RESUMO
The present study aimed to determine the antioxidative and anti-inflammatory effects of safranal on damage induced by CCl4. Experimental animals were divided into five groups. The first group was determined as the control group and no treatment was conducted. Second group rats were administered 1 mL/kg-day CCI4 during the experiment. Rats in Groups 3, 4 and 5 were administered 1 mL/kg-day CCI4 and 25 mg/kg, 50 mg/kg; 100 mg/kg safranal, respectively via gavage. Oxidative-antioxidant parameters, liver function enzymes and inflammatory cytokine levels were determined in liver samples obtained from the rats. Data analysis demonstrated that oxidative stress and inflammation markers were significantly higher in CCI4 administered groups (p<0.05). Antioxidant parameters in high-dose safranal administered groups were not different when compared to the control group. Safranal had ameliorating effects on the increased liver function enzymes activities in CCI4 administered groups. In conclusion, it was observed that CCI4 administration led to hepatic damage and increased oxidative stress and inflammatory cytokine levels. It was observed that particularly high-dose administration of safranal promoted the antioxidant system. Safranal administration was not effective on IL-1ß levels. However, high-dose (100 mg/kg) safranal was found to be inflammatory against TNF-α and IL-6 cytokines. In conclusion, it can be said that safranal has an anti-inflammatory potential and has a strong antioxidative effect.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Cicloexenos/uso terapêutico , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Terpenos/uso terapêutico , Animais , Intoxicação por Tetracloreto de Carbono , Inflamação/induzido quimicamente , Ratos , Ratos WistarRESUMO
Diarrhea is one of the leading causes of infant death in the world accounting for high child mortality rate. It is also present in different pathophysiologies related to several etiological agents. The aim of this study is to investigate the antidiarrheal effect of α -Terpineol (α-TPN) in different diarrhea models in rodents. The antidiarrheal effect of α-TPN in the treatment of acute diarrhea and enteropooling induced by castor oil or PGE2 in Swiss mice pretreated orally with saline (NaCl 0.9%), Loperamide (5 mg/kg) and α-TPN (6.25, 12.5, 25 and 50 mg/kg) was analyzed. Additionally, parameters of severity, total weight of faeces and post-treatment for 4 h were evaluated. Modulation of the opioid and cholinergic pathways was performed and intestinal transit model using activated charcoal as marker was also used. The effect of α-TPN on secretory diarrhea was investigated using the model of fluid secretion in intestinal loops isolated from cholera toxin-treated mice. α-TPN showed antidiarrheal effect (*p < 0.05), reducing the total stool amount (*55%, *48%, *44%, *24%) and diarrheal (*47%, *66%; *56%, 10%) respectively for the doses tested. All doses investigated in the enteropooling test presented significant changes (*46%, *78%, *66%, *41% respectively) in relation to the control. α-TPN through the muscarinic pathway reduced the gastrointestinal transit (*31%), besides inhibiting PGE2-induced diarrhea (*39%). α-TPN also reduced fluid formation and loss of Cl- ions, by interacting directly with GM1 receptors and cholera toxin, thus increasing the uptake of intestinal fluids. The results suggest an anti-diarrheal activity of α-TPN due to its anticholinergic action, ability to block PGE2 and GM1 receptors and interaction with cholera toxin in secretory diarrhea, making it a promising candidate drug for the treatment of diarrheal diseases.
