马兜铃酸肾毒性的研究进展

马兜铃酸（AA）为硝基菲类有机酸类化合物,是马兜铃、关木通、细辛、广防己等植物的主要成分。马兜铃酸药理作用广泛,有抗感染、抗癌、增强细胞免疫及终止妊娠等功能。目前,含有马兜铃酸的中药或中成药广泛应用于风湿及泌尿系统等多种疾病,由于服用含有马兜铃酸成分的中药而引起的肾脏损害报道日益增加,马兜铃酸。肾毒性作用越来越受到人们的重视。本文总结了近年来马兜铃酸化学结构、毒理作用基础及临床研究,并对其肾毒理作用机制进行综述,使其为临床合理应用含有马兜铃酸的中药或中成药制剂提供参考。通过设计安全有效的药用剂型,严格控制用药剂量和时间,避免长期或大剂量服用,预防并减少毒性作用,将使该药在临床上得到更广泛应用。     

A review on gentisic acid as a plant derived phenolic acid and metabolite of aspirin: Comprehensive pharmacology,toxicology, and some pharmaceutical aspects

Beneficial therapeutic effects of phenolic acids have been proven in various research projects including in vivo and in vitro studies. Gentisic acid (GA) is a phenolic acid that has been associated with useful effects on human health, such as antiinflammatory, antigenotoxic, hepatoprotective, neuroprotective, antimicrobial, and especially antioxidant activities. It is an important metabolite of aspirin and also widely distributed in plants as a secondary plant product such as Gentiana spp., Citrus spp., Vitis vinifera, Pterocarpus santalinus, Helianthus tuberosus, Hibiscus rosa‐sinensis, Olea europaea, and Sesamum indicum and in fruits such as avocados, batoko plum, kiwi fruits, apple, bitter melon, black berries, pears, and some mushrooms. This study was undertaken to review the pharmacological effects, pharmacokinetic properties as well as toxicity and pharmaceutical applications of GA.     

基于莽草酸/邻琥珀酰苯甲酸途径和聚酮途径合成蒽醌类化合物研究进展

蒽醌及其衍生物是植物体内十分重要的次级代谢产物,具有光保护、提高植物抗病性等多种功能,同时在医药、化工等领域也具有十分重要的应用。如何高效、快速地获得蒽醌类物质、提高植物体内蒽醌类物质的合成效率,已经成为现代合成生物学的研究热点。然而蒽醌类物质合成途径较为复杂,目前普遍认为在植物体内蒽醌类物质是通过莽草酸/邻琥珀酰苯甲酸途径和聚酮途径形成。综述近年来在植物体内莽草酸/邻琥珀酰苯甲酸途径和聚酮途径合成蒽醌母核结构的研究进展,为研究植物体内蒽醌类代谢物的合成与调控提供一定的理论基础。     

迷迭香酸药理作用及其递送系统的研究进展

迷迭香酸是从迷迭香等植物中分离得到的一种多酚类化合物,具有显著的抗氧化、抗炎、抗微生物、抗肿瘤及神经保护等作用。然而,由于溶解度差、渗透性低、光不稳定性、体内靶向性差、代谢速率快等缺点,限制了其药理活性及临床产品开发。药物递送系统能够在改善药物的理化性质、保护药物稳定性、发挥更佳给药途径和提高生物利用度等方面具有显著优点。通过对迷迭香酸的药理作用及新型药物载体用于迷迭香酸递送的研究进展进行综述,为迷迭香酸的药物开发和临床应用提供参考。     

大戟科4种药用植物及其内生真菌脂肪酸组分研究

目的 :研究大戟科药用植物和其内生真菌相互关系 ,为探索大戟科植物生物活性物质来源 ,开发新药资源奠定基础。方法 :用气相色谱分析了大戟科乌桕、大戟、泽漆、重阳木 4种药用植物新鲜叶、茎及其 28株内生真菌的脂肪酸组分 ,并比较它们的差异。结果 :植物脂肪酸主要为α-亚麻酸、棕榈酸、亚油酸、油酸 ;内生真菌脂肪酸主要为亚油酸、油酸和棕榈酸。结论 :内生菌可以自主合成脂肪酸 ,因此可以作为分类鉴定的参考依据之一。植物及内生菌脂肪酸在α-亚麻酸含量上表现出极大的差异 ,推测可能和内生菌营养吸收及内生菌和宿主植物相互作用有关。     

A Novel Triterpene Extract from Mistletoe Induces Rapid Apoptosis in Murine B16.F10 Melanoma Cells

