Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 577
Filtrar
1.
PLoS Negl Trop Dis ; 13(11): e0007822, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31756189

RESUMO

BACKGROUND: Tungiasis is a neglected tropical skin disease caused by the female sand flea (Tunga penetrans), which burrows into the skin causing intense pain, itching and debilitation. People in endemic countries do not have access to an effective and safe home treatment. The aim of this study was to determine the efficacy of a traditionally used and readily available mixture of neem and coconut oil for treatment of tungiasis in coastal Kenya. METHODOLOGY: Ninety-six children aged 6-14 years with at least one embedded viable flea were randomized to be treated with either a mixture of 20% neem (Azadirachta indica) seed oil in coconut oil (NC), or with a 0.05% potassium permanganate (KMnO4) foot bath. Up to two viable fleas were selected for each participant and monitored for 6 days after first treatment using a digital microscope for signs of viability and abnormal development. Acute pathology was assessed on all areas of the feet using a previously established score. Children reported pain levels and itching on a visual scale. RESULTS: The NC was not more effective in killing embedded sand fleas within 7 days than the current standard with KMnO4, killing on average 40% of the embedded sand fleas six days after the initial treatment. However, the NC was superior with respect to the secondary outcomes of abnormal development and reduced pathology. There was a higher odds that fleas rapidly aged in response to NC compared to KMnO4 (OR 3.4, 95% CI: 1.22-9.49, p = 0.019). NC also reduced acute pathology (p<0.005), and there was a higher odds of children being pain free (OR 3.5, p = 0.001) when treated with NC. CONCLUSIONS: Whilst NC did not kill more fleas than KMnO4 within 7 days, secondary outcomes were better and suggest that a higher impact might have been observed at a longer observation period. Further trials are warranted to assess optimal mixtures and dosages. TRIAL REGISTRATION: The study was approved by the Kenya Medical Research Institute (KEMRI) Scientific and Ethical Review Unit (SERU), Nairobi (Non-SSC Protocol No. 514, 1st April 2016) and approved by and registered with the Pharmacy and Poisons Board's Expert Committee on Clinical Trials PPB/ECCT/16/05/03/2016(94), the authority mandated, by Cap 244 Laws of Kenya, to regulate clinical trials in the country. The trial was also registered with the Pan African Clinical Trial Registry (PACTR201901905832601).


Assuntos
Óleo de Coco/administração & dosagem , Glicerídeos/administração & dosagem , Inseticidas/administração & dosagem , Terpenos/administração & dosagem , Tungíase/tratamento farmacológico , Administração Tópica , Adolescente , Animais , Criança , Pé/parasitologia , Pé/patologia , Humanos , Quênia , Permanganato de Potássio/administração & dosagem , Resultado do Tratamento , Tunga/efeitos dos fármacos , Tungíase/parasitologia , Tungíase/patologia
2.
J Anim Sci ; 97(11): 4557-4566, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31504564

RESUMO

The present study was conducted to evaluate the effects of dietary garcinol supplementation during late gestation (from the 90th day of pregnancy; day 90) and lactation on the acid-base balance of the umbilical cord blood and performance of sows and piglets. Sixty sows (Duroc × Yorkshire × Landrace; second- or third-parity; n = 20) were randomly divided into 3 gestation (day 90 of pregnancy) or lactation treatments, control diet (CON; basal diet), basal diet with 200 mg garcinol, and basal diet with 600 mg garcinol per kg of feed. The body weight (BW); backfat thickness and litter size of the sows; and birth weight, weaning weight, and mortality of piglets were recorded. Sows' blood and piglets' umbilical cord blood were collected for the measurements of hematological parameters and antioxidative and immune indexes, and acid-base balance parameters, respectively. The colostrum and milk and fecal samples of the sows were also collected for analysis of milk composition and apparent total tract nutrient digestibility. Garcinol had no effect on the BW and backfat thickness of the sows but significantly increased the birth weight and weaning weight of piglets (P < 0.05) and decreased the mortality (P < 0.05). Moreover, the white blood cell counts and neutrophil count, mean cell hemoglobin, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activity in the plasma of the sows were increased more significantly (P < 0.05) in the garcinol groups than that in the CON group, whereas the malondialdehyde (MDA) content was decreased (P < 0.05). The garcinol treatment significantly increased the pH, HCO3- and base excess values (P < 0.05), whereas it decreased the pCO2 and lactate content (P < 0.05) in the umbilical blood. Dry matter (DM), ash, and ether extract in the colostrum were similar between groups (P > 0.05), whereas the garcinol significantly increased the crude protein (CP) in the milk. In addition, the content of immunoglobulin A (IgA) and immunoglobulin G (IgG) in the plasma of piglets and in colostrum and milk of sows were increased more significantly (P < 0.05) in the garcinol groups than that in the CON group. The apparent total tract nutrient digestibility was similar between treatments. Collectively, this study indicates that sows fed with garcinol in late gestation and lactation showed improved maternal health and antioxidative status, milk protein content, acid-base balance in the umbilical cord blood, and growth performance in piglets, showing promise in natural plant extract nutrition for sows.


