Polymer-Based Wound Dressings Loaded with Essential Oil for the Treatment of Wounds: A Review.

Wound healing can result in complex problems, and discovering an effective method to improve the healing process is essential. Polymeric biomaterials have structures similar to those identified in the extracellular matrix of the tissue to be regenerated and also avoid chronic inflammation, and immunological reactions. To obtain smart and effective dressings, bioactive agents, such as essential oils, are also used to promote a wide range of biological properties, which can accelerate the healing process. Therefore, we intend to explore advances in the potential for applying hybrid materials in wound healing. For this, fifty scientific articles dated from 2010 to 2023 were investigated using the Web of Science, Scopus, Science Direct, and PubMed databases. The principles of the healing process, use of polymers, type and properties of essential oils and processing techniques, and characteristics of dressings were identified. Thus, the plants Syzygium romanticum or Eugenia caryophyllata, Origanum vulgare, and Cinnamomum zeylanicum present prospects for application in clinical trials due to their proven effects on wound healing and reducing the incidence of inflammatory cells in the site of injury. The antimicrobial effect of essential oils is mainly due to polyphenols and terpenes such as eugenol, cinnamaldehyde, carvacrol, and thymol.

Antinociceptive and anti-inflammatory activities of Ayapana triplinervis essential oil rich in thymohydroquinone dimethyl ether from Brazil.

Ayapana triplinervis (M.Vahl) R.M.King & H.Rob. (Asteraceae), popularly known as japana, is a tropical, aromatic subshrub widely used as tea to combat some diseases. The essential oil was obtained from the leaves by hydrodistillation (3 h), and the chemical composition was analyzed by gas chromatography coupled to mass spectrometry. For in vivo assays, Mus musculus/Swiss mice were used to evaluate oral acute toxicological (at dose of 2000 mg/kg); peripheral and central analgesic for abdominal contortion (doses of 6.25, 12.5, 25, 50 and 100 mg/kg), hot plate test (12.5, 25, 50, and 100 mg/kg) and formalin (25, 50 and 100 mg/kg); open field test (100 mg/kg); and anti-inflammatory by ear swelling induced by xylene (6.25,12.5, 25, 50, and 100 mg/kg). The yield of A. triplinervis essential oil (AtEO) was 4.6%, and the oxygenated monoterpene 2,5-dimethoxy-p-cymene was the major compound in this study (63.6%). AtEO at a dose of 2,000 mg/kg orally did not change the behavior patterns or mortality of the animals; liver and kidney biochemical levels were similar to the control group, indicating no liver and kidney toxicity. Moreover, AtEO, at doses of 6.25, 12.5, 25, 50, and 100 mg/kg, reduced abdominal contortions by 21%, 54%, 91%, 58%, and 55%, respectively. In the hot plate test, AtEO showed a significant increase in latency time in the 60-min interval at doses of 25 mg/kg (11.3 ± 3.3 s) and 100 mg/kg (11.9 ± 0.9 s). In the first phase of the formalin test, AtEO decreased paw licking time at doses of 25, 50, and 100 mg/kg, with inhibition of 22%, 38%, and 83%; in the second phase, the same doses, decreased licking time with inhibition of 24%, 34%, and 76%. AtEO did not present a significant change in the spontaneous locomotor activity of the animals. Doses of 6.25, 12.5, 25, 50, and 100 mg/kg significantly reduced ear edema induced by topical application of xylene with percentages of 40%, 39%, 54%, 45%, and 45%, respectively. So, AtEO demonstrated low acute oral toxicity and exhibited significant antinociceptive and anti-inflammatory actions, consistent with the use of A. triplinervis in traditional medicine.

