RESUMO
Pain is one of the most prevalent and difficult to manage symptoms in cancer patients, and conventional drugs present a range of adverse reactions. The development of ß-cyclodextrins (ß-CD) complexes has been used to avoid physicochemical and pharmacological limitations due to the lipophilicity of compounds such as p-Cymene (PC), a monoterpene with antinociceptive effects. Our aim was to obtain, characterize, and measure the effect of the complex of p-cymene and ß-cyclodextrin (PC/ß-CD) in a cancer pain model. Initially, molecular docking was performed to predict the viability of complex formation. Afterward, PC/ß-CD was obtained by slurry complexation, characterized by HPLC and NMR. Finally, PC/ß-CD was tested in a Sarcoma 180 (S180)-induced pain model. Molecular docking indicated that the occurrence of interaction between PC and ß-CD is favorable. PC/ß-CD showed complexation efficiency of 82.61%, and NMR demonstrated PC complexation in the ß-CD cavity. In the S180 cancer pain model, PC/ß-CD significantly reduced the mechanical hyperalgesia, spontaneous nociception, and nociception induced by non-noxious palpation at the doses tested (p < 0.05) when compared to vehicle differently from free PC (p > 0.05). Therefore, the complexation of PC in ß-CD was shown to improve the pharmacological effect of the drug as well as reducing the required dose.
Assuntos
Dor do Câncer , Ciclodextrinas , Neoplasias , beta-Ciclodextrinas , Humanos , Camundongos , Animais , Simulação de Acoplamento Molecular , beta-Ciclodextrinas/química , Dor/tratamento farmacológico , Dor/etiologia , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Analgésicos/química , SolubilidadeRESUMO
S. aureus are among the main bacteria causing problems related to multidrug resistance in nosocomial infections. Therefore, it is necessary to carry out a reliable and rapid diagnosis for the identification of the bacteria and characterization of its susceptibility profile, especially vancomycin, which is an alternative treatment against multidrug-resistant (MDR) S. aureus. Thus, the goal of this study was to characterize isolates of S. aureus regarding the resistance and virulence and to check the susceptibility to vancomycin, through different methods, for comparative purposes. Seventeen antimicrobials were tested to assess the susceptibility profile. It was evaluated the presence of identification (nuc), resistance (mecA and blaZ), biofilm (icaA and icaD) and siderophore (sfaD and sbnD) genes. The susceptibility to vancomycin was evaluated by Minimum Inhibitory Concentration (MIC) by broth microdilution (BMD), E-test, commercial panel (Kit), and Phoenix equipment. Most S. aureus (93,33%) was classified as MDR. These isolates were 100% positive for nuc, mecA, icaA, icaD, and sfaD genes; 96.67% for sbnD and 33.33% for blaZ. In relation to BMD, all methods correctly classified the susceptibility of the isolates; however, regarding the exact MIC value for vancomycin, Phoenix showed agreement of 63.33%, E-test (33.33%) and Kit (26.66%). In conclusion, most of S. aureus was considered MDR. Also, they presented resistance, biofilm production, and siderophores genes, showing the pathogenic potential of these bacteria. Besides, the Phoenix test was considered the most effective, as it presents advantages, such as identification of the microorganism and a greater number of antimicrobials tested at a time.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Vancomicina/farmacologia , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/microbiologia , Testes de Sensibilidade MicrobianaRESUMO
Morus nigra L. has been widely used in Brazilian folk medicine for the treatment of diabetes. We evaluate the chemical composition and antidiabetic properties of the hexane (Hex-Mn) and chloroform (Chlo-Mn) fractions obtained by partition of the crude ethanolic extract from the leaves in rats. Chemical composition analysis of Hex-Mn and Chlor-Mn was performed by gas chromatography-mass spectrometry (CG-MS). In vivo and in vitro studies were carried out to compare the antidiabetic activities of the Hex-Mn and Chlor-Mn fractions. Most of the compounds identified in Hex-Mn were α-linolenic acid, stigmast-5-en-3-ol and linolenic acid ethyl ester, while in Chlor-Mn, stigmast-5-en-3-ol, palmitic acid and α-linolenic acid were mainly identified. Only Hex-Mn treatment reduced both fasting and postprandial hyperglycemia. Additionally, Hex-Mn preserved body weight gain, preserved the hepatic glycogen content, and also reduced the thiobarbituric acid reactive substances and nitrite levels, as well as restored the superoxide dismutase. Furthermore, digestion of complex carbohydrates and intestinal glucose absorption was prevented by Hex-Mn treatment. Our results suggest that the antidiabetic activity of Hex-Mn may be explained, at least in part, by the insulin sensitivity increase, antioxidant properties and reduction in carbohydrate absorption in the small intestine.