Assuntos
Suplementos Nutricionais/análise , Leite/química , Suínos/fisiologia , Terpenos/administração & dosagem , Equilíbrio Ácido-Base/efeitos dos fármacos , Ração Animal/análise , Animais , Colostro/química , Dieta/veterinária , Feminino , Sangue Fetal/efeitos dos fármacos , Imunoglobulina A/sangue , Lactação/efeitos dos fármacos , Tamanho da Ninhada de Vivíparos/efeitos dos fármacos , Paridade , Gravidez , Distribuição Aleatória , Suínos/sangue , Suínos/imunologia , Desmame
3.
PLoS One ; 14(9): e0217190, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31498792

RESUMO

Neuropsychiatric systemic lupus erythematosus (NPSLE) is associated with learning and memory deficit. Murine model of lupus induced by pristane in BALB/c mice is an experimental model that resembles some clinical and immunological SLE pathogenesis. Nevertheless, there is no experimental evidence that relates this model to cognitive dysfunction associated with NR2A/2B relative expression. To evaluate cognitive impairment related to memory deficits in a murine model of lupus induced by pristane in BALB/c mice related to mRNA relative expression levels of NR2A/2B hippocampal subunits in short and long-term memory task at 7 and 12 weeks after LPS exposition in a behavioral test with the use of Barnes maze. A total of 54 female BALB/c mice 8-12 weeks old were included into 3 groups: 7 and 12 weeks using pristane alone (0.5 mL of pristane) by a single intraperitoneal (i.p.) injection. A control group (single i.p. injection of 0.5 mL NaCl 0.9%) and pristane plus LPS exposure using single i.p. pristane injection and LPS of E. coli O55:B5, in a dose of 3mg/kg diluted in NaCl 0.9% 16 weeks post-pristane administration. To determine cognitive dysfunction, mice were tested in a Barnes maze. Serum anti-Sm antibodies and relative expression of hippocampal NR2A/2B subunits (GAPDH as housekeeping gene) with SYBR green quantitative reverse transcription polymerase chain reaction and 2-ΔΔCT method were determined in the groups. Downregulation of hippocampal NR2A subunit was more evident than NR2B in pristane and pristane+LPS at 7 and 12 weeks of treatment and it is related to learning and memory disturbance assayed by Barnes maze. This is the first report using the murine model of lupus induced by pristane that analyzes the NMDA subunit receptors, finding a downregulation of NR2A subunit related to learning and memory disturbance being more evident when they were exposed to LPS.


Assuntos
Disfunção Cognitiva/genética , Hipocampo/metabolismo , Lúpus Eritematoso Sistêmico/genética , Transtornos da Memória/genética , Receptores de N-Metil-D-Aspartato/genética , Animais , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Expressão Gênica , Hipocampo/efeitos dos fármacos , Lipopolissacarídeos/administração & dosagem , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/fisiopatologia , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Memória de Longo Prazo/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Receptores de N-Metil-D-Aspartato/metabolismo , Terpenos/administração & dosagem
4.
Nanomedicine (Lond) ; 14(15): 2045-2065, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31368402

RESUMO

Aim: Garcinol (GAR)-loaded cationic nanoliposomes were developed to achieve potential antitumor efficacy on B16F10 melanoma cells in vitro and in vivo. Materials & methods: Two different phospholipids namely, distearoyl phosphatidylcholine (DSPC) and dipalmitoyl phosphatidylcholine (DPPC) were used in formulation to elucidate the difference in cellular uptake, cytotoxicity, in vivo tumor uptake (by scintigraphic imaging after technetium-99m radiolabeling) and therapeutic efficacy. Results: Different in vitro protocols, for example, MTT assay, apoptosis study, gene expression analysis, chromatin condensation and cytoskeleton breakdown analysis in B16F10 cell lines as well as scintigraphic analysis and tumor inhibition studies (B16F10 tumor xenograft model) revealed superiority of GAR-DPPC than GAR-DSPC and free GAR in melanoma prevention. Conclusion: Cationic nanoliposomal formulations could be a future medication for skin cancer treatment.


Assuntos
Antineoplásicos/administração & dosagem , Melanoma Experimental/tratamento farmacológico , Terpenos/administração & dosagem , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Cátions/química , Linhagem Celular Tumoral , Lipossomos/química , Masculino , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nanocápsulas/química , Terpenos/farmacocinética , Terpenos/uso terapêutico
5.
Biomolecules ; 9(4)2019 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-30959802

RESUMO

Essential oils are natural products with a complex composition. Terpenes are the most common class of chemical compounds present in essential oils. Terpenes and the essential oils containing them are widely used and investigated by their pharmacological properties and permeation-enhancing ability. However, many terpenes and essential oils are sensitive to environmental conditions, undergoing volatilization and chemical degradation. In order to overcome the chemical instability of some isolated terpenes and essential oils, the encapsulation of these compounds in nanostructured systems (polymeric, lipidic, or molecular complexes) has been employed. In addition, nanoencapsulation can be of interest for pharmaceutical applications due to its capacity to improve the bioavailability and allow the controlled release of drugs. Topical drug administration is a convenient and non-invasive administration route for both local and systemic drug delivery. The present review focuses on describing the current status of research concerning nanostructured delivery systems containing isolated terpenes and/or essential oils designed for topical administration and on discussing the use of terpenes and essential oils either for their biological activities or as permeation enhancers in pharmaceutic formulations.


