诺丽的化学成分及药理活性研究进展

波利尼西亚土著将诺丽(noni,海巴戟Morinda citrifolia)作为民间药物使用已有2 000多年历史,其化学成分主要包括蒽醌类、苯丙素类、黄酮类、萜类、糖苷类等,因其具有抗菌、抗氧化、抗炎、镇痛、抗肿瘤、调节免疫、抗糖尿病、保护肝脏、保护心血管等多种生物活性及保健功能而备受关注。对诺丽的化学成分及药理活性进行综述,以期为进一步合理开发和综合利用诺丽资源提供参考。     

Novel Compounds with new Anti‐Ulcergenic Activity from Convolvulus pilosellifolius Using Bio‐Guided Fractionation.

Oral administration of the total alcohol extract of Convolvulus pilosellifolius Desr. (250 and 500 md/kg) showed potent anti‐ulcerogenic activity in absolute ethanol‐induced ulcer model in rats; it showed percent protection of control ulcer by 69.2 and 84.6%, respectively, while standard ranitidine (100 mg/kg) exhibited 46.2%. Bio‐guided work leads to isolation of two novel compounds (1 and 2), which were identified through ¹H, ¹³C NMR, HMPC, HMQC and DEPT as: methyl 2‐(hydroxymethyl) octanoate, named as amanitate, and 16‐amino‐9,13‐dimethyl‐17‐(prop‐1‐en‐2‐yl)‐hexadecahydro‐1H‐cyclopenta[a] phenanthren‐3‐ol, named as asmatol. Both compounds (50 mg/kg) possessed anti‐ulcerogenic activity with 95.4% and 55.84% protection, respectively. Two known compounds (3 and 4) were also isolated and identified through comparison with authentic samples and confirmed through different NMR techniques as kampeferol and quercetin. These compounds also showed anti‐ulcerogenic activity with 78.38% and 5.38% protection, respectively. The cytoprotective mechanism explains the potent anti‐ulcerogenic activity of the total alcohol extract and the isolated compounds. The extract was highly safe as the LD₅₀ was more than 5000 mg/kg. These results were well supported by the sub‐chronic toxicity study, as the extract (500 mg/kg) administrated orally to rats for 35 consecutive days showed no alteration in the liver and kidney functions. Copyright © 2016 John Wiley & Sons, Ltd.     

An international multicentre study on the allergenic activity of air‐oxidized R‐limonene

Background. Limonene is a common fragrance terpene that, in its pure form, is not allergenic or is a very weak allergen. However, limonene autoxidizes on air exposure, and the oxidation products can cause contact allergy. Oxidized R‐limonene has previously been patch tested in multicentre studies, giving 2–3% positive patch test reactions in consecutive patients. Objectives. To investigate whether oxidized R‐limonene 3.0% in petrolatum, with a stable concentration of the main haptens, limonene hydroperoxides (Lim‐OOHs), could be a useful tool for the detection of contact allergy in an international setting. Methods. Oxidized R‐limonene 3.0% (Lim‐OOHs 0.33%) pet. was tested in 2900 consecutive dermatitis patients in Denmark, the United Kingdom, Singapore, Spain, Sweden, and Australia. Results. Overall, 5.2% (range 2.3–12.1%) of the patients showed a positive patch test reaction to oxidized R‐limonene. Doubtful reactions were found in 7.0% of the patients (range 0–24%). Few irritant reactions were seen. Conclusions. Oxidized R‐limonene at 3.0% pet. with a specified content of Lim‐OOHs 0.33% is a standardized and useful tool for the detection of contact allergy in dermatitis patients. Many patients showing positive patch test reactions to oxidized R‐limonene would not be informed of their fragrance allergy if this specific test had not been performed.     

Single-molecule inhibition of human kinesin by adociasulfate-13 and -14 from the sponge Cladocroce aculeata