Assuntos
Morus , Animais , Antioxidantes , Clorofórmio , Cromatografia Gasosa-Espectrometria de Massas , Hexanos , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta , Ratos , EstreptozocinaRESUMO
The frequent use of acaricides against the tick Rhipicephalus microplus increases the risk of development of resistance. Recent studies have revealed that Neoglaziovia variegata, an indigenous plant species known in Brazil as 'caroá', has a deleterious effect against R. microplus. In the current study, extracts of N. variegata were studied for their possible acaricidal properties. A hexane extract of N. variegata leaves was fractionated in a chromatography column and the fractions were tested in adult tick immersion tests in triplicate using three concentrations (5, 10 and 25 mg/ml). All the fractions had harmful effects on the ticks. However, three fractions were more efficaceous. Phytochemical analysis indicated that stigmast-5-en-3-ol and stigmastanol were most abundant; they might be responsible for the acaricidal effects, making them potentially useful as alternative agents to control the tick R. microplus.
Assuntos
Acaricidas , Bromeliaceae , Rhipicephalus , Infestações por Carrapato , Animais , Brasil , Hexanos , Larva , Extratos Vegetais/farmacologia , Folhas de PlantaRESUMO
In addition to seven known alkaloids (2, 6-11) and 1,2,4-trimethoxybenzene (1), three isoquinoline-derived alkaloids (3-5), namely, duguetinine (3), a compound based on an unprecedented oxahomoaporphine scaffold, and two new 8-oxohomoaporphine alkaloids, duguesuramine (4) and 11-methoxyduguesuramine (5), and a new asarone-derived phenylpropanoid (10) were isolated from the bark of Duguetia surinamensis. The isolation workflow was guided by HPLC-HRESIMS/MS and molecular networking-based analyses. Twenty-four known alkaloids were dereplicated from the D. surinamensis alkaloid-rich fraction network and were assigned by manual MS/MS interpretation. Their cytotoxic potential was evaluated.
Assuntos
Alcaloides/química , Annonaceae/química , Aporfinas/química , Cromatografia Líquida de Alta Pressão , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em TandemRESUMO
Peripheral nerve injury (PNI) is a serious public health problem that is linked with motor, sensory and autonomic deficits. Given the fact that this type of disorder leads to a decreased quality of life in most patients and adherence of available drugs is limited and have adverse effects, we investigated the efficacy of natural products in a PNI model. The search terms plants, medicinal, nerve regeneration, nerve crush, sciatic nerve as well as MeSH terms or free-text words were used to retrieve English language articles in PubMed, Scopus, Web of Science and LILACS published until July 2015. After sciatic nerve crush, natural products have improved significantly motor performance, sensory function and electrical conductance measured over weeks. Among the pharmacological targets suggested by the action of natural products, there were citations on the activation of the antiapoptotic signaling pathway, modulation in the expression of pro-inflammatory cytokines and neurotrophic factors. The systematic review provides scientific evidence that natural products are pharmacologically effective in the treatment of PNI such as sciatic nerve crush.
Assuntos
Produtos Biológicos/uso terapêutico , Regeneração Nervosa/efeitos dos fármacos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Animais , Humanos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Traumatismos dos Nervos Periféricos/metabolismo , Traumatismos dos Nervos Periféricos/patologia , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/patologia , Extratos Vegetais/uso terapêuticoRESUMO
Annona vepretorum Mart. (Annonaceae) is a species popularly known in Brazil as "araticum" and "pinha da Caatinga". We have evaluated the antinociceptive effects of A. vepretorum in formalin-, capsaicin-, and glutamate-induced orofacial nociception in mice. Male Swiss mice were pretreated with either saline (p.o.), A. vepretorum ethanol extract (Av-EtOH 25, 50 and 100 mg/kg, p.o.), or morphine (10 mg/kg, i.p.), before formalin, capsaicin, or glutamate was injected into the right upper lip. Pre-treatment with Av-EtOH at all doses produced a reduction in face-rubbing behavior induced by formalin in both phases, and these pre-treatments also produced a significant antinociceptive effect in the capsaicin and glutamate tests. Pre-treatment with naloxone (1.5 mg/kg, i.p.) did not reverse the antinociceptive activity of the extract at the dose of 100 mg/kg in the first phase of this test. Our results suggest that Av-EtOH might be useful in the treatment of orofacial pain.
