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Isopulegol, a terpene compound commonly present in the essential oils of several aromatic plants, may present a number of important pharmacological activities. Besides the screening of the antinociceptive effect of the monoterpene isopulegol (ISO) and its inclusion complex in β-cyclodextrins (ISO/CD), this study also aimed at investigating the signaling pathways involved in the antinociceptive response. The effects of ISO and ISO/CD on the central nervous system (CNS) were evaluated through open-field and rota-rod assays and the antinociceptive effects in formalin models, abdominal contortions by acetic acid, hot-plate and plantar mechanical hypernociception. Male and female mice (Mus musculus), weighing between 20–30 g, were divided into 6-animal groups. The oral administration of isopulegol and its complex showed significant antinociceptive effects in the 10, 5 and 1 mg/kg doses for both the formalin and abdominal contortion assays, with highlights on the 10 mg/kg dose of ISO and ISO/CD in both assays. Likewise, the 10 mg/kg dose was selected for the evaluation of the effects on the CNS, central and peripheral antinociceptive effect and screening of the signaling pathways involved in the analgesic potential. ISO and ISO/CD, both in the 10 mg/kg dose v.o., did not show any alteration to the parameters evaluated of the CNS and the results pointed to a possible acute antinociceptive action in the tests of formalin, abdominal contortion, hot-plate and plantar mechanical hypernociception, suggesting the involvement of these signaling pathways: opioid, potassium channel, cholinergic, nitric oxide, cyclic guanosin monophosphate, vaniloid and glutamatergic. The results suggest that ISO and ISO/CD carry a promising antinociceptive potential as a possible alternative to the pharmacological treatment of pain, showing that the inclusion of ISO in cyclodextrins enhance its pharmacological properties, once that the complexation process involves much lower amounts of the compound – what contributes to a better bioavailability and weaker probability for the development of undesired effects.

Products of natural origin remain important in the discovery of new bioactive molecules and are less damaging to the environment. Benzaldehyde is a product of the metabolism of plants, and similarly to oxygenated terpenes, it can have antibacterial activity against Staphylococcus aureus and toxic action against Drosophila melanogaster; we aimed to verify these activities. The broth microdilution tests determined the minimum inhibitory concentration (MIC) of benzaldehyde alone and in association with antibiotics and ethidium bromide (EtBr). Toxicity against Drosophila melanogaster was determined by fumigation tests that measured lethality and damage to the locomotor system. The results indicated that there was an association of norfloxacin and ciprofloxacin with benzaldehyde, from 64 μg/mL to 32 μg/mL of ciprofloxacin in the strain K6028 and from 256 μg/mL to 128 μg/mL of norfloxacin in the strain 1199B; however, the associations were not able to interfere with the functioning of the tested efflux pumps. In addition, benzaldehyde had a toxic effect on flies. Thus, the results proved the ability of benzaldehyde to modulate quinolone antibiotics and its toxic effects on fruit flies, thus enabling further studies in this area.

Purpose: Alternative methods for the use of animals in research have gained increasing importance, due to assessments evaluating the real need for their use and the development of legislation that regulates the subject. The principle of the 3R’s (replacement, reduction and refinement) has been an important reference, such that in vitro, ex vivo and cord replacement methods have achieved a prominent place in research. Methods: Therefore, due to successful results from studies developed with these methods, the present study aimed to evaluate the myorelaxant effect of the Dysphania ambrosioides essential oil (EODa) using a Sus scrofa domesticus coronary artery model, and the toxicity of both the Dysphania ambrosioides essential oil and its major constituent, α-terpinene, against Drosophila melanogaster in toxicity and negative geotaxis assays. Results: The EODa relaxed the smooth muscle of swine coronary arteries precontracted with K+ and 5-HT in assays using Sus scrofa domesticus coronary arteries. The toxicity results presented LC50 values of 1.546 mg/mL and 2.282 mg/mL for the EODa and α-terpinene, respectively, thus showing the EODa and α-terpinene presented toxicity to these dipterans, with the EODa being more toxic. Conclusions: Moreover, the results reveal the possibility of using the EODa in vascular disease studies since it promoted the relaxation of the Sus scrofa domesticus coronary smooth muscle.

Isopulegol (ISO) is an alcoholic monoterpene widely found in different plant species, such as Melissa officinalis, and has already been reported to have a number of pharmacological properties. Like other terpenes, ISO is a highly volatile compound that is slightly soluble in water, so its inclusion into cyclodextrins (CDs) is an interesting approach to increase its solubility and bioavailability. Thus, our aim was to evaluate the antiedematogenic and anti-inflammatory activity of isopulegol and a β-cyclodextrin–isopulegol inclusion complex (ISO/β-CD) in rodent models. For the anti-inflammatory activity evaluation, antiedematogenic plethysmometry and acute (peritonitis and pleurisy), as well as chronic (cotton pellet-induced granuloma) anti-inflammatory models, were used. The docking procedure is used to evaluate, analyze, and predict their binding mode of interaction with H1 and Cox-2 receptors. The animals (n = 6) were divided into groups: ISO and ISO/β-CD, negative control (saline), and positive control (indomethacin and promethazine). ISO and ISO/β-CD were able to reduce acute inflammatory activity by decreasing albumin extravasation, leukocyte migration, and MPO concentration, and reducing exudate levels of IL-1β and TNF-α. ISO and ISO/β-CD significantly inhibited edematogenic activity in carrageenan- and dextran-induced paw edema. Moreover, both significantly reduced chronic inflammatory processes, given the lower weight and protein concentration of granulomas in the foreign body granulomatous inflammation model. The results suggest that the inclusion of ISO in β-cyclodextrins improves its pharmacological properties, with the histamine and prostaglandin pathways as probable mechanisms of inhibition, and also reinforces the anti-inflammatory profile of this terpene.