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Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a phenol commonly found in grapes and wine, has been associated as protective in experimental models involving alterations in different neurotransmitter systems. However, studies are reporting that resveratrol could have adverse effects. This study evaluated if the association of a low dose of ketamine and resveratrol could induce behavioral manifestations associated with biochemical alterations. Moreover, the effects of treatment with resveratrol and/or ketamine on monoamine oxidase (MAO) activity, oxidative stress markers, and IL-6 levels in the brain were also investigated. Male Swiss mice received a low dose of ketamine (20 mg/kg) for 14 consecutive days, and resveratrol (10, 30, or 100 mg/kg) from day 8 up to day 14 of the experimental period, intraperitoneally. Locomotor, stereotyped behavior, Y-maze, novel recognition object test (NORT), and social interaction were quantified as well as ex vivo analysis of MAO activity, IL-6 levels, and oxidative stress markers (TBARS and total thiol levels) in brain tissues. Ketamine per se reduced the number of bouts of stereotyped behavior on day 8 of the experimental period. Resveratrol per se reduced the locomotor and exploratory activity in the open field, the time of exploration of new objects in the NORT, MAO-A activity in the striatum and increased the IL-6 levels in the cortex. These effects were attenuated when the mice were co-treated with ketamine and resveratrol. There was a decrease in MAO-A activity in the cortex of mice treated with ketamine + resveratrol 100 mg/kg. No significant alterations were found in oxidative stress markers. Resveratrol does not appear to cause summative effects with ketamine on behavioral alterations. However, the effect of resveratrol per se, mainly on locomotor and exploratory activity, should be better investigated., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Dexamethasone has a high anti-inflammatory efficacy in treating skin inflammation. However, its use is related to the rebound effect, rosacea, purple, and increased blood glucose levels. Nanotechnology approaches have emerged as strategies for drug delivery due to their advantages in improving therapeutic effects. To reduce dexamethasone-related adverse effects and improve the anti-inflammatory efficacy of treatments, we developed nanocarriers containing this corticosteroid and oleic acid. Nanocapsules and nanoemulsion presented dexamethasone content close to the theoretical value and controlled dexamethasone release in an in vitro assay. Gellan gum-based hydrogels were successfully prepared to employ the nanostructured systems. A permeation study employing porcine skin showed that hydrogels containing non-nanoencapsulated dexamethasone (0.025%) plus oleic acid (3%) or oleic acid (3%) plus dexamethasone (0.025%)-loaded nanocapsules provided a higher amount of dexamethasone in the epidermis compared to non-nanoencapsulated dexamethasone (0.5%). Hydrogels containing oleic acid plus dexamethasone-loaded nanocapsules effectively inhibited mice ear edema (with inhibitions of 89.26 ± 3.77% and 85.11 ± 2.88%, respectively) and inflammatory cell infiltration (with inhibitions of 49.58 ± 4.29% and 27.60 ± 11.70%, respectively). Importantly, the dexamethasone dose employed in hydrogels containing the nanocapsules that effectively inhibited ear edema and cell infiltration was 20-fold lower (0.025%) than that of non-nanoencapsulated dexamethasone (0.5%). Additionally, no adverse effects were observed in preliminary toxicity tests. Our study suggests that nanostructured hydrogel containing a reduced effective dose of dexamethasone could be a promising therapeutic alternative to treat inflammatory disorders with reduced or absent adverse effects. Additionally, testing our formulation in a clinical study on patients with skin inflammatory diseases would be very important to validate our study.

Musculoskeletal pain is a widely experienced public healthcare issue, especially after traumatic muscle injury. Besides, it is a common cause of disability, but this pain remains poorly managed. However, the pathophysiology of traumatic muscle injury-associated pain and inflammation has not been fully elucidated. In this regard, the transient receptor potential ankyrin 1 (TRPA1) has been studied in inflammatory and painful conditions. Thus, this study aimed to evaluate the antinociceptive and anti-inflammatory effect of the topical application of a TRPA1 antagonist in a model of traumatic muscle injury in rats. The mechanical trauma model was developed by a single blunt trauma impact on the right gastrocnemius muscle of Wistar male rats (250-350 g). The animals were divided into four groups (Sham/Vehicle; Sham/HC-030031 0.05%; Injury/Vehicle, and Injury/HC-030031 0.05%) and topically treated with a Lanette® N cream base containing a TRPA1 antagonist (HC-030031, 0.05%; 200 mg/muscle) or vehicle (Lanette® N cream base; 200 mg/muscle), which was applied at 2, 6, 12, 24, and 46 h after muscle injury. Furthermore, we evaluated the contribution of the TRPA1 channel on nociceptive, inflammatory, and oxidative parameters. The topical application of TRPA1 antagonist reduced biomarkers of muscle injury (lactate/glucose ratio), spontaneous nociception (rat grimace scale), inflammatory (inflammatory cell infiltration, cytokine levels, myeloperoxidase, and N-acetyl-β-D-glucosaminidase activities) and oxidative (nitrite levels and dichlorofluorescein fluorescence) parameters, and mRNA Trpa1 levels in the muscle tissue. Thus, these results demonstrate that TRPA1 may be a promising anti-inflammatory and antinociceptive target in treating muscle pain after traumatic muscle injury., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Nanotechnological products have been used as strategies to optimize the therapy and minimize the side effects of topical corticoids. The objective of this study was to develop hydrogels by the addition of sclerotium gum to the suspensions of desonide-loaded açai oil-based nanocapsules and to study their biological effect using an animal model of acute skin inflammation. The hydrogels presented a pH compatible with topical application (4.4 to 5.0), nanometric mean diameter (131 to 165 nm), pseudoplastic behavior, and stability under room conditions during 30 days. The in vitro skin permeation/penetration study demonstrated that a higher amount of desonide ( p  < 0.05) was retained in the epidermis from the nanotechnological-hydrogels (0.33 to 0.36 µg.cm 2 ) in comparison to the commercial gel cream (0.16 µg.cm 2 ). In the dermis, the nanostructured hydrogels promoted a lower DES retention compared to the non-nanostructured formulations ( p  < 0.05). This result may indicate a smaller amount of drug reaching the bloodstream and, thus, fewer side effects can be expected. Concerning the anti-inflammatory effect, the developed hydrogels reduced both ear edema and inflammatory cell infiltration, showing an effect comparable to the commercially available formulation, which presents twice the drug concentration. The hydrogels developed may be considered a promising approach to treat dermatological disorders.