Two merotriterpenoid hydroquinone sulfates designated adociasulfate-13 (1) and adociasulfate-14 (2) were purified from Cladocroce aculeata (Chalinidae) along with adociasulfate-8. All three compounds were found to inhibit microtubule-stimulated ATPase activity of kinesin at 15 µM by blocking both the binding of microtubules and the processive motion of kinesin along microtubules. These findings directly show that substitution of the 5′-sulfate in 1 for a glycolic acid moiety in 2 maintains kinesin inhibition. Nomarski imaging and bead diffusion assays in the presence of adociasulfates showed no signs of either free-floating or bead-bound adociasulfate aggregates. Single-molecule biophysical experiments also suggest that inhibition of kinesin activity does not involve adociasulfate aggregation. Furthermore, both mitotic and nonmitotic kinesins are inhibited by adociasulfates to a significantly different extent. We also report evidence that microtubule binding of nonkinesin microtubule binding domains may be affected by adociasulfates.Kinesin motor proteins are implicated in several vital eukaryotic cellular processes, including vesicle transport (1) and mitosis (2). They are composed of three distinct domains: a motor domain that both hydrolyzes ATP and steps along microtubules (MTs), a linker domain involved in dimerization, and a cargo binding tail domain. Inhibitors of these enzymes can provide key information concerning the mechanism of coupling ATP hydrolysis to the characteristic stepping motion of kinesins. In addition, kinesins control cellular functions that are often implicated in disease. Hence, kinesin inhibitors are highly sought. Of the known kinesin inhibitors, monastrol (3), terpendole E (4), HR22C16 (5), CK0106023 (6), S-trityl-l-cysteine (7), and the dihydropyrazoles (8), including ispinesib (9), inhibit ATPase activity of Eg5 allosterically, allowing ATP binding but preventing ADP release. Rose bengal lactone (RBL) inhibits MT-stimulated ATPase activity of kinesin (10). Thiazole inhibitors compete with ATP directly to inhibit Eg5 (11), whereas biaryl compounds GSK-1 and GSK-2 block interactions with nucleotides through an allosteric binding site (12). Adociasulfates are unique in that they are the only kinesin inhibitors with mechanisms of action that involve competition for binding to MTs (13, 14). Thus, they have the potential to be used as probes for kinesin functions unaffected by other inhibitors or drugs that target these functions specifically.Adociasulfates are a subfamily of sulfated triterpenoid hydroquinone compounds derived from marine sponges of the family Chalinidae. They have received attention for their inhibitory effect on kinesin family motors and H⁺-ATPase proton pump enzymes, where their activity has been linked to the presence of at least one sulfate group (15). Much of what is known about adociasulfate activity comes from studies of adociasulfate-2 [AS-2 (4)]. The compound is known to bind to kinesin and interfere with MT binding with minor effects on nucleotide interactions (13, 14). The idea that adociasulfates are 1:1 kinesin inhibitors has been questioned in a recent study suggesting that 4 forms extended aggregates that mimic the negatively charged microtubule surface and thereby, inhibit kinesin activity (16). The mode of binding to kinesin is a critical question for future drug development. Specific inhibition would make these compounds more suitable to target a small class of enzymes, whereas aggregation would make practical in vivo applications problematic. At the same time, aggregations of small molecules could be potentially interesting in nanobiological engineering, where artificial microtubule tracks are highly desirable.We report the discovery of two previously undescribed adociasulfates, which we designate adociasulfate-13 (1) and adociasulfate-14 (2), isolated from the marine sponge Cladocroce aculeata Pulitzer-Finali, 1982 (Fig. 1). Adociasulfate-8 (3) was also isolated from the same organism. We have used single-molecule biophysical measurements to assess the activity of these compounds against kinesin-1 and -5 family motor proteins. We also assessed whether the inhibitory activity of these compounds is connected to the formation of extended adociasulfate aggregates. Our results suggest that compounds 1, 2, and 3 inhibit both binding of kinesin to MTs and processive motion. The replacement of the 5′-sulfate with a glycolic acid moiety has little effect on kinesin inhibition, indicating that alternative functional groups may be capable of maintaining activity. We note that this observation significantly enhances the value of adociasulfates as a target for future drug development. We corroborate and extend the previously proposed theory that adociasulfates act as MT mimics, but we find no evidence that large aggregates of individual adociasulfate molecules could be responsible for the observed activity. We also provide evidence that adociasulfates inhibit kinesins at the single-molecule level.Open in a separate windowFig. 1.Chemical structures of adociasulfates.     

Contact allergy to air-exposed geraniol: clinical observations and report of 14 cases

Background. The fragrance terpene geraniol forms sensitizing compounds via autoxidation and skin metabolism. Geranial and neral, the two isomers of citral, are the major haptens formed in both of these activation pathways. Objectives. To investigate whether testing with oxidized geraniol detects more cases of contact allergy than testing with pure geraniol. Patients and methods. The pattern of reactions to pure and oxidized geraniol, and metabolites/autoxidation products, was studied to investigate the importance of autoxidation or cutaneous metabolism in contact allergy to geraniol. Pure and oxidized geraniol were tested at 2.0% petrolatum in 2227 and 2179 consecutive patients, respectively. In parallel, geranial, neral and citral were tested in 2152, 1626 and 1055 consecutive patients, respectively. Results. Pure and oxidized geraniol gave positive patch test reactions in 0.13% and 0.55% of the patients, respectively. Eight of 11 patients with positive patch test reactions to oxidized geraniol also reacted to citral or its components. Relevance for the positive patch test reactions in relation to the patients' dermatitis was found in 11 of 14 cases. Conclusions. Testing with oxidized geraniol could detect more cases of contact allergy to geraniol. The reaction pattern of the 14 cases presented indicates that both autoxidation and metabolism could be important in sensitization to geraniol.     