Assuntos
Desenho de Fármacos , Nanoestruturas/química , Óleos Voláteis/administração & dosagem , Terpenos/administração & dosagem , Administração Tópica , Animais , Sistemas de Liberação de Medicamentos , Humanos , Nanotecnologia , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Terpenos/química , Terpenos/isolamento & purificação
6.
J Immunol Res ; 2019: 2641098, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30937315

RESUMO

The inflammatory and autoimmune events preceding clinical symptoms in rheumatoid arthritis (RA) and other autoimmune diseases are difficult to study in human patients. Therefore, animal models that share immunologic and clinical features with human RA, such as pristane-induced arthritis (PIA), are valuable tools for assessing the primordial events related to arthritis susceptibility. PIA-resistant HIII and susceptible LIII mice were injected i.p. with pristane, and peritoneal lavage fluid was harvested in the early (7 days) and late (35 days) preclinical phases of PIA. Chemokine and cytokine levels were measured in lavage supernatant with ELISA, peritoneal inflammatory leukocytes were immunophenotyped by flow cytometry, and gene expression was determined by qRT-PCR. Leukocyte recruitment was quantitatively and qualitatively divergent in the peritoneum of HIII and LIII mice, with an early increase of CC chemokines (CCL2/CCL3/CCL5/CCL12/CCL22) in the susceptible LIII strain. Also, cytokines such as IL-12p40, IL-23, and IL-18 were elevated in LIII mice while IL-6 was increased in HIII animals. The results show that an early peritoneal CC chemokine response is an important feature of arthritis susceptibility and defines potential biomarkers in this model.


Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Quimiocinas CC/imunologia , Inflamação , Peritônio/imunologia , Animais , Artrite Experimental/induzido quimicamente , Biomarcadores , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Interleucina-6/imunologia , Masculino , Camundongos , Fenótipo , Terpenos/administração & dosagem
7.
Drug Deliv ; 26(1): 107-119, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30744434

RESUMO

The present study aimed to evaluate the penetration activity of O-acylterpineol derivatives both in vitro and in vivo, and to investigate the enhancing mechanism of O-acylterpineol derivatives which were synthesized by α-terpineol and fatty acid. The promoting activities on the isosorbide dinitrate patch were tested across full thickness rabbit skin both in vitro and in vivo. In order to elucidate the permeation mechanism, attenuated total reflection Fourier transform infrared spectroscopy, molecular modeling, and confocal laser scanning microscopy were introduced to investigate the regulation of enhancers in the skin permeability and biophysical properties. With in vitro cytotoxicity test and in vivo erythema model, the skin irritation of enhancers was also evaluated. Permeation studies showed 2-(4-methylcyclohex-3-en-l-yl) propan-2-yl tetradecanoate produced the obvious enhancement activity for ISDN both in vitro and in vivo from patches. These results were supported by ATR-FTIR, molecular modeling, and CLSM studies which revealed that O-acylterpineol could decrease the order of the alkyl chains in the skin lipids. Additionally, it was found that TER-C14 produced a relatively low skin irritation, compared with the TER which was assumed to be a safe compound. The present research suggested that some newly designed acylterpineol derivatives are shown to be suitable permeation enhancers for transdermal drug delivery, and the chain length of C14 seem to be safe and more favorable for the penetration of ISDN from DIA patches.


Assuntos
Dinitrato de Isossorbida/análogos & derivados , Modelos Moleculares , Absorção Cutânea/fisiologia , Terpenos/metabolismo , Animais , Células Cultivadas , Sinergismo Farmacológico , Humanos , Dinitrato de Isossorbida/administração & dosagem , Dinitrato de Isossorbida/química , Dinitrato de Isossorbida/metabolismo , Masculino , Microscopia Confocal/métodos , Técnicas de Cultura de Órgãos , Permeabilidade/efeitos dos fármacos , Coelhos , Absorção Cutânea/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Terpenos/administração & dosagem , Terpenos/química
8.
J Dairy Sci ; 102(3): 2011-2016, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30639018

