Antitumour effects of selected plant polyphenols,gallic acid and ellagic acid,on sensitive and multidrug‐resistant leukaemia HL60 cells

The aim of this study was to examine the antitumour effects of plant phenolic acids, gallic acid (GA) and ellagic acid (EA), on human promyelocytic leukaemia sensitive HL60 cell line and its resistant sublines exhibiting two MDR phenotypes: HL60/VINC (overexpressing P‐glycoprotein) and HL60/MX2 (characterized by the presence of mutated α isoform of topoisomerase II). Both studied compounds exerted comparable cytotoxic activities towards sensitive HL60 cells and their MDR counterparts. It was also found that GA and EA modulated the cellular level of reactive oxygen species in a dose‐dependent and time‐dependent manner. Furthermore, it was demonstrated that GA (IC₉₀) and EA (IC₅₀ and IC₉₀) significantly increased the percentage of sub‐G1 subpopulation of all studied leukaemia cells causing oligonucleosomal DNA fragmentation. Both compounds used at IC₉₀ triggered mainly the apoptotic death of these cells. However, GA had no effect on the activity of caspase‐3 as well as caspase‐8 in sensitive HL60 cells and their MDR counterparts. In contrast, EA provoked a significant activation of these caspases in all studied leukaemia cells. It was also found that lysosomes were not involved in triggering programmed death of sensitive HL60 and MDR cells by GA and EA.     

以水杨酸为假模板制备印迹聚合物对银杏酸的吸附性能研究

目的研究银杏酸吸附分离的新方法。方法采用分子印迹技术,以水杨酸为假模板分子,4-乙烯基吡啶为功能单体,通过分子自组装印迹技术合成对银杏酸具有高吸附性的印迹聚合物,运用核磁共振氢谱、红外光谱分析研究聚合物的印迹机制,扫描电镜考察聚合物的结构表征,HPLC和紫外检测法监测聚合物对总银杏酸的吸附结合特性。结果加入模板分子合成分子印迹聚合物(MIP)具备更好的三维空间结构和吸附性能,其中模板分子与功能单体以非共价键结合。在银杏外种皮提取液中MIP对银杏酸的吸附率达到95.9%;根据Scatchard分析聚合物,存在2种不同的结合位点,其中高亲和力结合位点饱和结合位点数(Q_(max1))=30 mg/g;低亲和力结合位点饱和结合位点数(Q_(max2))=80 mg/g。聚合物的吸附动力学为准二级动力学吸附。结论以水杨酸为模板制备MIP对银杏酸有很强的吸附性能,在银杏酸的分离精制中具有很好的推广应用前景。     

太子参化学成分、药理作用和应用的研究进展

太子参Pseudostellariae Radix是中国传统补益中药材之一,兼具药用和食疗功效,主要含有挥发油、多糖、环肽、生物碱、皂苷、酚类等成分,具有降血糖、抗炎、抗癌、保护细胞、抑制酪氨酸酶、免疫调节等药理作用。对太子参的化学成分及其药理作用,以及太子参在临床、食疗、保健食品、化妆品、兽药制剂和功能性饲料添加剂等方面应用进行总结,为太子参进一步开发利用提供依据。     

Digallic acid from Pistascia lentiscus fruits induces apoptosis and enhances antioxidant activities

The antioxidant and apoptotic activities of digallic acid, isolated from the fruits of Pistascia lentiscus, were investigated. The study demonstrated that digallic acid possessed pro‐apoptotic effects, as shown by provoking DNA fragmentation of K562 cells. It also revealed a significant antioxidant potential and effective scavenging activity against 2,2‐diphenyl‐1‐picrylhdrazyl (DPPH^·) and O₂^·? radicals, and reduced cupric ions. We conclude that this integrated approach to apoptotic and antioxidant assessment may be useful to maximize the beneficial effects associated with using P. lentiscus derivatives as medicinal and dietary compounds. Copyright © 2011 John Wiley & Sons, Ltd.     

