Efficacy of an Hypericum perforatum (St. John's wort) extract in preventing and reverting a condition of escape deficit in rats.
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The treatment of unselected depressed patients with an hydro-alcoholic extract of Hypericum perforatum has been reported to have an efficacy similar to that of classical antidepressants. In the present report, the effects of H. perforatum were studied on three animal models of depression: (i) an acute form of escape deficit (ED) induced by an unavoidable stress; (ii) a chronic model of ED, which can be maintained by the administration of mild stressors on alternate days; (iii) a model of anhedonia based on the finding that repeated stressors prevent the development of an appetitive behavior induced by vanilla sugar in satiated rats fed ad libitum. H. perforatum acutely protected animals from the sequelae of unavoidable stress; such an effect was partially prevented by the administration of SCH 23390 or (-)-pindolol. Moreover, H. perforatum reverted the ED maintained by repeated stressors and preserved the animal's capacity to learn to operate for earning a positive reinforcer. It was concluded that H. perforatum contains some active principle(s) endowed with antidepressant activity. (+info)
Performance and digestibilities of beef cattle fed diets supplemented with either soybean meal or roasted soybeans and implanted with Synovex.
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Two 160-d feedlot experiments, each consisting of 20 Angus-Hereford steers (216 +/- 5 kg BW, Exp. 1; 258 +/- 5 kg BW, Exp. 2) and 20 Angus-Hereford heifers (208 +/- 5 kg BW, Exp. 1; 236 +/- 5 kg BW, Exp. 2), were used to investigate the effects of supplementing diets with either roasted soybeans (RSB, roasted at 127 degrees C for 10 min) or soybean meal (SBM) and implanting or not implanting with an estrogenic growth promoter (SYN; Synovex-S, 20 mg of estradiol benzoate plus 200 mg of progesterone or Synovex-H, 20 mg of estradiol benzoate plus 200 mg of testosterone) on performance. The cattle were fed a basal diet of 15% orchardgrass silage, 15% corn silage, and 70% corn-based concentrate. Treatments were 1) no SYN and fed a SBM-supplemented diet, 2) no SYN and fed a RSB-supplemented diet, 3) SYN and SBM, and 4) SYN and RSB. Cattle in the SYN groups were reimplanted at 80 d. Four additional Angus-Hereford steers were used in a digestion and nitrogen balance experiment conducted during the first half of Exp. 1. For the total 160-d feedlot experiments, DMI for RSB compared with SBM was lower (P < .01; 8.5 vs 9.2 kg/d, SEM = .07) and ADG/DMI tended to be higher (P < .10; 165 vs 157 g/kg, SEM = 1.3). Final BW of steers fed RSB was similar (P > .10) to that of steers fed SBM (473 vs 478 kg, SEM = 5.6), as was ADG (1.39 vs 1.43 kg/d, SEM = .02). Dry matter intake for SYN-implanted steers was higher (P < .01) than for steers not implanted (9.2 vs 8.5 kg/d). Likewise, final BW (491 vs 460 kg) and ADG (1.49 vs 1.33 kg/d) were higher (P < .01), and ADG/DMI (166 vs 157 g/kg) tended to be higher (P < .10), for SYN-implanted steers than for steers not implanted. During the more rapid muscle growth period (0 to 80 d), DMI for RSB compared with SBM was lower (P < .01; 7.8 vs 8.6 kg/d, SEM = .07) and ADG/DMI was similar (P > .10; 181 vs 172 g/kg, SEM = 1.8). Dry matter intake for SYN-implanted steers was higher (P < .05) than for steers not implanted (8.4 vs 8.0 kg/d), as was ADG/DMI (P < .01, 182 vs 171 g/kg). During this more rapid growth period, the supplement x implant interaction for ADG was significant (P < .05; 1.35, 1.36, 1.59, and 1.44 kg/d for Treatments 1, 2, 3, and 4, respectively, SEM = .04). There were no differences in digestibilities or N balance. The results suggest that there is no improvement in performance under feedlot conditions when RSB replaces SBM in the diet of beef cattle, and, in young cattle, RSB may reduce the response expected by an estrogenic growth promoter. (+info)
Serotonin stimulates mitogen-activated protein kinase activity through the formation of superoxide anion.