RESUMO

Myrrh is an essential oil and natural flavoring approved by the US Food and Drug Administration, and it has antibacterial and antifungal activity against pathogens. Our objective was to determine the effect of an aqueous myrrh suspension on Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus counts in peptone solution and yogurt, as well as pH and titratable acidity of yogurt during 5 wk of storage at 1 to 4°C. The myrrh suspension (10% wt/vol) was prepared and incorporated into a pure culture dilution in peptone and into yogurt mix at a 1% (vol/vol) level. A control with no myrrh was also prepared, and 3 replications were conducted. Streptococcus thermophilus were enumerated using Streptococcus thermophilus agar with aerobic incubation at 37°C for 24 h, and Lactobacillus delbrueckii ssp. bulgaricus were enumerated using de Man, Rogosa, and Sharpe agar adjusted to pH 5.2, with anaerobic incubation at 43°C for 72 h. During the 8-h period after inoculation, S. thermophilus and L. delbrueckii ssp. bulgaricus counts in peptone solution at 37°C and 43°C, respectively, were not significantly different in the presence or absence of the aqueous myrrh suspension. Counts of S. thermophilus in yogurt containing myrrh (mean ± SD; 4.96 ± 0.58 log cfu/mL) were not significantly different from those in the control yogurt (4.87 ± 0.39 log cfu/mL). The log counts for L. delbrueckii ssp. bulgaricus in yogurt containing myrrh (5.04 ± 1.44 log cfu/mL) and those of the control (5.52 ± 1.81 log cfu/mL) did not differ, and the counts remained within 1 log of each other throughout 5 wk of storage. The pH of the yogurts containing the aqueous myrrh suspension was not significantly different from that of the control yogurts, and their pH values were within 0.1 pH unit of each other in any given week. Titratable acidity values remained steady around 1.1 to 1.2% lactic acid for both yogurt types throughout the storage period, with no significant differences between them. Yogurt culture bacteria can survive in the presence of a myrrh suspension in yogurt with no significant change in pH or titratable acidity. Therefore, it may be beneficial to add an aqueous myrrh suspension to yogurt.


Assuntos
Lactobacillus delbrueckii/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Streptococcus thermophilus/efeitos dos fármacos , Terpenos/farmacologia , Iogurte/microbiologia , Contagem de Colônia Microbiana , Fermentação , Lactobacillus delbrueckii/fisiologia , Substâncias Protetoras/administração & dosagem , Streptococcus thermophilus/fisiologia , Suspensões , Terpenos/administração & dosagem , Iogurte/análise
9.
Minerva Ginecol ; 71(3): 191-195, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30696240

RESUMO

BACKGROUND: Dysmenorrhea and chronic pelvic pain occur in a significantly higher percentage in women with endometriosis; this benign condition has an incidence ranging from 5% to 10% in the general population, while 35% to 50% of infertile women are affected. Treatment of the symptoms demands integrated approaches with the use of anti-inflammatory substances or drugs and lifestyle changes, including attention to diet. The use of traditional anti-inflammatory drugs over the long term is not very successful because of the fear of side effects so they are almost always used with a short-term formula of 7-10 days when the woman's general condition becomes difficult to bear. In recent years, particular attention has been paid to natural substances with recognized anti-inflammatory activities that, associated with one another, are able to synergize individual actions. A nutraceutical containing substances capable of fighting chronic pelvic pain has recently been put on the market. The possible action mechanism derives from a synergy of action between alpha-lipoic acid, palmitoiletanolamide (PEA) and myrrh (Pelvinox, Laborest Italia srl, Nerviano, Milan, Italy), whose action is so effective that it is able to replace the use of anti-inflammatory drugs. The aim of the study was to evaluate the effect of these active ingredients in women with endometriosis and chronic pelvic pain. METHODS: This multicenter study saw the recruitment of 60 women (divided between the three centers participating in the study, Siena, Bologna and Udine) aged between 20 and 39 suffering from endometriosis (ovarian) and chronic pelvic pain. All the women took one nutraceutical (Pelvinox) at a dose of two tablets per day for 6 months. RESULTS: The results showed a significant reduction in pain symptoms as regards dyspareunia, dysmenorrhea and chronic pelvic pain, while there was no change in the mean diameter of the endometriosis cysts. CONCLUSIONS: In light of the above, it is believed that substances such as alpha-lipoic acid, PEA and myrrh may play a very important role in this type of patient in the treatment of individual symptoms.


Assuntos
Dor Crônica/terapia , Suplementos Nutricionais , Endometriose/terapia , Doenças Ovarianas/terapia , Dor Pélvica/terapia , Adulto , Analgésicos/administração & dosagem , Dor Crônica/etiologia , Endometriose/complicações , Etanolaminas/administração & dosagem , Feminino , Humanos , Doenças Ovarianas/complicações , Ácidos Palmíticos/administração & dosagem , Dor Pélvica/etiologia , Terpenos/administração & dosagem , Ácido Tióctico/administração & dosagem , Adulto Jovem
10.
J Pharm Pharmacol ; 71(1): 129-138, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29411879

