Antiplatelet activity of geranylgeraniol isolated from Pterodon pubescens fruit oil is mediated by inhibition of cyclooxygenase-1

Geranylgeraniol is a natural isoprenoid with anti-inflammatory properties extracted from the Pterodon pubescens Benth. fruit oil (PpO). In this work, the antiplatelet effect of both PpO and geranylgeraniol is investigated. ADP-, thrombin- and arachidonic acid (AA)-induced aggregation in human and rabbit platelets showed a prime involvement of PpO and geranylgeraniol in the arachidonic acid cascade. The lack of any significant inhibition of platelet aggregation induced by U-46 619 and thrombin, associated with PpO and geranylgeraniol suppression of prostaglandin E(2) and thromboxane A(2) formation demonstrate, for the first time, the involvement of geranylgeraniol in the AA metabolisation by inhibiting the cyclooxygenase enzyme.     

Antinociceptive and anti-inflammatory effects of isolated fractions from Apium graveolens seeds in mice

The antinociceptive and anti-inflammatory effects of the aqueous and hexane extracts obtained from Apium graveolens L. (Apiaceae) seeds were evaluated. Formalin and xylene-induced ear edema tests were used in mice. The fractions were administered intraperitoneally at doses of 100-500?mg/kg body weight (BW). Both extracts with the xylene-induced ear edema test showed significant anti-inflammatory activity at all doses as compared with control. Only the hexane fraction reduced the nociception produced by formalin solution in the first phase (0-5?min) at 300, 400, and 500?mg/kg BW, and in the second phase (20-30?min) at 500?mg/kg BW. It is concluded that the hexane fraction has major contribution to the overall antinociceptive activity. Both fractions showed remarkable anti-inflammatory effect which supported the traditional use of Apium graveolens in diseases associated with inflammation.     

Antiulcerogenic and anti‐inflammatory activities of the essential oil from Pterodon emarginatus seeds

Objectives The objective of this work was to investigate the antiulcerogenic and anti‐inflammatory activities of the essential oil from Pterodon emarginatus seeds. Methods The following tests were used: ulcers induced by ethanol, indometacin and HCl/ethanol, and pleurisy induced by carrageenan in Swiss albino rats. The rats were treated by the oral route with essential oil of P. emarginatus seeds. Key findings The essential oil at 100, 300 and 500 mg/kg exhibited significant protection against ulcers induced by ethanol, indometacin and HCl/ethanol (P < 0.001). The essential oil caused a marked reduction in the exudate volume and inhibited leucocyte and neutrophil influx (P < 0.05) in carrageenan‐induced pleurisy. Moreover, the essential oil significantly decreased nitric oxide (NO) and interleukin‐1 (IL‐1) levels, without affecting tumour necrosis factor‐α production. Conclusions The results demonstrated the marked antiulcerogenic and anti‐inflammatory effects of the essential oil from P. emarginatus, which are, at least in part, a consequence of NO and IL‐1 modulation. P. emarginatus or its constituents might represent new therapeutic options to treat gastric ulcers and inflammatory diseases.     

In vitro and in vivo toxicological study of the Pterodon pubescens seed oil.

The oil of Pterodon pubescens seeds (PpSO) is known for its cercaricidal and anti-inflammatory effects. Its anti-rheumatic activity was recently reported using mice with collagen II-induced arthritis treated with a hydroalcoholic extract of PpSO, mimicking the wine infusion used in popular medicine. In the present study, PpSO was tested for acute toxicity, mutagenic activity and cytotoxicity for human peripheral blood mononuclear cells (PBMNC). PpSO was obtained after seed extraction with 100% ethanol and evaporation. Cytotoxicity was estimated using the tetrazolium salt reduction test (MTT assay) by PBMNC (2.5 x 10(5) cells/ml) after exposure to 0.07, 0.7 and 7 microg PpSO/ml for 24 and 48 h. In the mutagenesis assay, the Salmonella/mammalian microsome assay was employed with or without metabolization. Acute toxicity was studied on 30 (n = 10/group) male DBA1/J mice (20 +/- 2 g) after a single oral dose of 2, 4, and 8 g PpSO/kg b.w. The animals were observed for 24 h, anesthetized, sacrificed and autopsied. The organs were processed for histopathology by staining with hematoxylin-eosin. The IC50 of PpSO to PBMNC in RPMI 1640 supplemented with 5% fetal calf serum (FCS) was 2 and 1 microg PpSO/ml after 24 and 48 h, respectively. The mutagenic test performed with or without metabolic activation of PpSO did not show mutagenic activity for the concentrations tested (7 and 70 microg/ml). Mouse mortality or significant signs of acute toxicity (ocular, cardiovascular, gastrointestinal, motor or respiratory signs) for the PpSO doses tested was not observed. The organs did not show any macroscopic alterations. Histopathologic analysis of the tissues also did not demonstrate any lesions. The present study provides data to classify PpSO as non-cytotoxic to PBMNC, non-mutagenic, and non-toxic after acute administration since the PpSO doses tested were extremely higher than those used by the population.     

