BACKGROUND: Schinus terebinthifolia Raddi (Anacardiaceae) is rich in essential oil, distinguished by a predominance of monoterpenes and sesquiterpenes, it being widely used in traditional medicine for the treatment of inflammations.
OBJECTIVE: This study\'s objective was to investigate the chemical composition of the essential oil of S. terebinthifolia (EOST) collected in six states of Brazil, evaluate its anti-inflammatory effects in mice, and analyze the histochemistry and micromorphology of leaves and stems.
METHODS: Aerial parts of S. terebinthifolia were collected in six states of Brazil, and the essential oil was extracted by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). The histochemistry and micromorphology of leaves and stems were performed using standard reagents, light and field emission scanning electron microscopy, beyond energy-dispersive X-ray spectroscopy. The EOST were evaluated for anti-inflammatory activity and hyperalgesia using the carrageenan-induced paw edema methodology.
RESULTS: The EOST showed variation across the six states in its yield (0.40%-0.86%) and chemical composition: hydrocarbon monoterpenes (28.76%-47.73%), sesquiterpenes, (31.43%-41.76%), oxygenated monoterpenes (14.31%-19.57%), and oxygenated sesquiterpenes (4.87%-14.38%). Both α-pinene and limonene were predominant constituents of essential in five regions, except for one state where α-phellandrene and limonene were the dominant components. A comprehensive description of the leaf and stem micromorphology and histochemistry was performed. In the in vivo testing, all EOST samples exerted antiedematogenic and anti-hyperalgesic effects, when tested in a carrageenan-induced paw inflammation (mechanical and thermal hyperalgesia) model with oral doses of 30 mg/kg.
CONCLUSIONS: Our results indicate that the EOST samples collected in six Brazilian states differed in their chemical composition but not their anti-inflammatory and antihyperalgesic effects, which was correlated with the synergistic effect of its components, collaborating the etnhopharmacologycal use of this plant due to its an anti-inflammatory effect. Also, micromorphology and histochemistry of leaves and stems presented in this study provide anatomical and microchemical information, which aids species identification.

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UNASSIGNED: Drugs that inhibit the reuptake of serotonin, norepinephrine, and/or dopamine are widely used for treating depressive disorders and have emerged as effective drugs for neuropathic pain. They have no substantial anti-nociceptive effects but are considered, with gabapentin/pregabalin, first-line drugs for neuropathic pain.
UNASSIGNED: In this study, three different antidepressant agents were used in different doses to investigate their anti-hyperalgesic effects in rat models of neuropathic pain using hot plate and tail flick methods. They have different mechanisms of action; vilazodone hydrochloride is a selective serotonin inhibitor and a 5-HT1A partial agonist; talsupram hydrochloride is a selective noradrenaline inhibitor, and it has a high affinity for noradrenaline transporter (NET), whereas indatraline hydrochloride is a triple reuptake inhibitor that inhibits transporters for 5-HT (SERT), dopamine (DAT), and NET.
UNASSIGNED: All the drugs used in the experiment were found to have an anti-hyperalgesic effect in both tests compared to the sham group. When anti-hyperalgesic effects of the three agents were compared to each other, it was found that talsupram hydrochloride was significantly more effective than the two other drugs in hot plate test. However, there was no statistically significant difference in the tail flick test. Indatraline hydrochloride was more effective than vilazodone hydrochloride at the same doses in the tail flick test.
UNASSIGNED: Our data suggest that three drugs are effective analgesics in rat models of neuropathic pain and inhibition of noradrenaline reuptake represents the cornerstone of analgesic mechanisms of effective antidepressants.

