Anti-inflammatory and antinociceptive activity of Urera aurantiaca.

Urera aurantiaca Wedd. (Urticaceae) is a medicinal plant commonly used in traditional medicine to relieve pain in inflammatory processes. In the present study, the in vivo anti-inflammatory and antinociceptive effects of U. aurantiaca methanolic extract and its possible mechanisms of action were investigated. The extract showed anti-inflammatory activity in the ear edema in mice test (34.3% inhibition), myeloperoxidase (MPO) activity was markedly reduced in animals administered with the extract: within 49.6% and 68.5%. In the histological analysis, intense dermal edema and intense cellular infiltration of inflammatory cells were markedly reduced in the ear tissue of the animals treated with the extract. In the carrageenan-induced hind paw edema in rats assay the extract provoked a significant inhibition of the inflammation (45.5%, 5 h after the treatment) and the MPO activity was markedly reduced (maximum inhibition 71.7%), The extract also exhibited significant and dose-dependent inhibitory effect on the increased vascular permeability induced by acetic acid. The extract presented antioxidant activity in both 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis 3-ethylbenzothiazoline 6-sulfonic acid tests and its total phenol content was 35.4 ± 0.06 mg GAE/g of extract. Also, the extract produced significant inhibition on nociception induced by acetic acid (ED50 : 8.7 mg/kg, i.p.) administered intraperitoneally and orally. Naloxone significantly prevented this activity.

HPLC fingerprint of a flower extract of Tilia × viridis and correlation with antiproliferative and antioxidant activity.

Tilia species have been used in Europe and in America to treat anxiety and also for the treatment of colds, influenza, bronchitis, fever and inflammation. Tilia × viridis is a Tilia species distributed widely in Buenos Aires, Argentina. The flavonoids present in Tilia species have antioxidant properties, acting as reactive oxygen species (ROS) scavengers, principally on hydrogen peroxide (H(2)O(2)) and the superoxide anion (O(2)(·-)), which are involved in many diseases, including cancer. The aim of this study was to determine the phytochemical pattern of the ethanol extract of Tilia × viridis, principally the flavonoid content, and to evaluate the antiproliferative effects on both normal and tumoral cells, and the antioxidant activity in relation to H(2)O(2) modulation. The extract was found to present a selective antiproliferative activity on a lymphoma cell line and this was related to free radical scavenging activity. In addition, one of its main compounds, rutin, showed antioxidant effects related to peroxidase activity. T. × viridis may therefore be a source of antioxidant compounds that contribute to a selective antiproliferative action on tumoral cells, acting by modulation of H(2)O(2) levels.

In Vitro Antiplasmodial Activity of Sesquiterpene Lactones from Ambrosia tenuifolia.

The in vitro antiplasmodial activity of Ambrosia tenuifolia organic extract and its isolated sesquiterpene lactones, psilostachyin and peruvin, has been evaluated against Plasmodium falciparum F32 and W2 strains. The cytotoxicity of both compounds was determined on lymphoid cells, and their corresponding selectivity indexes (SIs) were calculated. Peruvin was the most active compound on F32 strain of P. falciparum with a 50% inhibitory concentration value (IC(50)) of 0.3 µg/mL (1.1 µM) whereas psilostachyin showed activity on both strains (IC(50) = 0.6 (2.1 µM) and 1.8 µg/mL (6.4 µM)). Fifty percent cytotoxic concentration (CC(50)) values (48 h) were 6.8 µg/mL (24.3 µM) and 10.0 µg/mL (37.9 µM) for psilostachyin and peruvin, respectively.

Different activities of Schinus areira L.: anti-inflammatory or pro-inflammatory effect.

