Xanthine Oxidase Inhibitory Activity of Flavonoids and Tannins from Hexachlamys edulis (Myrtaceae)

The acetone-water extract of Hexachlamys edulis (Myrtaceae) inhibited the enzyme xanthine oxidase (XO) in vitro . Bioassay-guided isolation led to the gallic acid ester in 2″ of myricitrin (desmanthin-1), (-)-epigallocatechin-3-O-gallate (EGG) and pentagalloylglucose as the main XO inhibitors of H. edulis . Desmanthin-1 and EGG were mixed-type inhibitors of XO with K _i values of 1.6×10⁻⁴ M and 1.8×10⁻⁴ M , respectively. Pentagalloylglucose was an uncompetitive XO inhibitor with a K _ESI of 6.7×10⁻⁶M . From the active n -butanol soluble part of the aqueous acetone extract of H. edulis , several flavonoids were isolated. The flavonoids were mainly myricetin-3-O-monoglycosides with the quercetin glycoside avicularin as a minor compound displaying a weak inhibitory activity towards XO.     

Effects of crinum glaucum aqueous extract on intestinal smooth muscle activity

Crinum glaucum aqueous extract (1–8 mg/mL) produced a concentration dependent, non-competitive inhibition of contractions induced by acetylcholine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) and calcium chloride (CaCl₂, 0.05–2 mM ) on the rat duodenum. Contractions of the guinea-pig ileum induced by acetylcholine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) and histamine (1.1 × 10⁻⁸–3.3 × 10⁻⁷M ) were inhibited by the extract (1–4 mg/mL). The extract (0.125–2.0 mg/mL) also, produced a concentration dependent relaxation of the guinea-pig taenia coli, precontracted with potassium chloride (40 mM ). It is concluded that the extract is a non-specific relaxant of the gastrointestinal smooth muscles used. © 1998 John Wiley & Sons, Ltd.     

Xanthine oxidase inhibiting effects of noni (Morinda citrifolia) fruit juice

Morinda citrifolia L. (noni), family Rubiaceae, has been used in Polynesia for over 2000 years for its reputed health benefits, one of which is its therapeutic effects on gout (langa e hokotanga hui). However, its healing mechanism has not been elucidated. This study showed that in an in vitro bioassay that Tahitian Noni^® Juice (TNJ) inhibited xanthine oxidase (XO) concentration dependently. Concentrations of 1, 5 and 10 mg/mL of TNJ inhibited XO by 11%, 113% and 148%, respectively, with an IC₅₀ of 3.8 mg compared with an IC₅₀ of 2.4 µm for allopurinol. Noni fruit juice concentrate (NFJC) also inhibited XO concentration dependently. Concentrations of 1 and 5 mg/mL NFJC inhibited XO in vitro by 184% and 159%, respectively. A 0.1 mg/mL methanol extract (NFJME) from the fractionation of noni fruit puree inhibited XO by 64%. It was elucidated that the noni fruit juice inhibitory effect on XO enzymes is the mechanism by which noni ameliorates gout and gout‐like diseases. Further, the results also support the traditional usage of noni in the treatment of gout. Copyright © 2009 John Wiley & Sons, Ltd.     

Different Effects of Some Isoquinoline Alkaloids from Argemone mexicana on Electrically Induced Contractions of Isolated Guinea-pig Ileum

The present study examines the effects of the extracts [petroleum ether, CHCl₃, CHCl₃/MeOH (9:1) and MeOH], partially purified fractions and pure compounds from Argemone mexicana on the electrically induced contractions of the isolated guinea-pig ileum (E.C.I.). The results of the experiments indicate that CHCl₃/MeOH (9:1) and MeOH extracts, tested at a concentration of 400, 200 and 100 μg/mL, dose-dependently reduced the guinea-pig ileum contractions, whereas the petroleum ether and CHCl₃ extracts did not affect it. Furthermore, the partially purified fractions II–V from the MeOH extract, each tested at concentrations of 200, 100 and 50 μg/mL also inhibited E.C.I. Finally the pure compounds 1–2 (5×10⁻⁶–1×10⁻⁵–5×10⁻⁵ M ) isolated and purified from the above fractions significantly reduced, in a dose dependent manner, the electrical contractions of the ileum, whereas compound 3 (5×10⁻⁶–1×10⁻⁵×10⁻⁵ M ) increased them. Since the active compounds 1–3 were respectively identified as protopine, allocryptopine and berberine by NMR, the observed effects could be related mainly to these compounds. © 1997 by John Wiley & Sons, Ltd.     