Burn injuries are underappreciated injuries associated with substantial morbidity and mortality. Overexposure to ultraviolet (UV) radiation has dramatic clinical effects in humans and is a significant public health concern. Although the mechanisms underlying UVB exposure are not fully understood, many studies have made substantial progress in the pathophysiology of sunburn in terms of its molecular aspects in the last few years. It is well established that the transient receptor potential ankyrin 1 (TRPA1), and vanilloid 1 (TRPV1) channels modulate the inflammatory, oxidative, and proliferative processes underlying UVB radiation exposure. However, it is still unknown which mechanisms underlying TRPV1/A1 channel activation are elicited in sunburn induced by UVB radiation. Therefore, in this review, we give an overview of the TRPV1/A1 channel-mediated signalling cascades that may be involved in the pathophysiology of sunburn induced by UVB radiation. These data will undoubtedly help to explain the various features of sunburn and contribute to the development of novel therapeutic approaches to better treat it., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Cubiu, an Amazonian fruit, is widely used as food and popular treatment for pathologies that present an inflammatory pattern, such as skin wound healing. However, there is still no confirmation in the scientific literature about the safety profile, as well as the anti-inflammatory, antioxidant, and healing actions of cubiu. This study is divided into two experimental protocols using Wistar rats. Thus, the first objective (protocol 1) of this study was to evaluate the toxicity of an oral administration of cubiu extract at different doses for 28 days. The macroscopic and microscopic analyses of the liver and kidney were performed, and the following analysis was determined in plasma: glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyl transpeptidase, glucose, triglycerides, total cholesterol, urea, creatinine, and uric acid. After, we conducted the second protocol aimed to establish the potential antioxidant and anti-inflammatory capacity of cubiu and its interaction with magnetic field in skin wound healing. On days 3, 7, and 14 of treatment, skin and blood samples were collected and analyzed: the oxidative stress biomarkers (reactive substances to thiobarbituric acid, nonprotein thiols, superoxide dismutase, catalase, and glutathione S-transferase), myeloperoxidase enzymatic activity, and cytokines levels (interleukin 1, interleukin 6, interleukin 10, and tumor necrosis factor-alpha). The cubiu has shown to be safe and nontoxic. Both cubiu and magnetic field promoted decreased levels of proinflammatory and prooxidant biomarkers (interleukin 1, interleukin 6, tumor necrosis factor-alpha, and reactive substances to thiobarbituric acid), as well as increased levels of anti-inflammatory and antioxidant biomarkers (interleukin 10, nonprotein thiols, and superoxide dismutase), with greater potential when treatments are used in association. Thus, cubiu promotes antioxidant and anti-inflammatory action in skin wound healing, while also improving results of the conventional treatment for skin healing (magnetic field) when used in association., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Jéssica Franco Dalenogare et al.)

UVB radiation-mediated inflammation and the oxidative process involve the transient receptor potential vanilloid 1 (TRPV1) channel activation in neuronal and non-neuronal cells. Once diosmetin has been identified as a novel TRPV1 antagonist, we evaluated the action of diosmetin from the inflammatory [ear oedema, myeloperoxidase (MPO) activity, histological changes, and cytokines levels] and oxidative [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and SOD activities] parameters in mice exposed to UVB radiation (0.5 j/cm 2 ). We also verified the action of diosmetin on UVB radiation-induced inflammatory parameters after cutaneous nerve fibers denervation by RTX (50 µg/kg s.c.). The topical treatment with the novel TRPV1 antagonist, diosmetin (1%; 15 mg/ear), reduced ear oedema, MPO activity, and MIP-2 and IL-1β cytokines levels by 82 ± 8%, 59 ± 10%, 40 ± 12%, and 85 ± 9%, respectively. The action of diosmetin on ear oedema and inflammatory cell infiltration was histologically confirmed. Topical diosmetin (1%) also reduced NADPH oxidase activity by 67 ± 10% and reverted SOD activity by 81 ± 13%. After cutaneous nerve fibers denervation using RTX, diosmetin reduced ear oedema, but not the inflammatory cell infiltration in mice exposed to UVB radiation. Diosmetin can be a promising molecule against skin inflammatory disorders as a result of sunburn induced by UVB radiation exposure.

Ethnopharmacological Relevance: Cutaneous inflammatory diseases, such as irritant contact dermatitis, are usually treated with topical corticosteroids, which cause systemic and local adverse effects limiting their use. Thus, the discovery of new therapeutic alternatives able to effectively treat skin inflammatory disorders, without causing adverse effects, is urgently needed., Aim of the Study: To investigate the topical anti-inflammatory effect of oleic acid (OA), a monounsaturated fatty acid, into Pemulen® TR2-based semisolid dosage forms, employing a croton oil-induced irritant contact dermatitis model in mice., Materials and Methods: Male Swiss mice were submitted to skin inflammation protocols by acute and repeated applications of croton oil. The anti-inflammatory activity of Pemulen® TR2 hydrogels containing OA was evaluated by assessing oedema, inflammatory cell infiltration, and pro-inflammatory cytokine IL-1β levels. The mechanisms of action of OA were evaluated using cytokine IL-1β application or pretreatment with the glucocorticoid antagonist mifepristone. Possible toxic effects of OA were also assessed., Results: Pemulen® TR2 3% OA inhibited the acute ear oedema [maximal inhibition (I max ) = 76.41 ± 5.69%], similarly to dexamethasone (I max  = 84.94 ± 2.16%), and also inhibited ear oedema after repeated croton oil application with I max  = 85.75 ± 3.08%, similar to dexamethasone (I max  = 81.03 ± 4.66%) on the day 7 of the experiment. Croton oil increased myeloperoxidase activity, which was inhibited by Pemulen® TR2 3% OA (I max  = 71.37 ± 10.97%) and by 0.5% dexamethasone (I max  = 96.31 ± 3.73%). Pemulen® TR2 3% OA also prevented the increase in pro-inflammatory cytokine IL-1β levels induced by croton oil (I max  = 94.18 ± 12.03%), similar to 0.5% dexamethasone (I max  = 87.21 ± 10.58%). Besides, both Pemulen® TR2 3% OA and 0.5% dexamethasone inhibited IL-1β-induced ear oedema with an I max of 80.58 ± 2.45% and 77.46 ± 1.92%, respectively. OA and dexamethasone anti-inflammatory effects were prevented by 100% and 91.43 ± 5.43%, respectively, after pretreatment with mifepristone. No adverse effects were related to Pemulen® TR2 3% OA administration., Conclusions: OA demonstrated anti-inflammatory efficacy similar to dexamethasone, clinically used to treat skin inflammatory conditions, without presenting adverse effects., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Neuronal and non-neuronal TRPA1 channel plays an active role in the pathogenesis of several skin inflammatory diseases. Although a recent study identified the TRPA1 channel activation upon UVB exposure, its role in inflammatory, oxidative, and proliferative processes underlying UVB radiation-induced sunburn was not yet fully understood. We evaluated the TRPA1 channel contribution in inflammatory, oxidative, and proliferative states on skin inflammation induced by UVB radiation in mice., Main Methods: TRPA1 role was evaluated from inflammatory (ear edema, myeloperoxidase, and N-acetyl-β-D-glycosaminidase activities, histological changes, and cytokines levels), proliferative (epidermal hyperplasia, PCNA, and TRPA1 levels), and oxidative (reactive oxygen intermediates measure, H 2 O 2 quantification, and NADPH oxidase activity) parameters caused by UVB radiation single (0.5 J/cm 2 ) or repeated (0.1 J/cm 2 ) exposure. We verified the contribution of non-neuronal and neuronal TRPA1 on UVB radiation-induced inflammatory parameters using RTX-denervation (50 μg/kg s.c.)., Key Findings: TRPA1 blockade by the selective antagonist Lanette® N HC-030031 reduced all parameters induced by UVB radiation single (at concentration of 1%) or repeated (at concentration of 0.1%) exposure. We evidenced an up-regulation of the TRPA1 protein after UVB radiation repeated exposure, which was blocked by topical Lanette® N HC-030031 (0.1%). By RTX-denervation, we verified that non-neuronal TRPA1 also interferes in some inflammatory parameters induction. However, cutaneous nerve fibers seem to be most needed in the development of UVB radiation-induced inflammatory processes., Significance: We propose the TRPA1 channel participates in the UVB radiation-induced sunburn in mice, and it could be a promising therapeutic target to treat skin inflammatory disorders., (Copyright © 2020. Published by Elsevier Inc.)