橡子化学成分及药理作用的研究进展

橡子为药食两用资源,有止肠风、冷热泻痢的功效,具有悠久的药用历史。橡子含有多种化学成分,至今已被鉴定的化学成分主要包括酚类、萜类、氨基酸以及矿质元素等,现代研究表明,其具有抗癌、降糖抗炎、抑菌和排铅等药理作用。对橡子的化学成分及药理作用的研究进展进行梳理并展开综述,以期更好地了解橡子的化学特征及药理作用,为扩大橡子的临床应用提供理论依据。     

气相色谱法测定杜香萜烯中的桧烯含量

目的:应用气相色谱法测定杜香萜烯中桧烯的含量.方法:以SE-30为固定液,涂布浓度为5%,柱温65℃,FID检测器,检测器温度200℃.结果:在该色谱条件下可分离并测定桧烯的含量,桧烯的线性范围为0.06～0.60mg·mL-1,r=0.9998(n=6).桧烯的平均回收率为100.3%,RSD=1.4%(n=5).结论:方法简便,结果准确,重现性好,可作为该制剂的质量控制指标.     

杜仲和西伯利亚人参的化学成分及药理作用

The bark and leaves of Eucommia ulmoides Oliv(Eucommiaceae) and "Siberian ginseng" (Ezoukogi inJapanese) prepared from the root bark or stem bark ofEleutherococcus senticosus Maxim (Acanthopanax senti-cosus Harms) have been used as tonic and anti-stressdrug. The extracts of Eucommia showed anti-hyperten-sive, anti-complementary, anti-oxidative, and anti-gastric ulcer effects, and promting collagen synthesis,accelating granuloma formation, and other pharmacologi-cal effects. The Siberian ginseng exhibited anti-fatigue,anti-stress, immuno-enhancing effect, CNS activity, andanti-depressive effect. By now, 40, 28, and 10 com-pounds have been isolated from Eucommia ulmoidesbark, Eucommia ulmoides leavs, and Siberian ginseng,respectively, and their structures were elucidated. Theirpharmacological activities were mainly due to lignans andiridoid glycosides.     

羌活药材的化学成分和药理活性研究进展

羌活为伞形科植物羌活Notopterygium incisum或宽叶羌活Notopterygium franchetii干燥后的根茎和根,从其中分离得到的主要化学成分包括挥发油及萜类、香豆素类、糖及糖苷类、酚酸类、聚烯炔、生物碱类等。药理研究表明,羌活具有抗炎抗菌、抗氧化、抗病毒、抗癌细胞增殖、解热镇痛等活性,且对心脑血管系统、消化系统、呼吸系统和中枢神经系统有显著影响。主要介绍中药羌活的化学成分及药理活性研究进展,并对其研究方向进行展望,为进一步研究其药效物质基础、作用机制及合理开发利用提供理论依据。     

基于UPLC-Q-TOF-MS的布芍调脂胶囊化学成分分析

目的:采用超高效液相色谱-四级杆-飞行时间串联质谱(UPLC-Q-TOF-MS)技术对中药复方布芍调脂胶囊中的化学成分进行定性分析。方法:采用Waters CORTECS UPLC C_(18)色谱柱(2. 1 mm×150 mm,1. 6μm),流动相甲醇-0. 1%甲酸水溶液进行梯度洗脱,柱温40℃,流速0. 24 mL·min~(-1),进样量1μL;质谱条件为X500R QTOF质谱仪,电喷雾离子源(ESI)分别在正、负离子模式下对色谱流出物进行高分辨四极杆飞行时间串联质谱检测,对各主要色谱峰进行归属。结果:通过高分辨质谱数据分析、结合参考文献数据以及对照品确认,共鉴别出53个化学成分,包括21个黄酮类,10个酚酸类,5个单萜及其苷类,7个二萜内酯类及10个倍半萜类成分,并对化合物的药材来源进行了归属,其中5个黄酮类化合物(芒果苷、异槲皮苷、香蒲新苷、异鼠李素-3-O-新橙皮苷、银椴苷)首次在布渣叶中发现。结论:UPLC-Q-TOF-MS联用技术为鉴别布芍调脂胶囊中化学成分提供简便、快速、准确的方法,鉴定得到的各类化学成分基本可涵盖组方中各药材的主要成分,为进一步阐明布芍调脂胶囊的药效物质基础、作用机制及优选质量控制指标提供了理论依据和技术方法。