotropic actions

We hypothesized that roasted Glycyrrhizae Radix (Glycyrrhizin Radix Praeparata, GRP) might modify anti-diabetic action due to compositional changes. Then we examined the anti-diabetic effect and mechanism of raw Glycyrrhizae Radix (GR) and GRP extracts and their major respective components, glycyrrhizin and glycyrrhetinic acid. In partial pancreatectomized (Px) diabetic mice, both GR and GRP improved glucose tolerance, but only GRP enhanced glucose-stimulated insulin secretion as much as exendin-4. Both GR and GRP extracts enhanced insulin-stimulated glucose uptake through peroxisome proliferation-activated receptor (PPAR)-gamma activation in 3T3-L1 adipocytes. Consistently with the results of the mice study, only GRP and glycyrrhetinic acid enhanced glucose-stimulated insulin secretion in isolated islets. In addition, they induced mRNA levels of insulin receptor substrate-2, pancreas duodenum homeobox-1, and glucokinase in the islets, which contributed to improving beta-cell viability. In conclusion, GRP extract containing glycyrrhetinic acid improved glucose tolerance better than GR extract by enhancing insulinotropic action. Thus, GRP had better anti-diabetic action than GR.     

Antimutagenicity of extracts from crude drugs in Chinese medicines

The antimutagenicity of extracts from crude drugs was studied by the Ames bioassay system. The crude drugs chosen were medical plants used very frequently as Chinese medicines. Each crude drug was extracted with hot water similar to the method of Chinese medical treatment. Antimutagenicity of the extract was found with 4 kinds of crude drugs, Paeoniae radix, Bupleuri radix, Hoelen and Glycyrrhizae radix. Each extract of the crude drug showed a different type of antimutagenic action from the others.     

Protective effects of Glycyrrhizae radix extract and its compounds in a renal hypoxia (ischemia)-reoxygenation (reperfusion) model.

Glycyrrhizae radix water extract (GRWE) and its two major constituents glycyrrhizin and 3-glycyrrhetinic monodesmoside, significantly suppressed LDH leakage and MDA release, whereas glycyrrhetinic acid had no effect. On the other hand, in rats subjected to ischemia-reperfusion, the activities of endogenous antioxidant enzymes including catalase and glutathione peroxidase showed recovery, whereas the levels of urea nitrogen and creatinine in serum were reduced by administration of glycyrrhizin orally for 30 days prior to ischemia-reperfusion. These results indicate that GRWE and its two constituents may be promising for amelioration of hypoxia (ischemia)-reoxygenation (reperfusion) injury and improvement of renal function by acting directly or indirectly as antioxidant and oxygen radical-scavenging agents.     

Interaction between Shaoyao–Gancao–Tang and a laxative with respect to alteration of paeoniflorin metabolism by intestinal bacteria in rats

Shaoyao-Gancao-Tang (SGT), a traditional Chinese herbal medicine (Kampo formulation) containing Shaoyao (Paeoniae Radix) and Gancao (Glycyrrhizae Radix), is co-administered with laxative sodium picosulfate as a premedication for relieving the pain accompanying colonoscopy. Paeoniflorin (PF), an active glycoside of SGT, is metabolized into the antispasmodic agent paeonimetabolin-I (PM-I) by intestinal bacteria after oral administration. The objective of the present study was to investigate whether the co-administered laxative (sodium picosulfate) influences the metabolism of PF to PM-I by intestinal bacteria. We found that the PF-metabolizing activity of intestinal bacteria in rat feces was significantly reduced to approximately 34% of initial levels by a single sodium picosulfate pretreatment and took approximately 6 days to recover. Repeated administration of SGT after the sodium picosulfate pretreatment significantly shortened the recovery period to around 2 days. Similar results were also observed for plasma PM-I concentration. Since PM-I has muscle relaxant activity, the present results suggest that repetitive administration of SGT after sodium picosulfate pretreatment might be useful to relieve the pain associated with colonoscopy.     

鹅膏菌中毒小鼠解毒药物的筛选

考察了几种中药对鳞柄白鹅膏中毒小鼠的解毒作用。鳞柄白鹅膏为极毒真菌,当其干燥子实体水溶液质量浓度>10mg/mL时,小鼠全部死亡,质量浓度为10mg/mL时,小鼠在9 h内全部死亡,选择这一浓度使小鼠中毒,使用所选中药对小鼠进行解毒试验。结果表明:水飞蓟(7.8 g/kg)、绿豆(3.9 g/kg)及甘草(1.3 g/kg)均能延迟小鼠的死亡时间,但与对照组相比差异不显著。灵芝(1.95 g/kg)对小鼠的死亡时间有明显的延迟作用,并与对照组相比差异显著(P<0.05)。同时使用灵芝剂量为首次解毒试验剂量的100倍水煎液(195 g/kg)和300倍水煎液(585 g/kg),以及按原料剂量为195 g/kg提取其中三萜及多糖用于对鹅膏中毒小鼠的解毒试验。结果表明:试验组小鼠的死亡时间均有延迟,其中195 g/kg剂量灵芝组和灵芝三萜试验组与对照组相比差异显著(P<0.05)。     

Induction of apoptosis with mitochondrial membrane depolarization by a glycyrrhetinic acid derivative in human leukemia K562 cells

Glycyrrhetinic acid (GA) is the active compound in Glycyrrhizae radix, a famous traditional Chinese medicine. Recently the anticancer activity of GA became the focus of scientific interest and many GA derivatives were developed as anti-tumor lead compounds. We previously reported that AEGA, a GA derivative, has proliferation inhibition and apoptosis-inducing activity in various human tumor cells. The present study was undertaken to further investigate the molecular mechanisms involved in AEGA-induced apoptosis in human leukemia K562 cells. AEGA can inhibit the growth of K562 cells in dose- and time-dependent manners determined by the MTT assay. Induction of apoptosis was evidenced by morphological changes and biochemical markers such as cell shrinkage, chromatin condensation and DNA ladder formation. Further mechanistic analysis revealed that AEGA induced apoptosis through the collapse of mitochondrial membrane potential, the accumulation of the cytosolic cytochrome c and the activation of caspase-9 and caspase-3. The apoptosis induction by AEGA was associated with the alteration in the ratio of Bcl-2/Bax protein expression. These results suggest that AEGA may induce apoptosis through a mitochondria-mediated pathway, and might have the therapeutic value against hematological malignancies.