Assuntos
Antidiarreicos/uso terapêutico , Cicloexenos/uso terapêutico , Diarreia/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Monoterpenos/uso terapêutico , Animais , Antidiarreicos/farmacologia , Óleo de Rícino/toxicidade , Monoterpenos Cicloexânicos , Cicloexenos/farmacologia , Diarreia/induzido quimicamente , Diarreia/fisiopatologia , Relação Dose-Resposta a Droga , Feminino , Motilidade Gastrointestinal/fisiologia , Masculino , Camundongos , Monoterpenos/farmacologiaRESUMO
α-Terpineol (TP) is present in a wide range of essential oils of the genus Eucalyptus, with recognized potential for a range of biological effects, such as analgesic. Hence, our study aimed to investigate the effect of TP on cancer pain induced by sarcoma 180 in Swiss mice. Our results showed that TP reduced significantly mechanical hyperalgesia and spontaneous and palpation-induced nociception, improved paw use without reducing tumor growth and grip strength. Importantly, no evident biochemical and hematological toxicity was oberved. Furthermore, TP increased the tissue antioxidant capacity due to ferric-reducing antioxidant power (FRAP) and glutathione (GSH). TP also reduced inducible nitric oxide synthase (iNOS) immunocontent in the tumors. Molecular docking estimated that TP binds within the same range of iNOS regions (other iNOS inhibitors), such as N-Nitroarginine methyl ester (L-NAME). These data provide strong evidence that TP may be an interesting candidate for the development of new safe analgesic drugs that are effective for cancer pain control.
Assuntos
Analgésicos/uso terapêutico , Dor do Câncer/tratamento farmacológico , Cicloexenos/uso terapêutico , Monoterpenos/uso terapêutico , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Sarcoma 180 , Analgésicos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Monoterpenos Cicloexânicos , Cicloexenos/farmacologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Monoterpenos/farmacologia , Nociceptividade/efeitos dos fármacos , Ligação ProteicaRESUMO
Natural products obtained in dietary components may aid the prevention and treatment of a variety of diseases. Reports in the scientific literature have demonstrated that the consumption of terpenes is a successful alternative in the treatment of several diseases, triggering beneficial biological effects in clinical and preclinical studies. The monoterpene limonene is largely used in alimentary items, cleaning products, and it is one of the most frequent fragrances used in cosmetics formulation. The therapeutic effects of limonene have been extensively studied, proving anti-inflammatory, antioxidant, antinociceptive, anticancer, antidiabetic, antihyperalgesic, antiviral, and gastroprotective effects, among other beneficial effects in health. In this review, we collected, presented, and analyzed evidence from the scientific literature regarding the usage of limonene and its activities and underlying mechanisms involved in combating diseases. The highlighting of limonene applications could develop a useful targeting of innovative research in this field as well as the development of a limonene-based phytomedicine which could be used in a variety of conditions of health and disease.
Assuntos
Cicloexenos/uso terapêutico , Síndrome Metabólica/prevenção & controle , Terpenos/uso terapêutico , Analgésicos/química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/química , Antioxidantes/farmacologia , Cicloexenos/química , Cicloexenos/farmacologia , Humanos , Limoneno , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/patologia , Osteoartrite/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Plantas/química , Plantas/metabolismo , Terpenos/química , Terpenos/farmacologiaRESUMO
Chronic musculoskeletal pain is one of the main symptoms found in Fibromyalgia with unclear etiology and limited pharmacological treatment. The aim of this study was to complex LIM in ß-cyclodextrin (LIM-ßCD) and then evaluate its antihyperalgesic effect in an animal model of chronic musculoskeletal pain. Differential scanning calorimetry and scanning electron microscopy was used for the characterization of the inclusion complex. Male Swiss mice were used for experimental procedures where mechanical hyperalgesia, thermal hyperalgesia, muscular strength, Fos immunofluorescence was studied after induction of hyperalgesia. Mechanism of action was also investigated through tail flick test and capsaicin-induced nociception. Endothermic events and morphological changes showed that the slurry complex method was the best method for the complexation. After induction of hyperalgesia, the oral administration of LIM-ßCD (50mg/kg) significantly increased the paw withdrawal threshold compared to uncomplexed limonene. Fos immunofluorescence showed that both compounds significantly decreased the number of Fos-positive cells in the dorsal horn. In nociceptive tests, FLU was able to reverse the antinociceptive effect of LIM-ßCD. After intraplantar administration of capsaicin, LIM was able to significantly decrease time to lick. LIM-ßCD has antihyperalgesic action superior to its uncomplexed form, with possible action in the dorsal horn of the spinal cord. These results suggest the possible applicability of LIM, uncomplexed or complexed with ßCD, in conditions such as FM and neuropathic pain, for which there are currently only limited pharmacological options.