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Our previous studies have shown that, through an active transport process, serotonin (5-HT) rapidly elevates O(-)(2). formation, stimulates protein phosphorylation, and enhances proliferation of bovine pulmonary artery smooth muscle cells (SMCs). We presently show that 1 microM 5-HT also rapidly elevates phosphorylation and activation of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinase (ERK) 1 and ERK2 of SMCs, and the enhanced phosphorylation is blocked by the antioxidants Tiron, N-acetyl-L-cysteine (NAC), and Ginkgo biloba extract. Inhibition of MAP kinase with PD-98059 failed to block enhanced O(-)(2). formation by 5-HT. Chinese hamster lung fibroblasts (CCL-39 cells), which demonstrate both 5-HT transporter and receptor activity, showed a similar response to 5-HT (i.e., enhanced mitogenesis, O(-)(2). formation, and ERK1 and ERK2 phosphorylation and activation). Unlike SMCs, they also responded to 5-HT receptor agonists. We conclude that downstream signaling of MAP kinase is a generalized cellular response to 5-HT that occurs secondary to O(-)(2). formation and may be initiated by either the 5-HT transporter or receptor depending on the cell type. (+info)
The purpose of this study was to determine whether dexamethasone attenuates the acute increase in macromolecular efflux from the oral mucosa elicited by an aqueous extract of smokeless tobacco (STE) in vivo, and, if so, whether this response is specific. Using intravital microscopy, we found that 20-min suffusion of STE elicited significant, concentration-related leaky site formation and an increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass 70 kDa) from the in situ hamster cheek pouch (P < 0.05). This response was significantly attenuated by dexamethasone (10 mg/kg iv). Dexamethasone also attenuated the bradykinin-induced leaky site formation and the increase in clearance of FITC-dextran from the cheek pouch. However, it had no significant effects on adenosine-induced responses. Dexamethasone had no significant effects on baseline arteriolar diameter and on bradykinin-induced vasodilation in the cheek pouch. Collectively, these data indicate that dexamethasone attenuates, in a specific fashion, the acute increase in macromolecular efflux from the in situ oral mucosa evoked by short-term suffusion of STE. We suggest that corticosteroids mitigate acute oral mucosa inflammation elicited by smokeless tobacco. (+info)
Antitumor and antiviral activity of Colombian medicinal plant extracts.
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Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity) and antiherpetic activity. MTT (Tetrazolium blue) and Neutral Red colorimetric assays were used to evaluate the reduction of viability of cell cultures in presence and absence of the extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type 2 (HSV-2). The 50% cytotoxic concentration (CC50) and the 50% inhibitory concentration of the viral effect (EC50) for each extract were calculated by linear regression analysis. Extracts from Annona muricata, A. cherimolia and Rollinia membranacea, known for their cytotoxicity were used as positive controls. Likewise, acyclovir and heparin were used as positive controls of antiherpetic activity. Methanolic extract from Annona sp. on HEp-2 cells presented a CC50 value at 72 hr of 49.6x10(3)mg/ml. Neither of the other extracts examined showed a significant cytotoxicity. The aqueous extract from Beta vulgaris, the ethanol extract from Callisia grasilis and the methanol extract Annona sp. showed some antiherpetic activity with acceptable therapeutic indexes (the ratio of CC50 to EC50). These species are good candidates for further activity-monitored fractionation to identify active principles. (+info)
B-cell proliferation activity of pectic polysaccharide from a medicinal herb, the roots of Bupleurum falcatum L. and its structural requirement.