Inflammatory dermatoses are prevalent worldwide, with impacts on the quality of life of patients and their families. The aim of this study was to determine the anti-inflammatory effects of Achyrocline satureioides oily extracts and nanocapsules on the skin using a mouse model of irritant contact dermatitis induced by croton oil, and a skin inflammation model induced by ultraviolet B (UVB) radiation. The mice were treated with 15 mg/ear oily extract (HG-OLAS) or nanocapsules (HG-NCAS) of A. satureioides incorporated into Carbopol® 940 hydrogels. We found that HG-OLAS and HG-NCAS formulations reduced ear edema in croton oil-induced lesions with maximum inhibitions of 54±7% and 74±3%, respectively. HG-OLAS and HG-NCAS formulations decreased ear edema induced by UVB radiation (0.5 J/cm2), with maximum inhibitions of 68±6% and 76±2% compared to the UVB radiation group, respectively. HG-OLAS and HG-NCAS modulated myeloperoxidase (MPO) activity after croton oil induction. Furthermore, croton oil and UVB radiation for 6 and 24 h, respectively, stimulated polymorphonuclear cells infiltration. The topical treatments reduced inflammatory processes, as shown by histological analysis. Together, the data suggest that topical application of A. satureioides oily extracts and nanocapsules produced antiedematogenic and anti-inflammatory effects. They constitute a compelling alternative for treatment of skin injuries.

Muscle pain is the most prevalent type of pain in the world, but treatment remains ineffective. Thus, it is relevant to develop trustable animal models to understand the involved pain mechanisms. Therefore, this study characterised the nociception and inflammation in a traumatic muscle injury model in rats. A single blunt trauma impact on the right gastrocnemius muscle of male Wistar rats (250-350 g) was used as model for muscle pain. Animals were divided into four groups (sham/no treatment; sham/diclofenac 1%; injury/no treatment; injury/diclofenac 1%) and the topical treatment with a cream containing 1% monosodium diclofenac (applied at 2, 6, 12, 24, and 46 h after muscle injury; 200 mg/muscle) was used as an anti-inflammatory control. Nociception (mechanical and cold allodynia, or nociceptive score) and locomotor activity were evaluated at 26 and 48 h after injury. Also, inflammatory and oxidative parameters were evaluated in gastrocnemius muscle and the creatine kinase (CK) activity and lactate/glicose levels in rat's serum and plasma, respectively. Muscle injury caused mechanical and cold allodynia, and increased nociceptive scores, without inducing locomotor impairment. This model also increased the inflammatory cells infiltration (seen by myeloperoxidase and N-acetyl-β-D-glucosaminidase activities and histological procedure), nitric oxide, interleukin (IL)-1β, IL-6, and dichlorofluorescein fluorescence in muscle samples; and CK activity and lactate/glicose ratio. The treatment with 1% monosodium diclofenac reduced inflammatory cells infiltration, dichlorofluorescein fluorescence and lactate/glicose levels. Thus, we characterised the traumatic muscle injury as a reproducible model of muscle pain, which makes it possible to evaluate promising antinociceptive and anti-inflammatory therapies., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The treatment of cutaneous inflammation with topical corticosteroids may cause adverse effects reinforcing the need for therapeutic alternatives to treat inflammatory skin disorders. We investigated the anti-inflammatory effect of oleic acid (OA), a fatty acid of the omega-9 (ω-9) family, and we point out it as an alternative to treat inflammatory skin disorders. OA was incorporated into Lanette ® - or Pemulen ® TR2-based semisolid preparations and the pH, spreadability, rheological behavior and in vivo anti-inflammatory performance in a UVB radiation-induced skin inflammation model in mice were assessed. The anti-inflammatory activity was verified after single or repeated treatment of the mouse ear following the UVB. The OA action on glucocorticoid receptors was investigated. Both semisolids presented pH values compatible with the deeper skin layers, appropriate spreadability factors, and non-Newtonian pseudoplastic rheological behavior. Pemulen ® 3% OA inhibited ear edema with superior efficacy than Lanette ® 3% OA and dexamethasone after a single treatment. Pemulen ® 3% OA and dexamethasone also reduced inflammatory cell infiltration. After repeated treatments, all formulations decreased the ear edema at 24 h, 48 h and 72 h after UVB. OA in semisolids, especially Pemulen ® TR2-based ones, presented suitable characteristics for cutaneous administration and its anti-inflammatory activity seems to occur via glucocorticoid receptors. OA was also capable to reduce croton oil-induced skin inflammation. Besides, the ex vivo skin permeation study indicated that OA reaches the receptor medium, which correlates with a systemic absorption in vivo. The natural compound OA could represent a promising alternative to those available to treat inflammatory skin disorders.

Antineoplastic therapy has been associated with pain syndrome development characterized by acute and chronic pain. The chemotherapeutic agent dacarbazine, used mainly to treat metastatic melanoma, is reported to cause painful symptoms, compromising patient quality of life. Evidence has proposed that transient receptor potential ankyrin 1 (TRPA1) plays a critical role in chemotherapy-induced pain syndrome. Here, we investigated whether dacarbazine causes painful hypersensitivity in naive or melanoma-bearing mice and the involvement of TRPA1 in these models. Mouse dorsal root ganglion (DRG) neurons and human TRPA1-transfected HEK293 (hTRPA1-HEK293) cells were used to evaluate the TRPA1-mediated calcium response evoked by dacarbazine. Mechanical and cold allodynia were evaluated after acute or repeated dacarbazine administration in naive mice or after inoculation of B16-F10 melanoma cells in C57BL/6 mice. TRPA1 involvement was investigated by using pharmacological and genetic tools (selective antagonist or antisense oligonucleotide treatment and Trpa1 knockout mice). Dacarbazine directly activated TRPA1 in hTRPA1-HEK293 cells and mouse DRG neurons and appears to sensitize TRPA1 indirectly by generating oxidative stress products. Moreover, dacarbazine caused mechanical and cold allodynia in naive but not Trpa1 knockout mice. Also, dacarbazine-induced nociception was reduced by the pharmacological TRPA1 blockade (antagonism), antioxidants, and by ablation of TRPA1 expression. TRPA1 pharmacological blockade also reduced dacarbazine-induced nociception in a tumor-associated pain model. Thus, dacarbazine causes nociception by TRPA1 activation, indicating that this receptor may represent a pharmacological target for treating chemotherapy-induced pain syndrome in cancer patients submitted to antineoplastic treatment with dacarbazine., (© 2019 UICC.)

Fibromyalgia is characterised mainly by symptoms of chronic widespread pain and comorbidities like depression. Although these symptoms cause a notable impact on the patient's quality of life, the underlying aetiology and pathophysiology of this disease remain incompletely elucidated. The transient receptor potential vanilloid type 1 (TRPV1) is a polymodal receptor that is involved in the development of nociceptive and depressive behaviours, while α-spinasterol, a multitarget TRPV1 antagonist and cyclooxygenase inhibitor, presents antinociceptive and antidepressant effects. The present study investigated the involvement of the TRPV1 channel and the possible effects of α-spinasterol on nociceptive and depressive-like behaviours in an experimental fibromyalgia model. The fibromyalgia model was induced with a subcutaneous (s.c.) injection of reserpine (1 mg/kg) once daily for 3 consecutive days in male Swiss mice. Reserpine administration depleted monoamines and caused mechanical allodynia. This dysfunction was inhibited by SB-366791 (1 mg/kg, oral route [p.o.]), a selective TRPV1 antagonist, with a maximum inhibition (I max ) of 73.4 ± 15.5%, or by the single or 3-day-repeated administration of α-spinasterol (0.3 mg/kg, p.o.), with an I max of 72.8 ± 17.8% and 78.9 ± 32.9%, respectively. SB-366791 also inhibited the increase of the reserpine-induced immobility time, with an I max of 100%, while α-spinasterol inhibited this parameter with an I max of 98.2 ± 21.5% and 100%, by single or repeated administration, respectively. The reserpine-induced mechanical allodynia and the thermal hyperalgesia were abolished by TRPV1-positive fibers desensitization induced by previous resiniferatoxin (RTX) administration. In summary, the TRPV1 channel is involved in the development and maintenance of nociception and depressive-like behaviours in a fibromyalgia model, while the α-spinasterol has therapeutic potential to treat the pain and depression symptoms in fibromyalgia patients., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Casearia decandra (guaçatonga) is popularly used as an anti-inflammatory. We investigated the antioxidant and anti-inflammatory effect of C.decandra leaves (CdE) ethanolic extract and of the rutin standard (present in the CdE)., Materials and Methods: Male adult Swiss mice were used (25-30 g; 5-6 animals by a group). CdE phytochemical analysis was performed by HPLC method. The antioxidant potential of CdE and rutin was assessed by different methods. Topical anti-inflammatory effect of CdE (0.001-1mg/ear) and rutin (0.003-0.03mg/ear) was evaluated by ear edema formation and inflammatory cells infiltration (MPO activity and histology) on a skin inflammation model induced by topical application of croton oil (1mg/ear)., Results: Rutin (27.81 ± 1.11 mg/g) was identified in CdE by HPLC analysis. The required amounts of CdE, rutin and ascorbic acid to reduce the initial concentration of radical DPPH by 50% (IC 50 ) were 7.77 (6.31-9.57) μg/mL, 3.62 (3.26-4.01) μg/mL and 3.74 (3.37-4.14) μg/mL with a radical DPPH reduction of 91 ± 1.2%, 91 ± 0.5%, and 96 ± 0.44% (at 30 μg/mL), respectively. Moreover, CdE and rutin presented H 2 O 2 scavenging activity with H 2 O 2 levels reduction of 41 ± 7% and 46 ± 6%, respectively and SOD-like activity of 60 ± 4% and 51 ± 14%, respectively. On the other hand, just rutin presented nitric oxide scavenging activity of 54 ± 6%. CdE and rutin topically applied inhibited the ear edema with a maximum inhibition of 70 ± 5% (1 mg/ear) and 78 ± 10% (0.03 mg/ear), respectively. Treatments reduced the MPO activity (42 ± 4% to CdE; 1mg/ear and 30 ± 8% to rutin; 0.03 mg/ear). Histologically, the topical treatments also reduced the dermis thickness and the inflammatory cells infiltration., Conclusion: We demonstrated the antioxidant and anti-inflammatory effect of C.decandra leaves and rutin. Its antioxidant potential may contribute to inflammatory process attenuation, supporting the C.decandra leaves used as a promising alternative in the therapy of the inflammatory diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Arachis hypogaea L. (peanut) leaves have been popularly used for the treatment of insomnia and inflammation, but no toxicological study has been performed for this plant preparation. This study aimed to examine the phytochemical composition of peanut leaf hydroalcoholic extract (PLHE) and describe its potential toxic effects and antioxidant and anti-inflammatory properties. The qualitative chemical analysis of PLHE by UHPLC-ESI-HRMS allowed the identification of eight metabolites types (totaling 29 compounds). The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay revealed that PLHE had strong antioxidant effects; it also exhibited nitric oxide (NO)-scavenging capacity. Human peripheral blood mononuclear cells (PBMCs) exposed to PLHE showed no reduced cell viability or increased free double-stranded DNA, NO, or reactive species production. PLHE reversed the cytotoxicity, pro-inflammatory (release of interleukin-1β), and pro-oxidant effects of H 2 O 2 on human PBMCs. Acute PLHE toxicity analysis was performed in vivo using the Organization for Economic Co-operation and Development (OECD) 423 guidelines. PLHE single injection (2000 mg/kg, intragastric) did not cause mortality or morbidity or induce changes in hematological or biochemical parameters after 14 days of administration. Thus, PLHE could be a source of bioactive compounds and possesses antioxidant and anti-inflammatory properties without elicitin cytotoxicity or genotoxicity in human PBMCs or acute toxicity in rats., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Complex regional pain syndrome I (CRPS-I) is a chronic painful pathology still undertreated. CTK 01512-2 is a recombinant version of the spider peptide Phα1β, and it functions as a voltage-gated calcium channel blocker and a transient receptor potential ankyrin 1 (TRPA1) antagonist with antinociceptive effect in different pain models. Here, we investigate the mechanisms involved in the acute and chronic nociceptive phases of a model of CPRS-I in mice and assess the antinociceptive effect of CTK 01512-2 using this model. Adult male and female mice C57BL/6 (20-30 g) were used to determine mechanical (von Frey test) or cold (acetone test) allodynia induction. Inflammatory parameters (serum and tibial nerve lactate levels, hind paw temperature and edema, or tissue cell infiltration) were evaluated after chronic post-ischemia pain (CPIP, a model of CPRS-I) induction. Anti-inflammatory and anti-neuropathic drugs or CTK 01512-2 were tested. First, we detected that CPIP-induced mechanical and cold allodynia in male and female mice in a similar way. In the acute phase (1 day after CPIP), an increase in inflammatory parameters were observed, as well as the anti-allodynic effect of anti-inflammatory compounds. In the chronic phase (17 days after CPIP), mice exhibited mechanical and cold allodynia, and anti-neuropathic drugs induced antinociception, while no inflammatory alterations were found. CTK 01512-2 reversed the CPIP allodynic effect in both nociceptive phases. Thus, this CPRS-I model can be used to understand the mechanisms involved in CPRS-I induced pain and inflammation. Besides, we observed that CTK 01512-2 has a valuable antinociceptive effect in this pain model., (Copyright © 2019 Elsevier B.V. All rights reserved.)

