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The lipid‐lowering action of the leaves of the Aleurites moluccanamethanol extract was studied in Triton W‐1339 and high‐fat‐diet fed rats. The serum lipids (total cholesterol, LDL‐ and HDL‐cholesterol and triglycerides) and body weight were found to be lowered by A. moluccana(300 mg/kg, b.w.) in rats with Triton‐induced hypercholesterolaemia and on a hyperlipaemic diet. The results suggest that the lipid lowering action of this natural product is mediated through inhibition of hepatic cholesterol biosynthesis and reduction of lipid absorption in the intestine. Copyright © 2002 John Wiley & Sons, Ltd.

The acrosome reaction is a regulated exocytotic process leading to a massive fusion between the outer acrosomal membrane and the cell membrane. In spite of the great amount of information available related to the acrosome reaction in several species, there is a remarkable paucity about the role of monomeric guanosine triphosphatases (GTPases) of the Rab family—well-established participants in exocytosis in other cell types—in the acrosome reaction. Western blot and immunofluorescence analysis indicate that Rab3A is present in human spermatozoa and localizes to the acrosomal region in the sperm head. One difficulty in studying the role of proteins in intact cells is the fact that they are unable to cross the cell membrane. Therefore, we established a working model of streptolysin O-permeabilized human spermatozoa. Permeabilized spermatozoa were able to respond in a regulated way to different stimuli, such as G protein activators and calcium. An acrosomal reaction was also triggered by a Rab3A peptide corresponding to the effector region. More important, recombinant Rab3A protein in the GTP-bound form caused acrosome exocytosis. The same protein loaded with GDP or Rab11 in the GTP-bound form was inactive. Also, recombinant GDI (GDP dissociation inhibitor)—a protein that releases Rab proteins from membrane—inhibited a GTPγS-stimulated acrosome reaction. Our results indicate that 1) permeabilized spermatozoa can be used to study the role of macromolecules in the acrosome reaction, 2) Rab3A is present in human spermatozoa, and 3) Rab3A or another Rab3 isoform is involved in the exocytosis of the acrosomal granule in human spermatozoa.

Polygodial, a sesquiterpene isolated from the bark of Drymis winteri given systemically, intraplantarly, or by spinal or supraspinal sites, produced antinociception when assessed in both phases of the formalin test and against capsaicin-induced pain. Polygodial, even at high doses, had no antinociceptive or antihyperalgesic effect when assessed in hot-plate assay or in glutamate-induced hyperalgesia, nor did it significantly interfere with the motor coordination of animals when tested in the rota-rod test. The polygodial antinociception assessed in the formalin test was not affected by i.p. treatment of animals with cyprodime, yohimbine, phaclofen, bicuculine, or nitric oxide precursor or by intrathecal administration of potassium channel blockers such as apamin, charybdotoxin, glibenclamide, or tetraethylammonium. In contrast, polygodial antinociception was significantly attenuated by i.p. treatment of animals with naloxone, naltrindole, 2-(3, 4-dichlorophenyl)-n-methyl-n-[(1S)-1-(3-isothiocynatophenyl)-2-(1- pry rolidinyl)ethyl]acetamide, p-chlorophenylalanine, prazosin, or by i. c.v. treatment with pertussis toxin. In addition, polygodial antinociception was not cross-tolerant to morphine, nor was its effect affected by the adrenalectomy of animals. Together, these results show that polygodial produces pronounced systemic, spinal, and supraspinal antinociception in mice, mainly preventing the neurogenic pain produced by formalin and capsaicin. The mechanism by which polygodial produces antinociception seems likely to involve an interaction with the opioid system, mainly kappa and delta subtypes, depend on the activation of G(i/o) protein sensitive to pertussis toxin, alpha(1)-adrenoceptors, and the serotoninergic system. Collectively, these results suggest that polygodial itself or its derivatives may have potential therapeutic value for the development of new analgesic drugs.

In order to obtain a better knowledge of the special behavior of phenylhydroxylamine as a nucleophile, the mechanism of its reaction with 2,6-dichlorobenzaldehyde, norcamphor, and cyclohexanone, and also the hydrophobic effect on its reaction with 2,6-dichlorobenzaldehyde and benzaldehyde, was studied. The results led us to assume that the planar molecule of phenylhydroxylamine should be placed parallel to the planar molecule of benzaldehyde in order to permit the attack of the lone electron pair of the nitrogen on the carbonyl group, forming, together with a hydrogen bond between the hydroxyl group and the carbonylic oxygen atom, a packed preassociation complex. This mechanism is not observed in the case of norcamphor or 2,6-dichlorobenzaldehyde due to the steric hindrances produced by the lack of planarity of these molecules. © 2000 John Wiley & Sons, Inc. Int J Chem Kinet 32: 453–459, 2000

