H. pectinata (L.) Poit - Traditional uses, phytochemistry and biological-pharmacological activities in preclinical studies: A systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: H. pectinata (L.) Poit, popularly known as "sambacaitá" or "canudinho", is a plant endemic to north-eastern Brazil. Its aerial parts, leaves and flowers have traditionally been used to treat gastrointestinal disorders, rhinopharyngitis, nasal congestion, bacterial and fungal infections, fever, colic, inflammation, and pain. AIM OF THE STUDY: The aim of this review was to provide information on the botanical characteristics, ethnomedicinal uses, phytochemistry and biological-pharmacological activities of H. pectinata. MATERIALS AND METHODS: This systematic review followed the Cochrane Handbook Collaboration and the PRISMA guidelines. The review question was what are the biological-pharmacological activities of H. pectinata presented in non-clinical studies. The search for articles was conducted in the Medline (via PubMed), Embase, Web of Science, Scopus, Virtual Health Library, SciELO, Google Scholar and the Brazilian Digital Library of Theses and Dissertations databases. Two reviewers independently selected the studies that met the inclusion criteria, extracted the data, and assessed the risk of bias of the included studies. RESULTS: 39 articles were included in this review, of which 19 reported in vitro experiments, 16 in vivo studies and 4 in vivo and in vitro experiments. H. pectinata is a plant widely used in folk medicine in north-eastern Brazil for the treatment of various ailments, such as respiratory diseases, gastrointestinal disorders, bacterial and fungal infections, and general inflammation. Supporting its popular use, several in vitro and in vivo pharmacological investigations of the essential oil and extract of H. pectinata have demonstrated their anti-inflammatory, antinociceptive, antioxidant, antidepressant, anticancer, hepatoregenerative, healing, and antimicrobial activities. H. pectinata has been reported to contain 75 bioactive constituents, comprising 9 flavonoids, 54 terpenes, and 12 other compounds. CONCLUSION: H. pectinata is a plant commonly used in traditional medicine. Phytochemically, it contains several bioactive constituents, including terpenes and flavonoids, and has been shown to have antinociceptive, anti-inflammatory, antimicrobial and antitumour activity, as well as hepatorregenerative and healing effects, and low toxicity.

The protective effects of naringenin, a citrus flavonoid, non-complexed or complexed with hydroxypropyl-ß-cyclodextrin against multiorgan damage caused by neonatal endotoxemia.

BACKGROUND: Endotoxemia is a severe and dangerous clinical syndrome that results in elevated morbidity, especially in intensive care units. Neonates are particularly susceptible to endotoxemia due to their immature immune systems. There are few effective treatments for neonatal endotoxemia. One group of compounds with potential in the treatment of neonatal inflammatory diseases such as endotoxemia is the flavonoids, mainly due to their antioxidant and anti-inflammatory properties. Among these, naringenin (NGN) is a citrus flavonoid which has already been reported to have anti-inflammatory, antioxidant, anti-nociceptive and anti-cancer effects. Unfortunately, its clinical application is limited by its low solubility and bioavailability. However, cyclodextrins (CDs) have been widely used to improve the solubility of nonpolar drugs and enhance the bioavailability of these natural products. OBJECTIVE: We, therefore, aimed to investigate the effects of NGN non-complexed and complexed with hydroxypropyl-ß-cyclodextrin (HPßCD) on neonatal endotoxemia injuries in a rodent model and describe the probable molecular mechanisms involved in NGN activities. METHOD: We used exposure to a bacterial lipopolysaccharide (LPS) to induce neonatal endotoxemia in the mice. RESULTS: It was found that NGN (100 mg/kg i.p.) exposure during the neonatal period reduced leukocyte migration and decreased pro-inflammatory cytokine (TNF-α, IL-1ß and IL-6) levels in the lungs, heart, kidneys or cerebral cortex. In addition, NGN upregulated IL-10 production in the lungs and kidneys of neonate mice. The administration of NGN also enhanced antioxidant enzyme catalase and SOD activity, reduced lipid peroxidation and protein carbonylation and increased the reduced sulfhydryl groups in an organ-dependent manner, attenuating the oxidative damage caused by LPS exposure. NGN decreased ERK1/2, p38MAPK and COX-2 activation in the lungs of neonate mice. Moreover, NGN complexed with HPßCD was able to increase the animal survival rate. CONCLUSION: NGN attenuated inflammatory and oxidative damage in the lungs, heart and kidneys caused by neonatal endotoxemia through the MAPK signaling pathways regulation. Our results show that NGN has beneficial effects against neonatal endotoxemia and could be useful in the treatment of neonatal inflammatory injuries.