Vasodilator Effects of the Extract of the Leaves of Cistus populifolius on Rat Thoracic Aorta

The effects of different extracts of Cistus populifolius L. on smooth muscle were studied. The aqueous extract inhibited in a dose dependent manner the noradrenaline (NA) (10⁻⁹–1.03×10⁻⁶ MSC ) and CaCl₂ (2×10⁻⁴–1.28×10⁻² MSC )-induced contractions in rat thoracic aorta. Furthermore, this extract induced relaxant effects in rat aorta precontracted with NA (10⁻⁶ MSC ) and with K⁺ (80 mMSC ). Two different vasodilator responses were observed on NA-induced contractions: one an endothelium-dependent response abolished by methylene blue but not by indomethacin, and the other an endothelium-independent response unaffected by methylene blue and indomethacin similar to that obtained with a flavone, luteolin (10⁻⁵ MSC ). The search for active constituents included a bioactivity-directed fractionation of the lyophilized aqueous extract (LAE) using vascular reactivity experiments. Four different fractions (Cl₂CH₂, Me₂CO, MeOH, H₂O) were analysed at two different concentrations (1 and 2 mg (dry plant)/mL). The methanol fraction was the most active on NA precontracted vascular segments with endothelium, whereas the water fraction was the most active on segments without endothelium. These relaxant effects were less on K⁺ (80 mMSC )-induced contractions. Due to these results we suggest that this plant contains interesting hydrophilic compounds with strong pharmacological action. The endothelium-independent relaxant effect is probably related to flavonoid constituents. However we cannot relate the endothelium-dependent relaxation to known natural compounds in Cistus species. The presence of these constituents with relaxing properties on smooth muscle could account for the use of Cistus plant in traditional medicine.     

Inhibitory effects of Cistus populifolius on contractile responses in the isolated rat duodenum

The medicinal plant Cistus populifolius L., shows an important dose-dependent spasmolytic activity. The ability of the Cistus extract to inhibit both acetylcholine (ACh) (3.4 × 10⁻⁸–6.8 × 10⁻⁵ M) and CaCl₂ (2 × 10⁻⁴–1.28 × 10⁻² M) -induced contractions and the relaxing effect on K⁺ (75 mM) -induced contractions may indicate a non-specific receptor antagonist. However, this action may be related to the influx of extracellular Ca²⁺. These antispasmodic effects are partly consistent with the use of C. populifolius in folk medicine for certain gastrointestinal disorders.     

Pharmacological studies of Striga senegalensis Benth (Scrophulariaceae) as an abortifacient

The methanol extract of Striga senegalensis Benth (Scrophulariaceae) was investigated on isolated rat uterus. Acetylcholine and the methanol extract of the plant produced dose related contractions of smooth muscle of the isolated rat uterus in vitro. Atropine in doses of 2 × 10⁻² to 32 × 10⁻² μg/mL antagonized dose dependently the contraction of the isolated rat uterus produced by both acetylcholine (1.6 × 10⁻¹ μg/mL) and the methanol extract (160 μg/mL). © 1998 John Wiley & Sons, Ltd.     