The antinociceptive action of the alkaloid cis-8, 10-di-n-propyllobelidiol hydrochloride dehydrate (DPHD), isolated from Siphocampylus verticillatus, given i.p., p.o., i.t., or i.c.v., was assessed in chemical and thermal models of nociception in mice, such as acetic acid-induced abdominal constriction, formalin- and capsaicin-induced licking, and hot-plate and tail-flick tests. DPHD given by i.p., p.o., i.t., or i.c.v. elicited significant and dose-related antinociception. At the ID50 level, DPHD was about 2- to 39-fold more potent than aspirin and dipyrone, but it was about 14- to 119-fold less potent than morphine. Its analgesic action was reversed by treatment of animals with p-chlorophenylalanine, naloxone, cyprodime, naltrindole, nor-binaltrorphimine, L-arginine, or pertussis toxin. Its action was also modulated by adrenal-gland hormones but was not affected by gamma-aminobutyric acid type A or type B antagonist, bicuculine, or phaclofen, nor was it affected by glibenclamide. DPHD, given daily for up to 7 days, did not develop tolerance to itself nor did it induce cross-tolerance to morphine. However, animals rendered tolerant to morphine presented cross-tolerance to DPHD. The antinociception of DPHD was not secondary to its anti-inflammatory effect, nor was it associated with nonspecific effects such as muscle relaxation or sedation. DPHD, in contrast to morphine, did not decrease charcoal meal transit in mice, nor did it inhibit electrical field stimulation of the guinea pig ileum or mouse vas deferens in vitro. Thus, DPHD produces dose-dependent and pronounced systemic, spinal, and supraspinal antinociception in mice, including against the neurogenic nociception induced by formalin and capsaicin. Its antinociceptive effect involves multiple mechanisms of action, namely interaction with mu, delta, or kappa opioid systems, L-arginine-nitric oxide and serotonin pathways, activation of Gi protein sensitive to pertussis toxin, and modulation by endogenous glucocorticoids.

Objective:This study describes the in vitro action of the hydroalcoholic extract and the 1,7-dihydroxy-2,3-dimethoxy xanthone isolated from P. cyparissiason agonist and ovalbumin induced contractions in trachea, from normal and actively sensitised guinea pigs.¶Results:The hydroalcoholic extract of P. cyparissias(0.125 to 1mg/ml), incubated with the guinea-pig trachea for 20 min, had no effect on the resting tone of the preparations, but caused a concentration-dependent, reversible and non competitive inhibition of contractions induced by acetylcholine, histamine, compound 48/80, bradykinin, substance P, prostaglandin E2and the stable analogue of thromboxane A2mimetic U 46619. The calculated mean IC50values for the hydroalcoholic extract were: 0.37, 0.51, 0.06, 0.32, 0.48, 0.3 and 0.17 mg/ml, respectively. Also, the extract of P. cyparissias(0.125 to 0.5 mg/ml) antagonised, in a graded manner (IC50of 0.46mg/ml) ovalbumin-induced contractions in guinea-pig trachea obtained from animals which had been actively sensitised to this antigen. Pre-incubation of the preparations with the purifed xanthone isolated from P. cyparssias(2.5 to 80 μg/ml; 10.0 to 310.0 μM) caused significant and concentration-dependent, reversible and non-competitive inhibition of the contractile responses elicited by acetylcholine, histamine, bradykinin, substance P, U 46619 and prostaglandin E2. The calculated mean IC50values for these effects were: 132.0, 73.0, 9.2, 32.0, 110.6 and 66.0 μM, respectively. At very high concentrations (155.0-620.0 μM) the xanthone also antagonised contraction induced by KCl in guinea-pig trachea (IC50of 190.0 μM).¶Conclusions:Taken together these and our previous in vivo results are consistent with the view that the active principles present in P.cyparissias, including the 1,7-dihydroxy-2,3-dimethoxy xanthone, antagonise, in a non competitive but, reversible manner the contractions induced by chemical inflammatory mediators in the guinea pig trachea in vitro. Thus, these results might explain at least in part, the medicinal use of this plant in the management of inflammation, asthma and allergy.

The antinociceptive effect of the novel xanthoxyline derivative 2-(4-bromobenzoyl)-3-methyl-4-6-dimethoxy benzofuran) (BMDB), given i.p., p.o., s.c., subplantarly, intrathecally or by i.c.v. routes was assessed in five models of chemical and thermal nociception in mice, namely acetic acid-induced abdominal constriction, formalin and capsaicin-induced licking, hot-plate and tail-flick tests. BMDB given by i.p., s.c., subplantarly or by i.c.v. routes elicited dose-related and long-lasting (4 hr) antinociception, but had no significant effect by p.o. route. At the ID50 level, this compound was about 15- to 100-fold more potent than aspirin and acetaminophen, but it was about 2- to 50-fold less potent than morphine. Its analgesic action was not influenced by naloxone, L-arginine, antagonist of alpha-1 adrenoceptor, prazosin, tau -aminobutyric acid (B) antagonist, phaclofen, after adrenalectomy, but was reversed in part by p-chlorophenylalanine methyl ester. Its analgesic action was not secondary to an anti-inflammatory effect, or was it associated with nonspecific effect such as muscle relaxant or sedative actions of animals. We conclude that BMDB produces dose-dependent spinal and supraspinal antinociception as evaluated in several algesic models in mice, including the neurogenic nociception responses induced by formalin and capsaicin. Its antinociceptive effect was insensitive to naloxone, suggesting the lack of involvement of endogenous opioid, was not modulated by adrenal glands and does not involve interaction with the L-arginine-nitric oxide pathway, activation of alpha-1 adrenoceptors or tau-aminobutyric acidB receptors, but requires, at least in part, the serotoninergic pathway.