RESUMO

OBJECTIVE: The aim of this study was to review herb-drug interaction studies with St John's wort (Hypericum perforatum L.) with a focus on the hyperforin content of the extracts used in these studies. METHODS: PUBMED was systematically searched to identify studies describing pharmacokinetic interactions involving St John's wort. Data on study design and the St John's wort extract or product were gathered to extract hyperforin content and daily dose used in interaction studies. KEY FINDINGS: This analysis demonstrates that significant herb-drug interactions (resulting in a substantial change in systemic exposure) with St John's wort products were associated with hyperforin daily dosage. Products that had a daily dose of <1 mg hyperforin were less likely to be associated with major interaction for drugs that were CYP3A4 or p-glycoprotein substrates. Although a risk of interactions cannot be excluded even for low-dose hyperforin St. John's wort extracts, the use of products that result in a dose of not more than 1 mg hyperforin per day is recommended to minimise the risk of interactions. CONCLUSIONS: This review highlights that the significance of herb-drug interactions with St John's wort is influenced by the nature of the herbal medicines product, particularly the hyperforin content.


Assuntos
Interações Ervas-Drogas , Hypericum/química , Floroglucinol/análogos & derivados , Terpenos/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Humanos , Farmacocinética , Floroglucinol/administração & dosagem , Floroglucinol/efeitos adversos , Floroglucinol/isolamento & purificação , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Terpenos/efeitos adversos , Terpenos/isolamento & purificação
11.
J Pharm Pharmacol ; 71(1): 93-103, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28990659

RESUMO

OBJECTIVES: St John's wort extract (SJW) and its component hyperforin (HPF) were shown to potently inhibit cytokine-induced STAT-1 and NF-κB activation in pancreatic ß cells and protect them against injury. This study aimed at exploring the time course of STAT-1 inhibition afforded by these natural compounds in the ß-cell line INS-1E. METHODS: INS-1E cells were pre-incubated with SJW extract (2-5 µg/ml) or HPF (0.5-2 µm) and then exposed to a cytokine mixture. In some experiments, these compounds were added after or removed before cytokine exposure. STAT-1 activation was assessed by electrophoretic mobility shift assay, apoptosis by caspase-3 activity assay, mRNA gene expression by RT-qPCR. KEY FINDINGS: Pre-incubation with SJW/HPF for 1-2 h exerted a remarkable STAT-1 downregulation, which was maintained upon removal of the compounds before early or delayed cytokine addition. When the protective compounds were added after cell exposure to cytokines, between 15 and 90 min, STAT-1 inhibition also occurred at a progressively decreasing extent. Upon 24-h incubation, SJW and HPF counteracted cytokine-induced ß-cell dysfunction, apoptosis and target gene expression. CONCLUSIONS: SJW and HPF confer to ß cells a state of 'cytokine resistance', which can be elicited both before and after cytokine exposure and safeguards these cells from deleterious cytokine effects.


Assuntos
Hypericum/química , Células Secretoras de Insulina/efeitos dos fármacos , Floroglucinol/análogos & derivados , Extratos Vegetais/farmacologia , Terpenos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Ensaio de Desvio de Mobilidade Eletroforética , Regulação da Expressão Gênica/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Floroglucinol/administração & dosagem , Floroglucinol/isolamento & purificação , Floroglucinol/farmacologia , Extratos Vegetais/administração & dosagem , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT1/antagonistas & inibidores , Fator de Transcrição STAT1/metabolismo , Terpenos/administração & dosagem , Terpenos/isolamento & purificação , Fatores de Tempo
12.
Microb Pathog ; 127: 220-224, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30529428

RESUMO

The aim of this study was to evaluate the resistance of Rhamdia quelen (silver catfish) to Aeromonas hydrophila infection after treatment with pure and nanoencapsulated forms either terpinen-4-ol, thymol, or carvacrol and the effects of these treatments on fish metabolic responses. After A. hydrophila inoculation, fish were treated with 30 min daily baths for 6 consecutive days with terpinen-4-ol, thymol, or carvacrol in their pure or nanoencapsulated forms at concentrations of 5, 10, 15 or 25 mg L-1. A positive control group, negative control group and saline group were also included. Survival was evaluated at the end of treatment for six consecutive days. Muscle and liver were collected to determine glucose and lactate levels. The fish treated with the nanoencapsulated form of the compounds had a high survival rate, similar to saline group and negative control groups. The carvacrol, thymol and terpinen-4-ol nanoencapsulated forms improved survival of silver catfish infected with A. hydrophila. Muscle and liver glucose and lactate levels are not indicated as biomarkers because they did not present any correlation between the metabolic state of the fish and the bacterial infection.