A Review of Phototoxic Plants, Their Phototoxic Metabolites, and Possible Developments as Photosensitizers.

This study provides a comprehensive overview of the current knowledge regarding phototoxic terrestrial plants and their phototoxic and photosensitizing metabolites. Within the 435,000 land plant species, only around 250 vascular plants have been documented as phototoxic or implicated in phototoxic occurrences in humans and animals. This work compiles a comprehensive catalog of these phototoxic plant species, organized alphabetically based on their taxonomic family. The dataset encompasses meticulous details including taxonomy, geographical distribution, vernacular names, and information on the nature and structure of their phototoxic and photosensitizing molecule(s). Subsequently, this study undertook an in-depth investigation into phototoxic molecules, resulting in the compilation of a comprehensive and up-to-date list of phytochemicals exhibiting phototoxic or photosensitizing activity synthesized by terrestrial plants. For each identified molecule, an extensive review was conducted, encompassing discussions on its phototoxic activity, chemical family, occurrence in plant families or species, distribution within different plant tissues and organs, as well as the biogeographical locations of the producer species worldwide. The analysis also includes a thorough discussion on the potential use of these molecules for the development of new photosensitizers that could be used in topical or injectable formulations for antimicrobial and anticancer phototherapy as well as manufacturing of photoactive devices.

Multitargeted molecular docking and dynamics simulation studies of flavonoids and volatile components from the peel of Citrus sinensis L. (Osbeck) against specific tumor protein markers.

Citrus sinensis (L.) Osbeck (Rutaceae), commonly known as the sweet orange, is a popular and widely consumed fruit with several medicinal properties. The present study aimed to perform the in silico screening of 18 flavonoids and eight volatile components from the peel of C. sinensis against apoptotic and inflammatory proteins, metalloprotease, and tumor suppressor markers. Flavonoids obtained higher probabilities than volatile components against selected anti-cancer drug targets. Hence, the data from the binding energies against the essential apoptotic and cell proliferation proteins substantiate that they may be promising compounds in developing effective candidates to block cell growth, proliferation, and induced cell death by activating the apoptotic pathway. Further, the binding stability of the selected targets and the corresponding molecules were analyzed by 100 ns molecular dynamics (MD) simulations. Chlorogenic acid has the most binding affinity against the important anti-cancer targets iNOS, MMP-9, and p53. The congruent binding mode to different drug targets focused on cancer shown by chlorogenic acid suggests that it may be a compound with significant therapeutic potential. Moreover, the binding energy predictions indicated that the compound had stable electrostatic and van der Waal energies. Thus, our data reinforce the medicinal importance of flavonoids from C. sinensis and expand the need for more studies, seeking to optimize results and amplify the impacts of further in vitro and in vivo studies. Communicated by Ramaswamy H. Sarma.

Evaluation of the antiedematogenic and anti-inflammatory properties of Ximenia americana L. (Olacaceae) bark extract in experimental models of inflammation.