Lippia alba essential oil: A powerful and valuable antinociceptive and anti-inflammatory medicinal plant from Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: In Brazilian popular medicine, Lippia alba leaves are used in teas to treat pain and inflammatory diseases. AIM OF THE STUDY: to evaluate the chemical composition, antinociceptive, and anti-inflammatory activities of Lippia alba essential oil and its major compound geraniol. MATERIAL AND METHODS: Lippia alba leaves were collected in Pará state, Brazil. The leaf essential oil was obtained using a modified Clevenger-type extractor. Then, the oil was analyzed by GC and GC-MS analyses. To evaluate the toxicity of LaEO and geraniol, the doses of 50, 300, and 2000 mg/kg were used in a mouse model. For antinociception tests, abdominal contortion, hot plate, and formalin tests were used; all groups were treated with LaEO and geraniol at doses of 25, 50, and 100 mg/kg; and to evaluate inflammation using the ear edema model. RESULTS: The constituents identified in the highest content were oxygenated monoterpenes: geraniol (37.5%), geranial (6.7%) and neral (3.8%). The animals treated with LaEO and geraniol demonstrated atypical behaviors with aspects of lethargy and drowsiness, characteristics of animals in a state of sedation; the relative weights showed no significant difference compared to the controls. In the abdominal contortion test, LaEO at 25 mg/kg, 50 mg/kg doses, and 100 mg/kg reduced the number of contortions, representing a percentage reduction of 84.64%, 81.23%, and 66.21% respectively. In the hot plate test, LaEO and geraniol increased the latency time at doses of 25, 50, and 100 mg/kg in all test periods; there was no statistical difference between LaEO and geraniol. In the first phase of the formalin test, only doses of 25 mg/kg and 100 mg/kg of LaEO showed significant activity, reducing the latency time by 53.40% and 58.90%. LaEO at doses of 25 mg/kg and 100 mg/kg reduced the size of the edema, demonstrating an anti-inflammatory activity of 59.38% (25 mg/kg) and 50% (100 mg/kg). CONCLUSION: Lippia alba essential oil and geraniol showed central/peripheral analgesic and anti-inflammatory potential and can be used as an alternative or complementary treatment to conventional drugs. More studies are needed to evaluate its action mechanisms and its analgesic effects.

Seasonal influence on the essential oil chemical composition of Hyptis crenata Pohl ex Benth.: a valuable plant from Marajó, Brazil.

Introduction: Essential oils (EOs) from the Hyptis genus have been reported as bactericides and fungicides. However, the properties of these oils can be affected by climatic factors, as well as the collection period, which promotes changes in the chemical composition of the oil. In this context, this study aimed to evaluate the climatological influences on the chemical composition of the essential oil from the leaves of Hyptis crenata. Methods: The leaves were collected in Marajó island (Brazil) monthly for a year. The EOs were obtained by hydrodistillation and analyzed by Gas Chromatography coupled to Mass Spectrometry (GC-MS). Pearson's correlation was used to evaluate the relationship between climatic parameters, content, and chemical composition of essential oil; multivariate analysis was used to evaluate the interrelationship between samples and their chemical constituents. Results and Discussion: The constituents with the highest contents (>2.0%) in essential oils during the studied period were 1,8-cineole (28.48% ± 4.32%), α-pinene (19.58% ± 2.29%), camphor (11.98% ± 2.54%), ß-pinene (9.19% ± 1.47%), limonene (6.12% ± 3.15%), α-terpineol (2.42% ± 0.25%) and borneol (2.34% ± 0.48%). ß-Pinene significantly correlated (p < 0.05) with precipitation and humidity. According to the chemometric tools, two groups were formed: chemical profile I, marked by 1,8 cineole, α-pinene, ß-pinene, borneol, α-terpineol, and limonene, while group II (July) presented a chemical type characterized by camphor. It is understood that the species in question can be a reliable source of biologically active components during different climatic periods in the Amazon. The chemical variability could have significant implications for the pharmaceutical industry and traditional medicine.

Volatile Profiles and DNA Barcodes of Myrtaceae Species with Occurrence in the Brazilian Amazon.

Myrtaceae family includes many species with taxonomic challenges, making it one of the most complex families to identify. This study used DNA barcoding to find molecular markers for species authentication based on the Myrtaceae family's chemical composition and genetic diversity. Essential oils and genetic material were extracted from the leaves of six different species: Eugenia uniflora, E. patrisii, Myrcia splendens, Psidium guajava, P. guineense, and Psidium sp. The samples were analyzed based on compound classes and grouped into two categories. Group I included samples with high amounts of oxygenated sesquiterpenes (3.69-76.05 %) and fatty acid derivatives (0.04-43.59 %), such as E. uniflora, Myrcia splendens, and E. patrisii. Group II included samples P. guajava, P. guineense, and Psidium sp., which had a significant content of monoterpene hydrocarbons (0.69-72.35 %), oxygenated sesquiterpenes (8.06-68.1 %), phenylpropanoids (0.45-22.59 %), and sesquiterpene hydrocarbons (0.27-21.84 %). The PsbA-trnH gene sequences had a high genetic variability, allowing the species to be distinguished. A phylogenetic analysis showed two main clusters with high Bootstrap values corresponding to the subtribes Eugeniineae, Myrciinae, and Pimentinae. The results suggest a weak correlation between genetic and chemical data in these Myrtaceae species.

