Antinociceptive Effect of a p-Cymene/ß-Cyclodextrin Inclusion Complex in a Murine Cancer Pain Model: Characterization Aided through a Docking Study.

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.

A novel eudesmol derivative from the leaf essential oil of Guatteria friesiana (Annonaceae) and evaluation of the antinociceptive activity.

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.

Characterization of Multidrug-Resistant Staphylococcus aureus Isolates and Comparison of Methods of Susceptibility to Vancomycin.

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.

Antidiabetic properties of oral treatment of hexane and chloroform fractions of Morus nigra leaves in streptozotocin-induced rats.

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.

Involvement of nuclear factor κB and descending pain pathways in the anti-hyperalgesic effect of ß-citronellol, a food ingredient, complexed in ß-cyclodextrin in a model of complex regional pain syndrome - Type 1.

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.

Acaricidal efficacy and chemical study of hexane extracts of the leaves of Neoglaziovia variegata (Bromeliaceae) against the tick Rhipicephalus microplus.

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.

ß-Cyclodextrin complex improves the bioavailability and antitumor potential of cirsiliol, a flavone isolated from Leonotis nepetifolia (Lamiaceae).

Cirsiliol is a flavone found in many Lamiaceae species with high cytotoxic activity against tumor cell lines. Although cirsiliol is being used in cancer therapy, its pharmacological potential is limited by its low solubility and bioavailability. In this paper, a cirsiliol-ß-cyclodextrin inclusion complex was developed in order to increase its solubility and bioavailability. The formation of inclusion complex was proved by scanning electron microscopy, Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) and solubility increment was verified through the ultraviolet-visible (UV-Vis) method. The cytotoxic effect against tumor cells (PC3, HCT-116 and HL-60 human cell lines, and S-180 murine cell line) and the antitumor activity in mice bearing sarcoma S-180 were also investigated. The inclusion complex was obtained with 71.45% of total recovery and solubility 2.1 times higher compared to the compound in its free form. This increment in solubility was responsible by a tumor growth inhibition potentiation (1.5 times greater compared to compound in its free form). In addition, this study showed that cirsiliol and its inclusion complex in ß-cyclodextrin have strong antitumor potential at low doses without promoting side effects commonly observed for conventional drugs as doxorubicin.

Structure-Based Molecular Networking for the Target Discovery of Oxahomoaporphine and 8-Oxohomoaporphine Alkaloids from Duguetia surinamensis.

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.

Terpenes as possible drugs for the mitigation of arthritic symptoms - A systematic review.

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.

DNA damage and primordial follicle activation after in vitro culture of sheep ovarian cortex in Morus nigra leaf extract / Dano ao DNA e ativação do folículo primordial após a cultivo in vitro do córtex ovariano de ovelha em extrato de folha de Morus nigra

This study evaluated the effect of Morus nigra leaf extract, with or without supplementation, on morphology, activation and DNA damage of preantral follicles cultured within sheep ovarian tissue. Ovaries were collected and divided into fragments, being one fixed for histological and Terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end labeling (TUNEL) analysis (fresh control). The remaining fragments were cultured for 7 days in alpha minimum essential media (α-MEM) supplemented with bovine serum albumin (BSA), insulin, transferrin, selenium, glutamine, hypoxanthine and ascorbic acid (α-MEM+; control medium) or into medium composed of M. nigra extract without supplements (0.1; 0.2 or 0.4mg/mL) or supplemented with the same substances described above for α-MEM+ (MN 0.1+; 0.2+ or 0.4+mg/mL). Then, tissues were destined to histological and TUNEL analysis. The α-MEM+ treatment had more morphologically normal follicles than all M. nigra extract treatments. However, α-MEM+ treatment also showed signs of atresia because the percentage of TUNEL positive cells was similar in α-MEM+ and in 0.1mg/mL M. nigra without and with supplements. Moreover, a reduction in the primordial follicles and an increase in the growing ones were observed in all treatments, except 0.2mg/mL M. nigra. In conclusion, the follicles cultured at 0.1mg/mL M. nigra extract were in good condition and able to continue their development, as demonstrated by the same rates of DNA damage and follicular activation as the control medium.(AU)