黄荆子不同溶剂提取物的抗炎镇痛作用

目的:观察黄荆子不同溶剂(氯仿、醋酸乙酯、水)提取部分的抗炎、镇痛作用。方法:采用二甲苯诱导小鼠耳郭肿胀和角叉菜胶诱导大鼠足肿胀建立炎症模型观察黄荆子不同溶剂提取物的抗炎作用;采用扭体法和热板法观察黄荆子不同溶剂提取物的镇痛作用。结果:氯仿提取部分(16,8 g.kg-1)对二甲苯诱导的小鼠耳肿胀抑制作用最为显著(P<0.01);氯仿提取部分(16 g.kg-1)能明显抑制角叉菜胶诱导的大鼠足肿胀(P<0.01)。对热和醋酸刺激引起的小鼠疼痛,水提物具有显著的镇痛作用(P<0.01),氯仿提取部分各剂量组镇痛作用不明显(P>0.05)。结论:黄荆子不同溶剂提取部位的抗炎镇痛作用有差异,氯仿提取物抗炎作用较强,水提取物的镇痛作用较强。     

Neurotoxicity to pigs and rodents from different fractions of Aeschynomene indica seeds

Aeschynomene indica seeds cause a vestibulo-cerebellar syndrome in pigs. This experiment studied the toxicity of different plant chemical fractions in pigs to determine a susceptible laboratory species to search for the plant's toxic principle. Hexanic, ethanolic and acetonic extracts of A. indica seeds were administered to 1 pig each. The ethanolic extract killed the experimental pig and 2/4 mice and 0/4 rats. The ethanolic extract was fractionated into ethyl acetate, butanolic. and aqueous remaining residues. The residues were administered by gavage at 0.9 g/kg to groups of 6 mice; those dosed with the ethyl acetate residue developed nervous signs and died. Administrated to 4 pigs, the residue caused clinical signs and histologic lesions similar than those observed in experimental intoxication of swine with A. indica seeds. The active principle of these seeds was in the ethyl acetate residue and mice can be used as an experimental species to test toxicity of substances isolated from this plant.     

Antimycobacterial activity of fractions and isolated compounds from Vetiveria zizanioides

The essential oil of Vetiveria zizanioides showed significant antimycobacterial activity against the drug-resistant strains of Mycobacterium smegmatis, which on activity guided fractionation afforded four bioactive fractions Vz-2, Vz-7, Vz-8, and Vz-9. Further purification of these bioactive fractions over preparative thin layer chromatographic resulted in the characterization of six compounds: 5, 10-pentadecadiyn-1-ol (1), α-curcumene (3), hydroxy junipene (4), (+) cycloisosativene (5), valencine (6), and selino 3,7 (11)-diene (7). All these compounds showed significant antimycobacterial activity against the drug-resistant strains (MDR-R and MDR-40) of M. smegmatis and their MIC was in the range of 31.25–62.5?μg/ml. These results may be of great help in antimycobacterial drug development from a very common, inexpensive, and non toxic natural product.     