Gallic Acid Exhibits Risks of Inducing Muscular Hemorrhagic Liposis and Cerebral Hemorrhage—Its Action Mechanism and Preventive Strategy

Gallic acid (3,4,5‐trihydroxybenzoic acid) (GA) occurs in many plants. The adverse effects of GA are seldom cited. GA (6–14 μM) provoked the hemorrhagic liposis of the cervical muscles and intracranial hemorrhage. The cause of these pathological events and the method for prevention are still lacking. Using the chicken embryo model and some selected nutraceutics such as folate, glutathione (GSH), N‐acetylcysteine, and vitamin E (Vit E), we carried out this study. Results revealed that the action mechanism of GA involved (i) inducing hypoxia with upregulated gene hif‐1α and downregulated ratio vegf‐r2/vegf‐a, leading to dys‐vascularization and myopathy; (ii) impairing cytochrome c oxidase; (iii) stimulating creatine kinase and lactate dehydrogenase release; (iv) eliciting carnitine accumulation and liposis via downregulating gene CPT1; (v) suppressing superoxide dismutase and stimulating NO, H₂O₂, and malondialdehyde; and (vi) depleting erythrocytic and tissue GSH, resulting in hemorrhage. When both Vit E and GSH were applied to the day 1 chicks, a better alleviation effect was revealed. Conclusively, GA potentially exhibits adverse effect by eliciting hemorrhagic liposis of cervical muscles and cerebral hemorrhage. Supplementation with GSH, Vit E, and N‐acetylcysteine is able to ameliorate these adverse effects, warranting the importance of restricting the clinical phytotherapeutic doses of GA and related compounds. Copyright © 2014 John Wiley & Sons, Ltd.     

Antifungal Activity of Gallic Acid In Vitro and In Vivo

Gallic acid (GA) is a polyphenol natural compound found in many medicinal plant species, including pomegranate rind (Punica granatum L.), and has been shown to have antiinflammatory and antibacterial properties. Pomegranate rind is used to treat bacterial and fungal pathogens in Uyghur and other systems of traditional medicine, but, surprisingly, the effects of GA on antifungal activity have not yet been reported. In this study, we aimed to investigate the inhibitory effects of GA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the NCCLS (M38‐A and M27‐A2) standard method in vitro, and GA was found to have a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 43.75 and 83.33 μg/mL. Gallic acid was also active against three Candida strains, with MICs between 12.5 and 100.0 μg/mL. The most sensitive Candida species was Candida albicans (MIC = 12.5 μg/mL), and the most sensitive filamentous species was Trichophyton rubrum (MIC = 43.75 μg/mL), which was comparable in potency to the control, fluconazole. The mechanism of action was investigated for inhibition of ergosterol biosynthesis using an HPLC‐based assay and an enzyme linked immunosorbent assay. Gallic acid reduced the activity of sterol 14α‐demethylase P450 (CYP51) and squalene epoxidase in the T. rubrum membrane, respectively. In vivo model demonstrated that intraperitoneal injection administration of GA (80 mg/kg d) significantly enhanced the cure rate in a mice infection model of systemic fungal infection. Overall, our results confirm the antifungal effects of GA and suggest a mechanism of action, suggesting that GA has the potential to be developed further as a natural antifungal agent for clinical use. Copyright © 2017 John Wiley & Sons, Ltd.     

毛诃子化学成分和药理作用的研究进展及其质量标志物（Q-Marker）预测分析

毛诃子Terminaliae Belliricae Fructus为藏族习用药材,在传统中医药以及多民族医药中使用广泛且悠久。现代研究表明毛诃子主要含有酚酸类、鞣质类、黄酮类、萜类、甾体类、木脂素类等化学成分,具有保肝、降血糖、调血脂与抗肿瘤等药理作用。基于对毛诃子的化学成分及药理作用的归纳总结,结合其质量控制研究现状,从传统药性、传统功效、化学成分可测性及药动学等方面对其质量标志物（quality marker,Q-Marker）进行预测。没食子酸、鞣花酸、柯里拉京、没食子甲酯、诃子鞣酸、单宁酸、奎宁酸、6-姜酚、儿茶素等成分可作为毛诃子的主要Q-Marker,以期为毛诃子进一步研究及质量标准的合理建立提供参考。     

Oleuropein: A natural antioxidant molecule in the treatment of metabolic syndrome