Chemical Compositions and Enantiomeric Distributions of Foliar Essential Oils of Chamaecyparis lawsoniana (A. Murray bis) Parl, Thuja plicata Donn ex D. Don, and Tsuga heterophylla Sarg.

As part of our continuing interest in the essential oil compositions of gymnosperms, particularly the distribution of chiral terpenoids, we have obtained the foliar essential oils of Chamaecyparis lawsoniana (two samples), Thuja plicata (three samples), and Tsuga heterophylla (six samples) from locations in the state of Oregon, USA. The essential oils were obtained via hydrodistillation and analyzed by gas chromatographic techniques, including chiral gas chromatography-mass spectrometry. The major components in C. lawsoniana foliar essential oil were limonene (27.4% and 22.0%; >99% (+)-limonene), oplopanonyl acetate (13.8% and 11.3%), beyerene (14.3% and 9.0%), sabinene (7.0% and 6.5%; >99% (+)-sabinene), terpinen-4-ol (5.0% and 5.3%; predominantly (+)-terpinen-4-ol), and methyl myrtenate (2.0% and 5.4%). The major components in T. plicata essential oil were (-)-α-thujone (67.1-74.6%), (+)-ß-thujone (7.8-9.3%), terpinen-4-ol (2.7-4.4%; predominantly (+)-terpinen-4-ol), and (+)-sabinene (1.1-3.5%). The major components in T. heterophylla essential oil were myrcene (7.0-27.6%), α-pinene (14.4-27.2%), ß-phellandrene (6.6-19.3%), ß-pinene (6.4-14.9%; >90% (-)-ß-pinene), and (Z)-ß-ocimene (0.7-11.3%). There are significant differences between the C. lawsoniana essential oils from wild trees in Oregon and those of trees cultivated in other geographical locations. The essential oil compositions of T. plicata are very similar, regardless of the collection site. There are no significant differences between T. heterophylla essential oils from the Oregon Coastal Range or those from the Oregon Cascade Range. Comparing essential oils of the Cupressaceae with the Pinaceae, there are some developing trends. The (+)-enantiomers seem to dominate for α-pinene, camphene, sabinene, ß-pinene, limonene, terpinen-4-ol, and α-terpineol in the Cuppressaceae. On the other hand, the (-)-enantiomers seem to predominate for α-pinene, camphene, ß-pinene, limonene, ß-phellandrene, terpinen-4-ol, and α-terpineol in the Pinaceae.

Forced swim stress exacerbates inflammation-induced hyperalgesia and oxidative stress in the rat trigeminal ganglia.

This study investigates the impact of combining psychophysical stress, induced by forced swim (FSS), with masseter inflammation on reactive oxygen species (ROS) production in trigeminal ganglia (TG), TRPA1 upregulation in TG, and mechanical hyperalgesia. In a rat model, we demonstrate that FSS potentiates and prolongs CFA-induced ROS upregulation within TG. The ROS levels in CFA combined with FSS group surpass those in the CFA-only group on days 4 and 28 post-treatment. FSS also enhances TRPA1 upregulation in TG, with prolonged expression compared to CFA alone. Furthermore, CFA-induced mechanical hyperalgesia is significantly prolonged by FSS, persisting up to day 28. PCR array analyses reveal distinct alterations in oxidative stress genes under CFA and CFA combined with FSS conditions, suggesting an intricate regulation of ROS within TG. Notably, genes like Nox4, Hba1, Gpx3, and Duox1 exhibit significant changes, providing potential targets for managing oxidative stress and inflammatory pain. Western blot and immunohistochemistry confirm DUOX1 protein upregulation and localization in TG neurons, indicating a role in ROS generation under inflammatory and stress conditions. This study underscores the complex interplay between psychophysical stress, inflammation, and oxidative stress in the trigeminal system, offering insights into novel therapeutic targets for pain management.