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Pectic polysaccharide fraction (BR-2) containing pharmacologically active pectic polysaccharide, bupleuran 2IIc, which was prepared from a medicinal herb, the roots of Bupleurum falcatum L., was administered orally to C3H/HeJ mice for 7 consecutive days. Proliferative responses of spleen cells were enhanced in the presence of the purified pectic polysaccharide, bupleuran 2IIc, but another B-cell mitogen, lipopolysaccharide (LPS) did not give a similar effect. In vitro studies using spleen cells showed that bupleuran 2IIc also stimulated lymphocytes, depleted of adherent cells or T cells. Bupleuran 2IIc treatment increased subpopulation of CD25+ and surface immunoglobulin M-positive (sIgM+) lymphocytes. Non-specific immunoglobulin secretion of spleen cells treated with bupleuran 2IIc was increased according to the culture time, and coexistence of interleukin-6 (IL-6) enhanced the secretion more than that of bupleuran 2IIc alone. These results suggest that bupleuran 2IIc proliferates B cells in the absence of macrophages, and the resulting activated B cells are then induced into antibody-forming cells in the presence of IL-6. Among the structural region of bupleuran 2IIc, ramified region (PG-1), which consists of rhamnogalacturonan core rich in neutral sugar chain, showed the potent mitogenic activity suggesting it to be an active site. Mitogenic activity of bupleuran 2IIc was reduced in the presence of antipolysaccharide antibody (antibupleuran 2IIc/PG-1-IgG), which recognizes the ramified region of bupleuran 2IIc as the antigenic epitope. Mitogenic activity of bupleuran 2IIc was also reduced by the addition of beta-d-GlcpA-(1-->6)-beta-d-Galp-(1-->6)-d-Galp or beta-d-GlcpA-(1-->6)-d-Galp, which are a part of the epitopes of antibupleuran 2IIc/PG-1-IgG. These results suggest that the epitopes in bupleuran 2IIc act as active sites of the polysaccharide during mitogenic activity. (+info)
Hyperforin, a major antidepressant constituent of St. John's Wort, inhibits serotonin uptake by elevating free intracellular Na+1.
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Extracts of Hypericum perforatum (St. John's Wort) are widely used for the treatment of depressive disorders and are unspecific inhibitors of the neuronal uptake of several neurotransmitters. Previous studies have shown that hyperforin represents the reuptake inhibiting constituent. To characterize the mechanism of serotonin reuptake inhibition, kinetic analyses in synaptosomes of mouse brain were performed. Michaelis-Menten kinetics revealed that hyperforin (2 microM) induces a decrease in V(max) by more than 50% while only slightly decreasing K(m), indicating mainly noncompetitive inhibition. By contrast, citalopram (1 nM) leads to an elevation of K(m) without changing V(max). Monensin, a Na(+)/H(+) exchanger, showed similar properties as hyperforin (decrease of V(max) without changing K(m)). Compared with classical antidepressants, such as selective serotonin reuptake inhibitors and tricyclic antidepressants, hyperforin is only a weak inhibitor of [(3)H]paroxetine binding relative to its effects on serotonin uptake. As monensin decreases serotonin uptake by increasing Na(+)/H(+) exchange, we compared the effects of hyperforin and monensin on the free intracellular sodium concentration ([Na(+)](i)) in platelets by measuring 1,3-benzenedicarboxylic acid, 4,4'-[1,4,10-trioxa-7, 13-diazacyclopentadecan-7,13-diylbis(5-methoxy-6, 2-benzofurandiyl)]bis-, tetraammonium salt (SBFI/AM) fluorescence. Both drugs elevated [Na(+)](i) over basal levels, with a maximal [Na(+)](i) of 69 +/- 16.1 mM (50 microM hyperforin) and 140 +/- 9.1 mM (10 microM monensin). Citalopram at concentrations relevant for [(3)H]serotonin uptake inhibition had no effect on [Na(+)](i). Although the mode of action of hyperforin seems to be associated with elevated [Na(+)](i) similar to those levels found with monensin, the molecular mechanism might be different, as even at high concentrations, hyperforin does not elevate free intracellular sodium concentration ([Na(+)](i)) up to the extracellular level, as monensin does. Hyperforin represents the first substance with a known preclinical antidepressant profile that inhibits serotonin uptake by elevating [Na(+)](i). (+info)
Stimulatory effects of silibinin and silicristin from the milk thistle Silybum marianum on kidney cells.
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The biochemical influence of flavonolignans from the milk thistle Silybum marianum has been tested on kidney cells of African green monkeys. Two nonmalignant cell lines were selected, with the focus of the work on the fibroblast-like Vero line. Proliferation rate, biosynthesis of protein and DNA, and the activity of the enzyme lactate dehydrogenase (as a measure of the cellular metabolic activity) were chosen as parameters for the effect of the flavonolignans. Silibinin and silicristin show remarkable stimulatory effects on these parameters, mainly in Vero cells; however, isosilibinin and silidianin proved to be inactive. In vitro experiments with kidney cells damaged by paracetamol, cisplatin, and vincristin demonstrated that administration of silibinin before or after the chemical-induced injury can lessen or avoid the nephrotoxic effects. The results warrant in vivo evaluations of the flavonolignan derivatives. (+info)