Phytochemical study onPrunus davidiana

From the stem ofPrunus davidiana, naringenin and its glucoside, kaempferol and its glucoside, dihydrokaempferol, kaempferide glucoside, hesperetin glucoside, quercetin glucoside, d-catechin and β-sitosterol glucoside were isolated.     

Catechin glycoside fromUlmus davidiana

Catechin and catechin glycoside named uldavioside A were isolated from the Korean folk medicineUlmus davidiana. Based on chemical and physicochemical evidences, their structure have been determined as (+)-catechin (1) and (+)-catechin-5-O-β-D-apiofuranoside (2).     

Anti-inflammatory activity ofElsholtzia splendens

Elsholtzia splendens Nakai has been used in North-East Asia as an ingredient of folk medicines for treating cough, headache and inflammation. The present investigation was carried out to establish its in vivo anti-inflammatory activity using several animal models of inflammation and pain. The 75% ethanol extract of the aerial part of E. splendens significantly inhibited mouse croton oil-induced, as well as arachidonic acid-induced, ear edema by oral administration (44.6% inhibition of croton oil-induced edema at 400 mg/kg). This plant material also showed significant inhibitory activity against the mouse ear edema induced by multiple treatment of phorbol ester for 3 days, which is an animal model of subchronic inflammation. In addition, E. splendens exhibited significant analgesic activity against mouse acetic acid-induced writhing (50% inhibition at 400 mg/kg), while indomethacin (5 mg/kg) demonstrated 95% inhibition. E. splendens (5-100 microg/mL) significantly inhibited PGE2 production by pre-induced cyclooxygenase-2 of lipopolysaccharide-treated RAW 264.7 cells, suggesting that cyclooxygenase-2 inhibition might be one of the cellular mechanisms of anti-inflammation.     

野菊花中黄酮类成分抗炎活性的虚拟筛选

目的 前期研究及文献报道均表明野菊花黄酮类成分有明显抗炎活性,但其药效物质基础和作用机制尚未明确。该研究应用分子对接技术虚拟筛选野菊花黄酮抗炎活性的药效物质。方法 搜集现已分离鉴定的34个野菊花黄酮类化合物组成配体数据库,选择IκB激酶β（IKK-β）、P38、环氧合酶 2 （COX-2）、肿瘤坏死因子（TNF）等4个与抗炎活性密切相关的靶点组成受体数据库,应用Discovery Studio 3.0 (DS3.0)软件进行分子对接。结果 通过分子对接虚拟筛选,筛选出打分总分高于阈值的黄酮类化合物共11个。结论 对比分析了原配体与野菊花黄酮作用于各靶点的主要活性位点,初步推断了野菊花黄酮抗炎活性的作用机制,为研发抗炎制剂类药物提供了一定的参考。     

Lignan and neolignan glycosides fromUlmus davidiana var.japonica

Four lignan xylosides and two neolignan glycosides were isolated from the stem and root barks of Ulmus davidiana var. japonica. Their structures were identified as lyoniside, nudiposide, 5'-methoxyisolariciresinol-9'-O-beta-D-xylopyranoside, isolariciresinol-9'-O-1-D-xylopyranoside, rel-trans-dihydrodehydroconiferyl alcohol 4'-O-alpha-L-rhamnopyranoside and icariside E3 by comparison of their spectral data with those reported in the literatures, respectively.     

Inhibitory activity of flavonoids from<Emphasis Type="Italic">Prunus davidiana</Emphasis> and other flavonoids on total ROS and hydroxyl radical generation