Assuntos
Aeromonas hydrophila/crescimento & desenvolvimento , Anti-Infecciosos/administração & dosagem , Doenças dos Peixes/tratamento farmacológico , Glucose/análise , Infecções por Bactérias Gram-Negativas/veterinária , Ácido Láctico/análise , Animais , Peixes-Gato , Cimenos , Doenças dos Peixes/microbiologia , Doenças dos Peixes/patologia , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/patologia , Fígado/patologia , Monoterpenos/administração & dosagem , Músculos/patologia , Análise de Sobrevida , Terpenos/administração & dosagem , Timol/administração & dosagem , Resultado do Tratamento
13.
Microb Pathog ; 128: 7-12, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30550845

RESUMO

Geraniol (GOH), a natural component of plant essential oils, exhibits potent antioxidant and anti-inflammatory properties. The aim of this study was to assess the protective effects and mechanisms of GOH on lipopolysaccharide (LPS)/d-galactosamine (D-GalN)-induced fulminant hepatic failure (FHF). Mice were treated with GOH (12.5, 25, and 50 µg/kg) 1 h before challenging LPS (60 mg/kg) and D-GalN (800 mg/kg). 8 h later LPS/D-GlaN treatment, mice were sacrificed and the serum and the liver tissues were collected for testing. The liver pathological changes were assessed by H & E staining. MPO activity, MDA level in liver tissues, and AST, ALT levels in serum were detected by specific detection kits. The levels of TNF-α and IL-1ß were detected by ELISA. The expression of NF-κB and PPARγ were detected by western blot analysis and qRT-PCR. The results showed that GOH had a protective effect on LPS/D-GalN-induced FHF, as evidence by the attenuation of liver pathological injury, MPO activity, MDA level, and serum AST and ALT levels. GOH reduced liver TNF-α and IL-1ß levels through inhibiting NF-κB signaling pathway activation. Furthermore, GOH increased PPARγ expression in FHF induced by LPS/D-GalN. In conclusion, the present study proved that GOH protects against LPS/D-GalN-induced FHF through inhibiting inflammatory response and increasing PPARγ expression.


Assuntos
Galactosamina/efeitos adversos , Lipopolissacarídeos/efeitos adversos , Falência Hepática Aguda/tratamento farmacológico , PPAR gama/metabolismo , Substâncias Protetoras/farmacologia , Terpenos/farmacologia , Monoterpenos Acíclicos , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Fígado/química , Fígado/lesões , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Óleos Voláteis/farmacologia , Óleos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Terpenos/administração & dosagem , Fator de Necrose Tumoral alfa/metabolismo
14.
BMC Complement Altern Med ; 18(1): 338, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30567535

RESUMO

BACKGROUND: (Trans)-3,7-Dimethyl-2,6-octadien-1-ol, commonly called geraniol (Ge-OH), is an acyclic monoterpene alcohol with well-known anti-inflammatory and antimicrobial properties. Ge-OH is a non-toxic compound classified as Generally Recognized As Safe (GRAS) by the US Food and Drug Administration and the European Food Security Agency. METHODS: Ge-OH was orally administered at a maximum daily dose of 8 mg kg(- 1) body weight for four weeks in a delayed release formulation capable of reaching the colon. Fecal microbiota and blood cytokines were analyzed before and after Ge-OH treatment, as well as IBS symptomatology by using Visual Analogue Scale (VAS-IBS). RESULTS: The results show that orally administered Ge-OH is a powerful modulator of the intestinal microbial ecosystem, capable of leading to increased relative abundances of Collinsella and especially Faecalibacterium, a well-known health-promoting butyrate producer consistently found to be decreased in IBS patients. Moreover, Ge-OH strongly improved the clinical symptoms of colitis by significantly reducing the score recorded by the VAS-IBS questionnaire. Clinical improvement was associated with a significant reduction in the circulating MIP-1ß, a chemokine found to be increased in several IBS patients. CONCLUSION: Ge-OH could be a powerful component for food supplement targeted to the treatment of IBS patients. TRIAL REGISTRATION: ISRCTN47041881 , retrospectively registered on 19th July 2018.


Assuntos
Disbiose/tratamento farmacológico , Síndrome do Intestino Irritável/tratamento farmacológico , Terpenos/administração & dosagem , Monoterpenos Acíclicos , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Suplementos Nutricionais/análise , Disbiose/microbiologia , Feminino , Microbioma Gastrointestinal , Humanos , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Síndrome do Intestino Irritável/microbiologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Adulto Jovem
15.
Int J Pharm ; 553(1-2): 428-440, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30385373

RESUMO

Essential oils containing monoterpenes are widely used in pharmaceuticals and cosmetic products on account of their wide range of bioactive properties (including anti-cancer activity). Two monoterpenes (citral and geraniol) were firstly tested for their anti-inflammatory activity in a RAW 264.7 cell line, demonstrating citral to have enhanced capacity to inhibit NO production (ca. 84% for citral and 52% for geraniol at the lowest tested concentration of 5 µg/ml). As citral showed higher NO inhibitory activity than geraniol, to measure the level of cytotoxicity of citral, AlamarBlue reduction assay was run in two cell models (non-tumoral HaCaT and tumoral A431). Citral exhibited a strong cytotoxic effect in both cell lines, i.e. cell viability lower that 10% after 24 h exposure at 100 µg/ml of monoterpene. An optimized solid lipid nanoparticles (SLNs) formulation for citral was further developed by design of experiments (22 factorial design), followed by accelerated stability testing (LUMiSizer®). An optimal SLN composed of 1 wt% of citral, 4 wt% of lipid and 2.5 wt% surfactant were successfully produced by hot high pressure homogenization (hot HPH) showing a mean particle size (Z-Ave) of 97.7 nm and polydispersity index of 0.249. The produced formulations were analyzed in a high-end dispersion analyzer LUMiSizer® to characterize any demixing phenomena, demonstrating to be long-term stable at room temperature (25 °C), exhibiting very low instability indices (0.032 after production and 0.042 after one month of storage).