The European mistletoe Viscum album L. is a plant used for remedies in cancer treatment. The benefit of commonly used aqueous extracts is controversial but the plant contains water insoluble triterpene acids providing interesting anticancer properties. Triterpene extracts (TE) from plants and single triterpenoids such as oleanolic acid (OA) or betulinic acid (BA) are known for their cytotoxic effects on cancer cell lines in vitro. We report here cytotoxic effects of a novel OA‐rich triterpene extract from mistletoe (V. album L., Santalaceae) solubilized by 2‐hydroxypropyl‐β‐cyclodextrin (2‐HP‐β‐CD) on B16.F10 mouse melanoma cells. The 2‐HP‐β‐CD solubilized triterpene extract (STE) was highly cytotoxic by causing DNA fragmentation, followed by loss of membrane integrity and intracellular adenosine‐5′‐triphosphate (ATP). Blocking the caspase machinery by inhibitors aborted DNA fragmentation and delayed the cytotoxic effects but did not prevent cell death. The solubilization by 2‐HP‐β‐CD allows a solvent‐free application of triterpene extracts in the in vitro setting. These findings suggest the use of STE from mistletoe as a solvent‐free anticancer drug for preclinical animal experiments and clinical trials. Copyright © 2012 John Wiley & Sons, Ltd.     

硫酸处理药用植物硬实种子的研究

报道了部分药用植物硬实种子萌发率过低和用适度浓硫酸浸泡处理种子以解除硬实,促进萌发的生理本质,为田间大面积人工育苗提供了理论依据。     

白桦酯酸及其衍生物的生物活性及作用机制研究进展

白桦酯酸是一种天然存在的五环戊烷型三萜类物质,通常是从白桦Betula platyphylla树皮中分离出来,在其他植物中也有发现,以游离糖苷和糖基衍生物的形式存在于不同植物中。通过对其化学结构的修饰可以得到多种多样的衍生物,研究表明白桦酯酸及其衍生物在抗肿瘤、抗病毒、消炎止痛、抑制脑神经及血管损伤和对其他常见疾病的治疗作用等方面具有积极的作用。综述了白桦酯酸及其衍生物的种类、生物活性及作用机制,以期为今后对其进一步的研究与应用提供理论参考。     

Parasitic loranthus from Loranthaceae rather than Viscaceae potently inhibits fatty acid synthase and reduces body weight in mice

AIM OF THE STUDY: Our previous results have shown one species of parasitic loranthus (Taxillus chinensis (DC.) Dancer) exhibits potent inhibition on fatty acid synthase (FAS) that is proposed to be a potential therapeutic target for treatment of obesity. However, the medicinal parasitic loranthus come from tens of plants of two families, the Loranthaceae and the Viscaceae. This study was carried out to figure out whether these parasitic loranthus from the two families have similar inhibitory ability on FAS, and whether the parasitic loranthus with potent inhibitory ability on FAS significantly reduce body weight of animal. MATERIALS AND METHODS: CD-1 mice were used to test the effects of samples on their body weight and food intake in 20 days. The reversible and irreversible inhibition on FAS was assayed to study the inhibitory ability of sixteen different medicinal plants from these two families, which were collected in nature. RESULTS: The reversible inhibitory ability of the extracts from the Loranthaceae was nearly 400-fold stronger than that from the Viscaceae. The species from the genus Taxillus Tieghem showed the best effect on FAS in both reversible and irreversible inhibition. Moreover, the difference in host plants did not affect markedly on the inhibitory ability of parasitic loranthus. The medicinal herb with high inhibitory ability on FAS significantly reduced the body weight and food intake of mice by oral administration. CONCLUSIONS: The medicinal herbs from the family Loranthaceae, rather than those from the family Viscaceae, should be suitable to apply as botanical sources of parasitic loranthus for weight control. The herbs from genus Taxillus Tieghem are the best.     

The inhibitory effects of 12 medicinal plants and their component compounds on lipid peroxidation

The antioxidative activities of 12 medicinal plants and the compounds isolated from them were investigated using the thiocyanate method to evaluate inhibitory effects on lipid peroxidation in the linoleic acid system. The peroxide levels gradually increased during incubation in the presence of linoleic acid over 3 days, and most of the plants inhibited lipid peroxidation. In particular, of the plants tested, Cudrania tricuspidata, Zanthoxylum piperitum, Houttuynia cordata and Ulmus parvifolia reduced lipid peroxidation more effectively as lipid peroxidation progressed, resulting in inhibition of about 80% relative to the control value by the 3rd day of incubation. In addition, the polyphenols isolated from the plants also showed marked and dose-dependent inhibitory effects on lipid peroxidation. The compounds with the strongest activities were 3,4-dihydroxylbenzoic acid, quercetin, the quercetin glycosides quercetin-3-O-beta-D-galactoside, quercetin-3-O-alpha-L-rhamnoside, quercetin-3-O-beta-D-glucoside and quercetin-3-O-rutinose, catechin, gallic acid, methyl gallate and rosamultin isolated from Zanthoxylum piperitum, Houttuynia cordata, Rosa rugosa and Cedrela sinensis. Moreover, quercetin glycosides showed stronger activity than quercetin, suggesting that glycosylation increases the antioxidative activity of quercetin. Our results indicate that the medicinal plants and their polyphenols show promise as therapeutic agents for various disorders involving free radical reactions.     