BACKGROUND: Leaves from Ocimum kilimandscharicum Gürke (Lamiaceae) are popularly used against articular pain.
OBJECTIVE: The aim of this study was to test the anti-inflammatory and anti-hyperalgesic (analgesic) properties of the essential oil and camphor isolated from O. Kilimandscharicum leaves (EOOK) in 4 models including zymosan induced-articular inflammation model in mice.
METHODS: For in vivo models, EOOK was tested in carrageenan-induced paw edema model with oral doses of 30, 100, and 300 mg/kg (oral administration = p.o.) and in zymosan-induced articular inflammation (including knee edema, leukocyte infiltration, mechanical hyperalgesia and nitric oxide), EOOK (100 mg/kg, p. o.) and camphor (30 mg/kg, p. o.) were tested. EOOK (100 mg/kg, p. o.) was tested in the rolling and also in the adhesion of leukocytes to the mesenteric microcirculation in situ model of carrageenan induced inflammation and EOOK (1, 3, 10, 30, and 60 μg/mL) was tested in vitro against neutrophils chemotaxis induced by N-formyl methionyl leucyl phenylalanine (fMLP).
RESULTS: The treatment with EOOK significantly inhibited the carrageenan-induced edema, mechanical and cold hyperalgesia. Both, EOOK and camphor inhibited all articular parameters induced by zymosan. In situ intravitral microscopy analysis, EOOK significantly inhibited carrageenan-induced leukocyte rolling and adhesion. In vitro neutrophils chemotaxis, EOOK inhibited the leukocyte chemotaxis induced by fMLP.
CONCLUSIONS: The present study showed that EOOK inhibited pain and inflammatory parameters contributing, at least in part, to explain the popular use of this plant as analgesic natural agent. This study also demonstrates that camphor and some known anti-inflammatory compounds present in EOOK could contribute for analgesic and anti-inflammatory articular properties.

Somatostatin released from the capsaicin-sensitive sensory nerves mediates analgesic and anti-inflammatory effects via the somatostatin sst4 receptor without endocrine actions. Therefore, sst4 is considered to be a novel target for drug development in pain including chronic neuropathy, which is an emerging unmet medical need. Here, we examined the in silico binding, the sst4-linked G-protein activation on stable receptor expressing cells (1 nM to 10 μM), and the effects of our novel pyrrolo-pyrimidine molecules in mouse inflammatory and neuropathic pain models. All four of the tested compounds (C1-C4) bind to the same binding site of the sst4 receptor with similar interaction energy to high-affinity reference sst4 agonists, and they all induce G-protein activation. C1 is the more efficacious (γ-GTP-binding: 218.2% ± 36.5%) and most potent (EC50: 37 nM) ligand. In vivo testing of the actions of orally administered C1 and C2 (500 µg/kg) showed that only C1 decreased the resiniferatoxin-induced acute neurogenic inflammatory thermal allodynia and mechanical hyperalgesia significantly. Meanwhile, both of them remarkably reduced partial sciatic nerve ligation-induced chronic neuropathic mechanical hyperalgesia after a single oral administration of the 500 µg/kg dose. These orally active novel sst4 agonists exert potent anti-hyperalgesic effect in a chronic neuropathy model, and therefore, they can open promising drug developmental perspectives.

Citral (CIT) is a monoterpene formed by the geranial and neral stereoisomers. CIT is the major compound of Cymbopogon citratus essential oil, commonly known as \"lemongrass\", and has demonstrated potential antihyperalgesic, anti-nociceptive and anti-inflammatory effects. However, CIT shows high volatility, low solubility in water and consequent low bioavailability, which limits its use. Therefore, the aim of this study was to evaluate cell viability, anti-hyperalgesic and anti-inflammatory effects of inclusion complexes of CIT on β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). Initially, physical mixture (PM) and freeze-dried inclusion (FD) complexes of CIT/β-CD and CIT/HP-β-CD were obtained in the molar ratio (1:1). The samples were characterized by DSC, TG/DTG, FT-IR, XRD, SEM and the complexation efficiency were performed by HPLC. Cell viability assay was performed by rezasurin reduction technique in J774 macrophages cell line. The motor activity through rota rod apparatus, mechanical hyperalgesia and pleurisy induced by carrageenan were evaluated in mice. The complexation of CIT was evidenced with β-CD and HP-β-CD by the characterization techniques analyzed. The complexation efficiency of CIT/β-CD and CIT/HP-β-CD were 78.6% and 71.7%, respectively. The CIT, CIT/β-CD and CIT/HP-β-CD showed cell viability in macrophages and did not interfere in the motor activity of mice. Besides that, the samples demonstrated antihyperalgesic and anti-inflammatory activity due to the reduction in total leukocytes and TNF-α levels. However, CIT/β-CD has better pharmacological effects among the three samples evaluated. Therefore, CIT/β-CD has potential for the development of products to treat inflammatory and pain reactions.