The anti-inflammatory drugs possess many serious side effects at doses commonly prescribed. It is really important to discover novel regulators of inflammation from natural sources with minimal adverse effects. Schinus areira L. is a plant native from South America and is used in folk medicine as an anti-inflammatory herb. For this study, the activity of aqueous extracts on inflammation and the effect on superoxide anion production in mice macrophages were assayed. Aqueous extracts were prepared by soaking herbs in cold water (cold extract), boiling water (infusion), and simmering water (decoction). Cold extract possess an anti-inflammatory activity. Decoction and infusion showed pro-inflammatory activity. Cold extract increased the production of superoxide anion. It has been proposed to use diverse methods to obtain extracts of S. areira L. with different effects. Cold extract, decoction, and infusion could be utilized as extracts or as pharmacological preparations for topical application.

Peroxidase secretion in rat submandibular glands induced by PGE2: role of cAMP and nitric oxide.

Free radicals are associated with the appearance of disorders such as tumours, CNS alterations and inflammatory pathologies. Their levels are known to be increased in inflammatory diseases due to the activity of prostaglandins, which are related to protein secretion including enzymes. Peroxidase is an oral enzyme that is implicated in the defence of the oral cavity. In this paper, investigations of the effect and mechanism of the activity of prostaglandin E2 (PGE2) on peroxidase secretion of female rat submandibular glands are reported. Results showed that PGE2 significantly increased the secretion of submandibular peroxidase and that this effect was mediated by an increase of intracellular cAMP and nitric oxide synthase activation. This could imply that prostaglandins play a modulatory role in diseases where free radicals are involved.

Modulatory effect of the adrenergic system upon fibroblast proliferation: participation of beta 3-adrenoceptors.

1. The beta3-adrenoceptor agonist ZD 7114, like the non-selective beta-adrenoceptor agonist isoprenaline, but unlike the beta1-adrenoceptor agonist dobutamine and the beta2-adrenoceptor agonist salbutamol, produced an increment on mouse embryonic fibroblast proliferation. The half-maximal stimulation of cell growth occurred at substantially lower concentrations with the beta3-adrenoceptor agonist (EC50: 5.5 x 10(-8) m) than with isoprenaline (EC50: 1.25 x 10(-6) m). 2. The selective beta3-adrenoceptor antagonist SR 5923 OA prevented the beta3-stimulated fibroblast proliferation. Conversely, practolol and butoxamine did not prevent fibroblast growth. 3. Additionally, a decrease of cAMP was obtained in fibroblasts cells upon stimulation with isoprenaline and ZD 7114. 4. The expression of beta-adrenoreceptors on fibroblast cells was also studied by radioligand binding. The Ki values in the presence of beta1- and beta2-adrenoceptor antagonist was two-fold higher than the Ki values for beta3 adrenoceptor antagonist indicating the presence of A3-receptor subtype. 5. Inhibitors of different intracellular coupling pathways including phospholipase C (U 73122), protein kinase C (staurosporine), calcium/calmodulin (trifluoroperazine) and calcium channel (verapamil), prevented the stimulatory actions of the selective beta3-adrenoceptor agonist ZD 7114. 6. The presence of beta3-adrenoceptors on embryonic mouse fibroblast cells may play a role in the modulation of cell growth and biologic activity. The mechanism by which ZD 7114 triggers cell proliferation and function, involves the activation of phospholipase C, PKC, calcium/calmodulin and the influx of calcium.

Different intracellular signals coupled to the antiproliferative action of aqueous crude extract from Larrea divaricata Cav. and nor-dihydroguaiaretic acid on a lymphoma cell line.

In this paper, we report the effect of standard NDGA, as compared to that of an aqueous extract of Larrea divaricata Cav., on BW 5147 lymphoma cell-line proliferation. To determine the mechanism of action, the effects of both on the level of intracellular cAMP, protein kinase C activity and calcium influx were studied. Moreover, the NDGA present in the aqueous extract of the plant was quantified. The aqueous extract and the standard NDGA showed antiproliferative action against these cells. While the antiproliferative activity of the aqueous extract was mediated by an increase in cAMP levels, and inhibition of PKC and calcium influx, the antiproliferative activity of NDGA was related only to the inhibition of PKC. Considering the amount of NDGA detected in the aqueous extract of the plant, at the concentrations analyzed in this case, antiproliferative activity of Larrea divaricata cannot be attributed to this compound, but could have an additive effect on the activity of other compounds.