Olive (Olea europaea Linn., Fam. Oleaceae) is commonly known as Zaytoon in Mediterranean region. Its fruits and oil are essential components of Mediterranean diets. Olive tree is a prevalent plant species and one of the important cultivated crops of Mediterranean region. Oleuropein is a phenolic constituents of olive, which, along with its related compounds, has been indicated to be majorly responsible for its beneficial effects. Oleuropein is a secoiridoid type of phenolic compound and consists of three structural subunits: hydroxytyrosol, elenolic acid, and a glucose molecule. It is also reported to be the chemotaxonomic marker of olive. The oleuropein is reported to possess a number of biological activities including action against dyslipidemia, antiobesity, antidiabetic, antioxidant, antiatherogenic, antihypertensive, antiinflammatory, and hepatoprotective actions. The scientific evidence supports the role of oleuropein as a potential agent against metabolic syndrome. The present review discusses chemistry of oleuropein along with potential role of oleuropein with reference to pathophysiology of metabolic syndrome.     

不同采收期苍耳草中酚酸类及蒽醌类成分的动态积累分析

目的分析不同采收期苍耳草Xanthium sibiricum中酚酸类及蒽醌类成分的动态变化。方法采用HPLC法测定不同采收期苍耳草中酚酸类成分绿原酸、新绿原酸、原儿茶醛、原儿茶酸、隐绿原酸、咖啡酸、1,3-二咖啡酰奎宁酸、阿魏酸、3,4-二咖啡酰奎宁酸、3,5-二咖啡酰奎宁酸、4,5-二咖啡酰奎宁酸及蒽醌类成分芦荟大黄素、大黄素、大黄酚的量。结果不同采收期苍耳草中酚酸类及蒽醌类成分的量呈动态变化,总酚酸量7月中旬较高,总蒽醌量7月下旬较高;绿原酸、原儿茶醛、阿魏酸、3,5-二咖啡酰奎宁酸、1,3-二咖啡酰奎宁酸5种主要酚酸总量7月中旬较高,其中绿原酸量以6月下旬较高,其余均以7月中旬较高。结论为确定苍耳草药材的适宜采收期提供依据。     

余甘子及其活性成分肝保护作用及机制的研究进展

余甘子来源于余甘子Phyllanthus emblica的干燥成熟果实,是我国重要的药食同源品种,具有抗炎、抗氧化、抗肿瘤和免疫调节等广泛的生物活性。通过对余甘子提取物及其所含没食子酸、鞣花酸及柯里拉京等活性成分的药理作用进行总结,发现其对肝损伤、病毒性肝炎、非酒精性脂肪肝、肝纤维化及肝癌等具有治疗作用,主要通过抑制脂质过氧化、降低炎症反应、抗肝细胞凋亡、调节脂质代谢、维持肝星状细胞稳态及促肝癌细胞凋亡等发挥肝保护作用。对余甘子及其单体活性成分治疗肝脏疾病的药理作用及其机制进行归纳分析,以期为其在防治肝脏疾病中的深入研究以及开发应用提供参考依据。     

对香豆酸的药理作用研究进展

对香豆酸主要存在于水果、蔬菜、谷物和真菌中,在中药中含量也很丰富。对香豆酸具有抗氧化、抗炎、免疫调节、抗肿瘤、抗血小板聚集、保护心血管、预防和改善糖尿病及神经保护作用。抗氧化活性是对香豆酸其他药理作用的基础。另外,对香豆酸对细菌有一定的抑制作用,还可抑制黑色素形成及延缓皮肤老化。对对香豆酸的主要药理作用进行综述,为药食两用资源的开发研究提供借鉴。     

鸡血藤化学成分、药理作用研究进展及其质量标志物（Q-Marker）预测

鸡血藤Spatholobi Caulis为藤茎类中药，在我国南方地区及东南亚国家药用历史悠久。研究表明鸡血藤成分复杂，主要包括黄酮类、苯丙素类、酚酸类等成分，具有调节血液系统、抗氧化、抗肿瘤及抗病毒等活性。通过对鸡血藤化学成分和药理作用进行综述，基于化学成分特有性、药性、药效、入血成分和成分可测性对鸡血藤的质量标志物（quality marker,Q-Marker）进行预测，表明儿茶素、染料木素、芒柄花素等黄酮类成分及原儿茶酸和没食子酸等酚酸类、芦荟大黄素等蒽醌类、3-羟基豆甾-5-烯-7-酮等甾体类、白芷内酯和spasuberol C等香豆素类可作为鸡血藤的主要Q-Marker，为鸡血藤的质量评价提供科学依据。     