Assuntos
Analgésicos/farmacologia , Annona/química , Dor Facial/prevenção & controle , Extratos Vegetais/farmacologia , Folhas de Planta/química , Analgésicos/química , Animais , Capsaicina , Relação Dose-Resposta a Droga , Antagonismo de Drogas , Etanol/química , Dor Facial/induzido quimicamente , Formaldeído , Ácido Glutâmico , Masculino , Camundongos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Medição da Dor/métodos , Fitoterapia , Extratos Vegetais/químicaRESUMO
CONTEXT: Chrysobalanus icaco L. (Chrysobalanaceae) has been used for the treatment of abdominal pain and cramps. OBJECTIVE: Assess the chemical and pharmacological profile of the lyophilized aqueous extract from C. icaco leaves (AEC). MATERIALS AND METHODS: Chromatographic methods were used to assess compounds from AEC. Mice were treated with vehicle (control group) or AEC (100, 200 or 400 mg/kg, p.o.) (group with 7-8 mice) and the analgesic profile was assessed employing the acetic acid-induced writhing, formalin, hot plate tests and hyperalgesia induced by carrageenan (CG) or tumour necrosis factor-alpha. The animal motor performance was assessed using rota-rod and grip strength tests. RESULTS: The chromatographic profile of AEC demonstrated the presence of terpenoid compounds. The acute pretreatment with AEC, at all doses, produced a significant (p < 0.01) inhibition of painful bahaviour (11.4 ± 3.6; 10.3 ± 2.8; 11.3 ± 2.2) when compared to the control group (24.7 ± 4.7) in acetic acid-induced writhing test. In the formalin test, AEC were effective in the second phase (p < 0.01) (57.2 ± 10.3; 56.3 ± 9.2; 54.7 ± 8.9) when compared to control group (121.9 ± 18.5). No response was observed in the hot plate test. The higher dose of AEC produced a significant (p < 0.01 or p < 0.05) inhibitory effect on the mechanical hyperalgesia test. AEC did not affect the motor performance of the mice. DISCUSSION: The terpenoids from AEC are known for its analgesic and anti-inflammatory properties. So, these results corroborate the experiments using the AEC in inflammatory pain protocols. CONCLUSION: Our results suggest that AEC act against inflammatory pain.
Assuntos
Analgésicos/farmacologia , Chrysobalanaceae , Medição da Dor/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta , Analgésicos/isolamento & purificação , Animais , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Liofilização , Masculino , Camundongos , Medição da Dor/métodos , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Água/farmacologiaRESUMO
Lonchocarpus araripensis Benth. is largely distributed in the northeast region of Brazil. It is popularly known as 'sucupira'. Recent studies have shown that some species of Lonchocarpus have interesting pharmacological activities. In this study, we evaluated the antinociceptive effect of a flavone isolated from L. araripensis. The chemical examination resulted in the isolation of 3,6-dimethoxy-6â³,6â³-dimethyl-(7,8,2â³,3â³)-chromeneflavone (DDF). The structure of the compound was established by spectral analysis. Antinociceptive activity of DDF was evaluated by measuring nociception by acetic acid, formalin and hot plate tests. The rota rod test was used to evaluate motor coordination. The results demonstrated that DDF was able to prevent acetic-acid-writhing-induced nociception (p < 0.001) in mice. Furthermore, DDF produced a significant reduction of the nociceptive behaviour at the early and late phases of paw licking in the formalin test. Also, DDF produced an inhibition of the nociceptive behaviour during a hot-plate test. No alteration in motor coordination was observed. These results confirm the hypothesis that DDF reduces the nociceptive behaviour in mice, probably through central mechanisms, but without compromising the motor coordination of animals.
