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1.
Eur Rev Med Pharmacol Sci ; 25(7): 3074-3082, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33877671

RESUMEN

OBJECTIVE: Fluxonorm® is a dietary supplement that includes water-soluble extracts of Solidago virga-aurea, Phyllantus niruri, Epilobium angustifolium, Peumus boldus and Ononis spinosa. The aim of the present study was to evaluate the tolerability and efficacy of Fluxonorm® in improving lower urinary tract symptoms in patients with benign prostatic hyperplasia (BPH) in combination with standard of care. PATIENTS AND METHODS: Lower urinary tract symptoms can be improved by a marked anti-inflammatory action on the lower urinary tract (irritative symptoms) and/or by an anti-proliferative action (obstructive symptoms) on the prostate. Thirty patients were enrolled to evaluate the effect of Fluxonorm® on improving lower urinary tract symptoms. All patients complained of lower urinary tract symptoms (LUTS), such as hesitancy, poor flow, intermittent flow, incomplete voiding (obstructive symptoms), as well as increased frequency, nocturia and urgency (storage symptoms). All patients were treated with one tablet of Fluxonorm® (1200 mg) daily for 30 days to corroborate the results of our observation in which the food supplement (800 µg/mL) was also studied on the human prostate cancer PC3 cell line (antiproliferative activity) and on prostaglandin (PG)E2 production (anti-inflammatory activity). In addition, the effect of this compound on cyclooxygenase-2 (COX-2) gene expression was investigated. Finally, a bioinformatic analysis was conducted with the aim of unravelling the mechanism of action underlying the observed bio-pharmacological effects. RESULTS: As hypothesized in our preclinical research, adding Fluxonorm® to the therapy of enrolled patients improved all studied clinical parameters, including maximum flow (Qmax), after one month of treatment. In the preclinical evaluation, this formulation reduced PC3 cell viability and PGE2 production. The effects were also paralleled by reduced COX-2 gene expression and Fluxonorm®'s partly related content of catechin. While docking studies pointed out to the putative inhibition of matrix metalloproteinse-2 by gallic acid, as a further mechanism underlying the observed anti-proliferative effects, in PC3 cells exposed to Fluxonorm®. CONCLUSIONS: Fluxonorm® improved the efficacy of standard therapy, in terms of antioxidant/anti-inflammatory effects, for the management of lower urinary tract symptoms (LUTS). This could be related, albeit partially, to the blunting effect of this compound on PGE2 production.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Síntomas del Sistema Urinario Inferior/tratamiento farmacológico , Extractos Vegetales/farmacología , Hiperplasia Prostática/tratamiento farmacológico , Sustancias Protectoras/farmacología , Antineoplásicos Fitogénicos/administración & dosificación , Proliferación Celular/efectos de los fármacos , Biología Computacional , Suplementos Dietéticos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Síntomas del Sistema Urinario Inferior/patología , Masculino , Células PC-3 , Extractos Vegetales/administración & dosificación , Hiperplasia Prostática/patología , Sustancias Protectoras/administración & dosificación , Células Tumorales Cultivadas
2.
J Biol Regul Homeost Agents ; 31(3): 531-541, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28889734

RESUMEN

Prostatitis is a common prostate disease that could be promoted by bacterial or non-bacterial infectious agents. In addition, inflammatory pathways involved in prostatitis have been increasingly studied, and herbal extracts endowed with anti-inflammatory effects are under investigation, individually or in combination, for their efficacy in alleviating the burden of inflammation, with possible improvements in symptoms. Serenoa repens (Serenoa), in combination with Crocus sativus (Crocus) and Pinus massoniana (Pinus), has previously shown to improve sexual function and limit urinary symptoms in patients suffering from concomitant erectile dysfunction and lower urinary tract symptoms. In this context, the aim of the present study is to evaluate the efficacy of Serenoa, Crocus and Pinus extracts, either alone or in combination, on immortalized prostate cells (PC3) and in an experimental model of bacterial prostatitis constituted by ex vivo prostate specimens challenged with lipopolysaccharide (LPS). We found that the tested extracts were able to reduce ROS production by PC3 cells and NFkB and PGE2 activity in prostate specimens challenged with LPS. In addition, the pharmacological association of the extracts displayed synergistic effects indicating a rational use of the mixture of the tested extracts as a novel anti-oxidant and anti-inflammatory formulation in bacterial prostatitis. Finally, we performed analytical and in vitro evaluation to better characterize the phytochemical profile and the mechanism of action of selected secondary metabolites.