Age- and Sex-Dependent Effects of Moderate Exercise on Endogenous Pain Inhibition in Rats.

Diffuse noxious inhibitory controls (DNICs), or the pain inhibits pain phenomenon, refer to reduced pain-like behaviors that are displayed following a noxious conditioning stimulus located far from the test stimulus and have also been referred to as "descending control of nociception" when measured in awake-behaving animals. In this study, we sought to determine the impact of moderate long-term exercise on the DCN response and determine if this effect differed across age and sex. After a six-week exercise program consisting of 30 min of moderate treadmill running 5 days a week, the animals' forepaws were injected with capsaicin, and DCN responses were assessed using thermal withdrawal latencies of the hind paw. Young, exercised male and female rats displayed prolonged DCN responses relative to their sedentary counterparts, with the young exercised male group displaying longer-lasting DCN facilitation than the young exercised females. Exercise did not impact DCN responses in either male or female aged rats. Additionally, the serum testosterone levels did not change following exercise in any group. Importantly, the levels of corticosterone did not change following the exercise program, indicating that changes in the DCN response are not due to stress-induced analgesia. Our findings suggest that moderate exercise can facilitate the DCN response in young animals, even when this exercise does not change the levels of serum testosterone.

Exploring the impact of seasonal variations on the chemical composition, antinociceptive, and anti-inflammatory properties of Pogostemon heyneanus Benth. essential oil.

Background: Pogostemon heyneanus leaves infusions are relevant in ethnopharmacology for treating colds, coughs, headaches, and asthma. Purpose: The essential oil chemical composition of a Pogostemon heyneanus specimen was monthly monitored from October 2021 to July 2022 to evaluate the climatic influences on its yield and chemical composition and antinociceptive, andanti-inflammatory properties. Methods: The leaves, collected monthly over a 10-month period, were submitted to hydrodistillation. The oils obtained were analyzed by gas chromatography coupled to a mass spectrometer and gas chromatography coupled to flame ionization detector. The P. heyneanus essential oil (PhEO) was tested in vivo to evaluate its peripheral analgesic actions through the abdominal writhing test induced by acetic acid, and peripheral analgesia by tail immersion. Neurogenic and inflammatory pain were evaluated by formalin test, and acute oral toxicity of the oil was also verified. Results: PhEO presented 27 chemical constituents with the highest predominance of patchoulol (43.6%-76.9%), α-bulnesene (0.2%-12.7%), α-guaiene (0.4%-8.9%), seychellene (3.8%-5.1%) and pogostol (0.0%-8.2%). The climatic parameters insolation, humidity, rainfall, and temperature did not influence the essential oil yield or the main chemical constituents, except for pogostol, which presented a strong (r = 0.73) and statistically significant (p < 0.05) correlation with temperature. PhEO did not display toxicity at the maximum 300 mg/kg dosage. The oil showed low peripheral and central analgesic action at 100 mg/kg, while in the neurogenic and inflammatory pain inhibition tests, no actions related to PhEO were observed. In the carrageenan-induced peritonitis test, PhEO did not reduce the migration of leukocytes to the peritoneal cavity compared to the control group. Conclusion: Pogostemon heyneanus is a resistant plant to seasonal influences and a source of patchoulol. Despite ethnopharmacological indications, no in-vivo biological activities such as neurogenic or inflammatory pain were identified in the present work. So, the low influence of the climatic parameters on chemical composition can infer that the low pharmacological activity is also not subject to climatic variations, that is, it does not change due to the climate.

Inflammation, brain connectivity, and neuromodulation in post-traumatic headache.