Assuntos
Analgésicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Fabaceae , Flavonoides/farmacologia , Nociceptividade/efeitos dos fármacos , Ácido Acético , Animais , Brasil , Fabaceae/química , Flavonas , Masculino , Camundongos , Medição da Dor , Extratos Vegetais/farmacologiaRESUMO
Xylopia laevigata (Annonaceae) is a medicinal plant used in folk medicine to treat pain and inflammation. Thus, we investigated the possible antioxidant, antinociceptive, and anti-inflammatory effects of X. laevigata leaf essential oil (EOX) in animal models. Our EOX sample showed the presence of γ-muurolene (17.78%), δ-cadinene (12.23%), bicyclogermacrene (7.77%), and α-copaene (7.17%) as main compounds. EOX presented a strong antioxidant potential according to the DPPH, TBARS, and nitrite production tests. Additionally, pretreatment with EOX, in mice, also significantly produced (P < 0.05 or P < 0.001) antinociceptive effect by reduction of nociceptive behavior (in formalin and writhing tests). The EOX showed c-Fos label in the olfactory bulb, piriform cortex, and periaqueductal gray. Acute administration of EOX exhibited a significant (P < 0.01 or P < 0.001) anti-inflammatory profile in the carrageenan-induced peritonitis and by the carrageenan-induced hindpaw edema tests in mice. Our results provide evidence for the use of X. laevigata by traditional medicine practitioners in the management of pain and inflammatory disorders.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Xylopia/química , Analgésicos/química , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Edema/tratamento farmacológico , Inflamação/tratamento farmacológico , Masculino , Camundongos , Nociceptividade/efeitos dos fármacos , Óleos Voláteis/química , Óleos Voláteis/uso terapêutico , Peritonite/tratamento farmacológico , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Sesquiterpenos/análiseRESUMO
O. basilicum leaves produce essential oils (LEO) rich in monoterpenes. The short half-life and water insolubility are limitations for LEO medical uses. ß-Cyclodextrin (ß-CD) has been employed to improve the pharmacological properties of LEO. We assessed the antihyperalgesic profile of LEO, isolated or complexed in ß-CD (LEO/ß-CD), on an animal model for fibromyalgia. Behavioral tests: mice were treated every day with either LEO/ß-CD (25, 50 or 100 mg/kg, p.o.), LEO (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.) or vehicle (saline), and 60 min after treatment behavioral parameters were assessed. Therefore, mice were evaluated for mechanical hyperalgesia (von Frey), motor coordination (Rota-rod) and muscle strength (Grip Strength Metter) in a mice fibromyalgia model. After 27 days, we evaluated the central nervous system (CNS) pathways involved in the effect induced by experimental drugs through immunofluorescence protocol to Fos protein. The differential scanning analysis (DSC), thermogravimetry/derivate thermogravimetry (TG/DTG) and infrared absorption spectroscopy (FTIR) curves indicated that the products prepared were able to incorporate the LEO efficiently. Oral treatment with LEO or LEO-ßCD, at all doses tested, produced a significant reduction of mechanical hyperalgesia and we were able to significantly increase Fos protein expression. Together, our results provide evidence that LEO, isolated or complexed with ß-CD, produces analgesic effects on chronic non-inflammatory pain as fibromyalgia.
Assuntos
Analgésicos/uso terapêutico , Fibromialgia/tratamento farmacológico , Monoterpenos/uso terapêutico , Ocimum basilicum/química , Óleos Voláteis/uso terapêutico , Proteínas Proto-Oncogênicas c-fos/genética , beta-Ciclodextrinas/química , Analgésicos/administração & dosagem , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiopatologia , Fibromialgia/genética , Fibromialgia/fisiopatologia , Força da Mão , Hiperalgesia/tratamento farmacológico , Hiperalgesia/genética , Hiperalgesia/fisiopatologia , Masculino , Camundongos , Monoterpenos/administração & dosagem , Monoterpenos/química , Monoterpenos/isolamento & purificação , Atividade Motora/efeitos dos fármacos , Óleos Voláteis/administração & dosagem , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Folhas de Planta/química , Regulação para Cima/efeitos dos fármacosRESUMO
The search for more effective and lower cost therapeutic approaches for wound healing remains a challenge for modern medicine. In the search for new therapeutic options, plants and their metabolites are a great source of novel biomolecules. Among their constituents, the monoterpenes represent 90% of essential oils, and have a variety of structures with several activities such as antimicrobial, anti-inflammatory, antioxidant and wound healing. Based on that, and also due to the lack of reviews concerning the wound-healing activity of monoterpenes, we performed this systematic review-which provides an overview of their characteristics and mechanisms of action. In this search, the terms "terpenes", "monoterpenes", "wound healing" and "wound closure techniques" were used to retrieve articles published in LILACS, PUBMED and EMBASE until May 2013. Seven papers were found concerning the potential wound healing effect of five compouds (three monoterpenes and two iridoid derivatives) in preclinical studies. Among the products used for wound care, the films were the most studied pharmaceutical form. Monoterpenes are a class of compounds of great diversity of biological activities and therapeutic potential. The data reviewed here suggest that monoterpenes, although poorly studied in this context, are promising compounds for the treatment of chronic wound conditions.