Asunto(s)
Crocus/química , Lipopolisacáridos/toxicidad , Pinus/química , Extractos Vegetales/farmacología , Prostatitis , Serenoa/química , Animales , Línea Celular , Masculino , Extractos Vegetales/química , Próstata/metabolismo , Próstata/patología , Prostatitis/inducido químicamente , Prostatitis/tratamiento farmacológico , Prostatitis/metabolismo , Prostatitis/patología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo
3.
J Biol Regul Homeost Agents ; 30(3): 883-888, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27655516

RESUMEN

The 77 amino prepropeptide apelin has been isolated from bovine stomach tissue and several smaller fragments, including apelin-13, showed high affinity for the orphan APJ receptor. The distribution of apelinergic fibers and receptors in the hypothalamus may suggest a role of apelin-13 on energy balance regulation, albeit the studies reporting the acute effects of apelin on feeding control are inconsistent. Considering the possible involvement of apelinergic system on hypothalamic appetite controlling network, in the present study we evaluated in the rat the effects of intrahypothalamic apelin-13 injection on food intake and the involvement of orexigenic and anorexigenic hypothalamic peptides and neurotransmitters. Eighteen rats (6 for each group of treatment) were injected into the ARC with either vehicle or apelin-13 (1-2 µg/rat). Food intake and hypothalamic peptide and neurotransmitter levels were evaluated 2 and 24 h after injection. Compared to vehicle, apelin-13 administration increased food intake both 2 and 24 h following treatment. This effect could be related to inhibited cocaine- and amphetamine-regulated transcript (CART) gene expression and serotonin (5-hydroxytryptamine, 5-HT) synthesis and release, and increased orexin A gene expression in the hypothalamus.


Asunto(s)
Apetito/efectos de los fármacos , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Conducta Alimentaria/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/uso terapéutico , Animales , Apetito/fisiología , Núcleo Arqueado del Hipotálamo/fisiología , Estimulación Eléctrica , Conducta Alimentaria/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Hipotálamo/metabolismo , Hipotálamo/ultraestructura , Inyecciones , Péptidos y Proteínas de Señalización Intercelular/administración & dosificación , Masculino , Actividad Motora/efectos de los fármacos , Neuropéptidos/genética , Neuropéptidos/fisiología , Neurotransmisores/genética , Neurotransmisores/fisiología , Ratas , Ratas Sprague-Dawley , Serotonina/fisiología , Sinaptosomas/metabolismo
4.
J Biol Regul Homeost Agents ; 30(4): 985-996, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-28078844

RESUMEN

A pivotal role in osteoporosis development is played by radical oxygen species (ROS), the increased production of which is related to inhibited osteoblastic activity and bone formation. A new field of research could involve medicinal plants with antioxidant and protective effects in osteoporosis. Furthermore, considering the multifactorial metabolic aspects of osteoporosis, the pharmacological association of multiple medicinal plants could improve patient response. The aim of the present study is to evaluate in vitro and in vivo the protective effects of a natural formula containing lactoferrin 12%, Equisetum arvensis ES 54%, soy isoflavones 34% and vitamin D3 0.002%, in PBMC and C2C12 cells and in the bone matrix of young (3-month-old) and aged (12-month-old) female Sprague-Dawley rats, following chronic (21 days) administration. In this context, we assayed the activities of several inflammation and bone homeostasis mediators, such as IL-6, TNFα, PGE2, osteoprotegerin, RANK, RANKL and NFkB. In vitro studies showed that natural formula (5-1000µg/ml) was able to significantly inhibit ROS and PGE2 production. In the same concentration range, the natural formula inhibited both TNFα and IL-6 gene expression. In the in vivo studies, we administered to young and aged female rats the natural formula at 5mg/rat for 21 days, finding a significant reduction in inflammatory PGE2 and NFkB activity. Nevertheless, we observed a significant increase in osteoprotegerin/RANKL ratio only in aged rats, compared to the respective control group. In conclusion, our findings corroborate the rational use of natural formula in the prevention and management of osteoporotic disease.


Asunto(s)
Antioxidantes/farmacología , Conservadores de la Densidad Ósea/farmacología , Remodelación Ósea/efectos de los fármacos , Animales , Biomarcadores/análisis , Huesos/efectos de los fármacos , Colecalciferol/farmacología , Modelos Animales de Enfermedad , Equisetum , Femenino , Inflamación , Isoflavonas/farmacología , Lactoferrina/farmacología , Osteoporosis/complicaciones , Reacción en Cadena de la Polimerasa , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Glycine max
5.
J Biol Regul Homeost Agents ; 28(4): 775-82, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25620186

RESUMEN

Imoviral™ is a natural product formulation containing a mixture of uncaria, shiitake and ribes extracts. All ingredients are recognized as antioxidant, anti-inflammatory agent and immunomodulant. In order to evaluate the rational basis of extract mixture as immunomodulatory agent, we tested the effect of Imoviral™ formulation on macrophage response to lipopolysaccharide (LPS)-induced stress. The effect was evaluated as variation of reactive oxygen species (ROS) and prostaglandin E2 (PGE2) production and as cytokine gene expression. The extract did not affect cell viability up to 250 µg/ml. Treatment with extract (10-150 µg/ml) reduced ROS and PGE2 production as well as IL-8 and TNF-α gene expression. A pre-treatment with extract blunted LPS-induced production of ROS and PGE2, markers of oxidative and inflammatory stress, as well as the gene expression of all cytokines tested, indicators, in vitro, of immune response activation. In conclusion, we demonstrated that Imoviral™ formulation could be a useful tool to modulate the immune function, reducing the oxidative and inflammatory markers related to bacterial attack. Experimental data suggest that Imoviral™ extract mixture could also represent a preventive pharmacological strategy to enhance cell resistance to bacterial infections.