Este estudo avaliou o efeito do extrato das folhas de Morus nigra, com ou sem suplementos, sobre a morfologia, a ativação e o dano ao DNA de folículos pré-antrais cultivados inclusos em tecido ovariano. Os ovários foram coletados e divididos em fragmentos, sendo um fixado para análise histológica e ensaio de marcação de terminações dUTP mediada por desoxinucleotidil transferase terminal (TUNEL) (controle fresco). Os fragmentos restantes foram cultivados durante 7 dias em meio essencial mínimo alfa (α-MEM) suplementado com albumina sérica bovina (BSA), insulina, transferrina, selênio, glutamina, hipoxantina e ácido ascorbico (α-MEM+; meio controle) ou em meio composto de extrato de M. nigra sem suplementos (0,1; 0,2 or 0,4mg/mL) ou suplementado com as mesmas substâncias descritas para α-MEM+ (MN 0,1+; 0,2+ or 0,4+mg/mL). Então, os tecidos foram destinados à análise histológica e TUNEL. O tratamento do α-MEM+ apresentou mais folículos morfologicamente normais que todos os tratamentos do extrato de M. nigra. No entanto, o tratamento com α-MEM+ também mostrou sinais de atresia, pois a porcentagem de células TUNEL positivas foi semelhante em α-MEM+ e em 0,1mg/mL M. nigra sem e com suplementos. Além disso, observou-se uma redução nos folículos primordiais e um aumento nos folículos em crescimento em todos os tratamentos, exceto 0,2mg/mL M. nigra. Em conclusão, os folículos cultivados com 0,1mg/mL de extrato de M. nigra estavam em boas condições e aptos a continuar seu desenvolvimento, como demonstrado pelas taxas de dano ao DNA e de ativação folicular semelhantes ao meio controle.(AU)

Citronellol, a monoterpene alcohol with promising pharmacological activities - A systematic review.

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.

Guaianolide sesquiterpene lactones and aporphine alkaloids from the stem bark of Guatteria friesiana.

Three guaianolide sesquiterpenes, denoted guatterfriesols A-C, and four aporphine alkaloid derivatives were isolated from the stem bark of the Amazonian plant Guatteria friesiana. Thus far, sesquiterpene lactones have not been described in Annonaceae. Structures of the previously undescribed compounds were established by using 1D and 2D NMR spectroscopy in combination with MS. The absolute stereochemistry was assigned via NOE NMR experiments, ECD spectroscopy, and theoretical calculations using the TDDFT approach. Among the isolated compounds, the alkaloid guatterfriesidine showed anti-glycation activity by inhibiting the formation of advanced glycation end-products (AGEs) through the prevention of oxidation in both BSA/methylglyoxal and BSA/fructose systems.

Influence of Flavonoids on Mechanism of Modulation of Insulin Secretion.

BACKGROUND: The development of alternatives for insulin secretion control in vivo or in vitro represents an important aspect to be investigated. In this direction, natural products have been progressively explored with this aim. In particular, flavonoids are potential candidates to act as insulin secretagogue. OBJECTIVE: To study the influence of flavonoid on overall modulation mechanisms of insulin secretion. METHODS: The research was conducted in the following databases and platforms: PubMed, Scopus, ISI Web of Knowledge, SciELO, LILACS, and ScienceDirect, and the MeSH terms used for the search were flavonoids, flavones, islets of Langerhans, and insulin-secreting cells. RESULTS: Twelve articles were included and represent the basis of discussion on mechanisms of insulin secretion of flavonoids. Papers in ISI Web of Knowledge were in number of 1, Scopus 44, PubMed 264, ScienceDirect 511, and no papers from LILACS and SciELO databases. CONCLUSION: According to the literature, the majority of flavonoid subclasses can modulate insulin secretion through several pathways, in an indication that corresponding molecule is a potential candidate for active materials to be applied in the treatment of diabetes. SUMMARY: The action of natural products on insulin secretion represents an important investigation topic due to their importance in the diabetes controlIn addition to their typical antioxidant properties, flavonoids contribute to the insulin secretionThe modulation of insulin secretion is induced by flavonoids according to different mechanisms. Abbreviations used: KATP channels: ATP-sensitive K+ channels, GLUT4: Glucose transporter 4, ERK1/2: Extracellular signal-regulated protein kinases 1 and 2, L-VDCCs: L-type voltage-dependent Ca+2 channels, GLUT1: Glucose transporter 1, AMPK: Adenosine monophosphate-activated protein kinase, PTP1B: Protein tyrosine phosphatase 1B, GLUT2: Glucose transporter 2, cAMP: Cyclic adenosine monophosphate, PKA: Protein kinase A, PTK: Protein tyrosine kinase, CaMK II: Ca2+/calmodulin-dependent protein kinase II, GSIS: Glucose-stimulated insulin secretion, Insig-1: Insulin-induced gene 1, IRS-2: Insulin receptor substrate 2, PDX-1: Pancreatic and duodenal homeobox 1, SREBP-1c: Sterol regulatory element binding protein-1c, DMC: Dihydroxy-6'-methoxy-3',5'-dimethylchalcone, GLP-1: Glucagon-like peptide-1, GLP-1R: Glucagon-like peptide 1 receptor.