Altered beta-adrenoceptor function associated to protein kinase C activation in hyperproliferative T lymphocytes.

beta-Adrenoceptor (betaAR) expression and function as well as its modulation via intracellular transduction signals, were analyzed on the T cell lymphoma BW5147. Independently to the kinetic of proliferation and relative to the number of receptors displayed in normal T lymphocytes, BW5147 cells displayed a decreased number of betaAR, uncoupled to adenylate cyclase, but coupled to protein kinase C stimulation. This last effect was impaired by a beta-antagonist and by blockers of the enzymatic pathways involved in T lymphocyte proliferation, inducing a recovery of betaAR sites. Down-regulation of betaAR would implicate the loss of a negative neuroimmune control mechanism for lymphocyte proliferation. The coupling of the remaining sites to a positive signal for cellular activation, would contribute to establish an hyperproliferative state.

Paradoxical role of PGE2 and cAMP in Actinobacillus actinomycetemcomitants strain Y4-induced lymphocyte proliferation.

An immune mechanism has been suggested in the pathogenesis of periodontal disease. Actinobacillus actinomycetemcomitants (Aa) has been implicated as one of the etiological agents that induces the major immune response together with a dense infiltrate of inflammatory cells. But the exact role of these immune cells in periodontal disease has not yet been clarified. In this study the T lymphocyte (TL) proliferative response was evaluated after having being exposed to free cell supernatant (SN) from Aa. Aa SN increased TL proliferation. This mitogenic effect of Aa SN was attenuated by pretreating TL with indomethacin (INDO) or acetylsalicylic acid (ASA) but not by polymyxin B. The inhibitory effect of INDO on cell proliferation was reversed by the addition of prostaglandin E2 (PGE2) to the culture assay. Moreover, when immune cells were exposed to Aa SN they were able to generate PGE2 at the same time as intracellular levels of cAMP decreased. Both, PGE2 release and decrease accumulation of cAMP in TL were blunted by treated lymphocytes with INDO. In this paper we demonstrate that cell free SN from Aa induces a mitogenic effect on murine lymphocytes. The mechanism involves the host's immunecompetent cells and the release of PGE2 and appears not to be induced by capsular-like polysaccharide antigen. Results show a paradoxical mitogenic effect of Aa SN accompanied by increased generation of PGE2 and decreased production of cAMP by lymphocytes.

Antimitogenic effect of Larrea divaricata Cav.: participation in arachidonate metabolism.

Aqueous extracts of the leaves of Larrea divaricata Cav. exert antimitogenic effects on tumor cells (BW 5147 murine immature T-lymphoma) and normal, stimulated lymphocytes. The effective concentration was four times smaller in the case of tumor cells than in the case of normal, stimulated lymphocytes. Inhibitor studies of arachidonate pathway suggest that the proliferative effect of the extract is due to the activation of lipoxygenase metabolism, while the inhibitory action could be a direct effect.

"In vivo" antitumor activity of Larrea divaricata C.: comparison of two routes of administration.

We have previously demonstrated that an aqueous extract from Larrea divaricata has an antiproliferative activity on T lymphoma (BW 5147) cells in culture. Moreover the extract has in vivo antitumor activity when it was administered to a pregnant rat which had a spontaneous mammary tumor. In this work, the effect of an extract of Larrea divaricata on a mammary carcinoma chemically induced with N-nitrosomethylurea in females rats was studied. The extract was administered at a dose of 250 mg/kg three times each week by two different routes, subcutaneous (s.c.) and intratumoral (i.t.). The antitumor activity of the extract was evaluated by the survival time and the percentage of tumors that decreased, remained static or increased. From tumors treated via i.t. with the extract, 7 decreased (58%), 4 remained static (33%), and 1 increased (8%); whereas from tumors treated via s.c. with the extract, 10 decreased (12%), 59 remained static (75%) and 9 increased (11%); The total number of control tumors was 80, none of them showed regression, 12 remained static (15%) and 68 increased (85%). The survival time of treated animals using both routes (s.c. and i.t.) was significantly greater (p < 0.05) than the saline-treated rats (control): extract 70 ± 19 days, n: 32; saline (control) 38 ± 22 days, n: 20. We conclude that the aqueous extract of this plant has an in vivo antitumor activity with the intratumor route being most effective in induction of tumor regression.