Edema is one of the obvious indicators of inflammation and a crucial factor to take into account when assessing a substance's capacity to reduce inflammation. We aimed to evaluate the antiedematogenic and anti-inflammatory profile of the hydroethanolic barks extract of Ximenia americana (HEXA). The possible antiedematogenic and anti-inflammatory effect of EHXA (50, 100 mg/kg and 250 mg/kg v.o) was evaluated using the paw edema induced by carrageenan, zymosan, dextran, CFA and by different agents inflammatory (serotonin, histamine, arachidonic acid and PGE2), and pleurisy model induced by carrageenan and its action on IL-1ß and TNF-α levels was also evaluated. HEXA demonstrated a significant antiedematogenic effect at concentrations of 50, 100 and 250 mg/kg on paw edema induced by carrageenan, zymosan and dextran. However, the concentration of 50 mg/kg as standard, demonstrating the effect in the subchronic model, induced CFA with inhibition of 59.06 %. In models of histamine-induced paw edema, HEXA showed inhibition of - 30 min: 40.49 %, 60 min: 44.70 % and 90 min: 48.98 %; serotonin inhibition - 30 min: 57.09 %, 60 min: 66.04 % and 90 min: 61.79 %; arachidonic acid inhibition - 15 min: 36.54 %, 30 min: 51.10 %, 45 min: 50.32 % and 60 min: 76.17 %; and PGE2 inhibition - 15 min: 67.78 %, 30 min: 62.30 %, 45 min: 54.25 % and 60 min: 47.92 %. HEXA significantly reduced (p < 0.01) leukocyte migration in the pleurisy model and reduced TNF-α and IL-1ß levels in pleural lavage (p < 0.0001). The results showed that HEXA has the potential to have an antiedematogenic impact in both acute and chronic inflammation processes, with a putative mode of action including the suppression or regulation of inflammatory mediators.

Health functions and related molecular mechanisms of Miconia genus: A systematic review.

The Miconia genus is traditionally used in folk medicine in Brazil and other tropical American countries and is represented by 282 species in this region. It is a multifaceted genus of medicinal plants widely used to treat rheumatoid arthritis (RA), pain, inflammatory diseases, and many more therapeutic applications. In the present study, we systematically identify and discuss the literature on in vivo and in vitro studies focusing on the therapeutic potentials and related molecular mechanisms of the Miconia genus. The review also assessed phytochemicals and their pharmacological properties and considered safety concerns related to the genus. Literature searches to identify studies on the Miconia genus were carried out through four main electronic databases, namely PubMed, Embase, Scopus, and Web of Science limited to Medical Subjects Headings (MeSH) and Descriptores en Ciencias de la Salud (DCS) (Health Sciences Descriptors) to identify studies published up to December 2022. The relevant information about the genus was gathered using the keywords 'Miconia', 'biological activities', 'therapeutic mechanisms', 'animal model, 'cell-line model', 'antinociceptive', 'hyperalgesia', 'anti-inflammatory', and 'inflammation'. The therapeutic potentials and mechanisms of action of 14 species from genus Miconia were examined in 18 in vitro studies and included their anti-inflammatory, anticancer, analgesic, antibacterial, cytotoxic, mutagenic, antioxidant, anti-leishmanial, antinociceptive, schistosomicidal, and anti-osteoarthritis potentials, and in eight in vivo studies, assessing their analgesic, antioxidant, antinociceptive, and anti-osteoarthritis activities. Some of the main related molecular mechanisms identified are the modulation of cytokines such as IL-1ß, IL-6, and TNF-α, as well as the inhibition of inflammatory mediators and prostaglandin synthesis. The limited number of studies showed that commonly available species from the genus Miconia are safe for consumption. Miconia albicans Sw.Triana and Miconia rubiginosa (Bonpl.) DC was the most frequently used species and showed significant efficacy and potential for developing safe drugs to treat pain and inflammation.

A (-)-Carvona Modula a Sinalização de Cálcio Intracelular com Ação Antiarrítmica em Corações de Ratos / (-)-Carvone Modulates Intracellular Calcium Signaling with Antiarrhythmic Action in Rat Hearts

Resumo Fundamento: A (-)-carvona é um monoterpeno encontrado em óleos essenciais com atividade antioxidante e anti-inflamátoria. Objetivos: O objetivo deste estudo foi analisar a propriedade antiarrítmica da (-)-carvona no coração de rato e seus efeitos sobre a sinalização de Ca+2 intracelular. Métodos: Os efeitos da (-)-carvona foram avaliados sobre a contratilidade atrial (0,01 - 4 mM) e ventricular (0,5 mM), e no eletrocardiograma (0,5mM). A fração de encurtamento, a corrente de cálcio do tipo L (ICa,L) e a sinalização de Ca+2 foram medidas no cardiomiócito isolado (0,5 mM). O efeito antiarrítmico foi avaliado no modelo de arritmia induzida por sobrecarga de cálcio (0,5 mM) (n = 5). Um p < 0,05 foi adotado como nível de significância estatística. Resultados: No átrio, a (-)-carvona causou inotropismo negativo de maneira concentração-dependente (EC50 0,44 ± 0,11 mM) e diminuiu o inotropismo positivo induzido pelo CaCl2 (0,1 - 8,0 mM) e BAY K8644 (5 - 500 nM), um agonista de canal de cálcio do tipo L. Em coração isolado, a (-)-carvona (0,5mM) reduziu a contratilidade ventricular em 73% e a frequência cardíaca (em 46%), aumentou o Pri (30,7%, tempo desde o início da onda P até a onda R) e o QTc (9,2%, uma medida de despolarização e repolarização dos ventrículos), sem mudar a duração do complexo QRS. A (-)-carvona diminuiu a fração de encurtamento (61%), a (ICa,L) (79%) e o transiente intracelular de Ca+2 (38%). Além disso, a (-)-carvona apresentou ação antiarrítmica, identificada pela redução do escore de arritmia (85%) e ocorrência de fibrilação ventricular. Conclusão: A (-)-carvona reduz a entrada de Ca+2 através de canais de Ca+2 do tipo L e, assim, diminui a contratilidade cardíaca e o Ca+2 intracelular e apresenta promissora atividade antiarrítmica no coração de ratos.

Abstract Background: (-)-Carvone is a monoterpene found in essential oils with antioxidant and anti-inflammatory activity. Objective: The aim of this paper was to analyze the antiarrhythmic property of (-)-carvone in the rat heart and its effects on the intracellular Ca2+ signaling. Methods: The effects of (-)-carvone were evaluated on the ventricular (0.5 mM) and atrial contractility (0.01 - 4 mM) and on electrocardiogram (0.5 mM). Fractional shortening, L-type calcium current (ICa,L) and Ca2+ signaling were measured in the isolated cardiomyocyte (0.5 mM). Antiarrhythmic effect was evaluated in arrhythmia model induced by calcium overload (0.5 mM) (n = 5). P < 0.05 was used as the significance level. Results: In the atrium, (-)-carvone evoked negative inotropism that was concentration-dependent (EC50 0.44 ± 0.11 mM) and decreased the positive inotropism evoked by CaCl2 (0.1 to 8.0 mM) or BAY K8644 (5 to 500 nM), an agonist of L-type Ca2+ channel. In isolated heart, (-)-carvone (0.5 mM) promoted reduction of ventricular contractility (73%) and heart rate (46%), increased PRi (30.7%, time from the onset of the P wave until the R wave) and QTc (9.2%, a measure of the depolarization and repolarization of the ventricles) without changing the QRS complex duration. (-)-Carvone decreased the fractional shortening (61%), ICa,L (79%) and Ca2+ intracellular transient (38%). Furthermore, (-)-carvone showed antiarrhythmic action, verified by decrease of the arrhythmia score (85%) and occurrence of ventricular fibrillation. Conclusion: (-)-Carvone decreases Ca2+ entry through L-type Ca2+ channels, reducing the cardiac contractility and intracellular Ca2+, and, therefore, presenting promising antiarrhythmic activity in the rat hearts.

Hesperetin-Based Hydrogels Protect the Skin against UV Radiation-Induced Damage.

UV radiation can cause damages, such as erythema, skin photoaging, and carcinogenesis. The adoption of protective measures against sun exposure is essential to prevent these damages, and the interest in using natural substances as an alternative for photoprotection is growing. Thus, hesperetin with antioxidant, anti-inflammatory, and anticancer properties is a promising substance to be used with photochemopreventive action and to protect the skin from damage induced by UV radiation. Therefore, the present study aimed to develop a topical formulation based on AAMVPC gel containing hesperetin and evaluate its photoprotective effect on the skin of rats exposed to UVA-UVB radiation. The animals were submitted to the irradiation protocol UVA-UVB, and at the end, erythema, lipid peroxidation, and activity of the antioxidant enzyme catalase and superoxide dismutase were evaluated. Additionally, it evaluated the activity of myeloperoxidase and histological changes. The formulation presented a rheological and spreadability profile suitable for cutaneous application. In vivo results demonstrated that the topical formulation of AAMVPC gel containing hesperetin at a concentration of 10% protected the skin from damage induced by UVA-UVB radiation, with the absence of erythema, lipid lipoperoxidation, and inflammation (low myeloperoxidase activity), and increased catalase and superoxide dismutase activities. The morphology and architecture of the dermo-epidermal tissue of these animals were like those observed under normal conditions (non-irradiated animals). Thus, the results showed that hesperetin was able to protect the animals' skin against UV radiation-induced skin damage and the protection mechanisms may be related to the antioxidant and anti-inflammatory properties of this natural product.

Pharmacological effects of a complex α-bisabolol/ß-cyclodextrin in a mice arthritis model with involvement of IL-1ß, IL-6 and MAPK.

Inflammatory arthritis is the most prevalent chronic inflammatory disease worldwide. The pathology of the disease is characterized by increased inflammation and oxidative stress, which leads to chronic pain and functional loss in the joints. Conventional anti-arthritic drugs used to relieve pain and other arthritic symptoms often cause severe side effects. α-bisabolol (BIS) is a sesquiterpene that exhibits high anti-inflammatory potential and a significant antinociceptive effect. This study evaluates the anti-arthritic, anti-inflammatory and antihyperalgesic effects of BIS alone and in a ß-cyclodextrin (ßCD/BIS) inclusion complex in a CFA-induced arthritis model. Following the intra-articular administration of CFA, male mice were treated with vehicle, BIS and ßCD/BIS (50 mg/kg, p.o.) or a positive control and pain-related behaviors, knee edema and inflammatory and oxidative parameters were evaluated on days 4, 11, 18 and/or 25. Ours findings shows that the oral administration of BIS and ßCD/BIS significantly attenuated spontaneous pain-like behaviors, mechanical hyperalgesia, grip strength deficit and knee edema induced by repeated injections of CFA, reducing the joint pain and functional disability associated with arthritis. BIS and ßCD/BIS also inhibited the generation of inflammatory and oxidative markers in the knee and blocked MAPK in the spinal cord. In addition, ours results also showed that the incorporation of BIS in cyclodextrin as a drug delivery system improved the pharmacological profile of this substance. Therefore, these results contribute to the pharmacological knowledge of BIS and demonstrated that this terpene appears to be able to mitigate deleterious symptoms of arthritis.

Enhancement of the functionality of women with knee osteoarthritis by a gel formulation with Caryocar coriaceum Wittm ("Pequi") nanoencapsulated pulp fixed oil.

Osteoarthritis (OA) is a degenerative joint disease that occurs when there is a change in the mechanical and biological properties of the articular cartilage and the subchondral bone; The condition is more prevalent in women than in men. Pequi oil (PO), which is extracted from the fruits of the pequi tree (Caryocar coriaceum Wittm), is widely used in traditional medicine in the Brazilian northeast for the management of inflammation and joint pain. The aim of this study was to develop a pharmaceutical formulation containing Carbopol® hydrogel nanoencapsulated with pequi pulp fixed oil (PeONC) and evaluate its therapeutic effect on functionality and pain in women with knee osteoarthritis. The study was divided into two stages: Stage 1 - preparation and physico-chemical characterization of the pharmaceutical formulation containing PeONC, cell viability assays and skin irritability testing. Step 2 - A double-blind randomized clinical trial evaluating knee symptoms, quality of life, pressure pain, function, muscle strength and range of motion. The nanoformulation was in a gel form, with a particle size of 209.5 ± 1.06 nm, a pH of 6.23 ± 0.45, a zeta potential of - 23.1 ± 0.4 mV, a polydispersity index of 0.137 ± 0.52, and containing nanocapsules with a spherical shape a polymeric wall and an oily nucleus. The gel showed no cytotoxicity and was not irritating to human skin. The treatment with PeONC increased the strength of the knee flexor and extensor muscles and the total motion range of the knee. In addition, the treatment reduced knee instability, pain, swelling, and locking; There was also an improvement in some items of the SF-36 quality of life questionnaire such as in respect of functional capacity and social aspects. In conclusion, PeONC was found to be a stable, safe formulation with no toxicity in respect of topical use in humans. Additionally, the treatment produced an increase in muscle strength and functionality that was associated with reduced knee symptoms and improved quality of life. Our findings showed that in a group of women treated with PeONC mitigated the symptoms of knee osteoarthritis.

Serum glial fibrillary acidic protein is a body fluid biomarker: A valuable prognostic for neurological disease - A systematic review.

Astrocytes are the most abundant cell type in the human central nervous system, and they play an important role in the regulation of neuronal physiology. In neurological disorders, astrocyte disintegration leads to the release of glial fibrillary acidic protein (GFAP) from tissue into the bloodstream. Elevated serum levels of GFAP can serve as blood biomarkers, and a useful prognostic tool to facilitate the early diagnosis of several neurological diseases ranging from stroke to neurodegenerative disorders. This systematic review synthesizes studies published between January 2012 and September 2021 that used GFAP as a potential blood biomarker to detect neurological disorders. The following electronic databases were accessed: MEDLINE, Scopus, and Web of Science. In all the databases, the following search strategy was used: ¨GFAP¨ OR ¨glial fibrillary acidic protein¨ AND ¨neurological¨ OR ¨neurodegenerative¨ AND ¨plasma¨ OR ¨serum¨. The initial search identified 1152 articles. After the exclusion criteria were applied, 48 publications that reported GFAP levels in neurological disorders were identified. A total of16 different neurological disorders that have plasmatic GFAP levels as a possible biomarker for the disease were described in the articles, being: multiple sclerosis, frontotemporal lobar degeneration, Alzheimer's disease, Parkinson disease, COVID-19, epileptic seizures, Wilson Disease, diabetic ketoacidosis, schizophrenia, autism spectrum disorders, major depressive disorder, glioblastoma, spinal cord injury, asthma, neuromyelitis optica spectrum disorder and Friedreich's ataxia. Our review shows an association between GFAP levels and the disease being studied, suggesting that elevated GFAP levels are a potentially valuable diagnostic biomarker in the evaluation of different neurological diseases.

Seroprevalence of SARS-CoV-2 antibodies in radio and television workers.

We investigated the seroprevalence of SARS-CoV-2 antibodies in individuals working in radio and television stations (TV) in Sergipe state, Northeast Brazil. This cross-sectional study was conducted from December 1 to December 20, 2020, a period which was considered as the beginning of the second wave of COVID-19 in the state. One hundred and thirteen professionals from the three largest media companies in the state were included in this study. Venous blood was collected using venipuncture and a fluorescence immunoassay for qualitative detection and differentiation of IgM and IgG antibodies against SARS-CoV-2 was performed. Twenty-eight media workers had detectable levels of SARS-CoV-2 antibodies (11 IgM+, 6 IgM+/ IgG+, and 11 IgG+) and the estimated seroprevalence was 24.8 % (95 % CI 17.7 - 33.5). Our findings showed a high seroprevalence of SARS-CoV-2 antibodies in radio and TV workers during the second wave of COVID-19 in Brazil.

Bradykinin-target therapies in SARS-CoV-2 infection: current evidence and perspectives.

Coronavirus disease 2019 (COVID-19) is a potentially fatal disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that preferentially infects the respiratory tract. Bradykinin (BK) is a hypotensive substance that recently emerged as one of the mechanisms to explain COVID-19-related complications. Concerning this, in this review, we try to address the complex link between BK and pathophysiology of COVID-19, investigating the role of this peptide as a potential target for pharmacological modulation in the management of SARS-CoV-2. The pathology of COVID-19 may be more a result of the BK storm than the cytokine storm, and which BK imbalance is a relevant factor in the respiratory disorders caused by SARS-CoV-2 infection. Regarding this, an interesting point of intervention for this disease is to modulate BK signaling. Some drugs, such as icatibant, ecallantide, and noscapine, and even a human monoclonal antibody, lanadelumab, have been studied for their potential utility in COVID-19 by modulating BK signaling. The interaction of the BK pathway and the involvement of cytokines such as IL-6 and IL1 may be key to the use of blockers, even if only as adjuvants. In fact, reduction of BK, mainly DABK, is considered a relevant strategy to improve clinical conditions of COVID-19 patients. In this context, despite the current unproven clinical efficacy, drugs repurposing that block B1 or B2 receptor activation have gained prominence for the treatment of COVID-19 in the world.

Phytochemical screening and cardiovascular effects of the ethanol extract of Erythroxylum passerinum mart.

Species of Erythroxylum genus are popularly used as anti-inflammatories and in the treatment of renal and respiratory disorders. Although it has been reported that species from the Erythroxylum genus induce cardiovascular effects, E. passerinum had not been studied specifically in this respect. However, previous phytochemical studies of E. passerinum demonstrated the presence of compounds which can have potential activity on the cardiovascular system. In this study, phytochemical screening of the ethanol extract of E. passerinum (EEEP) detected polyphenols, but not alkaloids. EEEP caused hypotension, bradycardia and vasorelaxation in rats. The vasorelaxation was attenuated by Nw-nitro-L-arginine methyl ester (L-NAME) or L-NAME + indomethacin (INDO), but not by INDO alone. Vasorelaxation was also significantly attenuated after endothelium removal or after incubation with high K+, 4-aminopyridine, glibenclamide or tetraethylammonium, but was not affected by pre-contraction with serotonin. Thus, EEEP induces hypotension and endothelium-dependent and independent vasorelaxation, which seems to involve the nitric oxide and K+-channels.

Neuroprotective and anti-inflammatory effect of pectolinarigenin, a flavonoid from Amazonian Aegiphila integrifolia (Jacq.), against lipopolysaccharide-induced inflammation in astrocytes via NFκB and MAPK pathways.

Neurodegenerative diseases affect millions of people worldwide. Regardless of the underlying cause, neuroinflammation is the greatest risk factor for developing any of these disorders. Pectolinarigenin (PNG) is an active flavonoid with several biological properties, anti-metastatic and anti-inflammatory activity. This study investigate the biological effects of PNG in macrophage and astrocyte cultures, with focus on elucidating the molecular mechanisms involved in the PNG activity. J774A.1 murine macrophage or cerebral cortex primary astrocytes primary cultures were treated with different concentration of PNG (1-160 µM) and the inflammatory process was stimulated by LPS (1 µg/ml) and the effect of PNG in different inflammatory markers were determined. PNG did not affect astrocyte or macrophage viability. Moreover, this flavonoid reduced NO• release in macrophages, attenuated astrocyte activation by preventing the overexpression of glial fibrillary acidic protein, and decreased the release of inflammatory mediators, IL-1ß and IL-6 induced by LPS by the glial cell, as well as enhanced basal levels of IL-10. In addition, PNG suppressed NFκB, p38MAPK and ERK1/2 phosphorylation in astrocytes culture induced by LPS. The results show clear evidence that this novel flavonoid protects astrocytes against LPS-induced inflammatory toxicity. In conclusion, PNG presents neuroprotective and anti-inflammatory property through the inhibition of inflammatory signaling pathways.

Resistance training improves cardiac function and cardiovascular autonomic control in doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is an anticancer chemotherapy drug that is widely used in clinical practice. It is well documented that DOX impairs baroreflex responsiveness and left ventricular function and enhances sympathetic activity, cardiac sympathetic afferent reflexes and oxidative stress, which contribute to hemodynamic deterioration. Because resistance training (RT)-induced cardioprotection has been observed in other animal models, the objective of this study was to assess the effects of RT during DOX treatment on hemodynamics, arterial baroreflex, cardiac autonomic tone, left ventricular function and oxidative stress in rats with DOX-induced cardiotoxicity. Male Wistar rats were submitted to a RT protocol (3 sets of 10 repetitions, 40% of one-repetition maximum (1RM) of intensity, 3 times per week, for 8 weeks). The rats were separated into 3 groups: sedentary control, DOX sedentary (2.5 mg/kg of DOX intraperitoneal injection, once a week, for 6 weeks) and DOX + RT. After training or time control, the animals were anesthetized and 2 catheters were implanted for hemodynamic, arterial baroreflex and cardiac autonomic tone. Another group of animals was used to evaluate left ventricular function. We found that RT in DOX-treated rats decreased diastolic arterial pressure, heart rate, sympathetic tone and oxidative stress. In addition, RT increased arterial baroreflex sensitivity, vagal tone and left ventricular developed pressure in rats with DOX-induced cardiotoxicity. In summary, RT is a useful non-pharmacological strategy to attenuate DOX-induced cardiotoxicity.

Efecto antinociceptivo y antiinflamatorio del aceite esencial de Lippia pedunculosa Hayek y su complejo de inclusión de ß-ciclodextrina / Antinociceptive and anti-inflammatory effect of Lippia pedunculosa Hayek essential oil and its ß-cyclodextrin inclusion complex

Lippia pedunculosa Hayek (EOLp) presenta efectos tripanocidas y amebicidas. En este trabajo se estudia su aceite esencial en modelos experimentales de analgesia e inflamación una vez que la prevalencia del dolor en la población genera un gran sufrimiento y discapacidad, y los medicamentos que se usan con mayor frecuencia tienen efectos secundarios indeseables. También se evalúa si la formulación del complejo de inclusión EOLp/ß-ciclodextrina (ß-CD) fue capaz de mejorar la actividad antinociceptiva de la EOLp sola. Los datos se evaluaron mediante análisis de varianza (ANOVA), seguido de la prueba de Tukey. Las diferencias se consideraron significativas si p<0,05. EOLp presentó un mejor efecto antinociceptivo en comparación con el complejo de inclusión EOLp/ß-CD. De esta manera, las ciclodextrinas parecen no ser eficientes para aceites esenciales con sustancias de peróxido. Sin embargo, en peritonitis, EOLp redujo la migración total de leucocitos y los niveles de IL-1ß en el líquido peritoneal, lo que confirma su efecto antiinflamatorio. Los efectos observados sugieren que EOLp es una buena y prometedora opción para el tratamiento de la inflamación y los trastornos relacionados con el dolor.

Lippia pedunculosa Hayek (EOLp) presents tripanocid and amebicid effects. However essential oil needs to be further studied in experimental models of analgesia and inflammation once the prevalence of pain in the population generates great suffering and disability and the drugs most often used have undesirable side effects. We also evaluated whether the inclusion complex formulation EOLp/ß-cyclodextrin (ß-CD) was able to improve the antinociceptive activity of the EOLp alone. Data were evaluated by analysis of variance (ANOVA), followed by Tukey's test. Differences were considered significant if p<0.05. EOLp presented better antinociceptive effect when compared to the EOLp/ß-CD inclusion complex. Thus, cyclodextrins appear not to be efficient for essential oils with peroxide substances. However, in peritonitis, EOLp reduced total leucocyte migration and IL-1ß levels in the peritoneal fluid, which confirmed its anti-inflammatory effect. The observed effects suggest that EOLp is the best promising option for the treatment of inflammation and pain-related disorders.