Assuntos
Iridoides/farmacologia , Monoterpenos/farmacologia , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Iridoides/uso terapêutico , Monoterpenos/uso terapêutico , Extratos Vegetais/uso terapêutico , Plantas Medicinais/químicaRESUMO
Chronic diseases such as cancer, diabetes, neurodegenerative and cardiovascular diseases are characterized by an enhanced state of oxidative stress, which may result from the overproduction of reactive species and/or a decrease in antioxidant defenses. The search for new chemical entities with antioxidant profile is still thus an emerging field on ongoing interest. Due to the lack of reviews concerning the antioxidant activity of lichen-derived natural compounds, we performed a review of the antioxidant potential and mechanisms of action of natural compounds isolated from lichens. The search terms "lichens", "antioxidants" and "antioxidant response elements" were used to retrieve articles in LILACS, PubMed and Web of Science published until February 2014. From a total of 319 articles surveyed, 32 met the established inclusion and exclusion criteria. It was observed that the most common isolated compound studied was usnic acid, cited in 14 out of the 32 articles. The most often described antioxidant assays for the study of in vitro antioxidant activity were mainly DPPH, LPO and SOD. The most suggested mechanisms of action were scavenging of reactive species, enzymatic activation and inhibition of iNOS. Thus, compounds isolated from lichens are possible candidates for the management of oxidative stress, and may be useful in the treatment of chronic diseases.
Assuntos
Elementos de Resposta Antioxidante , Antioxidantes/química , Líquens/química , Neoplasias/tratamento farmacológico , Antioxidantes/farmacologia , Benzofuranos/metabolismo , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/química , Sequestradores de Radicais Livres/metabolismo , Humanos , Oxirredução , Estresse Oxidativo , Picratos/administração & dosagem , Picratos/químicaRESUMO
Hecogenin is a steroidal sapogenin largely drawn from the plants of the genus Agave, commonly known as 'sisal', and is one of the important precursors used by the pharmaceutical industry for the synthesis of steroid hormones. Hecogenin acetate (HA) is a steroidal sapogenin-acetylated that produces antinociceptive activity. Thus, we evaluate the antihyperalgesic profile of HA in mice in inflammatory models, as well as its possible involvement with c-fos expression on spinal cord area and cytokines to produces analgesic profile. Acute pretreatment with HA (5, 10, or 20 mg/kg; i.p.) inhibited the development of mechanical hyperalgesia induced by carrageenan, TNF-α, dopamine and PGE2. Additionally, the immunofluorescence data demonstrated that acute pretreatment with HA, at all doses tested, significantly inhibited Fos-like expression in the spinal cord dorsal horn normally observed after carrageenan-inflammation. Moreover, HA did not affect the motor performance of the mice as tested in the Rota rod test. This antinociceptive profile seems to be related, at least in part, to a reduction of pro-inflammatory cytokines, as IL-1ß. The present results suggest that HA attenuates mechanical hyperalgesia by blocking the neural transmission of pain at the spinal cord levels and by cytokines-inhibitory mechanisms.