三种冬凌草素和毛萼乙素体外对人血管生成的影响

 目的研究4种二萜化合物(冬凌草甲素、信阳冬凌草甲素、冬凌草乙素、毛萼乙素,分别简称为SH-A、SX-A、SH-B、ER-B)在体外对血管生成的影响,为发现新的抗肿瘤药物提供线索。方法采用人脐静脉内皮细胞ECV304增殖、迁移试验及小管形成试验研究了4种化合物对血管生成的影响。结果4种二萜化合物对ECV304(人脐静脉内皮细胞系)的增殖、迁移、小管形成具有不同程度的抑制作用,IC₅₀值分别在1.47×10^-5～3.76×10^-5mol·L^-1(抑制作用SX-A>SH-A>SH-B>ER-B)、8.01×10^-7～5.41×10^-6mol·L^-1(抑制作用SH-B最强,而SH-A、SX-A和ER-B相仿)和4.25×10^-7～2.80×10^-6mol·L^-1内(抑制作用SH-B>SH-A>SX-A>ER-B),抑制血管迁移、小管形成的IC₅₀值均低于抑制增殖的IC₅₀。结论4种二萜化合物在体外对人脐静脉内皮细胞系血管形成均有不同程度的抑制作用,值得作为抗肿瘤药物的候选物进一步深入研究。     

β-glucuronidase inhibition and diuretic activity of Fabiana imbricata R. & P. (Solanaceae)

The hydroalcoholic extract of Fabiana imbricata inhibited the enzyme β-glucuronidase (β-gluc) in vitro. Bioassay-guided isolation led to scopoletin as the main active constituent of F. imbricata. Scopoletin was a noncompetitive inhibitor of β-D-glucuronidase with a K_i value of 4 × 10^?5 M. A single oral dose of 250 mg/kg body weight F. imbricata extract produced a significant increase (p<0.05) in the urine output of rats. The diuretic effect of the extract was weak in comparison with hydrochlorothiazide at 25 mg/kg. In the acute oral toxicity study in rats, ‘Pichi’ was shown to be a low toxicity crude drug at doses up to 5 g crude extract/kg body weight. At concentrations up to 0.50 mg/mL, the crude extract did not increase the number of chromosome aberrations in the in vitro human lymphocyte assay.     

Inhibiting Activity of Some Glucoindolalkaloids and Iridoids from Sickingia williamsii on Electrically Induced Contractions of Isolated Guinea-pig Ileum

The present study examined the effects of the extracts (petroleum ether, CHCl₃, CHCl₃/MeOH (9:1) and MeOH), partially purified fractions and pure compounds (mainly alkaloids and iridoids) from Sickingia williamsii on the electrically induced contractions of the isolated guinea-pig ileum. The results of our experiments indicate that CHCl₃/MeOH (9:1) and CHCl₃ extracts, tested at concentrations of 300, 150 and 30 μg/mL, dose-dependently reduced the guinea-pig ileum electrical contractions, whereas MeOH and petroleum ether extracts did not affect it. Furthermore, both the partially purified fractions I–IV each tested at concentrations of 500, 250 and 100 μg/mL from the CHCl₃/MeOH (9:1) extract and some pure compounds (10⁻⁴ M , 5×10⁻⁵ M and 2.5×10⁻⁵ M ) isolated and purified from the above fractions significantly reduced, in a dose dependent manner, the electrical contractions of the ileum. As the active pure compounds possess an indole nucleus or/and an iridoid nucleus in their structures, the inhibitory effects appear to depend on these structures.     

Effects of chalcones isolated from licorice roots on leukotriene biosynthesis in human polymorphonuclear neutrophls

The effects of chalcones and flavanones isolated from Sinkiang Licorice (Glycyrrhiza inflata Bat.) on leukotriene B₄(LTB₄) and C₄(LTC₄) formation in human polymorphonuclear neutrophils (PMNs) were investigated. Licochalcone A (2-methoxy-4,4′-dihydroxy-5-α,α-dimethyl-allylchalcone) and licochalcone B (2-methoxy-3,4,4′-trihydroxychalcone), at concentrations of 10^?3 to 10^?6 M, inhibited calcium ionophore A 23187 (A 23187)-induced LTB₄ and LTC₄ formation in human PMNs. The concentration of licochalcones A required for 50% inhibition (LC₅₀) of LTB₄ and LTC₄ formation was 4.6 × 10^?7 and 4.2×10^?6 M, respectively, using 2 μM A 23187. The IC₅₀ values of licochalcone B for LTB₄ and LTC₄ formation were also 1.2 × 10^?6 and 2.0×10^?6 M, respectively. In addition, licochalcones A and B significantly increased cyclic AMP level in human PMNs at concentrations of 10^?4 to 10^?3 M. Licochalcones A and B were found to reduce the elevation of the cytosolic free calcium concentration induced by calcium ionomycine, dose-dependently, in the presence of 1 mM Ca²⁺ or 1 mM EGTA.     

海洋来源真菌Aspergillus sydowi PFW-13中的吲哚-喹唑啉类生物碱及其抗肿瘤活性

 目的研究海洋来源真菌萨氏曲霉(Aspergillus sydowi)PFW-13发酵产物中的抗肿瘤活性次级代谢产物。方法采用活性追踪的方法、利用色谱手段分离获得单体化合物,根据波谱分析及其理化性质确定其结构,利用SRB法评价单体化合物的细胞毒活性。结果获得6个吲哚-喹唑啉类生物碱,其结构分别鉴定为fumiquinazolines A(1)、fumiquinazolines C(2)、fu-miquinazolines D(3)、fumiquinazolines F(4)、fumiquinazolines G(5)、fumiquinazolines J(6),其中化合物6为新天然产物。化合物2和6对肿瘤细胞tsFT210、A549、BEL-7402、HL60和P388的半数抑制浓度(IC₅₀)在1×10^-5～1×10^-4mol·L^-1之间。结论以上化合物均为首次从该种真菌中分离得到。     

Effects of aqueous extract of Baphia nitida on isolated cardiac tissues

The pharmacological action of cold aqueous extract of fresh leaves of Baphia nitida was studied on cardiac preparations. The extract (5.0 × 10^?3 g mL) reduced the rate and force of contraction of the isolated rabbit heart. The rate and force of contraction of the spontaneously beating rat atria was dose-dependently reduced by 5.0 × 10^?4 to 2.5 × 10^?2 g/mL of the extract and this effect was not antagonized by 3.45 × 10^?7 M atropine. The extract (5.0 × 10^?2 g mL) completely blocked the positive chronotropic and inotropic effects of 10 mM CaCI² but only reduced that of 1.61 × 10^?7 M isoprenaline. The effect of the extract on CaCI₂-induced responses of the rat atria was not affected by 3 × 10^?7 M propranolol. The use of this extract for treating palpitation locally may be related to its negative chronotropic and inotropic effects.     

重组人组织型纤溶酶原激活剂缺失变体的溶栓作用及对血小板聚集和胞浆游离钙离子浓度的影响

 目的 研究重组人组织型纤溶酶原激活剂缺失变体(reteplase,Ret)的溶栓作用以及对离体家兔血小板聚集功能和对血小板静息状态胞浆内游离钙浓度的影响。方法 家兔血栓模型采用动-静脉旁路法,血小板聚集实验采用比浊法,血小板静息状态胞浆内游离钙浓度采用Fura-2荧光测定法。结果Ret(3.75×10⁵,7.50×10⁵,15.0×10⁵U·kg^-1)对家兔动-静脉旁路所形成的血栓有明显溶栓作用,可明显减轻血栓干湿重量,并呈一定的剂量依赖性。Ret(1 000,3 000,10 000 U·mL^-1)对ADP诱导的血小板聚集可产生浓度依赖性的抑制作用,并可明显降低血小板静息状态的[Ca²⁺]_i,并呈一定的浓度依赖性。结论Ret具有明显的血栓溶解作用,可明显抑制ADP诱导的血小板聚集,并明显降低血小板静息状态的[Ca²⁺]_i。     

雷公藤内酯醇抑制脂多糖诱导的PC-12细胞COX-2的表达

 目的　了解雷公藤内酯醇(TP)对PC-12细胞增殖和表达环氧化酶-2(COX-2)及合成前列腺素E₂ (PGE₂ )的影响 ,探讨TP应用于痴呆治疗的可能机制。方法　采用神经生长因子 (NGF)诱导培养PC-12细胞 ,用不同浓度的TP(0,0.28×10^-6,2.8×10^-6,2.8×10^-6mol·L^-1)预处理后 ,加或不加脂多糖(LPS),分别用氚-胸腺嘧啶核苷(³H-TdR)掺入法、竞争酶联免疫吸附试验(ELISA)、半定量逆转录-聚合酶联反应(RT-PCR)法、细胞酶联免疫法及蛋白免疫印迹 (Western-blot)法检测PC-12细胞的增殖活性、细胞培养上清液中PGE² 的水平、细胞COX-2mRNA及蛋白表达水平。同时提取各组细胞蛋白 ,测定其核转录因子 (NF-κB)活性。结果　TP对LPS诱导的PC-12细胞的COX-2mRNA ,蛋白表达 [空白对照与不同浓度下分别为[(0.34±0.12 )×10^-6,(1.92±0.26)×10^-6,(1.78±0.32)×10^-6,(1.14±0.22)×10^-6,(0.48±0.14 )×10^-6mol·L^-1,P <0.01]及PGE₂ 的合成 [分别为(2.28±0.32)×10^-6,(32.86±6.23)×10^-6,(31.28±5.44)×10^-6,(18.43±3.92)×10^-6,(4.18±1.79)×10^-6mol·L^-1,P<0.01]具有不同程度的抑制作用,与TP浓度(0～28×10^-6mol·L^-1)呈明显正相关性(分别为r=0.94和r=0.92),且对LPS激活的PC-12细胞的核转录因子NF-κB活性有明显的抑制作用[分别为(0.16±0.08)×10^-6,(1.39±0.18)×10^-6,(1.09±0.14)×10^-6,(0.52±0.15)×10^-6,(0.28±0.09)×10^-6mol·L^-1,P<1.01]。实验未观察到TP对PC-12细胞增殖的影响。结论TP可显著抑制LPS诱导的PC-12细胞COX-2细胞COX-2的表达及其产物PGE₂的合成,这种作用可能通过TP抑制PC-12细胞核转录因子NF-κB活性而实现。     

Endothelium-dependent vasodilator effect of extract prepared from the seeds of Areca catechu on isolated rat aorta

Arecae semen extract relaxed aortic ring preparations of isolated rat aorta that contained endothelium from 3×10⁻⁷ g/mL, reaching a maximum of 86% at 10⁻⁵ g/mL. Its relaxation did not occur in specimens without endothelium, and was inhibited by pretreatment with 10⁻⁴ M N^G-nitro-1-arginine methylester. One of the active components was arecoline which is a muscarinic receptor agonist. Another active component was condensed tannin contained in Arecae semen. © 1997 John Wiley & Sons, Ltd.     

有机硒化合物的抗炎及抗变态反应作用

 目的：有机硒化合物具有多种活性，为此研究3种合成的有机硒化合物的抗炎作用和抗变态反应作用,并分析构效关系。方法：药物对小鼠巴豆油性耳肿胀的影响;对组胺(histamine,His)、过敏性慢反应物质(slow-reacting substance of anaphylaxis SRS-A)所致离体豚鼠回肠收缩的影响;致敏豚鼠肺中SRS-A的提取及药物的拮抗实验。结果：3种化合物能不同程度地抑制小鼠巴豆油性耳肿胀(〖WTBX〗P＜0.05或P〖WTBZ〗＜0.01)。50%抑制离体豚鼠回肠收缩时的药物浓度(IC₅₀)分别为对His:1.25×10^-5,1.58×10^-4，1.25×10^-4 mol/L,对SRS-A:8.9×10^-6，1.25×10^-4，1.12×10^-4mol/L。致敏豚鼠肺释放SRS-A的抑制浓度:10^-4mol/L。结论：3药中9108对受体的拮抗作用最强。该类化合物的化学结构中苯环(B)邻位酯基取代的化合物具有强的受体拮抗作用。它们的抗炎及抗免疫作用与其对His及SRS-A的受体拮抗作用及SRS-A的阻释作用有关。     

Aqueous Extract of Rosmarinus officinalis L. Inhibits Neutrophil Influx and Cytokine Secretion