To investigate the topical anti-inflammatory activity of the crude extract of Cariniana domestica fruit peels (CdE), its dichloromethane, n-butanol, and ethyl acetate (EtAc) fractions, and steroids (β-sitosterol, lupeol, and stigmasterol) isolated from the EtAc fraction in models of irritant contact dermatitis (ICD) croton oil-induced in mice. We induced skin inflammation by single (acute; 1 mg/ear) and multiple (chronic; 0.4 mg/ear) croton oil application. We topically applied C. domestica (CdE, fractions, and gel formulations) and β-sitosterol, lupeol, and stigmasterol immediately after applying croton oil. HPLC-DAD chromatography of the EtAc fraction and stability of the gel formulations were verified. HPLC-DAD of the EtAc fraction revealed the stigmasterol, lupeol, and β-sitosterol presence. CdE and EtAc fraction gels showed no organoleptic or pH changes at room temperatures. CdE and dichloromethane, n-butanol, and EtAc (1 mg/ear) fractions decreased the acute ear edema with maximum inhibition (I max ) of 97 ± 2, 86 ± 1, 81 ± 4, and 95 ± 2%, respectively. CdE and EtAc fraction gel presented similar effects, with respective I max of 85 ± 6% (3%;15 mg/ear) and 82 ± 2% (1%;15 mg/ear). β-sitosterol (7.5 μg/ear), lupeol (10 μg/ear), and stigmasterol (5.7 μg/ear) also reduced this parameter by 46 ± 8, 51 ± 7, and 62 ± 7%, respectively. All topical treatments reduced the inflammatory cells' infiltration in the acute ICD model. CdE reduced the ear edema by 77 ± 4% (1 mg/ear) and the inflammatory cell infiltration in the chronic ICD model. CdE's anti-inflammatory effect was accompanied by a minimum development of adverse effects. C. domestica demonstrates a promising potential for the development of a topical anti-inflammatory agent. Graphical abstract Cariniana domestica, popularly known as jequitibá-roxo, presented topical anti-inflammatory activity in an acute and chronic irritant contact dermatitis croton oil-induced in mice. The crude extract (solutions and gel formulations) and different fractions obtained from fruit peels of C. domestica showed topical antiinflammatory activity on skin inflammation models with minimum adverse effects in preliminary toxicological studies (behavior and biochemical parameters). Moreover, the HPLC analysis revealed the presence of β-sitosterol, stigmasterol and lupeol, which also presented topical anti-inflammatory effect in the acute irritant contact dermatitis croton oil-induced. Our findings support the use of this species as a promising topical antiinflammatory agent.

Background: Tabernaemontana catharinensis, popularly known as snake skin, has been empirically used as an anti-inflammatory to treat cutaneous skin disorders. However, no study proves its effectiveness as a topical anti-inflammatory., Study Design: We investigated the topical anti-inflammatory effect of T.catharinensis leaves crude extract (TcE) in irritant contact dermatitis models in mice and its preliminary toxicity profile., Methods: The topical anti-inflammatory effect was evaluated by ear thickness measurement, inflammatory cell infiltration (MPO activity measurement and histological procedure) and cytokines levels. TcE qualitative phytochemical analysis was performed by UHPLC-ESI-HRMS and the TcE effect (therapeutic dose; 10 µg/ear) on preliminary toxicological parameters was also evaluated (on the 14° day of experiment)., Results: TcE (10 μg/ear) prevented the development of ear edema induced by cinnamaldehyde, capsaicin, arachidonic acid, phenol, and croton oil with maximum inhibition of 100% to cinnamaldehyde, arachidonic acid, phenol, and croton oil and 75 ± 6% to capsaicin. Besides, the TcE (10 μg/ear) also prevented the increase of MPO activity by 96 ± 2%, 48 ± 7%, 100%, 87 ± 8%, and 93 ± 4%, respectively, to the same irritant agents. The positive controls also prevented both ear edema and the increased of MPO activity by 100% and 42 ± 8% (HC-030031), 54 ± 6% and 80 ± 4% (SB-366791), 100% and 54 ± 5% (indomethacin), 100% and 80 ± 4% (dexamethasone in skin inflammation model induced by phenol) and 100% and 97 ± 3% (dexamethasone in inflammation model induced by croton oil), respectively. TcE also prevented the inflammatory cells infiltration and the increase of MIP-2, IL-1β and TNF-α levels irritant agents-induced. TcE topical anti-inflammatory effect may be attributed to the combined effect of indole alkaloids, terpenes, and phenolic compounds found in the extract and identified by dereplication method. The TcE' therapeutic dose proved to be safe in preliminary toxicological tests., Conclusion: Our results suggest that TcE could be an interesting strategy for the treatment of inflammatory diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Inflammatory skin diseases treatments currently used cause adverse effects. Nasturtium officinale (watercress) is used popularly as an anti-inflammatory. However, until now, no study proved its effectiveness as a topical treatment to inflammatory skin diseases. The topical anti-inflammatory activity of N. officinale crude extract leaves (NoE) on an irritant contact dermatitis (ICD) model croton oil-induced in mice was investigated., Materials and Methods: ICD models were induced by a single (1 mg/ear; acute) or repeated (0.4 mg/ear; chronic; 9 days total) croton oil application. NoE and dexamethasone solutions' (diluted in acetone; 20 μL/ear) or NoE gel, dexamethasone gel and base gel (15 mg/ear) were topically applied immediately after croton oil application. The NoE topical anti-inflammatory effect was evaluated for inflammatory parameters (ear edema, inflammatory cells infiltration, and inflammatory cytokines levels). NoE topical anti-inflammatory mechanism (NF-κB pathway and effect glucocorticoid-like) were assessed by western blot and ear edema analyses, respectively. UHPLC-MS/MS chromatography, gels accelerated stability and preliminary study of adverse effects was also performed., Results: UHPLC-MS/MS of the NoE revealed the presence of coumaric acid, rutin, and ferulic acid. NoE gels stability study showed no relevant changes at low temperature. NoE, dexamethasone, NoE gel and dexamethasone gel inhibited the ear edema croton oil-induced by 82 ± 6% (1 mg/ear), 99 ± 1% (0.1 mg/ear), 81 ± 8% (3%) and 70 ± 6% (0.5%) for the acute model, and 49 ± 7% (1 mg/ear), 80 ± 4% (0.1 mg/ear), 41 ± 8% (3%) and 46 ± 14% (0.5%) for the chronic model, respectively. The same treatments also reduced the inflammatory cells infiltration by 62 ± 3% (1 mg/ear), 97 ± 2% (0.1 mg/ear), 60 ± 3% (3%) and 66 ± 6% (0.5%) for the acute model, respectively, and 25 ± 8% (1 mg/ear) to NoE and 83 ± 13% to dexamethasone to the chronic model. NoE and NoE gel reduced the pro-inflammatory cytokines levels (acute ICD model) by 62 ± 5% and 71 ± 3% (MIP-2) and 32 ± 3% and 44 ± 4% (IL-1β), while dexamethasone solution's and gel reduced by 79 ± 7% and 44 ± 4% to MIP-2 and 98 ± 2% and 83 ± 9% to IL-1β, respectively. NoE' and dexamethasone' solutions inhibited the reduction of IkB-α protein expression induced by croton oil by 100% and 80 ± 14%, respectively. Besides, the mifepristone (glucocorticoid receptor antagonist) pre-treatment prevented the topical anti-edematogenic effect of NoE' and dexamethasone' solutions by 61 ± 5% to NoE and 78 ± 16% to dexamethasone. The repeated topical application of NoE did not cause adverse effects., Conclusion: Our results suggest the N. officinale use in the cutaneous inflammatory process treatment and demonstrate the NoE potential to develop a promising topical anti-inflammatory agent to treat inflammatory disorders., (Copyright © 2018 Elsevier B.V. All rights reserved.)