Comparative study of the anti-edematogenic effects of anethole and estragole

BackgroundAnethole and estragole are monoterpene position isomers and constituents of essential oils from aromatic plants and were used in this study with the aim of analyzing their anti-inflammatory activity.MethodsThe anti-edematogenic effects of anethole and estragole were evaluated through plethysmometry in Swiss mice.ResultsAnethole inhibited carrageenan-induced edema at doses of 3, 10 and 30 mg/kg from 60 to 240 min after induction. However, the inhibitory effects of estragole were observed only from 60 to 120 min at the two highest doses. Anethole and estragole similarly inhibited edema elicited by substance P, bradykinin, histamine and TNF-α but were different in the inhibition of serotonin-elicited edema. In addition, only estragole inhibited sodium nitroprusside-induced edema.ConclusionsAnethole and estragole showed different profiles in the anti-inflammatory response to substance P, bradykinin, histamine, serotonin and TNF-α. NO is involved only in the inhibition mechanism of estragole.     

Peripheral antinociception and anti-edematogenic effect of a sulfated polysaccharide from Acanthophora muscoides

BackgroundSulfated polysaccharides from red marine algae have presented a variety of potentially therapeutic biological effects, however, their antinocicpetive and anti-inflammatory properties are not well understood.MethodsMale Swiss mice were pretreated with a sulfated polysaccharidic fraction obtained from the marine alga Acanthophora muscoides (AmII) (1, 3 or 9 mg/kg, iv) 30 min prior to either receiving an injection of 0.8% acetic acid or 1% formalin or prior to a thermal stimulus. AmII (1, 3 or 9 mg/kg, sc) was evaluated on carrageenan-, dextran- bradykinin-, histamine- and serotonin-induced rat paw edema models. AmII (500 jig, sc) was also injected into the paw. Additionally, mice were treated with the total sulfated polysaccharides from A. muscoides (Am-TSP) (20 mg/kg, ip) for 14 days.ResultsAmII reduced the number of acetic acid-induced writhes and licking time in the second phase of the formalin test, but it did not alter the response latency in the hot plate test, suggesting that its antinociceptive action occurs through a peripheral mechanism. AmII did not reduce carrageenan-induced paw edema and MPO activity. However, it reduced dextran-, histamine- and serotonin- induced paw edemas, but not bradykinin-induced edema, suggesting that histamine is the major target of AmII anti-edematogenic activity. AmII inj ected into the paw did not evoke local edema. Furthermore, Am-TSP induced no consistent signs of systemic damage, as revealed by body mass, organs wet weight and by biochemical, hematological and histopathological analyses.ConclusionAmII has important antinociceptive and anti-inflammatory properties and represents an important therapeutic agent warranting future studies.     

Phytochemical and antitrypanosomal investigation of the fractions and compounds isolated from Artemisia elegantissima

Context: Trypanosoma brucei brucei (T.b. brucei) infection causes death in cattle, while the current treatments have serious toxicity problems. However, natural products can be used to overcome the problems associated with parasitic diseases including T.b. brucei.

Objective: Artemisia elegantissima Pamp (Asteraceae) was evaluated phytochemically for its constituents and antitrypanosomal potential against T.b. brucei for the first time. Scopoletin isolated from A. elegantissima has shown better potential then the standard drug suramin, used against T.b. brucei.

Materials and methods: The ethanol extract of the aerial parts of A. elegantissima was fractionated by column and preparative thin-layer chromatography into six fractions (A–F) yielding 13 compounds, these were evaluated for their antitrypanosomal activity against T.b. brucei at different concentrations.

Results: Thirteen compounds were isolated from A. elegantissima: (Z)-p-hydroxy cinnamic acid, stigmasterol, β-sitosterol, betulinic acid, bis-dracunculin, dracunculin, scopoletin, apigenin, dihydroluteolin, scoparol, nepetin, bonanzin, and 3′,4′-dihydroxy bonanzin. The fractions D–F were found to be active at the concentration of 20?µg/ml and three compounds isolated from these fractions, scopoletin (MIC?≤0.19?µg/ml), 3′,4′-dihydroxy bonanzin (MIC?=?6.25?µg/ml) and bonanzin (MIC?=?20?µg/ml), were found to be highly active.

Discussion and conclusion: Artemisia elegantissima was phytochemically and biologically explored for its antitrypanosomal potential against T.b. brucei. The number and orientation of phenolic hydroxyl groups play an important role in the antitrypanosomal potential of coumarins and flavonoids. The compounds 3′,4′-dihydroxy bonanzin and scopoletin with low MIC values, hold potential for use as antitrypanosomal drug leads.     