Cyclohexene-fused 1,3-oxazines with selective antibacterial and antiparasitic action and low cytotoxic effects.

Oxazine derivatives, a class of heterocyclic compounds, exhibit a variety of biological properties, such as anticonvulsant and antitumor activities. In this study, we evaluated the effect of two cyclohexene-fused 1,3-oxazines (cis­1-benzyl-N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (1) and trans­N-phenyl-1,4,4a,5,8,8a-hexahydro-3,1-benzoxazin-2-imine (2)) in cultures of Bacillus cereus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica, Serratia marcescens, Shigella flexneri and Staphylococcus aureus by the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC). Additionally, the ex vivo antiparasitic activity of oxazines was assessed against Schistosoma mansoni, a helminth that is one of the major agents of the disease schistosomiasis Also, oxazines were evaluated on three tumor cell lines, NCI-H292 (human lung carcinoma), MCF-7 (human breast adenocarcinoma) and HEp-2 (human cervix carcinoma), and two normal cell lines (Vero and red blood cells). Bioassays revealed that oxazine 2 is more effective against bacteria than oxazine 1, with the lowest MIC and MBC values of 3.91 and 32.5µg/mL, respectively. Similarly, compound 2 demonstrated higher antiparasitic activity than 1, and scanning electron microscopy analysis showed several morphological alterations in the tegument of worms in a concentration-dependent manner. In contrast, both oxazines exhibited low cytotoxic effects on cancer and normal cell lines. These results indicated that oxazines exerted direct effects on bacteria and parasite schistosomes. More importantly, since schistosomiasis control programs rely on one drug, praziquantel, oxazines may have the potential to become new antischistosomal agents.

HPLC-DAD analysis, antinociceptive and anti-inflammatory properties of the ethanolic extract of Hyptis umbrosa in mice.

Hyptis umbrosa (syn. Mesosphaerum sidifolium) (Lamiaceae Family) has been used to treat several conditions such as gastrointestinal disorders, skin infections, nasal congestion, fever and cramps. The objective of this study was to evaluate the chemical composition, analgesic and anti-inflammatory profiles of ethanol extract from leaves of Hyptis umbrosa (EEB). HPLC-DAD was used to determine the fingerprint chromatogram of the extract. Male Swiss mice were orally pretreated with EEB (100, 200 or 400 mg/kg; 60 min before initiating algesic stimulation) and antinociceptive activity was assessed using the acetic acid-induced writhing model, formalin test and hyperalgesia induced by glutamate or capsaicin. Also, peritonitis was induced by the intrathoracic injection of carrageenan to quantify the total number of leukocytes. The presence of phenolic compounds in the extract was confirmed using HPLC-DAD. The treatment with EEB, at all doses, produced a significant analgesic effect against acetic acid-induced antinociceptive activity. In the formalin test, only the 400-mg/kg-dose of EEB had a significant effect in the first phase. However, all doses tested were able to reverse nociception in the second phase. The effect of all doses of EEB also showed a significant antinociceptive effect in the glutamate and capsaicin tests and inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity. The present study suggests that the EEB possesses peripheral analgesic action and showed potential in reducing the spreading of the inflammatory processes. Also, it seems to be related with vanilloid and glutamate receptors.

Inhibition of the TetK efflux-pump by the essential oil of Chenopodium ambrosioides L. and α-terpinene against Staphylococcus aureus IS-58.