There is a major, unmet need for the treatment of cancer pain, and new targets and medicines are required. The transient receptor potential ankyrin 1 (TRPA1), a cation channel expressed by nociceptors, is activated by oxidizing substances to mediate pain-like responses in models of inflammatory and neuropathic pain. As cancer is known to increase oxidative stress, the role of TRPA1 was evaluated in a mouse model of cancer pain. Fourteen days after injection of B16-F10 murine melanoma cells into the plantar region of the right hind paw, C57BL/6 mice exhibited mechanical and thermal allodynia and thigmotaxis behavior. While heat allodynia was partially reduced in TRP vanilloid 1 (TRPV1)-deficient mice, thigmotaxis behavior and mechanical and cold allodynia were absent in TRPA1-deficient mice. Deletion of TRPA1 or TRPV1 did not affect cancer growth. Intrathecal TRPA1 antisense oligonucleotides and two different TRPA1 antagonists (HC-030031 or A967079) transiently attenuated thigmotaxis behavior and mechanical and cold allodynia. A TRPV1 antagonist (capsazepine) attenuated solely heat allodynia. NADPH oxidase activity and hydrogen peroxide levels were increased in hind paw skin 14 days after cancer cell inoculation. The antioxidant, α-lipoic acid, attenuated mechanical and cold allodynia and thigmotaxis behavior, but not heat allodynia. Whereas TRPV1, via an oxidative stress-independent pathway, contributes partially to heat hypersensitivity, oxidative stress-dependent activation of TRPA1 plays a key role in mediating thigmotaxis behavior and mechanical and cold allodynia in a cancer pain model. TRPA1 antagonists might be beneficial in the treatment of cancer pain., (© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Diosmetin is an O‑methylated flavone found naturally in citrus fruit, and it was identified in Amphilophium crucigerum (L.), a plant popularly used as an analgesic. This compound had different pharmacological effects and presented a chemical structure like the flavonoid eriodyctiol that exhibited antinociceptive effects by TRPV1 antagonism. However, the possible antinociceptive effect of this compound was not well documented. Thus, the goal of the present study was to evaluate the antinociceptive effect of diosmetin and its mechanism of action. The diosmetin effect on different pain models and its possible adverse effects were assessed on adult Swiss male mice (25-30 g). Mice spinal cord samples were used on calcium influx and binding assays using TRPV1 agonists. First, it was observed that the diosmetin reduced calcium influx mediated by capsaicin in synaptosomes and displace the specific binding to [ 3 H]-resiniferatoxin in membrane fractions from the spinal cord of mice. Diosmetin (0.15 to 1.5 mg/kg, intragastric, i.g.) presented antinociceptive and antiedematogenic effect in the capsaicin intraplantar test and induced antinociception in a noxious heat test (48 °C). Also, treatment with diosmetin reduced mechanical and heat hypersensitivity observed in a model of inflammatory or neuropathic pain. Acute diosmetin administration in mice did not induce locomotor or body temperature changes, or cause liver enzyme abnormalities or alter renal function. Moreover, there were no observed changes in gastrointestinal transit or induction of ulcerogenic activity after diosmetin administration. In conclusion, our results support the antinociceptive properties of diosmetin which seems to occur via TRPV1 antagonist in mice., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Tabernaemontana catharinensis, popularly known as snakeskin, is used in traditional medicine to treat skin inflammatory disorders. To confirm the topical anti-inflammatory effect of T. catharinensis leaves, we evaluated the therapeutic effect of crude extract (TcE) and its different fractions on irritant contact dermatitis model in mice and verified its anti-inflammatory action mechanism., Materials and Methods: The qualitative phytochemical analysis of TcE and its dichloromethane, n-butanol and ethyl acetate fractions was performed by UHPLC-ESI-HRMS. The gel accelerated stability was performed to ensure the effectiveness formulation. We investigated the TcE' inhibitory effect, its fractions and a gel formulation containing TcE in irritant contact dermatitis models induced by unique (1000 μg/ear) and multiple (400 μg/ear) croton oil application, evaluated by the ear edema formation, inflammatory cell infiltration (MPO activity measurement and histological procedure) and pro-inflammatory cytokines levels. The action glucocorticoid-like of TcE was investigated using a glucocorticoid receptor antagonist (mifepristone; 50 mg/kg, s.c.)., Results: The treatments (10 μg/ear) reduced the ear edema and MPO activity by 100% and 94 ± 3% (TcE) 85 ± 4% and 88 ± 3% (dichloromethane fraction), 83 ± 6% and 73 ± 11% (n-butanol fraction) and 86 ± 6% and 93 ± 4% (ethyl acetate fraction) and 100% (dexamethasone solution), respectively to the acute ICD model. The TcE and dexamethasone gel (15 mg/ear) also reduced by 66 ± 6% and 70 ± 5% the ear edema and by 58 ± 14% and 84 ± 4% the MPO activity, respectively. To the chronic ICD model, the TcE and dexamethasone (10 μg/ear) also reduced the ear edema (66 ± 6% and 70 ± 5%) and the MPO activity (58 ± 14% and 84 ± 4%); on the 9th day of the experiment. TcE and dexamethasone also reduced the pro-inflammatory cytokines (MIP-2, IL-1β and TNF-α) levels in acute ICD model induced by croton oil. Besides, mifepristone prevented the topical anti-edematogenic effect of TcE' and dexamethasone' solutions by 97 ± 9% to TcE and 75 ± 15% to dexamethasone. The accelerated stability study of T.catharinensis gels showed no relevant changes at low temperatures. The dereplication of the TcE and fractions revealed the presence of indole alkaloids, triterpenes, and flavonoids by UHPLC-ESI-HRMS. These classes of compounds are known in the literature for present potential anti-inflammatory action, supporting the results obtained., Conclusion: The results confirm the topical popular use ofT.catharinensis leaves in the treatment of skin inflammation and demonstrate the TcE' potential for the development of a promising topical anti-inflammatory agent to treat inflammatory disorders., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Thermal injury promotes tissue inflammation and pain, which is difficult to control. Different peripheral mechanisms seem to be involved in burn pain, such as free radical-induced damage, but further study is still needed to understand how oxidant substances induced nociceptor sensitization. The transient receptor potential ankyrin 1 (TRPA1) is an ion channel activated by oxidants substances, and it could be sensitized after tissue inflammation. This study evaluated the TRPA1 involvement in nociception and inflammation produced by a thermal injury model. Male Wistar rats were used. The concentration of the TRPA1 antagonist (HC-030031, 0.05%) on base cream was chosen using allyl isothiocyanate intraplantar test. Then, the base cream containing HC-030031 was tested on the thermal injury model (induced by warm water immersion of hind paw, under anesthesia), and silver sulfadiazine (1%) was used as a positive control. Cream treatments on the hind paw were done daily (200 mg/paw) for 6 days after thermal injury. Also, nociception (static and dynamic mechanical allodynia, heat allodynia, and spontaneous pain) or edema were evaluated. On day 6, inflammatory and oxidative parameters were assessed. The base cream containing HC-030031 produced antinociceptive and anti-inflammatory effects (reduced the edema and inflammatory cells infiltration) and decreased the levels of hydrogen peroxide, or superoxide dismutase and NADPH oxidase activities after thermal injury. Thus, this study showed the involvement of the TRPA1 receptor in the nociception and inflammation caused by thermal injury and suggested that TRPA1 antagonists might be useful as novel treatments for pain and inflammation by topical application., (Copyright © 2018. Published by Elsevier B.V.)