The relaxant action of osthole isolated from Angelica pubescens in guinea-pig trachea

The effect of osthole, isolated from Angelica pubescens, on the contraction of guinea-pig trachea was studied. Osthole (25–100 mol/l), theophylline (10–1000 mol/l) and higher concentrations of nifedipine (0.1–100 mol/l) suppressed the contraction response curves of tracheal smooth muscle caused by carbachol, prostaglandin F₂ (PGF₂), U46619 (thromboxane A₂ analogue) and leukotriene C₄ (LTC₄) in a concentration-dependent manner. The contraction caused by high K⁺ (120 mmol/1) and cumulative concentrations of CaCl₂ (0.03–3 mmol/1) was also inhibited concentration-dependently by osthole (25–100 mol/l), theophyl line(10–1000 mol/l) and lower concentrations of nifedipine (0.01–0.1 mol/l). The relaxant actions of osthole were not affected by propranolol (1 mol/l), glibenclamide (10 mol/l) or removal of tracheal epithelium. Osthole (100 mol/l) was still effective in causing tracheal relaxation in the presence of nifedipine (1 mol/l). In Ca²⁺-free- and EGTA (0.2 mmol/1)-containing medium, the relaxing effect of osthole was more potent than in normal Krebs solution. Osthole (25 and 50 mol/l) caused 2.9 and 6.5, or 3.0 and 5.6 fold, respectively, increase in potency of forskolin or sodium nitroprusside in causing tracheal relaxation but did not affect that by cromakalim. Osthole (50 mol/l) enhanced the increase in tissue cAMP and cGMP levels induced by forskolin and sodium nitroprusside, respectively, and in higher concentrations (100 and 250 mol/l), itself increased markedly tissue cAMP and cGMP contents. Osthole (10–250 mol/l) inhibited the activity of cAMP and cGMP phosphodiesterases in a concentration-dependent manner. It is concluded that osthole exerts a nonspecific relaxant effect on the trachealis by inhibiting the cAMP and cGMP phosphodiesterases. Correspondence to: C. M. Teng at the above address     

The presynaptic effect of fractions isolated from the sponge Tedania ignis

Two fractions from the sponge Tedania ignis which have presynaptic effects were isolated. In neuromuscular junctions of Rana pipiens, the crude fraction decreases the amplitude of the evoked endplate potential and increases the frequency of miniature endplate potentials (MEPP), without effects on their amplitude or shape. Elution with 1 M acetic acid through Sephadex G15 produces three peaks, only one of which contains the biological activity. The compounds in this peak possess a molecular weight close to 900. Elution with 1M acetic acid through BioGel P2 produces 9 peaks, only 2 of which are biologically active. One of these fractions (f alpha) increases the frequency of MEPP and another fraction (f beta) inhibits the evoked release of neurotransmitter. None of the fractions change the amplitude or shape of MEPP, nor do they modify the resting membrane or action potentials in frog muscle. The action of f alpha occurs in low (15 microM) Ca2+, while the effect of f beta is antagonized by raising the extracellular Ca2+ concentration above 1.8 MM. Fraction beta antagonizes the increase of acetylcholine release produced by the venom of the black widow spider Latrodectus mactans mactans. This antagonistic action of f beta is reversible and the effect of the spider venom reappears if the sponge toxin is washed out with normal Ringer's solution.     

New oleanane-type triterpenoid saponins isolated from the seeds of Celosia argentea

Three new oleanane-type triterpenoid saponins named celosins H (1), I (2), and J (3) were isolated from the seeds of Celosia argentea L. Their structures were characterized as 3-O-β-d-xylopyranosyl-(1 → 3)-β-d-glucuronopyranosyl-polygalagenin 28-O-β-d-glucopyranosyl ester, 3-O-β-d-glucuronopyranosyl-medicagenic acid 28-O-β-d-xylcopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-β-d-fucopyranosyl ester, and 3-O-β-d-glucuronopyranosyl-medicagenic acid 28-O-α-l-arabinopyranosyl-(1 → 3)-[β-d-xylcopyranosyl-(1 → 4)]-α-l-rhamnopyranosyl-(1 → 2)-β-d-fucopyranosyl ester by NMR, MS, and chemical evidences, respectively. In our opinion, celosins H–J could be used as chemical markers for the quality control of C. argentea seeds.     