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Monoterpenos/farmacologia , Nanopartículas , Monoterpenos Acíclicos , Animais , Anti-Inflamatórios/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Humanos , Lipídeos/química , Camundongos , Monoterpenos/administração & dosagem , Óxido Nítrico/metabolismo , Óleos Voláteis/administração & dosagem , Óleos Voláteis/farmacologia , Tamanho da Partícula , Células RAW 264.7 , Tensoativos/química , Terpenos/administração & dosagem , Terpenos/farmacologia
16.
Minerva Med ; 109(5): 358-362, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30338679

RESUMO

BACKGROUND: Painful distal symmetric polyneuropathy (pDSPN) is one of the most common and invalidating complications of diabetes mellitus, both of type 1 and type 2. Mechanisms responsible for the occurrence of the pDSPN are multifactorial and involve metabolic pathways regulating inflammation, microvessel circulation, axonal degeneration and so on. Several therapeutic approaches have been proposed to treat pain and each of them showed positive effects associated to drug-related side effects. METHODS: Twenty-five consecutive patients with diagnosis of diabetes mellitus and pDSPN and tried to manage pain with a dietary supplement composed of a mixture of natural extracts (ß-caryophyllene, myrrh, carnosic acid) and PEA. This is a nutraceutical with potential multiple effects on metabolic, pain and vascular compartments, a profile considered useful in pDSPN. Patients were enrolled and polyneuropathy evaluated by means of nerve conduction study. Pain was assessed using VAS score scale and MNSI. Each patient was evaluated at T0 (time of enrollment) and at T1 (after 16 weeks of treatment). RESULTS: Supplement administration was well tolerated and induced unexpectedly significant amelioration of polyneuropathy with increase amplitude and reduction of pain. No side effects were reported. CONCLUSIONS: This fixed combination could well be considered as a potential nutraceutical option to manage pDSPN in diabetic patients.


Assuntos
Neuropatias Diabéticas/dietoterapia , Suplementos Nutricionais , Abietanos/administração & dosagem , Abietanos/uso terapêutico , Adulto , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/fisiopatologia , Etanolaminas/administração & dosagem , Etanolaminas/uso terapêutico , Feminino , Humanos , Masculino , Medição da Dor , Ácidos Palmíticos/administração & dosagem , Ácidos Palmíticos/uso terapêutico , Sesquiterpenos Policíclicos , Sesquiterpenos/administração & dosagem , Sesquiterpenos/uso terapêutico , Índice de Gravidade de Doença , Nervo Sural/fisiopatologia , Terpenos/administração & dosagem , Terpenos/uso terapêutico , Resultado do Tratamento , Adulto Jovem
17.
J Pharm Pharmacol ; 70(12): 1688-1699, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30277563

RESUMO

OBJECTIVES: The human skin microbiota is mainly composed of bacteria belonging to the genera Staphylococcus, Cutibacterium, Micrococcus and Corynebacterium, but on the skin of the face and back, ca. 50% of the total microbiota is represented by the bacterium Cutibacterium acnes. The aim of this research was to evaluate the impact of C. martini EO and its major compound, geraniol, on C. acnes. METHODS: The minimum inhibitory concentration against C. acnes strains, phenotypic changes and responses of the proteome was determined. In addition, was assessed the effect of compounds in RNA-binding assay, on C. acnes-exposed keratinocytes and on the C. acnes type distribution on shoulder skin. KEY FINDINGS: The range of the MIC was 0.7 to 1.6 mg/ml for the three main C. acnes types. There were no cytotoxic effects of compounds in the absence or presence of C. acnes; after 7 days of exposure to C. martini EO, we could not detect a major shift of the C. acnes types on shoulder skin that was found to be dominated by C. acnes strains of types II and IA2. CONCLUSIONS: Our work gives novel insight into the skin microbiota-interacting properties of C. martini EO.