长叶胡颓子体外抑制肿瘤细胞增殖的研究

目的研究长叶胡颓子乙醇提取物、三萜酸部位、熊果酸对4株肿瘤细胞增殖的体外抑制作用以及熊果酸抗肿瘤作用机制。方法采用MTT法测定长叶胡颓子乙醇提取物、三萜酸部位和熊果酸在25、50、100、200μg/mL时对人胃癌细胞SGC-7901、BGC-823、肠癌细胞LOVO、HCT-8实体瘤细胞增殖的体外抑制作用;并在上述药物剂量下,观察熊果酸作用72 h后对SGC-7901细胞形态的影响,以及作用24 h后对SGC-7901细胞凋亡的诱导作用。结果长叶胡颓子乙醇提取物、三萜酸部位、熊果酸对4株肿瘤细胞的增殖具有较强的体外抑制作用,其中对于胃癌细胞的抑制作用为熊果酸〉三萜酸部位〉乙醇提取物;对肠癌细胞的抑制作用为三萜酸部位〉熊果酸〉乙醇提取物,同时熊果酸能显著改变SGC-7901细胞的形态,并且SGC-7901细胞的凋亡率与熊果酸的剂量呈相关性。结论三萜酸是长叶胡颓子发挥体外抗肠癌细胞增殖作用的主要有效部位;熊果酸是其发挥体外抗胃癌细胞增殖作用的主要活性成分,熊果酸抑制胃癌细胞增殖机制为诱导细胞凋亡,为开发新的抗癌药物提供参考。     

Ursolic, oleanolic and betulinic acids: antibacterial spectra and selectivity indexes

ETHNOPHARMACOLOGICAL RELEVANCE: Ursolic acid (UA), oleanolic acid (OA) and betulinic acid (BA), three hydroxyl pentacyclic triterpenoic acids (HPTAs) naturally found in a large variety of vegetarian foods, medicinal herbs and plants have been investigated for antibacterial activity. AIM OF THE STUDY: To determine the antibacterial activity of UA, OA and BA, as well as the toxic impact on eukaryotic cells. MATERIALS AND METHODS: Minimum inhibitory concentrations were determined against five reference strains (Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 & ATCC 29213, Enterococcus faecalis ATCC 29212 and Pseudomonas aeruginosa ATCC 27853), as well as five antibiotic-resistant clinical isolates. Toxicity was evaluated against MRC-5 and HaCaT cell lines. RESULTS: No antibacterial activity was observed for BA; while OA and more particularly UA, did show a moderate to good antibacterial activity, but limited to Gram-positive bacteria. Nevertheless, OA and UA were devoid of antibacterial activities against clinical isolates. Moreover, viability and cytotoxic assays demonstrated that the three compounds induced a significant cytotoxicity. CONCLUSIONS: Despite of a relative similar chemical structure; UA, OA and BA harboured different antibacterial activities, with more significant ones for UA. However, considering both viability and toxicity values, these compounds seem to have a significant impact on eukaryotic cell viability.     

年龄、体重及合并用药对丙戊酸清除率的影响

 目的探讨影响儿童体内丙戊酸清除率的因素。方法对156例接受丙戊酸单药或联合用药治疗的门诊癫痫患者进行血药浓度监测。分析不同年龄组、体重组及合并用药组稳态血药浓度ρ_ss与剂量的比值(ρ_ss/D)的变化趋势。结果随着年龄、体重的增加,丙戊酸清除率呈下降趋势,联合使用卡马西平和苯巴比妥可使丙戊酸清除率增加。结论年龄、体重及合并用药等因素显著影响丙戊酸的清除速率。     

药用植物组织培养与脱落酸

脱落酸在植物的许多生理过程中起着至关重要的作用,而且它在药用植物生物技术领域研究中的地位不断提升.文章对脱落酸在药用植物组织培养和种质离体保存、改变药用植物次级代谢物的积累等方面的各种作用进行了综述.     

新疆紫草咖啡酸及迷迭香酸糖基转移酶的克隆及功能研究

咖啡酸及其衍生物是传统中药材紫草的重要水溶性有效成分,具有抗菌、抗氧化、保护心脑血管、抗肝纤维化和保肝、抗病毒及抗肿瘤等多种生物学活性。由于该类化合物经苯丙烷途径合成,而UDP-葡萄糖基转移酶(UDP-glycosyltransferases,UGTs)对苯丙烷途径的调控发挥重要作用,因此推测紫草细胞中存在糖基转移酶参与咖啡酸或/和其衍生物的修饰。该研究通过挖掘新疆紫草Arnebia euchroma转录组数据克隆获得15条糖基转移酶候选基因全长,并通过原核表达检测了对咖啡酸及迷迭香酸的体外活性。结果表明AeUGT_01,AeUGT_02,AeUGT_03,AeUGT_04,AeUGT_10可催化咖啡酸或/和迷迭香酸生成1~3种糖基化产物。这些糖基转移酶处于不同的系统进化分支,与同分支其他糖基转移酶具有底物或催化功能的相似性。因此推测糖基转移酶不同分支通过独立进化不断扩张而产生了趋同进化现象,糖基转移酶的底物宽泛性是这一现象产生的基础。上述工作为进一步研究新疆紫草咖啡酸及迷迭香酸糖基转移酶体内功能奠定了基础,有助于明确咖啡酸衍生物的形成及调控机制;也为咖啡酸及迷迭香酸的糖基化修饰提供了工具酶。     

吡虫啉对金银花绿原酸含量影响的初步研究

目的：研究内吸性化学杀虫剂吡虫啉对金银花中绿原酸含量的影响。方法：采用高效液相色谱法，色谱柱为十八烷基键合硅胶柱，流动相为乙腈-0．4％磷酸（13：87）；检测波长为327nm。结果：吡虫啉对金银花中绿原酸的含量有一定的影响，施药后绿原酸含量与对照相比有所升高，而且随施用药剂浓度增加，绿原酸含量增加。结论：吡虫啉对金银花绿厚酸的含量有影响，其中20％吡虫啉可溶性液剂4000倍液对金对银花中的绿原酸含量有显著影响．     

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。     

Ursolic Acid Inhibits Acid Sphingomyelinase in Intestinal Cells

Ursolic acid (UA) has antiinflammatory and anticancer effects on mammalian cells. Increase in acid sphingomyelinase (SMase) is associated with several inflammatory diseases including inflammatory bowel diseases. The enzyme has become a target for drug discovery. The present study examined the roles of UA on acid SMase in intestinal cells. We found that UA specifically inhibited acid SMase activity in both human colon cancer Caco‐2 cells and rat nontransformed IEC‐6 intestinal cells in a dose‐dependent manner, with 50% inhibition occurred at 30 μM for Caco‐2 cells and less than 20 μM for IEC‐6 cells. In comparison with some chemicals known to inhibit acid SMase, UA appeared most effective. The decreased acid SMase activity was not associated with significant accumulation of cellular sphingomyelin but significant increase in phosphatidylcholine, the donor of choline for sphingomyelin synthesis. Western blot analysis showed a decreased enzyme levels in the cells after UA stimulation, but real time quantitative polymerase chain reaction (qPCR) failed to show a parallel reduction of acid SMase mRNA after UA stimulation. Finally, UA had no direct effect on acid SMase activity in cell‐free extracts. In conclusion, UA has inhibitory effects on acid SMase synthesis and the effect occurs presumably at posttranslational levels. Copyright © 2012 John Wiley & Sons, Ltd.     

Carbenoxolone and triterpenoids inhibited mucin secretion from airway epithelial cells

This study investigated whether carbenoxolone, oleanolic acid and ursolic acid affect ATP-induced mucin secretion from cultured airway epithelial cells. Confluent primary hamster tracheal surface epithelial (HTSE) cells were metabolically radiolabeled using (3)H-glucosamine for 24 h and chased for 30 min in the presence of varying concentrations of each agent to assess the effects on (3)H-mucin secretion. The possible cytotoxicity of each agent was investigated with a lactate dehydrogenase assay. The results were as follows: (1) carbenoxolone, oleanolic acid and ursolic acid significantly inhibited the secretion of airway mucin induced by ATP; (2) none of the compounds showed significant cytotoxicity at any concentration. This result suggests that carbenoxolone, oleanolic acid and ursolic acid can regulate 'mucin secretion induced by ATP'--phenomenon simulating mucus overproduction from inflamed airway epithelial cells--y directly acting on airway mucin-secreting cells.     

柳属植物化学成分及药理作用研究进展

柳属植物资源丰富,全球约有520种,其树皮、枝、叶、花絮等部位均可入药,具有悠久的药用历史。该属化学成分多样,包括黄酮类、水杨酸及其衍生物类、苯丙素类、萜类、蒽醌类、甾体类等多种结构,具有抗肿瘤、镇痛抗炎、抗氧化、降血糖、调节神经系统、促进脂肪分解等药理作用。通过查阅中国知网、PubMed等数据库,对2008—2018年有关柳属植物的研究进行归纳总结,综述了其化学成分及药理作用的研究进展,为该属植物药用活性成分及其作用机制的研究提供参考依据,进一步促进该属植物的合理开发与利用。