Vasorelaxation of rat thoracic aorta caused by osthole isolated from Angelica pubescens.

The pharmacological effects of osthole on isolated rat thoracic aorta were examined. Osthole inhibited norepinephrine (NE, 3 microM)-induced phasic and tonic contractions in rat thoracic aorta in a concentration-dependent manner (40-200 microM). The tonic contraction elicited by NE was also relaxed by the addition of osthole. This relaxing effect of osthole was not affected by indomethacin (20 microM) and was still observed in endothelium-denuded rat aorta. Methylene blue (50 microM) partially antagonized this relaxing effect of osthole. In high-K+ medium (80 mM), the Ca2+ (0.03-3 mM)-induced vasocontraction was inhibited concentration dependently by osthole (20-100 microM). Addition of osthole (100 microM) at the plateau of the K+ (80 mM)-induced contraction caused relaxation. Methylene blue (50 microM) did not antagonize this relaxation. In Ca(2+)-free medium, the caffeine (10 mM)-induced phasic contraction was also suppressed by osthole in a concentration-dependent manner. Although the cAMP level was not changed by osthole, the cGMP level of rat aorta was increased by osthole in a concentration-dependent manner. The increase in cGMP level caused by osthole was completely blocked by methylene blue. [3H]Inositol monophosphate formation caused by NE was not affected by osthole at a concentration of 200 microM. The 45Ca2+ influx elicited by either NE or high K+ was inhibited by osthole in a concentration-dependent manner. It is concluded that osthole relaxes rat thoracic aorta by virtue of its Ca(2+)-channel blocking properties and by elevating cGMP levels in vascular smooth muscle.     

Hepatoprotection of D-galactosamine-induced toxicity in mice by purified fractions from Garcinia kola seeds

The hepatoprotective effect of a biflavonoid complex, kolaviron, and its fractions from Garcinia kola seeds, together with the possible mechanisms involved was investigated in mice intoxicated with a single dose of D-galactosamine (GalNH(2)). Likewise, the ability of vitamin E to attenuate the toxicity was examined. Kolaviron, was separated by thin-layer chromatographic technique into three fractions; Fraction I, Fraction II and Fraction III with RF values of 0.48, 0.71 and 0.76, respectively. Pretreatment with kolaviron, fraction I and fraction II at a dose of 100 mg/kg for seven consecutive days before challenge with a single dose of GalNH(2) (800 mg/ kg) significantly (P<0.05) decreased serum alanine (ALT) and aspartate (AST) aminotransferases by 67%, 70%, 71% and 39%, 35%, 46%, respectively over GalNH(2)-only intoxicated mice. Vitamin E elicited respectively 65% and 39% reduction in the GalNH(2)-induced increase in the activities of these enzymes. In addition, pretreatment with kolaviron and fraction II significantly (P<0.05) decreased the activity of microsomal gamma-glutamyl transferase (gamma-GT) by 42% and 46%, respectively. Administration of kolaviron to GalNH(2)-intoxicated mice also restored glucose-6-phosphatase to level that was comparable to the control (P<0.05). These extracts except fraction III prevented the accumulation of serum and microsomal lipid peroxidation products, and also prevented the depletion of reduced glutathione (GSH) levels in the liver of GalNH(2)-intoxicated mice. Kolaviron, fraction I and fraction II at a dose of 100 mg/kg caused an induction of glutathione-S-transferase (GSH transferase) and uridyl glucuronosyl transferase (UDPGT) activities by 31%, 34%, 35% and 29%, 65%, 56%, respectively. GalNH(2)-induced toxicity was essentially prevented as indicated by a liver histopathologic study of liver slices from mice pretreated with kolaviron, fraction I and fraction II. This study shows that treatment with kolaviron, fraction I and fraction II (purified fractions from Garcinia kola) appeared to enhance the recovery from GalNH(2)-induced hepatotoxicity, and that the fractions I and II may therefore be responsible for the observed antihepatotoxic effect of kolaviron. This protection may be due to the ability of these extracts to induce the expression of phase II drug metabolizing enzymes.     