Asunto(s)
Uña de Gato , Citocinas/genética , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Ribes , Hongos Shiitake , beta-Glucanos/farmacología , Humanos , Macrófagos/inmunología , Macrófagos/metabolismo , Estrés Oxidativo , Células U937
6.
J Biol Regul Homeost Agents ; 26(2): 295-302, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22824756

RESUMEN

Visfatin, also known as pre-B cell colony enhancing factor (PBEF) or nicotinamide phosphoribosyltransferase (NAMPT), is a cytokine that is produced by adipose tissue, skeletal muscle, liver and immune cells. We studied the effects of visfatin/PBEF/NAMPT on feeding behavior, hypothalamic steady state concentrations of aminergic neurotransmitters and hypothalamic mRNA levels of anorexigenic peptides, such as cocaine- and amphetamine-regulated transcript (CART) peptide, corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), and orexigenic peptides, such as agouti-related peptide (AgRP) and neuropeptide Y (NPY). Forty-eight rats were injected in the arcuate nucleus (ARC) of the hypothalamus with either saline or visfatin/PBEF/NAMPT (3 microg). Food intake was recorded 1, 2 and 24 h following injection, and either dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytryptamine, 5-HT) or peptide gene expression were evaluated 2 and 24 h after visfatin/PBEF/NAMPT administration. Compared to vehicle, visfatin/PBEF/NAMPT significantly increased food intake, as evaluated 1, 2 and 24 h post-injection. Visfatin/PBEF/NAMPT treatment led to a significant decrease of DA steady state concentration, CART and CRH mRNA levels. Consequently, visfatin/PBEF/NAMPT could play an orexigenic role in the ARC, and the effect could be mediated by modulation of DA, CART and CRH activity in the hypothalamus.


Asunto(s)
Conducta Alimentaria/efectos de los fármacos , Hipotálamo/fisiología , Neurotransmisores/fisiología , Nicotinamida Fosforribosiltransferasa/farmacología , Proteína Relacionada con Agouti/fisiología , Animales , Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Núcleo Arqueado del Hipotálamo/fisiología , Hormona Liberadora de Corticotropina/fisiología , Dopamina/fisiología , Hipotálamo/efectos de los fármacos , Masculino , Proteínas del Tejido Nervioso/fisiología , Proopiomelanocortina/fisiología , Ratas , Ratas Wistar
7.
Minerva Med ; 103(1): 13-21, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22278065

RESUMEN

AIM: Aim of this study was to evaluate the effects of phytocomplexes of Uncaria, Shiitake and Ribes in terms of viability and inflammatory response on immune cell-derived cultures. METHODS: Standardized extracts of Uncaria, Shitake and Ribes and their commercial formulation were tested on cell lines PBMC, U937 and macrophage. The activity was evaluated in terms of cell viability (MTT test), variations of oxidative marker release (ROS and PGE2) and modulatory effects on immune response (gene expression of IL-6, IL-8 and TNFα, RT-PCR). RESULTS: Cell viability was not affected by extracts, except subtle variations observed only at higher doses (>250 µg/mL). The extract mixture was well tolerated, with no effects on cell viability up to doses of 500 µg/mL. Pre-treatment of macrophages with subtoxic doses of the extracts reduced the basal release of oxidative markers and enhanced the cell response to exogenous oxidant stimulation, as revealed by ROS and PGE2 release reduction. The same treatment on macrophage resulted in a selective modulation of the immune response, as shown by an increase of IL-6 mRNA and, partially, IL-8 mRNA, while a reduction was observed for TNFα mRNA. CONCLUSION: Data confirm that extracts and their formulations can act as regulator of the immune system with mechanisms involving the oxidative stress and the release of selected proinflammatory cytokines.