Since reactive oxygen species (ROS) and hydroxyl radicals (*OH) play an important role in the pathogenesis of many human degenerative diseases, much attention has focused on the development of safe and effective antioxidants. Preliminary experiments have revealed that the methanol (MeOH) extract of the stem of Prunus davidiana exerts inhibitory/scavenging activities on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, total ROS and peroxynitrites (ONOO-). In the present study, the antioxidant activities of this MeOH extract and the organic solvent-soluble fractions, dichloromethane (CH2Cl2), ethyl acetate (EtOAc), and n-butanol (n-BuOH), and the water layer of P. davidiana stem were evaluated for the potential to inhibit *OH and total ROS generation in kidney homogenates using 2',7'-dichlorodihydrofluorescein diacetate (DCHF-DA), and for the potential to scavenge authentic ONOO-. We also evaluated the inhibitory activity of seven flavonoids isolated from P. davidiana stem, kaempferol, kaempferol 7-O-beta-D-glucoside, (+)-catechin, dihydrokaempferol, hesperetin 5-O-beta-D-glucoside, naringenin and its 7-O-beta-D-glucoside, on the total ROS, *OH and ONOO- systems. For the further elucidation of the structure-inhibitory activity relationship of flavonoids on total ROS and *OH generation, we measured the antioxidant activity of sixteen flavonoids available, including three active flavonoids isolated from P. davidiana, on the total ROS and *OH systems. We found that the inhibitory activity on total ROS generation increases in strength with more numerous hydroxyl groups on their structures. Also, the presence of an ortho-hydroxyl group, whether on the A-ring or B-ring, and a 3-hydroxyl group on the C-ring increased the inhibitory activity on both total ROS and *OH generation.     

半枝莲黄酮类化学成分分析

目的 分析半枝莲黄酮类化学成分。方法 采用硅胶、Sephadex LH-20等多种色谱方法,依据波谱数据对其结构进行分析和鉴定。结果 半枝莲中共分离了12个化合物,分别为圣草酚、野黄芩素、三裂鼠尾草素、黄芩苷、芹菜素、汉黄芩素、4''-羟基汉黄芩素、木犀草素、4'',5-二羟基-3'',5'',6,7-四甲氧基黄酮、柚皮素、7-羟基-5,8,2''-三甲氧基黄烷酮、大波斯菊苷。结论 分离得到的化合物类型均为黄酮苷元和苷类化合物,可为半枝莲的黄酮成分分析提供一定的科学依据。     

Anti-platelet effects of flavonoids and flavonoid-glycosides from Sophora japonica

A methanol extract of Sophora japonica was subjected to anti-platelet activity guided fractionation affording the isolation of four flavonoids and six flavonoid-glycosides: biochanin A (1), irisolidone (2), genistein (3), sissotrin (4), sophorabioside (5), genistin (6), tectoridin (7), apigenin (8), quercitrin (9), and rutin (10). The structure of each compound was determined by a variety of spectroscopic methods. Among the compounds, 1, 3, and 7 showed approximately 2.5-6.5 fold greater inhibitory effects on arachidonic acid (AA) and U46619 induced platelet aggregation (IC50: 19.9 and 99.8 microM; 20.3 and 53.8 microM; 25.9 and 123.4 microM, respectively) than acetylsalicylic acid (ASA, IC50: 63.0 and 350.0 microM). Compound 2 was an approximately 22-40 fold stronger inhibitor than ASA on AA and U46619 induced aggregation (IC50: 1.6 and 15.6 microM, respectively).     

润燥清肺膏止咳、抗炎、抑菌的药效学研究

目的 探讨润燥清肺膏的止咳、抗炎、抑菌的药效学作用。方法 将50 只小鼠及豚鼠各随机分为5 组,分别为模型组、阳性对照药急支糖浆组和润燥清肺膏高、中、低剂量组,采用氨水喷雾致咳小鼠模型及枸橼酸喷雾致咳豚鼠模型评价止咳作用;将60 只大鼠随机分为6 组,分别为正常组、模型组、阳性对照药急支糖浆组和润燥清肺膏高、中、低剂量组,采用脂多糖致急性支气管炎模型大鼠评价抗炎作用;将50 只小鼠随机分为5 组,分别为模型组、阳性对照药急支糖浆组和润燥清肺膏高、中、低剂量组,采用醋酸致小鼠腹腔毛细血管通透性增高及巴豆油致小鼠耳肿胀等模型评价其抗炎作用;采用体外抑菌实验,评价其抑菌作用。结果 润燥清肺膏高、中、低各剂量组豚鼠咳嗽潜伏期明显延长(P< 0.05、0.01)、咳嗽次数明显减少(P< 0.01);润燥清肺膏能减轻急性支气管炎大鼠模型黏膜上皮细胞的坏死和脱落,抑制黏膜层和黏膜下层炎性细胞浸润;润燥清肺膏高、中剂量组明显抑制醋酸所致小鼠腹腔毛细血管通透性的增高(P< 0.05、0.01);润燥清肺膏高、中、低各剂量组明显地抑制小鼠耳肿胀(P< 0.05、0.01)。润燥清肺膏对金黄色葡萄球菌、表皮葡萄球菌、肺炎克雷伯菌和大肠杆菌有不同程度的抑制作用。结论 润燥清肺膏对急性支气管炎模型大鼠支气管病变有抑制作用,具有明显的止咳、抗炎、抑菌作用。     