Anti-inflammatory properties of extracts, fractions and lignans isolated from Phyllanthus amarus

This study assessed the anti-inflammatory effect of the extracts and purified lignans obtained from Phyllanthus amarus. Given orally, the hexane extract (HE), the lignan-rich fraction (LRF), or the lignans phyltetralin, nirtetralin, niranthin, but not hypophyllanthin or phyllanthin, inhibited carrageenan (Cg)-induced paw oedema and neutrophil influx. The HE, the LRF or nirtetralin also inhibited the increase of IL1-beta tissue levels induced by Cg. Furthermore, bradykinin (BK)-, platelet activating factor (PAF)- and endothelin-1 (ET-1)-induced paw oedema were significantly inhibited by the HE or LRF while histamine- and substance P-induced paw oedema were unaffected. Finally, nirtetralin or phyltetralin caused inhibition of paw oedema induced by PAF or ET-1. These results show that the HE, the LRF and the lignans niranthin, phyltetralin and nirtetralin exhibited marked anti-inflammatory properties and suggest that these lignans seem to be the main active principles responsible for the anti-inflammatory properties reported for the HE of P. amarus.     

Mechanism of action of a hypoglycemic principle isolated from fenugreek seeds

Mechanism of action of an orally active hypoglycemic principle isolated from water extract of seeds of Trigonella foenum graecum (fenugreek) was investigated in alloxan induced subdiabetic and overtly diabetic rabbits of different severities. The active principle was orally administered to the subdiabetic and mild diabetic rabbits (five in each group) at a dose of 50 mg/kg body weight for 15 days. The treatment produced significant attenuation of the glucose tolerance curve and improvement in the glucose induced insulin response, suggesting that the hypoglycemic effect may be mediated through stimulating insulin synthesis and/or secretion from the beta pancreatic cells of Langerhans. Prolonged administration of the same dose of the active principle for 30 days to the severely diabetic rabbits (n = 5) lowered fasting blood glucose significantly, but could elevate the fasting serum insulin level to a much lower extent, which suggests an extra-pancreatic mode of action for the active principle. The effect may also be by increasing the sensitivity of tissues to available insulin. The hypoglycemic effect was observed to be slow but sustained, without any risk of developing severe hypoglycemia.     

Arctigenin isolated from the seeds of Arctium lappa ameliorates memory deficits in mice

The seeds of Arctium lappa L. (AL, family Asteraceae), the main constituents of which are arctiin and arctigenin, have been used as an herbal medicine or functional food to treat inflammatory diseases. These main constituents were shown to inhibit acetylcholinesterase (AChE) activity. Arctigenin more potently inhibited AChE activity than arctiin. Arctigenin at doses of 30 and 60?mg/kg (p.?o.) potently reversed scopolamine-induced memory deficits by 62?% and 73?%, respectively, in a passive avoidance test. This finding is comparable with that of tacrine (10?mg/kg p.?o.). Arctigenin also significantly reversed scopolamine-induced memory deficits in the Y-maze and Morris water maze tests. On the basis of these findings, arctigenin may ameliorate memory deficits by inhibiting AChE.     

Neurotoxic effects of three fractions isolated from Tityus serrulatus scorpion venom

Scorpion venoms contain low molecular weight basic polypeptides, neurotoxins, that are the principal toxic agents. These toxins act on ion channels, promoting a derangement that may result in an abnormal release of neurotransmitters. In the present study we investigated some of the effects of the F, H and J fractions isolated from Tityus serrulatus scorpion venom on the central nervous system of rodents. The venom was partially purified by gel filtration chromatography. The neurotoxic effect of these fractions was studied on convulsive activity after intravenous injection, and on electrographic activity and neuronal integrity of rat hippocampus when injected directly into this brain area. The results showed that intravenous injection of the F and H fractions induced convulsions, and intrahippocampal injection caused electrographic seizures in rats and neuronal damage in specific hippocampal areas. Fraction J injected intravenously reduced the general activity of mice in the open field but induced no changes when injected into the brain. These results suggest that scorpion toxins are able to act directly on the central nervous system promoting behavioural, electrographic and histological modifications.