Assuntos
Citocinas/metabolismo , Medula Espinal/efeitos dos fármacos , Compostos de Espiro/farmacologia , Compostos de Espiro/uso terapêutico , Esteroides/farmacologia , Esteroides/uso terapêutico , Animais , Carragenina/toxicidade , Hiperalgesia/induzido quimicamente , Hiperalgesia/prevenção & controle , Interleucina-1beta/metabolismo , Masculino , Camundongos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
In the present study, it was evaluated the chemical composition and the antinociceptive activity of the essential oil obtained from the leaves of Guatteria friesiana. Seven compounds corresponding to 96.2% of the crude essential oil were identified. The main components identified were the mixture of ß-eudesmol and α-eudesmol (58.1%), and γ-eudesmol (16.8%). A new α-eudesmol derivative, named 5-hydroxy-α-eudesmol, was isolated together with the known compounds ß-eudesmol and a mixture of α-eudesmol, ß-eudesmol and γ-eudesmol of the essential oil. The chemical structures were determined by 1D and 2D NMR, and MS experiments. Essential oil has significant antinociceptive properties, which are related probably with the involvement of the opioid receptors and K+-ATP channels.
Assuntos
Annonaceae , Guatteria , Óleos Voláteis , Óleos Voláteis/química , Guatteria/química , Annonaceae/química , Folhas de Planta/química , Analgésicos/farmacologiaRESUMO
The anti-inflammatory and redox protective effects of the citronellal (CT) were evaluated using in vivo and in vitro tests. Intraperitoneal (i.p.) administration of CT (50, 100, and 200 mg/kg) inhibited (p < 0.05) the carrageenan-induced leukocyte migration to the peritoneal cavity. Additionally, the carrageenan- and arachidonic acid-induced rat hind paw edema was significantly inhibited (p < 0.05) by i.p. administration of 100 and 200 mg/kg of the compound. When the redox activity was evaluated, CT (200 mg/kg) significantly reduced hepatic lipoperoxidation (p < 0.001), as well as oxidation of plasmatic (p < 0.05) and hepatic (p < 0.01) proteins. The results of the present study support the hypothesis that CT possesses anti-inflammatory and redox protective activities. It is suggested that its effects are associated with the inhibition of the enzymes in the arachidonic acid pathway, which prevent cell migration by inhibiting leukotriene production, edema formation and the increase of reactive oxygen species in tissues. Therefore, CT is of potential benefit to manage inflammatory disorders and correlated damages caused by oxidant agents.
Assuntos
Aldeídos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Monoterpenos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Monoterpenos Acíclicos , Animais , Ácido Araquidônico , Carragenina , Edema/induzido quimicamente , Membro Posterior , Masculino , Oxirredução , Ratos , Ratos WistarRESUMO
Complex regional pain syndrome type 1 (CRPS-1) is a painful syndrome without effective treatment. In order to explore possible new treatments, we used an animal model of CRPS-1 to examine the effects of ß-Citronellol (ßCT), a monoterpene found in a variety of plants that has been shown to have analgesic effects. We aimed to assess its effects alone, and complexed with ß-cyclodextrin (ßCD), which has been previously used to enhance the effects of a number of medicines. The ßCT-ßCD was characterized physiochemically using high performance liquid chromatography (HPLC) and differential scanning calorimetry (DSC) and shown to have 80% efficiency. In the animal model, Swiss mice were treated with ßCT, ßCT-ßCD, vehicle, pregabalin or sham and evaluated for hyperalgesia and motor coordination. Inflammatory mediators were measured by Western blot or ELISA and the descending pain pathway by immunofluorescence. ßCT was shown to have an anti-hyperalgesic effect (without affecting motor coordination) that reduced inflammatory mediators and activated the descending pain pathway, and these effects were increased with complexation in ßCD. Our results showed ßCT-ßCD to be a promising treatment for CRPS-1.