A balanced intake of fatty acids (FA) of both omega-6 (n-6) and -3 (n-3) series is essential for memory. The Mediterranean diet (MD), rich in n-3 polyunsaturated FA (PUFA) and low n-6/n-3 PUFA ratio, has shown beneficial influences on health. Inversely, the Western diet contains saturated fats, including hydrogenated vegetable fat (HVF, rich in trans fat) and interesterified fat (IF), making the n-6/n-3 PUFA ratio high. Due to the health impairments caused by HVF, it has been replaced by IF in processed foods. We compared an MD (balanced n-6/n-3 PUFA ratio) with Western diets 1 (WD1, rich in trans fat) and 2 (WD2, rich in IF) on memory process per se and following scopolamine (SCO) administration, which induces amnesia in rats. While MD exerted protective effects, WD1 and WD2 showed declined memory per se, showing higher susceptibility to SCO-induced memory deficits. In addition, WD1 and WD2 showed increased proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL)-1β, IL-6] and decreased anti-inflammatory cytokines (IL-10) in plasma. IL-1β was higher in the hippocampus of WD1, which was reflected on histological assessments. Significant correlations between cognitive decline and inflammatory markers reinforce our hypothesis: MD-like fats may act preventively on cognitive loss, while WD-like fats may facilitate this., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Gout is a disorder that triggers a severe inflammatory reaction which generates episodes of intense pain and discomfort to the patient. Arctium minus (Hill) Bernh. (Asteraceae) is known as "burdock" and displays anti-inflammatory, antinociceptive, against rheumatic pain and radical-scavenging activities. Species of the genus Arctium have been used in assistant therapy of gout and other inflammatory processes. We investigated the antinociceptive and anti-edematogenic effects of the crude extract of A. minus seeds in an acute gout attack model induced by intra-articular injection of monosodium urate (MSU) crystals in adult male Swiss mice (25-30 g). The crude extract of A. minus (100 mg/kg, p.o.) reduced the mechanical allodynia induced by the injection of MSU (1.25 mg/site, i.a.) from 4 until 8 h after its administration. A. minus seeds crude extract prevented mechanical allodynia at doses of 30 and 100 mg/kg, but not 10 mg/kg. Allopurinol (10 µg/mL) and A. minus crude extract (10-300 µg/mL) inhibited the xanthine oxidase activity in vitro. The A. minus seeds crude extract did not cause adverse effects since did not change the toxicological parameters evaluated. A. minus crude extract can be used as an assistant therapy of gout pain, supporting its traditional use, without causing adverse effects.

Background and Purpose: Postoperative pain is one of the most common manifestations of acute pain and is an important problem faced by patients after surgery. Moreover, neuronal trauma or chemotherapeutic treatment often causes neuropathic pain, which induces disabling and distressing symptoms. At present, treatments of both painful conditions are inadequate. α-Spinasterol, which is well characterized as a transient receptor potential vanilloid 1 antagonist, has anti-inflammatory, antioxidant and antinociceptive effects. Therefore, we investigated its antinociceptive potential on postoperative and neuropathic pain, as well as its effect on COX-1 and COX-2 activities., Experimental Approach: Nociceptive responses in a postoperative pain model (surgical incision-induced) or different neuropathic pain models (trauma or chemotherapy-induced) were investigated in mice., Key Results: Oral administration of α-spinasterol reduced postoperative pain, when given as a pre- (0.5 h before incision) or post-treatment (0.5 h after incision), and reduced cell infiltration in the injured tissue. α-Spinasterol also reduced the mechanical allodynia induced by partial sciatic nerve ligation and the mechanical and cold allodynia induced by paclitaxel. Moreover, α-spinasterol inhibited COX-1 and COX-2 enzyme activities without altering the body temperature of animals. Importantly, α-spinasterol did not alter spontaneous or forced locomotor activity. Furthermore, it did not cause gastric damage or liver and kidney changes, nor did it alter cell viability in the cerebral cortex and spinal cord slices of mice., Conclusion and Implications: α-Spinasterol is an effective and safe COX inhibitor with antinociceptive effects in postoperative and neuropathic pain models. Therefore, it is an interesting prototype for the development of novel analgesic drugs., (© 2017 The British Pharmacological Society.)

The present study shows the development of a topical formulation (hydrogel) containing silibinin-loaded pomegranate oil based nanocapsules suspension and its evaluation as an alternative for the treatment of cutaneous UVB radiation-induced damages. For this, an animal model of skin injury induced by UVB radiation was employed. Gellan gum was used as gel forming agent by its direct addition to nanocapsules suspension. The hydrogels showed adequate pH values (5.6-5.9) and a silibinin content close to the theoretical value (1mg/g). Through vertical Franz diffusion cells it was demonstrated that nanocapsules decreased the silibinin retention in the semisolid formulation. All formulations were effective in reducing mice ear edema and leukocyte infiltration induced by UVB radiation 24h after the treatments. After 48h, only the hydrogels containing nanocapsules or silibinin associated with pomegranate oil demonstrated anti-edematogenic effect, as well as the positive control (hydrogel containing silver sulfadiazine 1%). After 72h, the hydrogel containing unloaded pomegranate oil based nanocapsules still presented a small activity. In conclusion, the results of this investigation demonstrated the feasibility to prepare a semisolid formulation presenting performance comparable to the traditional therapeutic option for skin burns (silver sulfadiazine) and with prolonged in vivo anti-inflammatory activity compared to the non-nanoencapsulated compounds., (Copyright © 2017. Published by Elsevier B.V.)