Anti-inflammatory action of phenolic compounds fromGastrodia elata root

Previous screening of the pharmacological action of Gastrodia elata (GE) root (Orchidaceae) showed that methanol (MeOH) extracts have significant anti-inflammatory properties. The anti-inflammatory agents of GE, however, remain unclear. In this experiment, MeOH extracts of GE were fractionated with organic solvents for the anti-inflammatory activity-guided separation of GE. Eight phenolic compounds from the ether (EtOEt) and ethyl acetate (EtOAc) fractions were isolated by column chromatography: 4-hydroxybenzaldehyde (I), 4-hydroxybenzyl alcohol (II), benzyl alcohol (III), bis-(4-hydroxyphenyl) methane (IV), 4(4'-hydroxybenzyloxy)benzyl methylether (V), 4-hydroxy-3-methoxybenzyl alcohol (VI), 4-hydroxy-3-methoxybenzaldehyde (VII), and 4-hydroxy-3-methoxybenzoic acid (VIII). To investigate the anti-inflammatory and anti-oxidant activity of these compounds, their effects on carrageenan-induced paw edema, arachidonic acid (AA)-induced ear edema and analgesic activity in acetic acid (HAc)-induced writhing response were carried out in vivo; cyclooxygenase (COX) activity, reactive oxygen species (ROS) generation in rat basophilic leukemia (RBL 2H3) cells and 1,1-diphenyl-2-picryl-hydroazyl (DPPH) scavenging activity were determined in vitro. These phenolic compounds not only had anti-inflammatory and analgesic properties in vivo, but also inhibited COX activity and silica-induced ROS generation in a dose-dependent manner. Among these phenolic compounds, compound VII was the most potent anti-inflammatory and analgesic. Compound VII significantly inhibited silica-induced ROS generation and compound VI significantly increased DPPH radical scavenging activity. Compounds I, II and III significantly inhibited the activity of COX-I and II. These results indicate that phenolic compounds of GE are anti-inflammatory, which may be related to inhibition of COX activity and to anti-oxidant activity. Consideration of the structure-activity relationship of the phenolic derivatives from GE on the anti-inflammatory action revealed that both C-4 hydroxy and C-3 methoxy radicals of benzyl aldehyde play an important role in anti-inflammatory activities.     

铁皮石斛叶总黄酮泡腾颗粒剂的制备与抗氧化活性研究

目的 获得铁皮石斛叶黄酮提取物泡腾颗粒剂的制作工艺并测定其抗氧化能力。方法 采取L₉(3⁴)正交设计法,以粒度、溶化时间为评价指标,考察乳糖的用量、柠檬酸与碳酸氢钠的配比、PEG6000的用量对泡腾颗粒剂影响,以最佳处方制备泡腾颗粒剂,并采用《中国药典》2015年版方法对其进行质量评价。采用NaNO2比色法测定制剂中总黄酮的含量。采用DPPH法测定制剂的抗氧化能力。结果 最佳处方为乳糖用量40%,柠檬酸与碳酸氢钠的配比1.3:1,PEG6000用量9%。所得制剂符合《中国药典》2015年版相关标准,其总黄酮含量为(1.29±0.08)mg·g^-1,DPPH清除能力的IC₅₀为(3.77±0.10)mg·mL^-1。结论 本论文将铁皮石斛叶黄酮提取物制备成吸收快、生物利用度高、便于运输携带的泡腾颗粒制剂,该制剂黄酮含量丰富,具有较好的抗氧化能力。     

Accurate prediction of xanthine oxidase inhibition based on the structure of flavonoids

The flavonoid family shows a high potential for inhibition of xanthine oxidase. Currently, more than 4,000 flavonoids are known. The data of this study indicate that a planar structure is necessary for high inhibitory activity towards xanthine oxidase. Moreover, the contribution of a hydroxyl conjugate turns out to be a constant factor when the natural logarithm of IC(50) values is taken. This finding allows us to accurately predict the IC(50) value of any given hydroxyl group added to the basic flavone structure towards xanthine oxidase. This new method may provide an important research tool for elucidating the role that flavonoids may have in radical related diseases.     