The use of natural products is crucial to suppress the development of these micro-organisms and to reduce the concentration necessary to inhibit these microrganisms, reducing the toxicity risks also. In this study, the essential oil from Chenopodium ambrosioides Leaves and its main constituent α-Terpinene were used in the antibacterial and potentiating activity of antibiotics and ethidium bromide assays, against the bacterial strains Staphylococcus aureus IS-58, carriers of efflux pumps. The Minimum Inhibitory Concentration (MIC) was determined using a microdilution method. The capacity of the aforementioned was also tested in combination with tetracycline and ethidium bromide, with the aim of improving the activity of the antibacterials. The MIC of the C. ambrosioides L. essential oil and of α-Terpinene were above 1024 µg/mL, comprising a clinically irrelevant value. However, when associated with the antibiotics, the C. ambrosioides L. essential oil, significantly decreased the MIC of tetracycline and ethidium bromide. The efflux pump is the only mechanism the bacteria possesses to reduce the toxicity of ethidium bromide, and thus this reduction in the MIC demonstrates that the C. ambrosioides L. essential oil is an effective option in the inhibition of the efflux pump present in these micro-organisms.

Natural products assessed in animal models for orofacial pain – a systematic review

ABSTRACT Orofacial pain is related to tissues of the head, face, neck and all the intraoral structures; it is rather debilitating to the patient and also difficult to treat. There are relatively few studies dedicated to the use of natural products to alleviate orofacial pain in preclinical experiment models (performed in experimental animals which provide support for clinical trials). Main objectives of the present systematic review summarize the studies on natural products assessed in animal models for orofacial pain seeking to give evidence to future development of new pharmaceutical products to manage the orofacial pain. Our review includes a thorough search of literature using the terms of orofacial pain, facial pain, medicinal plants and natural products. This search was performed using to retrieve English language articles in Medline-PubMed, Scopus and Web of Science. A total of eighteen studies were included in our survey for the inclusion criteria. Firstly, this review identified 210 citations from electronic search, after removal of duplicates and screening for relevant titles and abstracts, a total of eighteen articles were selected to the inclusion criteria established. Our findings suggest that natural products can be a promising or a trump tool for the development of new drugs to treat orofacial pain conditions, but the researchers that deal with experimental preclinical trials of new drugs (including natural products or synthetic drugs) for orofacial pain conditions urgently need to show translational evidence (with clinical approach) of these compounds.

Phytochemical screening and analgesic profile of the lyophilized aqueous extract obtained from Chrysobalanus icaco leaves in experimental protocols.

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.

Enhancement of orofacial antinociceptive effect of carvacrol, a monoterpene present in oregano and thyme oils, by ß-cyclodextrin inclusion complex in mice.

Orofacial pain is associated with diagnosis of chronic pain of head, face, mouth, neck and all the intraoral structures. Carvacrol, a naturally occurring isoprenoid with diverse class of biological activities including anti-inflammatory, analgesic, antitumor and antioxidant properties. Now, the antinociceptive effect was studied in mice pretreatment with carvacrol (CARV) and ß-cyclodextrin complex containing carvacrol (CARV-ßCD) in formalin-, capsaicin-, and glutamate- induced orofacial nociception. Mice were pretreated with vehicle (0.9% Nacl, p.o.), CARV (10 and 20mg/kg, p.o.), CARV-ßCD (10 and 20mg/kg, p.o.) or MOR (10mg/kg, i.p.) before the nociceptive behavior induced by subcutaneous injections (s.c.) of formalin (20µl, 2%), capsaicin (20µl, 2.5µg) or glutamate (20µl, 25µM) into the upper lip respectively. The interference on motor coordination was determined using rotarod and grip strength meter apparatus. CARV-ßCD reduced the nociceptive during the two phases of the formalin test, whereas CARV did not produced the reduction in face-rubbing behavior in the initial phase. CARV-ßCD (20mg/kg, p.o.) produced 49.3% behavior pain while CARV alone at 20mg/kg, p.o, produced 28.7% of analgesic inhibition in the second phase of formalin test. CARV, CARV-ßCD and Morphine (MOR) showed a significant reduction against nociception caused by capsaicin or glutamate injection. Thus the encapsulation of carvacrol in ß-cyclodextrin can acts as a considerable therapeutic agent with pharmacological interest for the orofacial pain management.

Orofacial antinociceptive effect of the ethanolic extract of Annona vepretorum Mart. (Annonaceae).

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.