Post-traumatic headache (PTH) is a debilitating condition that affects individuals with different levels of traumatic brain injury (TBI) severity. The difficulties in developing an effective treatment are related to a lack of understanding the complicated mechanisms and neurobiological changes in brain function after a brain injury. Preclinical studies have indicated that peripheral and central sensitization of the trigeminal nociceptive pathways contributes to PTH. While recent brain imaging studies have uncovered widespread changes in brain functional connectivity following trauma, understanding exactly how these networks contribute to PTH after injury remains unknown. Stimulation of peripheral (trigeminal or vagus) nerves show promising efficacies in PTH experimental animals, likely mediated by influencing TBI-induced pathological plasticity by decreasing neuroinflammation and neuronal apoptosis. Non-invasive brain stimulations, such as transcranial magnetic or direct current stimulations, show analgesia for multiple chronic pain conditions, including PTH. Better mechanistic understanding of analgesia achieved by neuromodulations can define peripheral and central mechanisms involved in the development, the resolution, and the management of PTH.

Sex differences in visceral sensitivity and brain activity in a rat model of comorbid pain: a longitudinal study.

ABSTRACT: Temporomandibular disorder (TMD) and irritable bowel syndrome (IBS) are 2 chronic overlapping pain conditions (COPCs) that present with significant comorbidity. Both conditions are more prevalent in women and are exacerbated by stress. While peripheral mechanisms might contribute to pain hypersensitivity for each individual condition, mechanisms underlying the comorbidity are poorly understood, complicating pain management when multiple conditions are involved. In this study, longitudinal behavioral and functional MRI-based brain changes have been identified in an animal model of TMD-like pain (masseter muscle inflammation followed by stress) that induces de novo IBS-like comorbid visceral pain hypersensitivity in rats. In particular, data indicate that increased activity in the insula and regions of the reward and limbic systems are associated with more pronounced and longer-lasting visceral pain behaviors in female rats, while the faster pain resolution in male rats may be due to increased activity in descending pain inhibitory pathways. These findings suggest the critical role of brain mechanisms in chronic pain conditions and that sex may be a risk factor of developing COPCs.

Seasonal Variation in Essential Oil Composition and Antioxidant Capacity of Aniba canelilla (Lauraceae): A Reliable Source of 1-Nitro-2-phenylethane.

Aniba canelilla (Kunth) Mez essential oil has many biological activities due to its main compound 1-nitro-2-phenylethane (1N2F), followed by methyleugenol, a carcinogenic agent. This study analyzed the influence of seasonality on yields, antioxidant capacity, and 1N2F content of A. canelilla leaf and twig essential oils. Essential oils (EOs) were extracted with hydrodistillation and analyzed with gas chromatography coupled to mass spectrometry and a flame ionization detector. Antioxidant capacity was measured using the free radical scavenging method (DPPH). Chemometric analyses were carried out to verify the influence of climatic factors on the production and composition of EOs. 1-Nitro-2-phenylethane was the major constituent in A. canelilla EOs throughout the seasonal period (68.0-89.9%); methyleugenol was not detected. Essential oil yields and the 1N2F average did not show a statistically significant difference between the dry and rainy seasons in leaves and twigs. Moderate and significant correlations between major compounds and climate factor were observed. The twig oils (36.0 ± 5.9%) a showed greater antioxidant capacity than the leaf oils (20.4 ± 5.0%). The PCA and HCA analyses showed no statistical differences between the oil samples from the dry and rainy seasons. The absence of methyleugenolin in all months of study, described for the first time, makes this specimen a reliable source of 1N2F.

Siparuna guianensis Essential Oil Antitumoral Activity on Ehrlich Model and Its Effect on Oxidative Stress.

This work aims to evaluate the chemical composition, in vitro antioxidant capacity, and in vivo antitumoral activity of S. guianensis essential oil against Ehrlich's ascitic carcinoma and the effects on oxidative stress. The animals (Mus musculus) received a daily dose of S. guianensis oil orally (100 mg/kg) for 9 days. The main constituents of essential oil were curzerenone (16.4±1.5 %), drimenol (13.7±0.2 %), and spathulenol (12.4±0.8 %). S. guianensis oil showed antioxidant activity, inhibiting 11.1 % of DPPH radicals (95.7 mgTE/g); and 15.5 % of the ß-carotene peroxidation. The group treated with S. guianensis showed a significant reduction in tumor cells (59.76±12.33) compared to the tumor group (96.88±19.15). Essential oil of S. guianensis decreased MDA levels and increased SOD levels in liver tissue. The essential oil of S. guianensis reduced oxidative stress, and showed antitumor and antioxidant activity, being characterized as a new chemical profile in the investigation of pathologies such as cancer.

Seasonality, Composition, and Antioxidant Capacity of Limonene/δ-3-Carene/(E)-Caryophyllene Schinus terebinthifolia Essential Oil Chemotype from the Brazilian Amazon: A Chemometric Approach.

Schinus terebinthifolia Raddi is widely used in traditional Brazilian medicine to treat respiratory diseases, as an antiseptic, anti-inflammatory, and hemostatic agent. This study aimed to evaluate the influence of climatic parameters on the yield, antioxidative capacity, and chemical composition of the S. terebinthifolia leaf essential oil. The specimen was collected monthly from October 2021 to September 2022. Leaf essential oils (EOs) were obtained by hydrodistillation, and their chemical compositions were analyzed by gas chromatography/mass spectrometry (GC/MS). Statistical analyses were performed to verify the climatic influences on the yields, chemical composition, and antioxidative capacity. The DPPH (2,2-diphenyl-1-picrylhydrazyl) radical-scavenging and inhibition of ß-carotene/linoleic acid oxidation assays were performed to assess the antioxidant activity. The leaf essential oil yields ranged from 0.1% (July) to 0.7% (May and September), averaging 0.5 ± 0.2%. There was no significant difference in essential oil production during the dry (0.4 ± 0.2%) and rainy (0.6 ± 0.1%) seasons. The main chemical constituents identified in essential oils were limonene (11.42-56.24%), δ-3-carene (8.70-33.16%) and (E)-caryophyllene (4.10-24.98%). The limonene annual average was 43.57 ± 12.74% and showed no statistical difference during the dry (40.53 ± 13.38%) and rainy (52.68 ± 3.27%) seasons. Likewise, the annual average of δ-3-carene was 22.55 ± 7.11%, displaying no statistical difference between dry (26.35 ± 7.90%) and rainy (31.14 ± 1.63%) seasons. The annual average of (E)-caryophyllene was 11.07 ± 7.15% and this constituent did not show a statistical difference in Tukey's test (p > 0.05) during the dry (12.72 ± 7.56%) and rainy (6.10 ± 1.78%) season. Limonene showed a moderate positive and significant correlation (p < 0.05) with precipitation (r = 0.56) and a weak correlation with temperature (r = -0.40), humidity (r = 0.40), and insolation (r = -0.44). All samples inhibited the oxidation in the ß-carotene/linoleic acid system (22.78-44.15%) but displayed no activity in the DPPH method.

Chemical composition, antinociceptive and anti-inflammatory activities of the curzerene type essential oil of Eugenia uniflora from Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: The Eugenia uniflora leaf infusion is widely used in folk medicine to treat gastroenteritis, fever, hypertension, inflammatory and diuretic diseases. AIM OF THE STUDY: This work evaluated the acute oral toxic, antinociceptive, and anti-inflammatory activities of the curzerene chemotype of Eugenia uniflora essential oil (EuEO). MATERIAL AND METHODS: EuEO was obtained by hydrodistillation and analyzed by GC and GC-MS. The antinociceptive action in mice was evaluated for the peripheral and central analgesic activity using abdominal contortion and hot plate tests (50, 100, and 200 mg/kg); xylene-induced ear swelling was carried out for the nociception test, and carrageenan-induced cell migration test. Spontaneous locomotor activity was assessed in the open field test to rule out any nonspecific sedative or muscle relaxant effects of EuEO. RESULTS: The EuEO displayed a yield of 2.6 ± 0.7%. The major compounds classes were oxygenated sesquiterpenoids (57.3 ± 0.2%), followed by sesquiterpene hydrocarbons (16.4 ± 2.6). The chemical constituents with the highest concentrations were curzerene (33.4 ± 8.5%), caryophyllene oxide (7.6 ± 2.8%), ß-elemene (6.5 ± 1.8%), and E-caryophyllene (4.1 ± 0.3%). Oral treatment with EuEO, at doses of 50, 300, and 2000 mg/kg, did not change the behavior patterns or mortality of the animals. EuEO (300 mg/kg) did not cause a reduction in the number of crossings in the open field compared to the vehicle group. The aspartate aminotransferase (AST) level was higher in EuEO-treated groups (50 and 2000 mg/kg) when compared to the control group (p < 0.05). EuEO, at doses of 50, 100, and 200 mg/kg, reduced the number of abdominal writhings by 61.66%, 38.33%, and 33.33%. EuEO did not show increased hot plate test time latency in any of the intervals analyzed. At 200 mg/kg, EuEO decreased paw licking time, with inhibition of 63.43%. In formalin-induced acute pain, EuEO decreased paw licking time at doses of 50, 100, and 200 mg/kg in the first phase, with inhibition of 30.54%, 55.02%, and 80.87%. The groups treated with EuEO at doses of 50, 100, and 200 mg/kg showed ear edema reduction of 50.26%, 55.17%, and 51.31%, respectively. Moreover, EuEO inhibited leukocyte recruitment only at a dose of 200 mg/kg. The inhibitory values of leukocyte recruitment after 4 h of carrageenan application were 4.86%, 4.93%, and 47.25% for 50, 100, and 200 mg/kg of essential oil, respectively. CONCLUSION: The EuEO, curzerene chemotype, has significant antinociceptive and anti-inflammatory activities and low acute oral toxicity. This work confirms the antinociceptive and anti-inflammatory of this species as the traditional use.

Intraganglionic reactive oxygen species mediate inflammatory pain and hyperalgesia through TRPA1 in the rat.

Reactive oxygen species (ROS) are generated in nociceptive pathways in response to inflammation and injury. ROS are accumulated within the sensory ganglia following peripheral inflammation, but the functional role of intraganlionic ROS in inflammatory pain is not clearly understood. The aims of this study were to investigate whether peripheral inflammation leads to prolonged ROS accumulation within the trigeminal ganglia (TG), whether intraganglionic ROS mediate pain hypersensitivity via activation of TRPA1, and whether TRPA1 expression is upregulated in TG during inflammatory conditions by ROS. We demonstrated that peripheral inflammation causes excess ROS production within TG during the period when inflammatory mechanical hyperalgesia is most prominent. Additionally, scavenging intraganglionic ROS attenuated inflammatory mechanical hyperalgesia and a pharmacological blockade of TRPA1 localized within TG also mitigated inflammatory mechanical hyperalgesia. Interestingly, exogenous administration of ROS into TG elicited mechanical hyperalgesia and spontaneous pain-like responses via TRPA1, and intraganglionic ROS induced TRPA1 upregulation in TG. These results collectively suggest that ROS accumulation in TG during peripheral inflammation contributes to pain and hyperalgesia in a TRPA1 dependent manner, and that ROS further exacerbate pathological pain responses by upregulating TRPA1 expression. Therefore, any conditions that exacerbate ROS accumulation within somatic sensory ganglia can aggravate pain responses and treatments reducing ganglionic ROS may help alleviate inflammatory pain.

Antidepressant Effects of Essential Oils: A Review of the Past Decade (2012-2022) and Molecular Docking Study of Their Major Chemical Components.

Depression is a mental disorder that affects more than 300 million people worldwide. The medications available for treatment take a long time to exhibit therapeutic results and present several side effects. Furthermore, there is a decrease in the quality of life of people suffering from this affliction. Essential oils are traditionally used to relieve the symptoms of depression due to the properties of the constituents of these oils to cross the blood-brain barrier acting on depression-related biological receptors associated with reduced toxicity and side effects. In addition, compared to traditional drugs, they have several administration forms. This review provides a comprehensive assessment of studies on plants whose essential oil has exhibit antidepressant activity in the past decade and the mechanism of action of the major components and models tested. An additional in silico study was conducted with the frequent compounds in the composition of these essential oils, providing a molecular approach to the mechanism of action that has been reported in the past decade. This review is valuable for the development of potential antidepressant medications in addition to providing a molecular approach to the antidepressant mechanism of action of the major volatile compounds that have been reported in the past decade.

P2X7 receptor contributes to long-term neuroinflammation and cognitive impairment in sepsis-surviving mice.

Introduction: Sepsis is defined as a multifactorial debilitating condition with high risks of death. The intense inflammatory response causes deleterious effects on the brain, a condition called sepsis-associated encephalopathy. Neuroinflammation or pathogen recognition are able to stress cells, resulting in ATP (Adenosine Triphosphate) release and P2X7 receptor activation, which is abundantly expressed in the brain. The P2X7 receptor contributes to chronic neurodegenerative and neuroinflammatory diseases; however, its function in long-term neurological impairment caused by sepsis remains unclear. Therefore, we sought to evaluate the effects of P2X7 receptor activation in neuroinflammatory and behavioral changes in sepsis-surviving mice. Methods: Sepsis was induced in wild-type (WT), P2X7-/-, and BBG (Brilliant Blue G)-treated mice by cecal ligation and perforation (CLP). On the thirteenth day after the surgery, the cognitive function of mice was assessed using the novel recognition object and Water T-maze tests. Acetylcholinesterase (AChE) activity, microglial and astrocytic activation markers, and cytokine production were also evaluated. Results: Initially, we observed that both WT and P2X7-/- sepsis-surviving mice showed memory impairment 13 days after surgery, once they did not differentiate between novel and familiar objects. Both groups of animals presented increased AChE activity in the hippocampus and cerebral cortex. However, the absence of P2X7 prevented partly this increase in the cerebral cortex. Likewise, P2X7 absence decreased ionized calcium-binding protein 1 (Iba-1) and glial fibrillary acidic protein (GFAP) upregulation in the cerebral cortex of sepsis-surviving animals. There was an increase in GFAP protein levels in the cerebral cortex but not in the hippocampus of both WT and P2X7-/- sepsis-surviving animals. Pharmacological inhibition or genetic deletion of P2X7 receptor attenuated the production of Interleukin-1ß (IL-1ß), Tumor necrosis factor-α (TNF-α), and Interleukin-10 (IL-10). Conclusion: The modulation of the P2X7 receptor in sepsis-surviving animals may reduce neuroinflammation and prevent cognitive impairment due to sepsis-associated encephalopathy, being considered an important therapeutic target.

Sensory and muscular functions of the pelvic floor in women with endometriosis - cross-sectional study.

PURPOSE: The aim of this study was to analyze the sensory and muscle functions of the pelvic floor in women with endometriosis, trying to improve overall knowledge/findings regarding pelvic floor muscle functions in patients with endometriosis. METHODS: Sample size calculated as 92 patients with endometriosis, aged between 18 and 45 years, not virgin, without other causes of pain and could not be pregnant. Patients underwent the Pelvic Floor Sensorial and Muscle Function Exam (EFSMAP). Descriptive data were recorded with mean and standard deviation, median (range), and absolute and relative frequency. The Kolmogorov-Smirnov test was used to observe the normality of quantitative variables. The significance level adopted for this study was 5%. RESULTS: Of 92 women assessed, 93.3% had pain and 75% had increased tone in the levator ani muscle; 50.4% had impaired pelvic floor relaxation with median strength of 3 by the Oxford scale and endurance of 2 s. CONCLUSIONS: The patients had a high prevalence of pain and dysfunction of the pelvic floor muscles, such as low muscle endurance and difficulty to relax. It shows that these patients should be referred to a pelvic floor physiotherapist, as soon as they have the diagnosis of endometriosis, to be assessed to prevent and/or treat pelvic floor impairments.

Stability and Antioxidant Activity of Pouteria macrophylla Fruit Extract, a Natural Source of Gallic Acid.

Pouteria macrophylla (cutite) fruits are rich in phenolic acids, resulting in antioxidant and skin depigmenting activity. The aim of this study, then, is to evaluate the cutite extract stability under three variations of light, time, and temperature using a Box-Behnken experimental design to analyze through the surface response the variations of the total phenolic content (TPC), antioxidant activity (AA), and gallic acid content (GA). A colorimetric assay was also performed, and a decrease in the darkening index was noticed due to the high phenolic coloration in the presence of light, indicating less degradation to extract stability. The experimental planning showed variations in all responses, and second-order polynomial models were calculated and considered predictable, as well as the effects were significant. The TPC exhibited a variation in less concentrated samples (0.5% p/v) at higher temperatures (90 °C). In contrast, the temperature was the only influential variable for AA, where only higher temperatures (60-90 °C) were able to destabilize the fruit extract. Differently, GA showed only the concentration as the influential variable, exhibiting that neither temperature nor time of exposure could affect the gallic acid content stability of P. macrophylla extract. For this, P. macrophylla extract was shown to be highly stable, providing a great perspective on cosmetic application.