Rosmarinus officinalis L. phenolic compounds have attracted considerable attention because of their antioxidant and antimicrobial properties, including its ability to treat inflammatory disorders. In this work, we investigated the in vivo and in vitro effects of R. officinalis aqueous extract on neutrophil trafficking from the blood into an inflamed tissue, on cell‐derived secretion of chemical mediators, and on oxidative stress. Anti‐inflammatory activity was investigated using carrageenan‐induced inflammation in the subcutaneous tissue of male Wistar rats orally treated with the R. officinalis extract (100, 200, or 400 mg/kg). The leukocyte influx (optical microscopy), secretion of chemical mediators (prostaglandin E2 (PGE2), TNF‐α, interleukin 6 (IL‐6), leukotriene B4 (LTB4), and cytokine‐induced neutrophil chemoattractant 1 by enzyme‐linked immunosorbent assay), and the anti‐oxidative profile (super oxide dismutase (SOD), glutathione peroxidase, and thiobarbituric acid reactive substance (TBARS) spectrophotometry) were quantified in the inflamed exudate. N‐Formyl‐methionine‐leucine‐phenylalanine‐induced chemotaxis, lipopolysaccharide‐induced NO₂^? production (Greiss reaction), and adhesion molecule expression (flow cytometry) were in vitro quantified using oyster glycogen recruited peritoneal neutrophils previous treated with the extract (1, 10, or 100 µg/mL). Animals orally treated with phosphate‐buffered saline and neutrophils incubated with Hank's balanced salt solution were used as control. R. officinalis extract oral treatment caused a dose‐dependent reduction in the neutrophil migration as well as decreased SOD, TBARS, LTB4, PGE2, IL‐6, and TNF‐α levels in the inflamed exudate. In vitro treatment with R. officinalis decreased neutrophil chemotaxis, NO₂^? production, and shedding of L‐selectin and β2 integrin expressions. Results here presented show that R. officinalis aqueous extract displays important in vivo and in vitro anti‐inflammatory actions by blocking pathways of neutrophil migration and secretion, suggesting its therapeutic application to acute inflammatory reactions. Copyright © 2014 John Wiley & Sons, Ltd.     

Pharmacological activity of the extracts of two Satureja obovata varieties on isolated smooth muscle preparations

Aqueous extracts of two varieties of Satureja obovata Lag. subsp. obovata: var. valentina and var. obovata, exhibited a dose-dependent inhibitory effect on the contractions induced by acetylcholine (Ach) (3.4 × 10^?8?6.8 × 10^?5M) and CaCl₂ (2 × 10^?4?1.28 ? 10^?2M) in rat duodenum and by noradrenaline (NA) (10^?9?5.12 × 10^?7 M) and CaCl₂ (2 × 10^?4?1.28 × 10^?2 M) in rat aorta. The extracts also produced relaxant effects in both tissue preparations precontracted with K⁺ (75 mM) and in rat aorta precontracted with NA (10^?6 M). Vasodilatory effects of the two extracts were attenuated when the endothelium was removed. The inhibitory effects of var. valentina were stronger. These results indicated a smooth muscle relaxant effect that could account for the use of these extracts in traditional medicine.     

Effects of baicalein isolated from Scutellaria baicalensis on interleukin 1β- and tumor necrosis factor α-induced adhesion molecule expression in cultured human umbilical vein endothelial cells

We examined the effects of nine flavonoids isolated from Scutellariae radix on interleukin-1β (IL-1β)- and tumor necrosis factor-α (TNF-α)- induced adhesion molecule expression in cultured human umbilical vein endothelial cells (HUVECs). Among them, we found that baicalein (5,6,7-trihydroxy flavone) dose-dependently inhibited IL-1β and TNF-α-induced endothelial leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1) expressions. Its 50% inhibitory concentrations (IC₅₀) for the IL-1β-induced ELAM-1 and ICAM-1 expressions were 2.3×10⁻⁵ M and 4.0×10⁻⁵ M, respectively. The IC₅₀ for the TNF-α-induced ELAM-1 and ICAM-1 expressions were 1.5×10⁻⁵ M and 3.1×10⁻⁵ M, respectively. In addition, protein C-kinase (PKC) inhibitor H7 also inhibited the ELAM-1 and ICAM-1 expressions induced by IL-1β and TNF-α.