Anti-inflammatory, analgesic and antipyretic activity of aqueous extract of fresh leaves of Coccinia indica

This study was aimed to evaluate both post- and pre-treatment anti-inflammatory activities of the aqueous extract of fresh leaves of Coccinia indica in rats using the carrageenan-induced paw oedema method at various dose levels. Analgesic and antipyretic properties were evaluated using tail flick model and yeast-induced hyperpyrexia, respectively. Ceiling effect of the extract was observed at 50 mg/kg in pre-treatment carrageenan test. In post-treatment studies, a dose-dependent anti-inflammatory effect was observed in the dose range of 25–300 mg/kg. The effect was equivalent to diclofenac (20 mg/kg) at 50 mg/kg but it was significantly pronounced at higher doses. Effectiveness of extract in the early phase of inflammation suggests the inhibition of histamine and serotonin release. The extract produced marked analgesic activity comparable to morphine at 300 mg/kg, which suggests the involvement of central mechanisms. A significant reduction in hyperpyrexia in rats was also produced by all doses of extract with maximum effect at 300 mg/kg comparable to paracetamol. In conclusion, this study has established the anti-inflammatory activity, analgesic and antipyretic activity of C. indica and, thus, justifies the ethnic uses of the plant.     

Neuroprotective and anti-inflammatory effects of flavonoids isolated from Rhus verniciflua in neuronal HT22 and microglial BV2 cell lines

The neuroprotective and anti-inflammatory activities of the methanolic extract of Rhus verniciflua Stokes (Anacardiaceae) were investigated with mouse hippocampal and microglial cells. Bioactivity-guided isolation yielded 10 flavonoids including fustin (1), fisetin (2), sulfuretin (3), butein (4), butin (5), eriodictyol (6), morin hydrate (7), quercetin (8), kaempferol (9) and isoliquiritigenin (10). Among the isolated flavonoids, compounds 2–5 significantly protected the murine hippocampal HT22 cells against glutamate-induced neurotoxicity and attenuated reactive oxygen species (ROS) generations. In addition, these flavonoids significantly maintained antioxidative defense systems preserving the activities of superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GSH-Px) and the content of glutathione (GSH) decreased by glutamate insult. These compounds also showed significant inhibitory effects on LPS-induced nitric oxide (NO) production in BV2 cells. Especially, compound 4 dose-dependently suppressed the expression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These results suggest that these flavonoids possess therapeutic potentials as a multipotent agent against neurodegenerative diseases related to oxidative stress and pathological inflammatory responses.     

Anti-inflammatory effect of Pinus sibirica oil extract in animal models

The anti-inflammatory effect of the oil extract of seeds of Pinus sibirica Du Tour was evaluated and compared with phenylbutazone. Oral administration of this extract at a dose of 300 mg/kg showed anti-inflammatory activity in the carrageenin-induced edema test in rats. In addition, P. sibirica oil extract showed analgesic properties in the hot-plate test and antipyretic properties in adjuvant-induced local hyperthermia, both in rats. In conclusion, these results provide evidence for the potential usefulness of P. sibirica oil extract, a defined mixture of long-chain polyunsaturated fatty acids, sterols, tocopherols and polyphenols, in inflammatory disorders.     