"In vivo" and "in vitro" antitumoral action of Larrea divaricata Cav.

We previously reported that aqueous extract of Larrea divaricata Cav. had an antiproliferative activity upon tumoral lymphoid cells (BW 5147), without affecting normal immunity. To determine the probable mechanism of the inhibitory action of the extract upon cell growth, the participation of intracellular signals involved in the inhibition of cell proliferation, namely the activation of adenylate cyclase system was studied. The production of cyclic 3', 5 adenosine monophosphate (cAMP) in presence and absence of extract was analized. The extract increased the cAMP levels, but neither the cAMP production nor the inhibitory effect of the extract on proliferation were blocked by a beta adrenergic receptor antagonist (propranolol) or by histaminergic receptor antagonists (cimetidine and mepyramine). So, we concluded that the antiproliferative activity of the extract of BW 5147 cells would be mediated by an increase in cAMP intracellular levels no related to the activation of the membrane receptors here studied. In parallel, the extract was administered to a pregnant rat with a spontaneous mammarian carcinoma and "in vivo" antitumoral activity was found.

In vitro antibacterial activity of Argentine folk medicinal plants against Salmonella typhi.

Boiling water extracts of 132 samples from 54 plant families, commonly used in Argentine folk medicine, were screened for antibacterial activity against Salmonella typhi. The agar-well diffusion method was used. A reference concentration-response curve for ampicillin was used to estimate the apparent activity of the samples. Twenty four species showed antibacterial activity. Cassia occidentalis roots, Heimia salicifolia aerial parts, Punica granatum fruit pericarp and Rosa borboniana flowers produced some of the more active extracts. Taking into account the multiple resistance of Salmonella typhi, these findings could be useful in the search for new clinically useful antimicrobials.

Antibacterial activity of alimentary plants against Staphylococcus aureus growth.

Alimentary plants were screened for antibacterial activity against a penicillin G resistant strain of Staphylococcus aureus. Twenty-five samples of plant material corresponding to 21 species from 13 families were used. Both aqueous and ethanol extracts were obtained from them. Antibacterial activity was determined by the agar-well diffusion method, using cephazolin as a standard antibiotic. Seventeen ethanol extracts were found active. Eugenia caryophyllata (clavo de olor*) flowers, Myristica fragans (nuez moscada*) seeds, Theobroma cacao (cacao*) seed bark, Triticum sp (trigo*) fruit, Zea mays (maíz*) fruit and Piper nigrum (pimienta*) ripe fruit produced some of the more active extracts (* = Argentine vulgar names).

Screening of plants used in Argentine folk medicine for antimicrobial activity.

Screening of 132 extracts from Argentine folk-medicinal plants for antimicrobial activity has been conducted using a penicillin G resistant strain of Staphylococcus aureus, Escherichia coli and Aspergillus niger as test microorganisms. Cephazolin, ampicillin and miconazole were used as standard antibiotics and concentration-response curves were obtained using the agar-well diffusion method. Boiling water extracts of plant materials were tested and 12 species were active against Staphylococcus aureus, whereas 10 were effective against Escherichia coli and 4 against Aspergillus niger. Tabebuia impetiginosa bark, Achyrocline sp. aerials parts, Larrea divaricata leaves, Rosa borboniana flowers, Punica granatum fruit pericarp, Psidium guineense fruit pericarp, Lithrea ternifolia leaves and Allium sativum bulbs produced some of the more active extracts.