商陆化学成分及药理作用和临床应用研究进展

商陆为《中国药典》收载品种,包括商陆Phytolacca acinosa与垂序商陆P.americana,具有重要的药用价值。商陆的特征性化学成分是三萜皂苷,此外还有黄酮、酚酸、甾醇、多糖等成分。现代药理学研究表明,商陆具有利尿、抗菌、抗病毒、抗炎、抗肿瘤等作用;临床上多用其治疗乙型肝炎、银屑病、过敏性紫癜等疾病。对商陆的化学成分、药理作用和临床疗效进行了总结,以期为商陆的开发利用及深入研究提供参考。     

Glycyrrhizic acid as the antiviral component of Glycyrrhiza uralensis Fisch. against coxsackievirus A16 and enterovirus 71 of hand foot and mouth disease

Ethnopharmacological relevance

The radices of Glycyrrhiza uralensis Fisch. and herbal preparations containing Glycyrrhiza spp. have been used for thousands of years as an herbal medicine for the treatment of viral induced cough, viral hepatitis, and viral skin diseases like ulcers in China. Glycyrrhizic acid (GA) is considered the principal component in Glycyrrhiza spp. with a wide spectrum of antiviral activity.

Aim

The present study attempt to validate the medicinal use of Glycyrrhiza uralensis for hand, foot and mouth disease (HFMD) and further to verify whether GA is an active antiviral component in the water extract of Glycyrrhiza uralensis.

Materials and methods

Radices of Glycyrrhiza uralensis Fisch. were extracted with hot water. The chemical contents of the extract were profiled with HPLC analysis. The antiviral activity of the extract and the major components was evaluated against infection of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) on Vero cells. The cytopathic effect caused by the infection was measured with MTT assay. Infectious virion production was determined using secondary infection assays and viral protein expression by immunoblotting analysis.

Results

The extract at 1000 μg/ml suppressed EV71 replication by 1.0 log and CVA16 by 1.5 logs. The antiviral activity was associated with the content of GA in the extract since selective depletion of GA from the extract by acid precipitation resulted in loss of antiviral activity. In contrast, the acid precipitant retained antiviral activity. The precipitant at a concentration of 200 μg/ml inhibited EV71 and CVA16 replication by 1.7 and 2.2 logs, respectively. Furthermore, GA dose-dependently blocked viral replication of EV71 and CVA16. At 3 mM, GA reduced infectious CVA16 and EV71 production by 3.5 and 2.2 logs, respectively. At 5 mM, CVA16 production was reduced by 6.0 logs and EV71 by 4.0 logs. Both EV71 and CVA16 are members of Enterovirus genus, time-of-drug addition studies however showed that GA directly inactivated CVA16, while GA anti-EV71 effect was associated with an event(s) post virus cell entry.

Conclusions

This study validated the medicinal usefulness of radices Glycyrrhiza uralensis against the etiological agents of HFMD. In addition to the identification of GA as the antiviral component of Glycyrrhiza uralensis against EV71 and CVA16 infection, this study also reveals that GA inhibits EV71 and CVA16 with distinct mechanisms.     

Effects of Piperine,Cinnamic Acid and Gallic Acid on Rosuvastatin Pharmacokinetics in Rats

The purpose of this study was to investigate the potential pharmacokinetic interactions with natural products (such as piperine (PIP), gallic acid (GA) and cinnamic acid (CA)) and rosuvastatin (RSV) (a specific breast cancer resistance protein, BCRP substrate) in rats. In Caco₂ cells, the polarized transport of RSV was effectively inhibited by PIP, CA and GA at concentration of 50 μM. After per oral (p.o.) coadministration of PIP, CA and GA (10 mg/kg) significantly increased intravenous exposure (AUC_last) of RSV (1 mg/kg) by 73.5%, 62.9% and 53.3% (p < 0.05), respectively than alone group (control). Compared with the control (alone) group, p.o. coadministration of PIP, CA and GA (10 mg/kg) significantly increased the oral exposure (AUC_last) of RSV (5 mg/kg) by 2.0‐fold, 1.83‐fold (p < 0.05) and 2.34 ‐fold (p < 0.05), respectively. Moreover, the cumulative biliary excretion of RSV (5 mg/kg, p.o.) was significantly decreased by 53.3, 33.4 and 39.2% at the end of 8 h after p.o. co‐administration of PIP, CA and GA (10 mg/kg), respectively. Taken together, these results indicate that the natural products such as PIP, CA and GA significantly inhibit RSV transport in to bile and increased the plasma exposure (AUC_last) of RSV. Copyright © 2012 John Wiley & Sons, Ltd.     