Asunto(s)
Citocinas/metabolismo , Sistema Inmunológico/efectos de los fármacos , Fitoterapia/métodos , Preparaciones de Plantas/farmacología , Ribes , Hongos Shiitake , Uncaria , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/inmunología , Citocinas/genética , Dinoprostona/metabolismo , Combinación de Medicamentos , Expresión Génica/efectos de los fármacos , Expresión Génica/inmunología , Humanos , Sistema Inmunológico/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Estrés Oxidativo/inmunología , Estrés Oxidativo/efectos de la radiación , Preparaciones de Plantas/química , Especies Reactivas de Oxígeno/metabolismo , Ribes/química , Hongos Shiitake/química , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Células U937/efectos de los fármacos , Células U937/inmunología , Uncaria/química
8.
Eur J Pharmacol ; 430(2-3): 269-72, 2001 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-11711041

RESUMEN

We have studied the effects of cocaine- and amphetamine-regulated transcript (CART) peptide-(55-102), leptin, orexin-A and orexin-B on basal and depolarization (K(+) 15 mM)-induced serotonin (5-hydroxytryptamine, 5-HT) release from rat hypothalamic neuronal endings (synaptosomes) in vitro. We have found that leptin and CART peptide-(55-102) have no effect on 5-HT release, while orexin-A and orexin-B inhibit depolarization-stimulated serotonin release. We can conclude that leptin and CART peptide-(55-102), which play a physiological role as feeding inhibitors, do not acutely affect 5-HT release from hypothalamic synaptosomes; on the other hand, feeding induced by orexin-A and orexin-B could be partially explained by decreased 5-HT release.


Asunto(s)
Hipotálamo/efectos de los fármacos , Péptidos y Proteínas de Señalización Intracelular , Proteínas/farmacología , Serotonina/metabolismo , Animales , Proteínas Portadoras/farmacología , Relación Dosis-Respuesta a Droga , Hipotálamo/metabolismo , Leptina/farmacología , Masculino , Proteínas del Tejido Nervioso/farmacología , Neuropéptidos/farmacología , Orexinas , Potasio/farmacología , Ratas , Ratas Wistar , Factores de Tiempo , Tritio
9.
Peptides ; 22(6): 975-8, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11390028

RESUMEN

We have studied the neuromodulatory effects of three synthetic peptides, structurally related to chromatin-derived acidic peptides (ACPs): ACP-1 (Asp-Asp-Ser-Asp-Glu-Glu-Asn), corresponding to the C-terminal fragment of the largest subunit of eukaryotic RNA polymerase II; a more lipophilic derivative, ACP-2 (Ala-Ile-Ser-Pro-Asp-Asp-Ser-Asp-Glu-Glu-Asn); and its phosphorylated form ACP-3 (Ala-Ile-Ser-Pro-Asp-Asp-Ser(P)-Asp-Glu-Glu-Asn). Rat hypothalamic synaptosomes, loaded with [(3)H]norepinephrine or [(3)H]dopamine, were perfused with the above peptides, both basally and during a depolarizing stimulus. We have found: ACP-1 inhibited both dopamine and norepinephrine release; ACP-2 inhibited dopamine release, without affecting norepinephrine release; ACP-3 was almost ineffective, except for a weak dopamine inhibiting effect only at a higher concentration.


Asunto(s)
Catecolaminas/biosíntesis , Cromatina/metabolismo , Hipotálamo/metabolismo , Péptidos/química , Péptidos/metabolismo , Animales , Dopamina/metabolismo , Relación Dosis-Respuesta a Droga , Masculino , Norepinefrina/antagonistas & inhibidores , Fosforilación , Ratas , Ratas Wistar , Sinaptosomas/metabolismo
10.
Eur J Pharmacol ; 409(2): 103-7, 2000 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-11104823

RESUMEN

Cocaine- and amphetamine-regulated transcript (CART) peptide-(55-102) and thyrotropin releasing hormone (TRH) play an anorectic role in the hypothalamus. Catecholamines are also involved in appetite control and we have previously found that leptin, an adipocyte-derived anorectic hormone, inhibits hypothalamic norepinephrine and dopamine release. We have studied the effect of CART peptide-(55-102) and TRH on basal and depolarization (K+ 15 mM)-induced norepinephrine and dopamine release from rat hypothalamic neuronal endings (synaptosomes) in vitro. We have found that basal catecholamine release was not modified; both CART peptide-(55-102) and TRH, the former with a higher sensitivity, dose-dependently inhibited depolarization-induced dopamine release, and did not affect the stimulated norepinephrine release. Considering the role played by dopamine in the central mechanisms of reward, these findings suggest that the inhibition of dopamine release could underlie the decreased appetitive behaviour induced by CART peptide-(55-102) and TRH.


Asunto(s)
Dopamina/metabolismo , Hipotálamo/efectos de los fármacos , Proteínas del Tejido Nervioso/farmacología , Sinaptosomas/efectos de los fármacos , Hormona Liberadora de Tirotropina/farmacología , Animales , Relación Dosis-Respuesta a Droga , Hipotálamo/metabolismo , Masculino , Norepinefrina/metabolismo , Ratas , Ratas Wistar , Sinaptosomas/metabolismo
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