In vivo and in silico anti-inflammatory properties of the sesquiterpene valencene.

Valencene (VLN) is a sesquiterpene found in juices and essential oils of citrus species such as Cyperus rotundus. Considering the evidence that this species has anti-inflammatory effects, the present study aims to evaluate the anti-inflammatory activity of VLN in vivo and in silico. Swiss mice (n = 6) were orally treated according to their treatment groups as follows: VLN (10, 100 or 300 mg/kg), negative control (0.9% saline), and positive controls (indomethacin 25 mg/kg or promethazine 6 mg/kg). The anti-inflammatory activity was evaluated in murine models of acute and chronic inflammation. The inhibition of acute inflammation was evaluated in models of paw edema induced by different inflammatory agents (carrageenan, dextran, histamine, and arachidonic acid (AA)) and carrageenan-induced pleurisy and peritonitis. The modulation of chronic inflammation was evaluated in a granuloma model induced cotton pellets implantation. The interaction with inflammatory targets was evaluated in silico using molecular docking analysis. The administration of VLN to challenged mice significantly inhibited paw edema formation with no significant difference between the administered doses. The compound also reduced albumin extravasation, leukocyte recruitment, and the production of myeloperoxidase (MPO), IL-1ß, and TNF-α in both pleural and peritoneal lavages. According to the mathematical-statistical model observed in silico analysis, this compound has favorable energy to interact with the cyclooxygenase enzyme (COX-2) and the histamine 1 (H1) receptor. Finally, animals treated with the sesquiterpene showed a reduction in both granuloma weight and concentration of total proteins in a chronic inflammation model. Given these findings, it is concluded that NLV presents promising pharmacological activity in murine models of acute and chronic inflammation.

Anti-inflammatory and antinociceptive effect of Hyptis martiusii BENTH leaves essential oil.

Hyptis martiusii Benth. also known as "cidreira brava", has some activities verified in the literature, such as antiulcerogenic, antimicrobial and antiedematogenic. This study aimed to verify the anti-inflammatory and antinociceptive effect of the leaves essential oil. For the evaluation of the anti-inflammatory activity of OEHM (100 mg/kg/p.o.), models paw edema induced by dextran and histamine, peritonitis and vascular permeability were used. Regarding the anti-nociceptive activity of the OEHM, abdominal contortion tests by acetic acid, formalin, hot plate (50.75 and 100 mg/kg/p.o.), open field and mechanical plantar hyper-nociception (100 mg/kg/p.o.) were carried out. OEHM (100 mg/kg) showed anti-inflammatory activity, being able to remarkably deducing the paw edema induced by dextran and histamine, the total number of cell leukocytes/neutrophils in peritonitis, and exudate in vascular permeability. In antinociceptive activity, the OEHM did not promote significant effect in central nervous system in the open field assay, remarkably reduced abdominal contortions (50, 75 and 100 mg/kg), the time in the formalin assay and the mechanical hyper-nociception (100 mg/kg); however, only doses between 75 and 100 mg/kg were capable of ameliorating the reponse latency time. Regarding the probable mechanism of action, the antinociceptive activity includes the participation in the activation of opioid, TRPV1, and α2-noradrenergic systems. In short, data obtained here reveal that OEHM has anti-inflammatory and antinociceptive activity, implying that its action may be involved in the mechanism of inhibition or liberation of pro-inflammatory mediators involved in pain and inflammation.

Potentiation of antibiotic activity by Passiflora cincinnata Mast. front of strains Staphylococcus aureus and Escherichia coli.

The development of new drugs from plants is an interesting alternative approach to overcoming microbial resistance. Passiflora cincinnata shows resistance to diseases and pests and a higher concentration of chemical components that may be useful in the pharmaceutical industry. We investigated the potential antimicrobial and antibiotic-modifying activity of hydroalcoholic extracts of leaves, stems, bark, pulp and seeds of P. cincinnata. The extracts were prepared by homogenization of material in 50% ethanol. Minimum inhibitory concentration (MIC) was determined by the broth dilution method, and the bacterial strains tested were Staphylococcus aureus and Escherichia coli. Antibiotic-modifying activity was evaluated against the strains S. aureus 03 and E. coli 08, using a subinhibitory concentration of extract. The antibiotics tested were: amikacin, gentamicin, ampicillin, potassium benzylpenicillin and oxacillin. The extracts did not show antimicrobial activity of clinical relevance, where the MIC was equal to or greater than 1024 µg/mL. S. aureus showed 13 events, while E. coli showed only 4 events. Among these events, 14 involved synergistic activity, potentiating the effect of the antibiotics, and only 3 events demonstrated antagonistic activity toward ampicillin. Hydroalcoholic extracts are potential antimicrobial agents when combined with conventional drugs little utilized in in vivo treatment.

D-limonene exhibits superior antihyperalgesic effects in a ß-cyclodextrin-complexed form in chronic musculoskeletal pain reducing Fos protein expression on spinal cord in mice.

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.

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.