当归活性成分生物合成与调控研究进展

当归为伞形科植物当归Angelica sinensis的干燥根，具有补血活血、调经止痛、润肠通便的功效。酚酸类、黄酮类、香豆素类、多糖类及苯酞类等活性成分是当归发挥药效的物质基础。近年来，已有大量研究对当归中部分成分的生物合成途径进行解析，并对途径中关键酶基因及转录因子进行克隆与表达分析。当归活性成分合成和积累的调控因素主要包括早期抽薹和生境条件，可以影响合成途径中的基因表达，进而改变活性成分的含量。通过对当归中已被解析的活性成分生物合成途径及这些成分的调控因素进行综述，为当归的品质提升、品种改良和精准栽培提供理论基础。     

甘草酸和甘草次酸对芍药苷在大鼠体内药动学参数的影响

目的 研究甘草酸及其代谢产物甘草次酸对芍药中主要活性成分芍药苷在大鼠体内药动学特征的影响,探索芍药与甘草配伍用药的合理性.方法 大鼠单独ig给予芍药苷或分别与甘草酸、甘草次酸联合用药,于不同时间点采集血样,LC-MS测定芍药苷血药浓度,建立药物浓度-时间曲线,采用DAS2.1.1软件计算、分析药动学参数.结果 甘草酸能减小芍药苷Cmax、tmax,降低芍药苷AUC;甘草次酸能增加芍药苷Cma、tmax,显著提高芍药苷AUC.结论 甘草提高芍药苷生物利用度可能与甘草酸的代谢产物甘草次酸的作用相关.     

桂枝中羧酸及其衍生物的化学成分研究

目的研究桂枝Cinnamomi Ramulus的化学成分。方法采用硅胶柱色谱、凝胶柱色谱、制备高效液相色谱等现代分离方法和技术对其化学成分进行分离纯化,并根据波谱数据进行结构鉴定。结果从桂枝70%乙醇提取物中分离得到15个羧酸及其衍生物,分别鉴定为桂枝酸A(1)、二氢红花菜豆酸(2)、rel-5-(3S,8S-dihydroxy-1R,5S-dimethyl-7-oxa-6-oxobicyclo[3,2,1]-oct-8-yl)-3-methyl-2Z,4E-pentadienoic acid(3)、香草酸(4)、丁香酸(5)、对羟基苯甲酸(6)、反式肉桂酸(7)、反式邻羟基肉桂酸(8)、erythro-guaiacylglycerol-8′-vanillic acid ether(9)、水杨酸(10)、decumbic acid(11)、邻羟基苯丙酸(12)、原儿茶酸(13)、邻香豆酸葡萄糖苷(14)、cryptamygin-B(15)。结论化合物1为新化合物,化合物2、3、9～12为首次从该植物中分离得到。     

咖啡酸酰胺类衍生物的合成及调脂活性研究

目的设计并合成天然产物咖啡酸的酰胺类衍生物,并对该系列化合物进行体外抗脂质代谢紊乱活性评价。方法以咖啡酸为起始原料,卡特缩合剂(BOP)为缩合剂,与十四种胺依次反应制得目标产物,利用人肝癌HepG2细胞评价该类衍生物的调脂活性。结果设计并合成14个咖啡酸酰胺类化合物CA1～CA14,均经波谱技术确证结构。药理实验结果表明,14个化合物对HepG2细胞呈现不同程度的调血脂活性,其中衍生物CA6的调血脂活性优于先导物咖啡酸和阳性药辛伐他汀。结论化合物CA6、CA7和CA11均为未见文献报道的咖啡酸酰胺类新化合物,其中CA6和C11具有潜在的调脂生物活性,值得进一步深入研究。