Anti-inflammatory and analgesic actions of etoricoxib (an NSAID) combined with misoprostol

This study has evaluated the anti-inflammatory and analgesic responses of etoricoxib, a selective COX-2 non-steroidal anti-inflammatory drug combined with misoprostol in pre-clinical assays. Groups of animals (mice and rats) were subjected to rat’s paw edema induced by carrageenan, and writhing and formalin tests in mice. Treatment with etoricoxib, misoprostol, and etoricoxib combined with misoprostol inhibited the inflammation process by 35 %, 30 %, and 61 %, respectively in the rat paw edema induced by carrageenan with the greatest effects being obtained in the group treated with etoricoxib combined to misoprostol. In the writhing test, etoricoxib inhibited the number of writhes by 33 %, and by 27 % when combined with misoprostol. In the first phase of the formalin test (nociceptive), treatment with the combination of etoricoxib and misoprostol inhibited significantly this process by 45 %, while in the second phase (inflammatory), etoricoxib inhibited this by 97 %, the etoricoxib + misoprostol inhibited this by 78 %, respectively. The responses observed have demonstrated that the combination of etoricoxib and misoprostol increased the anti-inflammatory response, but it did not show effect in the peripheral analgesic response. Received 30 August 2006; revised 27 October 2006; accepted 31 October 2006     

Antioxidant flavonoids and chlorogenic acid from the leaves ofEriobotrya japonica

The antioxidant activity of Eriobotrya japonica was determined by measuring the radical scavenging effect on DPPH (1,1-diphenyl-2-picrylhydrazyl) radical and lipid peroxidation produced when mouse liver homogenate was exposed to the air at 37 degrees C, using 2-thiobarbituric acid (TBA). The methanol extract and its fractions of Eriobotrya japonica leaves showed strong antioxidant activity. The antioxidant activity of EtOAc and n-BuOH soluble fractions were stronger than the others, and were further purified by repeated silica gel, MCl gel CHP-20P, and Sephadex LH-20 column chromatography. Antioxidant chlorogenic acid, quercetin-3-sambubioside from n-BuOH fraction, and methyl chlorogenate, kaempferol- and quercetin-3-rhamnosides, together with the inactive ursolic acid and 2 alpha-hydroxyursolic acid from EtOAc fraction were isolated. Antioxidant flavonoids and chlorogenic acid also showed prominent inhibitory activity against free radical generation in dichlorofluorescein (DCF) method.     

中药蒲黄黄酮成分高效液相色谱测定及质量评价

对中药蒲黄属(Typha)的4种原植物花粉及部分种类的花丝、雌花和叶子中的5种黄酮单体成分,进行高效液相色谱测定[μ Bondpak C₁₈柱,水—异丙醇—四氢呋喃(83.5∶14∶2.5)作流动相,检测波长287 nm],对其质量作了初步比较,并对蒲黄的质量标准提出初步建议。     

Comparative study of flavonoids in experimental models of inflammation

The anti-inflammatory activities of flavonols (quercetin, rutin and morin) and flavanones (hesperetin and hesperidin) were investigated in animal models of acute and chronic inflammation. Rutin was only effective in the chronic process, principally in adjuvant arthritis. On neurogenic inflammation induced by xylene, only the flavanones were effective; besides, these compounds were the most effective on subchronic process. The most important compound in reducing paw oedema induced by carrageenan was quercetin.     

Anti-inflammatory mode of isoflavone glycoside sophoricoside by inhibition of lnterleukin-6 and cyclooxygenase-2 in inflammatory response

Soy, high dietary intake for the oriental population, is a main source of isoflavonoids. Sophoricoside (SOP) an isoflavone glycoside was isolated from immature fruits of Sophora japonica (Leguminosae family) and its inhibitory effect on chemical mediators involved in inflammatory response was investigated in this study. SOP inhibited the interleukin (IL)-6 bioactivity with an IC50 value of 6.1 microM whereas it had no effects on IL-1beta and TNF-alpha bioactivities. SOP was identified as a selective inhibitor of cyclooxygenase (COX)-2 activity with an IC50 value of 4.4 microM, but did not show inhibitory effect on the synthesis of COX-2. However, SOP had no effect on the production of reactive oxygen species including superoxide anions and nitric oxide. These results revealed that in vitro anti-inflammatory action of SOP is significantly different from that of genistein known as a phytoestrogen of soy products. This experimental study has documented an importance of dietary soy isoflavonoids as multifunctional agents beneficial to human health, and will help to clarify protective mechanisms of SOP against inflammatory conditions.