Assuntos
Cymbopogon , Queratinócitos/efeitos dos fármacos , Óleos Voláteis/farmacologia , Propionibacterium acnes/efeitos dos fármacos , Monoterpenos Acíclicos , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Óleos Voláteis/administração & dosagem , Pele/efeitos dos fármacos , Terpenos/administração & dosagem , Terpenos/farmacologia
18.
Int J Pharm ; 551(1-2): 133-140, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30171899

RESUMO

The nanomicelles have recently drawn a great deal of attention for drug delivery into the skin. However, these carriers have only deposited in hair follicles and furrows, and drug in the micelles may not therapeutically reach into viable skin layers. The aim of this study was to formulate a combination of nanomicelles with terpenes to overcome this challenge and evaluate their potential for topical drug delivery into the skin. The nanomicelles were characterised with respect to size, size distribution (PDI), zeta potential, morphology and encapsulation efficiency (%). The drug accumulation and penetration were examined by tape stripping method in the skin. The colloidal stability of nanomicelles was followed with respect to size and PDI values. The nanomicelles were about 25-30 nm in size with narrow distribution. All of them had slightly negative surface charge, spherical shapes and high encapsulation efficiency (%). The tape stripping data revealed that nanomicelles consisting of terpinolene led to accumulation of more drug in the stripped skin as compared with commercial product and nanomicelles without terpene. Also, micelle formulations consisting of terpinolene (2.0%) had the highest colloidal stability. Consequently, combination of nanomicelles with terpinolene could be a feasible approach for enhancement of skin drug delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Micelas , Nanoestruturas/administração & dosagem , Terpenos/administração & dosagem , Administração Cutânea , Animais , Poloxâmero/administração & dosagem , Pele/metabolismo , Suínos , Tacrolimo/administração & dosagem
19.
Biomed Pharmacother ; 107: 957-966, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30257408

RESUMO

Garcinol, a polyisoprenylated benzophenone, has been demonstrated to exert anti-cancer effects in various tumor cells. However, the effect of garcinol on cervical cancer (CC) cell progression and the related molecular mechanism remains poorly understood. Accumulating evidence has verified that downregualtion of T-cadherin is closely associated with tumorigenesis, suggesting that T-cadherin might be a potential therapeutic target for cancer treatment. In the present study, Hela and SiHa cells were treated with different concentrations of garcinol (0, 5, 10, and 25 u M), and T-cadherin siRNA was synthesized and transfected into Hela and SiHa cells combined with garcinol (25 u M) treatment. We found that garcinol dose-dependently suppressed cell viability, colony formation, invasion, migration, cell cycle progression, and promoted cell apoptosis in CC cell lines, as well as inhibited tumor growth in xenograft model. Importantly, our results showed that garcinol treatment increased the expression of T-cadherin both in vitro and in vivo, and knockdown of T-cahderin partially reversed garcinol-induced inhibition of CC development via activating P13 K/AKT signaling pathway in CC cell lines. Thus, these findings demonstrated the tumor suppressive function of garcinol on CC progression, and emphasized that the T-cadherin/P13 K/AKT was a potential mechanism involved in the antumor effects of garcinol.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Caderinas/genética , Terpenos/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Terpenos/administração & dosagem , Regulação para Cima/efeitos dos fármacos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
20.
JCI Insight ; 3(15)2018 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-30089723

RESUMO

Severe lung inflammation and alveolar hemorrhage can be life-threatening in systemic lupus erythematosus (SLE) patients if not treated early and aggressively. Neutrophil influx is the driver key of this pathology, but little is known regarding the molecular events regulating this recruitment. Here, we uncover a role for IL-16/mir-125a in this pathology and show not only that IL-16 is a target for miR-125a but that reduced miR-125a expression in SLE patients associates with lung involvement. Furthermore, in the pristane model of acute "SLE-like" lung inflammation and alveolar hemorrhage, we observed reduced pulmonary miR-125a and enhanced IL-16 expression. Neutrophil infiltration was markedly reduced in the peritoneal lavage of pristane-treated IL-16-deficient mice and elevated following i.n. delivery of IL-16. Moreover, a miR-125a mimic reduced pristane-induced IL-16 expression and neutrophil recruitment and rescued lung pathology. Mechanistically, IL-16 acts directly on the pulmonary epithelium and markedly enhances neutrophil chemoattractant expression both in vitro and in vivo, while the miR-125a mimic can prevent this. Our results reveal a role for miR-125a/IL-16 in regulating lung inflammation and suggest this axis may be a therapeutic target for management of acute lung injury in SLE.


Assuntos
Interleucina-16/genética , Pulmão/imunologia , Lúpus Eritematoso Sistêmico/imunologia , MicroRNAs/metabolismo , Pneumonia/imunologia , Adulto , Animais , Linhagem Celular , Modelos Animais de Doenças , Epitélio/imunologia , Epitélio/patologia , Feminino , Regulação da Expressão Gênica/imunologia , Humanos , Interleucina-16/imunologia , Pulmão/citologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Lúpus Eritematoso Sistêmico/complicações , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/imunologia , Pessoa de Meia-Idade , Infiltração de Neutrófilos/imunologia , Neutrófilos/imunologia , Pneumonia/induzido quimicamente , Pneumonia/patologia , Cultura Primária de Células , Terpenos/administração & dosagem , Terpenos/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA