Citral ((2E)-3,7-dimethylocta-2,6-dienal), a bioactive component of lemongrass, inhibits oxidant activity, nuclear factor kappa B (NF-κB) activation, and cyclooxygenase-2 (COX-2) expression, even as it activates peroxisome proliferator-activated receptor (PPAR)-α and γ. Additionally, citral produces long-lasting inhibition of transient receptor potential (TRP) channels that are found in sensory neurons, such as TRPV1–3 and TRPM8, while it transiently blocks TRPV4 and TRPA1. Here, the effect of citral in experimental models of acute inflammation and hyperalgesia in mice, and the underlying citral mechanisms of action were investigated. ADMET properties and molecular targets were predicted using the online server. The immunomodulatory and antihyperalgesic effects of citral were evaluated, using mechanical and thermal stimuli, at different time-points on carrageenan, lipopolysaccharides (LPS), and zymosan-induced paw edema and hyperalgesia in mice. ADMET analysis ensures that the citral has not violated Lipinski’s rule of five, indicating its safety consumption, and molecular target prediction software identified that citral is a potential fatty acid amide hydrolase (FAAH) inhibitor. Oral treatment with citral (50–300 mg/kg) significantly inhibited carrageenan-induced paw edema and thermal allodynia. Furthermore, citral modulated the inflammation induced by LPS and zymosan, toll-like receptor (TLR) 4, and TLR2/dectin-1 ligands, respectively. Moreover, pretreatment with cannabinoid receptor type 2 (CB2R) antagonists and ATP-sensitive K+ channel inhibitor, but not with a cannabinoid receptor type 1 (CB1R) antagonist, significantly reversed the anti-inflammatory effect of citral. Intriguingly, citral did not cause any relevant action in the central nervous system, and it was safe when assessed in a 14 day toxicity assay in male mice. Therefore, citral constitutes a promising, innovative, and safe molecule for the management of immunoinflammatory conditions and pain states.

No abstract

Rosmarinic acid (RA), an ester of caffeic acid and 3, 4-dihydroxyphenyllactic acid, has anti-inflammatory and neuroprotective activities. Herein, this study investigated in silico the drug-likeness and the potential molecular targets to RA. Moreover, it tested the antidepressant-like potential of RA in the lipopolysaccharide (LPS)-induced depression model. RA (MW = 360.31 g/mol) meets the criteria of both Lipinski's rule of five and the Ghose filter. It also attends to relevant pharmacokinetic parameters.Target prediction analysis identified RA's potential targets and biological activities, including the peroxisome proliferator-activated receptor (PPAR) and the cannabinoid receptors CB 1 and CB 2 . In vivo, RA's acute, repetitive, and therapeutic administration showed antidepressant-like effect since it significantly reduced the immobility time in the tail suspension test and increased grooming time in the splash test. Further, the pretreatment with antagonists of CB 1 , CB 2 , and PPAR-γ receptors significantly blocked the antidepressant-like effect of RA. Altogether, our findings suggest that cannabinoid receptors/PPAR-γ signaling pathways are involved with the antidepressant-like effect of RA. Moreover, this molecule meets important physicochemical and pharmacokinetic parameters that favor its bioavailability. RA constitutes a promising, innovative, and safe molecule for the pharmacotherapy of major depressive disorder.

No abstract

Jaboticaba, Plinia cauliflora (Mart.) Kausel, is a Brazilian berry traditionally used in folk medicine as a treatment for some health conditions. Phenolic compounds such as flavonoids and anthocyanins have previously been detected in the fruit. This current study aimed to evaluate the toxicological effects of jaboticaba peel extract (JPE) on Artemia salina, L929, and MDA-MB-231 cell lines. Besides, JPE antioxidant, acetylcholinesterase, and antifungal activities, and elemental analysis CHNS were also tested. JPE had moderate toxicity (LD 50 = 360.92 g mL −1 ) on A. salina, the non-toxic effect on L929 cell line, and decreased the viability of cancer cell line MDA at 1,000 µg mL -1 and 500 µg mL -1 concentrations. The antioxidant activity toward 2,2-diphenyl-1-picrylhydrazyl (DPPH) performed IC 50 = 37.45 ± 0.17 µg mL -1 , whereas 45.7% of acetylcholinesterase activity was inhibited. By its elemental composition, JPE is an alternative food supplement and dermocosmetic component. Antifungal potential toward Candida strains was not observed. Experimental section Plant material and chemicalsJaboticaba belongs to the Plinia cauliflora (Mart.) Kausel specie. However, synonyms such as Myrciaria cauliflora (Mart.) O.Berg may be used to name it (Sobral et al. 2015). Powder of macerated P. cauliflora peel was commercially purchased from Chá & Cia -Ervas Medicinais, M40382 (Sao Paulo, Brazil). Standard ascorbic acid, 2,2-diphenyl-1-picrylhydrazyl (DPPH), acetylcholine iodide (AChI), 5,5´-dithiobis-(2-nitrobenzoic acid) (DTNB), physostigmine (Eserin), dimethyl sulfoxide (DMSO), dulbecco's modified Eagle's medium (DMEM)glutamax, thiazolyl blue tetrazolium bromide (MTT), Roswell Park Memorial Institute medium (RPMI), (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) (HEPES), and fetal bovine serum (FBS) were purchased from Sigma Aldrich (USA). Penicillin and streptomycin were obtained from Vitrocell, Brazil. Candida standard strains C. albicans, American Type Culture Collection (ATCC) 10231; C. glabrata (Taniwaki, M.H.), Collection of Tropical Cultures (CCT) 0728; C. krusei, (FTI) CCT 1517; and C. guilliermondii (CCT), 1890 were obtained from Foundation André Tosello, Brazil, (3-(N-morpholino)-propane sulphonic acid (MOPS) was purchased from J.T. Backer (Germany). Tryptic Soy Broth (TSB) was obtained from HiMedia (India).Amphotericin B was obtained from Laboratório Cristália (Brazil). Extract preparationTo prepare the jaboticaba peel extract (JPE), 10 g of the vegetal material was extracted with 400 mL of 70% ethanol for 72 h in the dark, and the yield was 13%. The extract was filtered, evaporated under low pressure (Rotavapor® R-210, Buchi, Switzerland) and lyophilized (ALPHA 1-4 LD plus, Christ, Germany) under 1.9 mbar pressure and -14 °C.

No abstract

BACKGROUND: Psoriatic arthritis is the most frequent and impactful comorbidity among psoriatic patients and appears in most cases after skin disease. Dermatologists play a key role in its early diagnosis and treatment. OBJECTIVES: To determine the prevalence of psoriatic arthritis and associated variables among patients with plaque psoriasis seen at a reference center for treating psoriasis. DESIGN AND SETTING: Retrospective cross-sectional study conducted among 300 patients at an outpatient clinic in a university center in Juiz de Fora, MG, Brazil. METHODS: Standardized records of 300 patients with plaque psoriasis were examined. Demographic data and medical variables relating to psoriasis (Psoriasis Area and Severity Index (PASI), family history, age at onset and disease progression) and psoriasis arthritis (CASPAR criteria) were evaluated. Laboratory and radiographic tests in the medical records were reviewed. RESULTS: Seventy-three (24.3%) of these 300 patients with plaque psoriasis had psoriatic arthritis. Asymmetric oligoarthritis (58.9%) was the most common clinical form, followed by polyarthritis (20.5%), distal interphalangeal arthritis (15.2%) and spondyloarthritis (5.4%). Dactylitis was present in 21.9% and enthesitis in 35.6% of patients. Compared with patients without arthritis, patients with arthritis had higher average age, higher frequency of positive family history of psoriasis, longer duration of evolution and higher PASI rates. CONCLUSION: Psoriatic arthritis is often underdiagnosed. Since dermatologists perform the initial approach, these professionals need to be trained to diagnose this comorbidity and treat it, together with rheumatologists.Prevalence of psoriatic arthritis among patients with plaque psoriasis: a Brazilian retrospective study | ORIGINAL ARTICLE

Background: Posttraumatic stress disorder (PTSD) is a psychiatric condition that manifests through a broad range of symptoms and shares several phenotypes with anxiety and depression. Refractory PTSD affects 10 – 30% of the patients and highlights the need for alternative pharmacotherapy. The suggested involvement of the endocannabinoid system (ECS) with the emotional processes has enlightened the use of Cannabis sp. Then, this study aimed to evaluate the therapeutic effects of a broad-spectrum Cannabis oil on anxiety- and depressive-like behaviors triggered by stressors from combined nature. In addition, this study investigated the effect of the oil on central cannabinoid receptor 1 and serum levels of cytokines, chemokines, and growth factors. Methods: Mice were randomized into five groups (vehicle; Cannabis oil; fluoxetine; single oral dose) and submitted to acute restraint and chronic unpredictable stress. Then, they were behaviorally assessed in the elevated plus-maze test (EPMT), forced swimming test (FST), splash test (ST), and open field test (OFT). The tetrad cannabinoid assay evaluated the central effect of the oil. Serum biomarkers levels were measured by a multiplex bead-based assay. Results: Cannabis oil (0.1 mg/kg, p.o.) significantly reduced the anxiety-like behavior in EPMT in the acute restraint stress model (p < 0.05) as compared to vehicle. Moreover, compared to the vehicle, Cannabis oil significantly reverted the despair and anhedonic-like behaviors in FST (p < 0.05) and ST (p < 0.05), respectively, in chronically stressed mice. Yet, compared to vehicle, therapy with Cannabis oil did not induce cannabinoid-tetrad (p < 0.0001); downregulated granulocyte-macrophage colony-stimulating factor (GM-CSF; p < 0.01) and advanced glycation end-products (RAGE; p < 0.0001); and upregulated vascular endothelial growth factor (VEGF; p < 0.01) serum levels. Conclusion: Altogether, our data suggest the potential of the broad-spectrum Cannabis oil to improve symptoms related to anxiety and depression caused by traumatic events.