Assuntos
Monoterpenos Acíclicos/uso terapêutico , Analgésicos/uso terapêutico , Portadores de Fármacos/química , Hiperalgesia/tratamento farmacológico , Distrofia Simpática Reflexa/tratamento farmacológico , beta-Ciclodextrinas/química , Animais , Anti-Inflamatórios/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Ingredientes de Alimentos , Masculino , Camundongos , Subunidade p50 de NF-kappa B/metabolismo , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
AIMS: To evaluate the antinociceptive effects of citronellal (CTL) on formalin-, capsaicin-, and glutamate-induced orofacial nociception in mice and to investigate whether such effects might involve a change in neural excitability. METHODS: Male mice were pretreated with CTL (50, 100, and 200 mg/kg, ip), morphine (5 mg/kg, ip), or vehicle (distilled water plus one drop of Tween 80 0.2%) before formalin (20 microL, 2%), capsaicin (20 microL, 2.5 microg) or glutamate (40 microL, 25 microM) injection into the right vibrissa. Sciatic nerve recordings were made using the single sucrose gap technique in rats. The data obtained were analyzed by ANOVA followed by Dunnett's test for the behavioral analyses and by the Student t test for CAP evaluation. RESULTS: Pretreatment with CTL was effective in reducing nociceptive face-rubbing behavior in both phases of the formalin test, which was also naloxone-sensitive. CTL produced significantly antinociceptive effect at all doses in the capsaicin- and glutamate- tests. Rota-rod testing indicated that such results were unlikely to be provoked by motor abnormality. Recordings using the single sucrose gap technique revealed that CTL (10 mM) could reduce the excitability of the isolated sciatic nerve through a diminution of the compound action potential amplitude by about 42.4% from control recordings. CONCLUSION: These results suggest that CTL might represent an important tool for management and/or treatment of orofacial pain.
Assuntos
Aldeídos/uso terapêutico , Analgésicos/uso terapêutico , Capsaicina/efeitos adversos , Dor Facial/tratamento farmacológico , Formaldeído/efeitos adversos , Glutamatos/efeitos adversos , Monoterpenos/uso terapêutico , Nociceptores/efeitos dos fármacos , Dor/prevenção & controle , Fármacos do Sistema Sensorial/efeitos adversos , Potenciais de Ação/efeitos dos fármacos , Monoterpenos Acíclicos , Animais , Dor Facial/induzido quimicamente , Masculino , Camundongos , Morfina/uso terapêutico , Atividade Motora/efeitos dos fármacos , Entorpecentes/uso terapêutico , Condução Nervosa/efeitos dos fármacos , Ratos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacosRESUMO
BACKGROUND: Arthritis is a syndrome associated with exacerbated inflammation, joint destruction and chronic pain and disability. Chronic treatment of arthritis is associated with several side effects and high abandonment. Therefore, there has been an ongoing search for alternative treatments to overcome these problems. PURPOSE: Natural products, which are already widely used for their biological, cosmetic and pharmacotechnic properties, are a possible source for new drugs. Terpenes, a large class of organic compounds produced mainly by plants and trees, are a promising natural product and have already been shown to be effective in treating chronic pain, particularly of an inflammatory origin. STUDY DESIGN AND METHODS: This review identifies the main terpenes with anti-arthritic activity reported in the last 10 years. A survey was conducted between December 2017 and June 2018 in the PUBMED, SCOPUS and Science Direct databases using combinations of the descriptors terpenes, arthritis and inflammation. RESULTS: The results showed that terpenes have promising biological effects in relation to the treatment of arthritis, with the 24 terpenes identified in our survey being effective in the modulation of inflammatory mediators important to the physiopathology of arthritis, such as IL-6, IL-17, TNF-α, NFκB, and COX-2, among others. It is important to note that most of the studies used animal models, which limits, at least in part, the direct translation to humans of the experimental evidence produced by the studies. CONCLUSION: Together, our finds suggest that terpenes can modulate the immuno-regulatory and destructive tissue events that underlie the clinical presentation and the progression of arthritis and are worthy of further clinical investigation.
Assuntos
Artrite/tratamento farmacológico , Inflamação/tratamento farmacológico , Terpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Artrite/metabolismo , Artrite/fisiopatologia , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Terapia de Alvo Molecular/métodos , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Many diseases, such as inflammatory and central nervous system disorders, currently have a limited number of effective side-effect free treatments. Citronellol (CT) is a monoterpene alcohol present in the essential oil of several plants used in cooking and traditional medicine, such as those of the genus Cymbopogon and Citrus, with pharmacological activities already described in the literature. The aim of this review was to summarize the pharmacological activities already attributed to CT that could be used in treatments for humans. The databases PubMed, MedLine, Scopus, Lilacs and Scielo were searched using the terms "Citronellol" and "Drug effect". 32 articles were identified and used in the study. Twenty-one articles demonstrated CT activities, including antibiotic and antifungal effects in vitro, and 11 properties including analgesic and anticonvulsant effects in vivo, besides presenting low toxicity. In view of the need to discover new drugs and the activities reported for CT, it can be stated that CT is a promising molecule to target in future pharmacological studies.