Objective:To study the acute anti-inflammatory and anti-allergic properties of an extract of D. winteri.¶Material and Methods:Paw oedema induced in rats with various stimuli and anaphylactic shock in mice.¶Results:The hydroalcoholic extract (HE) of D. winteri (Winteraceae)(30 to 100 mg/kg, p.o., 1 h prior) inhibited carrageenan (300 μg/paw) and dextran (100 μg/paw)-induced paw oedema formation in a dose-dependent manner, with mean ID50values of 49 and < 30 mg/kg, respectively. The HE of D. winteri(30 to 100 mg/kg) also inhibited paw oedema induced by bradykinin (BK) (3 nmol), substance P (SP) (10 nmol) and PAF-acether (PAF) (10 nmol), in a dose-dependent manner, with mean ID50values of 56, 63, and 58 mg/kg, respectively. However, the HE inhibited the rat paw oedema induced by prostaglandin E2(PGE2) (10 nmol) (29 ± 7 and 33 ± 2% at 60 and 240 min) to a smaller extent, and had no effect on oedema elicited by histamine (100 nmol). In adrenalectomized animals, the inhibition by the HE of D. winteri(100 mg/kg, p.o., 1 h prior) of BK-elicited oedema (3 nmol/paw) was significantly smaller when compared with that observed in control animals. When assessed in rats actively sensitised to ovalbumin (OVO), the oedema caused by OVO (6 μg/paw) was significantly inhibited by HE of D. winteri(30 to 100 mg/kg, p.o.), with a mean ID50of about 65 mg/kg. The HE of D. winteri(100 and 200 mg/kg, p.o.) significantly increased survival rate when assessed in anaphylactic shock in mice actively sensitised to the antigen. The protective effect was long-lasting, being observed for up to 15 h. Dexamethasone, used as positive control (0.5, 1 and 2 mg/kg) produced a long-lasting (up to 24 h) increase in the survival rate of the animals.¶Conclusions:These results confirm and extend our previous studies, and demonstrate the clear oral anti-inflammatory and anti-allergic properties of the active principle(s) present in the barks of D. winteri, thus confirming its reported medicinal use in folk medicine for the management of airway diseases.

This study reports the oral anti-inflammatory profile of the crude extract (CE) ofMandevilla velutina, a plant which has been previously demonstrated to selectively antagonize bradykinin response of the isolated tissues on rat paw oedema and pleurisy caused by different phlogistic agents. The CE (50 to 200 mg/kg), given 60 min before, inhibited in a dose-dependent manner bradykinin (BK) and cellulose sulphate-induced paw oedema, maximal inhibition of 59% and 65%, respectively. In the same range dose the CE also significantly antagonized pleural exudate and cell infiltration caused by these substances, maximal inhibition of 34% and 46%, respectively. In addition, the CE (100 and 200 mg/kg) also inhibited paw oedema induced by serotinin, PAF-acether and zymozan, maximal inhibition of 55%, 38% and 46%, respectively, but enhanced histamine oedema. However, the CE revealed only partial or no inhibition in pleural exudate caused by these agents. The CE (100 and 200 mg/kg) also inhibited in a dose and time-dependent manner carrageenan-induced paw oedema with a maximal inhibition of 44%, but only partially affected carrageenan-induced pleural exudate. The CE also partially inhibited dextran oedema, but even at a higher dose (400 mg/kg) it failed to interfere withBothrops Jaracaca-induced paw oedema. The CE inhibited BK and to a lesser extent cellulose sulphate-induced cell migration, but failed to interfer with the differential leukocyte migration in the pleural cavity. These findings provide evidence that the CE fromM. velutina, besides antagonizing kinin action, exhibit an oral anti-oedematogenic activity against a variety of phologistic agents, but it was more effective in inhibiting those models where kinins are more involved.

This work describes the antinociceptive effect of a triterpene glycoside, niga-ichigoside F1 (1), obtained from an EtOAc extract of the aerial parts of Rubus imperialis. When evaluated against an HOAc-induced writhing model, it exhibited an ID50 value of 3.1 mg/kg (ip). Moreover, in a formalin-induced pain model, both phases of pain were inhibited by compound 1, with ID50 values of 2.6 (first phase) and 2.7 (second phase) mg/kg, (ip), respectively.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.