This study aimed to investigate the feasibility of producing semisolid formulations based on nanocapsule suspensions containing the association of the coenzyme Q10 and vitamin E acetate by adding gellan gum (2%) to the suspensions. Furthermore, we studied their application as an alternative for the treatment of inflammation induced by ultraviolet B (UVB) radiation. For this, an animal model of injury induced by UVB-radiation was employed. All semisolids presented pH close to 5.5, drug content above 95% and mean diameter on the nanometric range, after redispersion in water. Besides, the semisolids presented non-Newtonian flow with pseudoplastic behavior and suitable spreadability factor values. The results also showed that the semisolid containing coenzyme Q10-loaded nanocapsules with higher vitamin E acetate concentration reduced in 73±8% the UVB radiation-induced ear edema. Moreover, all formulations tested were able to reduce inflammation parameters evaluated through MPO activity and histological procedure on injured tissue and the semisolids containing the nanoencapsulated coenzyme Q10 reduced oxidative parameters assessment through the non-protein thiols levels and lipid peroxidation. This way, the semisolids based on nanocapsules may be considered a promising approach for the treatment and prevention of skin inflammation diseases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The medicinal plant generally known as monkey's comb (Amphilophium crucigerum) has been popularly described for the treatment of neuropathic and inflammatory pain, specially seeds preparations., Aim of the Study: The goal of the present study was to evaluate the antinociceptive effect of the crude extract (Crd) and dichloromethane fraction (Dcm) of A. crucigerum seeds, and investigate the involvement of transient receptor potential vanilloid 1 (TRPV1) receptor in this effect., Materials and Methods: Male Swiss mice were used in this study. The effects of Crd and Dcm was tested on capsaicin-induced Ca 2+ influx or the specific binding of [ 3 H]-resiniferatoxin. Moreover, after treatment with Crd or Dcm, animals were exposed to acute pain (hot water tail-flick and capsaicin intraplantar test) or chronic pain models (injection of complete Freund's adjuvant or partial ligation of the sciatic nerve). Acute adverse effects were also noted: locomotor activity, corporal temperature, hepatic or renal damage, gastrointestinal transit alteration, and ulcerogenic activity., Results: The oral administration of Crd or Dcm resulted in an antinociceptive effect in the hot water tail-flick (48°C) and capsaicin intraplantar tests. Furthermore, these preparations exhibited antinociceptive and anti-inflammatory effects in a chronic inflammatory pain model, and antinociceptive effects in a neuropathic pain model. Moreover, Crd and Dcm reduced capsaicin-induced Ca 2+ influx and diminished the [ 3 H]-resiniferatoxin specific binding to spinal cord membranes. Acute adverse events were not found with Crd or Dcm administration., Conclusion: In conclusion, our results support the analgesic effect of A. crucigerum and suggest the presence of compounds that may act as TRPV1 antagonists., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The aim of the study was to evaluate the anti-inflammatory activity of the S. paranense crude extract, S. paranense alkaloid fraction, and solanine alkaloid. These samples reduce the croton oil-induced ear edema in a dose-dependent manner and a maximum inhibition of 81%, 98%, and 80% in the doses of 1.0, 0.73, and 0.37 mg/ear, respectively. Moreover, the samples inhibit the MPO activity with an inhibition maximum of 51%, 40%, and 46% in the doses of 1.0, 0.73, and 0.37 mg/ear, respectively. Similar results were found for dexamethasone 0.10 mg/ear (positive control), which showed inhibitions of ear edema and MPO activity of 100% and 65%, respectively. These results found probably are related to the presence of solanine which is present in significant quantity in the alkaloid fraction and others as rutin and rosmarinic, chlorogenic, and gallic acids. These results support the use of S. paranense for the treatment of inflammatory skin disorders.

Ethnopharmacological Relevance: Ethnopharmacological studies are important tools as records and documentation of the empirical uses of medicinal plants in traditional communities with the purpose of generating useful knowledge to lead to the development of new medicines, biodiversity conservation and enhancement of knowledge and local culture. Poikilacanthus glandulosus is widely used by the population of City of Santiago, in Brazil, nevertheless, it does not have any validation regarding its use and its medicinal effects., Aim: The objective of this study was to perform one ethnopharmacological survey about P. glandulosus in the City of Santiago and determine the anti-inflammatory activity in order to prove its uses in popular medicine., Methods: Personal and ethnopharmacological data were collected through a prepared questionnaire. The phytochemical analysis was performed observing the individual methodology for each reaction and by HPLC-UV. The antiedematogenic and anti-inflammatory (cell infiltration and histological procedure) activities of the P. glandulosus (0.01-1000μg/ear) were evaluated in the ear edema model induced by topical application of croton oil., Results: P. glandulosus is known in City of Santiago as "Gaiana" and its macerated leaves and branches are prepared with alcohol or sugarcane liquor especially for insect bites, cicatrization and inflammation. HPLC analysis revealed the presence of maslinic acid (2.024±0.10mg/g), uvaol (0.124±0.02mg/g) and sitosterol (0.502±0.05mg/g). The topical application of crude extract of P. glandulosus reduced in a dose-dependent manner the croton oil-induced ear edema and myeloperoxidase activity (neutrophils infiltration marker) with maximum inhibition of 87±2% and 64±12%, respectively at 1000µg/ear. Dexamethasone (100µg/ear), used as a positive control, inhibited croton oil-induced ear edema in 89±3% and decreased myeloperoxidase activity in 50±3%. Both P. glandulosus as dexamethasone reduced cell infiltration when evaluated by histological procedure CONCLUSION: This work allowed us to understand the specie P. glandulosus through ethnopharmacological study and it showed that the crude extract presented antiedematogenic and anti-inflammatory actions, proving their traditional use as anti-inflammatory., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Solanum corymbiflorum is popularly known as "baga-de-veado" and its leaves are applied on inflamed legs, scabies, tick bite, boils, mastitis, low back pain and otitis. The aim of this study was evaluate anti-inflammatory in vivo activity and relate this activity with antioxidant compounds present in the extract of S. corymbiflorum leaves. The extract from S. corymbiflorum leaves topically applied was able to reduce the croton oil-induced ear edema and myeloperoxidase (MPO) activity with maximum inhibition of 87±3% and 45±7%, rescpectively in the dose of 1mg/ear. Similar results were found for positive control dexamethasone, which presented inhibitions of ear edema and MPO activity of 89±3% and 50±3%, respectively in a dose of 0.1mg/ear. These findings are due, at least in part, the presence of polyphenols (195.28mg GAE/g) and flavonoids, as chlorogenic acid (59.27mg/g), rutin (12.72mg/g), rosmarinic acid, caffeic acid and gallic acid found by high performance liquid chromatography (HPLC) analysis. This species showed potencial antioxidant by 1,1-diphenyl-2-picrylhydrazyl (DPPH), and carbonyl groups in proteins methods which may be related with the presence of this compounds. This species possess anti-inflammatory activity confirming their popular use for the local treatment of skin inflammatory disorders., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)