The objective of the present study was to evaluate the antinociceptive effects of phytol using chemical and thermal models of nociception in mice and to assess its antioxidant effects in vitro. Phytol was administered intraperitoneally (i.p.) to mice at doses of 25, 50, 100, and 200 mg/kg. In the acetic acid-induced writhing test, phytol significantly reduced the number of contortions compared to the control group (P < 0.001). In the formalin test, phytol reduced significantly the amount of time spent in paw licking in both phases (the neurogenic and inflammatory phases), this effect being more pronounced in the second phase (P < 0.001). Phytol also provoked a significant increase in latency in the hot plate test. These antinociceptive effects did not impaire the motor performance, as shown in the rotarod test. Phytol demonstrated a strong antioxidant effect in vitro in its capacity to remove hydroxyl radicals and nitric oxide as well as to prevent the formation of thiobarbituric acid reactive substances (TBARS). Taken as a whole, these results show the pronounced antinociceptive effects of phytol in the nociception models used, both through its central and peripheral actions, but also its antioxidant properties demonstrated in the in vitro methods used.

Context: Several studies have demonstrated that essential oils and their major components have antioxidant activity. p-Cymene is a monoterpene and a major constituent of essential oils of various species of plants. Objective: This paper evaluated the antioxidant potential of p-cymene in the hippocampus of mice by determining the levels of thiobarbituric acid reactive substances (TBARS), nitrite content, and activity of catalase (CAT) and superoxide dismutase (SOD). Materials and methods: Swiss mice were intraperitoneally treated with 0.05% Tween 80 dissolved in 0.9% saline solution, ascorbic acid 250 mg/kg, and p-cymene at doses of 50, 100, and 150 mg/kg, respectively. After treatment, all groups were observed for 24 h, afterwards, the groups were euthanized for removal of the brain and dissection of the hippocampus. Results:The results of treatment with p-cymene were a significant decrease in lipid peroxidation and nitrite content at a dose of CYM 50: 65.54%, CYM 100: 73.29%, CYM 150: 89.83%, and CYM 50: 71.21%; CYM 100: 68.61% and CYM 150:67%, respectively, when compared with the control group. The results showed that at all tested doses, p-cymene produces an increase in SOD and catalase activity significantly at a dose of CYM 50: 22.7%, CYM 100: 33.9%, CYM 150: 63.1%, and CYM 50: 119.25%, CYM 100: 151.83% and CYM 150: 182.70%, respectively, when compared with the vehicle-treated group. Discussion and conclusion: The result of this study shows that p-cymene has an antioxidant potential in vivo and may act as a neuroprotective agent in the brain. This compound may present a new strategy in the development of treatment for many diseases in which oxidative stress plays an important pathophysiological role.

Anacardic acid (AA), a compound extracted from cashew nut liquid, exhibits numerous pharmacological activities. The aim of the current investigation was to assess the anti-inflammatory, antinociceptive, and antioxidant activities of AA in mouse models. For this, Swiss albino mice were pretreated with AA (10, 25, 50 mg/kg, intraperitoneally, ip) 30 min prior to the administration of carrageenan, as well as 25 mg/kg of prostaglandin E2, dextran, histamine, and compound 48/80. The antinociceptive activity was evaluated by formalin, abdominal, and hot plate tests, using antagonist of opioid receptors (naloxene, 3 mg/kg, ip) to identify antinociceptive mechanisms. Results from this study revealed that AA at 25 mg/kg inhibits carrageenan-induced edema. In addition, AA at 25 mg/kg reduced edema and leukocyte and neutrophilic migration to the intraperitoneal cavity, diminished myeloperoxidase activity and malondialdehyde concentration, and increased the levels of reduced glutathione. In nociceptive tests, it also decreased licking, abdominal writhing, and latency to thermal stimulation, possibly via interaction with opioid receptors. Taken together, these results indicate that AA exhibits anti-inflammatory and antinociceptive actions and also reduces oxidative stress in acute experimental models, suggesting AA as a promising compound in the pharmaceutical arena.

cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. the peptides obtained possessed the amino acid sequences, GVVDiLKGAAKDLAGH and GVVDiLKGAAKDLAGHLASKV, with monoisotopic masses of [M + H] ± = 1563.8 Da and [M + H] ± = 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1-16) and Ocellatin-K1(1-21). Functional analysis revealed that Ocellatin-K1(1-16) and Ocellatin-K1(1-21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1-16) and Ocellatin-K1(1-21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and nf-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1-16) and Ocellatin-K1(1-21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. these functional properties suggest possible to neuromodulatory therapeutic applications.The skin of amphibians has been the subject of interest and study of several research groups as well as pharmaceutical industries, due to the abundance and diversity of bioactive molecules with potential biotechnological applications, especially for the production of new drugs 1 . The characteristic way of living of amphibians is divided between aquatic and the terrestrial environment 2 . They possess a highly sensitive skin that is essential to its respiration and is highly vulnerable to environmental aggressions, such as desiccation, attack of microorganisms, ultraviolet radiation, and injuries 3 . This vulnerability has culminated in the development of an innate defense system as a survival strategy based on the expression, production, accumulation, and secretion of bioactive www.nature.com/scientificreports www.nature.com/scientificreports/ against E. coli with MIC of 125 μg/mL (Fig. 4) and inhibition percentage corresponding to 34.17 ± 11.66%. The optical density (630 nm) of E. coli decreased in a dose-dependent manner, showing significant reduction on viability for both the ocellatins at concentrations between 125 and 1000 μg/mL. The value 125 μg/mL of MIC is too high to be characterized as having significant antibacterial potential. Moreover, only Ocellatin-K1(1-16) showed any significant activity against S. aureus featuring MICs of 31.25 μg/mL and inhibition percentage corresponding to 30.79 ± 10.27%. This activity was not seen to be conc...

Casearia sylvestris Swartz is a medicinal plant widely distributed in Brazil. It has anti-inflammatory, antiulcer and antitumor activities and is popularly used to treat snakebites, wounds, diarrhea, flu and chest colds. Its leaves are rich in oxygenated tricyclic cis-clerodane diterpenes, particulary casearins. Herein, we evaluated the antioxidant activities of a fraction with casearins (FC) isolated from C. sylvestris and histological changes on the central nervous system and livers of Mus musculus mice. Firstly, in vitro studies (0.9, 1.8, 3.6, 5.4 and 7.2 μg/mL) revealed EC50 values of 3.7, 6.4 and 0.16 µg/mL for nitrite, hydroxyl radical and TBARS levels, respectively. Secondly, FC (2.5, 5, 10 and 25 mg/kg/day) was intraperitoneally administered to Swiss mice for 7 consecutive days. Nitrite levels in the hippocampus (26.2, 27.3, 30.2 and 26.6 µM) and striatum (26.3, 25.4, 34.3 and 27.5 µM) increased in all treated animals (P < 0.05). Lower doses dropped reduced glutathione, catalase and TBARS levels in the hippocampus and striatum. With the exception of this reduction in TBARS formation, FC displayed only in vitro antioxidant activity. Animals exhibited histological alterations suggestive of neurotoxicity and hepatotoxicity, indicating the need for precaution regarding the consumption of medicinal formulations based on Casearia sylvestris.