BACKGROUND: Caryocar brasiliense, popularly known as pequi, is widely distributed in the Amazon rainforest and Brazilian savannah. The fruit obtained from pequi is used in cooking and has folk use as an anti-inflammatory and for the treatment of respiratory disease. Until now, these two properties had not been scientifically demonstrated for Pequi oil in a carrageenan model.
OBJECTIVE: Our group determined the composition and safe use of Pequi oil from the Savannah of Campo Grande, and the anti-inflammatory and anti-nociceptive activities of this pequi oil were investigated in vivo models.
METHODS: Doses of 300, 700, and 1000 mg/kg of Pequi oil were administered orally (p.o.) to Swiss male mice, and three parameters of inflammation (mechanical hyperalgesia, cold, hyperalgesia, and oedema) were analyzed in a carrageenan model to induce an inflammatory paw state.
CONCLUSIONS: The effects of Pequi oil were also carrageenan in pleurisy model, formalin, and acetic acid induced nociception. Oral administration of 1,000 mg/kg orally Pequi oil (p.o.) inhibited (*P<0.05), the migration of total leukocytes, but not alter plasma extravasation, in the pleurisy model when compared to control groups. The paw edema was inhibited with doses of 700 (P <0.05) and 1,000 mg (P<0.001) of pequi oil after 1, 2, and 4 hours after carrageenan. Pequi oil (1,000 mg/kg) also blocked the mechanical hyperalgesy and reduced cold allodynia induced by carrageenan in paw (P <0.05). Pequi oil treatment (1,000 mg/kg) almost blocked (P < 0.001) all parameters of nociception observed in formalin and acid acetic test.
CONCLUSIONS: This is the first time that the analgesic and anti-inflammatory effects of Pequi oil have been shown.

Palicourea crocea (Sw.) Roem. and Schult., \"douradinha,\" are used by treat inflammation (edema). Croceaine A (PC-1) was isolated from P. crocea (MEPC) leaves and studied for its antioxidant and anti-inflammatory activity, as well as concentrations of constituents and acute toxicity. The phenols and polyphenolics compounds and HPLC/DAD were determined. The antioxidant activity were evaluated for DPPH, ABTS, and MDA. MEPC (300, 100, and 300 mg/kg) and PC-1 (10 and 30 mg/kg) were tested for anti-inflammatory effects in paw edema, pleurisy, cold sensitivity, and mechanical hyperalgesia. Acute toxicity is also described. MEPC contained high concentrations of phenolic and flavonoid compounds (≤ 800.35 mg/g), as well as caffeic acid, ferulic acid, rutin, and quercetin, revealed by HPLC-DAD analysis. MEPC displayed antioxidant activity against ABTS radicals (IC50 = 68.5 μg/mL) and MDA (74%). MEPC and alkaloid PC-1 demonstrated an anti-edematogenic effect in Cg-induced paw edema in 2 and 4 h, and also significantly reduced mechanical hyperalgesia, cold response to acetone in mice, at 3 and 4 h after injection, as well as leukocyte migrationin the pleurisy model. No toxicity was detected by MEPC. For the first time, P. crocea was evaluated for its antioxidant, systemic anti-inflammatory, and anti-hyperalgesic activities.

A novel series of EP4 agonists and antagonists have been identified, and then used to validate their potential in the treatment of inflammatory pain. This paper describes these novel ligands and their activity within a number of pre-clinical models of pain, ultimately leading to the identification of the EP4 partial agonist GSK726701A.

BACKGROUND: 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).
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.
CONCLUSIONS: 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.
CONCLUSIONS: Our results suggest that AEC act against inflammatory pain.