A fibromialgia é uma síndrome dolorosa crônica que afeta até 5% da população mundial. Pode associar-se com distúrbios do sono, do humor e fadiga, e cursar com incapacidade funcional. Sua patogênese envolve distúrbio de modulação central da dor, comprometimento do sistema inibitório descendente e hiperatividade da substância P. Em função da vasta sintomatologia apresentada pelos pacientes e da natureza multifatorial da sua patogênese, seu tratamento ideal requer uma abordagem multidisciplinar incluindo a associação de terapia farmacológica e não farmacológica. A terapia farmacológica atualmente preconizada nessa síndrome inclui, entre outros compostos, antidepressivos, moduladores dos canais de cálcio, relaxantes musculares e analgésicos. O tratamento não farmacológico é realizado, na maioria dos casos, por meio de educação do paciente, atividade física aeróbica supervisionada e terapia cognitivo-comportamental. No entanto, muitos pacientes não apresentam respostas satisfatórias ou apresentam efeitos colaterais associados ao uso dos fármacos a longo prazo, além de referirem dificuldades em permanecer em uma terapia baseada em exercícios e medicina física. Há, portanto, um crescente interesse por parte dos médicos e pacientes por uma terapia alternativa e complementar na fibromialgia. Nesta revisão, os autores discorrem sobre as diversas modalidades terapêuticas empregadas nessa doença, enfatizando as evidências da terapia não farmacológica e do uso de medicina alternativa e complementar nesses pacientes. Fibromyalgia is a chronic painful syndrome that affects up to 5% of the world population. It is associated with sleep and mood disorders, fatigue, and functional disability. Its pathogenesis involves a disorder of the central modulation of pain, impairment of the descending inhibitory system, and hyperactivity of substance P. Because of the extensive symptomatology of patients with fibromyalgia and its multifactorial pathogenesis, its ideal treatment requires a multidisciplinary approach including the association of pharmacological and non-pharmacological therapies. The pharmacological therapy currently recommended for the syndrome includes antidepressants, calcium-channel modulators, muscle relaxants, and analgesics. In most cases, the non-pharmacological treatment consists of patient education, supervised aerobic physical activity, and cognitive-behavioral therapy. However, many patients do not respond satisfactorily, or have side effects associated with the long-term use of drugs, in addition to reporting difficulties in adhering to a therapy based on exercises and physical medicine. Thus, physicians and patients are increasingly interested in an alternative and complementary therapy for fibromyalgia. This review approaches the different therapeutic modalities used in fibromyalgia, emphasizing the evidence of non-pharmacological therapy and use of alternative and complementary medicine for these patients

Among the natural products, Brazilian propolis stands out because it is considered a source for the discovery of new bioactive compounds. In the last decade, a new Brazilian propolis has been described, known as red propolis due to its reddish pigment. Since then, numerous studies revealing its major components and their pharmacological activity have been described. Thes, this research had the objective of performing an integrative review of the literature on the biological activity of Brazilian red propolis. Scientific studies in the PubMed, SciElo and LILACS database were reviewed and analyzed using an inductive approach and indirect documentation technique. A total 418 publications were found, and onclusion and exclusion criteria were subsequently applied, selecting a total of 18 articles. The Brazilian propolis presents numerous pharmacological properties, especially the antibacterial, antfugal, antoxidant and anti-inflammatory effects. In addition, the chemical composition of this substance is different from other types of propolis already reported in the literature, presenting flavonoids never before reported. In this way, its chemical characteristics suggest probable therapeutic use for the human organism.

Thiosemicarbazones are well known for their broad spectrum of action, including antitumoral and antiparasitic activities. Thiosemicarbazones work as chelating binders, reacting with metal ions. The objective of this work was to investigate the in silico, in vitro, and in vivo toxicity and oxidative stress of 2‐acetylpyridine‐N(4)‐orthochlorophenyl thiosemicarbazone (TSC01). The in silico prediction showed good absorption by biological membranes and no theoretical toxicity. Also, the compound did not show cytotoxicity against Hep‐G2 and HT‐29 cells. In the acute nonclinical toxicological test, the animals treated with TSC01 showed behavioral changes of stimulus of the central nervous system (CNS) at 300 mg/kg. One hour after administration, a dose of 2000 mg/kg caused depressive signs. All changes disappeared after 24 h, with no deaths, which suggest an estimated LD50 of 5000 mg/kg and GSH 5. The group treated with 2000 mg/kg had an increase of water consumption and weight gain in the second week. The biochemical parameters presented no toxicity relevance, and the analysis of oxidative stress in the liver found an increase of lipid peroxidation and nitric oxide. However, histopathological analysis showed organ integrity was maintained without any changes. In conclusion, the results show the low toxicological potential of thiosemicarbazone derivative, indicating future safe use.

Padina sanctae-crucis Børgesen is distributed worldwide in tropical and subtropical seas; belongs to the Dictyotaceae family, and has proven to be an exceptional source of biologically active compounds. Four compounds were isolated and identified, namely: dolastane diterpene new for the genus Padina; phaeophytin and hidroxy-phaeophytin new for the family Dictyotaceae, and; mannitol first described in this species. Saturated fatty acids as compared to the percentages of unsaturated fatty acids were shown to be present in greater abundance. Palmitic and linolenic acid were the main saturated and unsaturated acids, respectively. Cytotoxic and antioxidant activities were evaluated using human erythrocytes. In vivo evaluations of acute toxicity and genotoxicity were performed in mice. Methanolic extract of P. sanctae-crucis presented antioxidant activity and did not induce cytotoxicity, genotoxicity or acute toxicity. Since Padina sanctae-crucis is already used as food, has essential fatty acids for the nutrition of mammals, does not present toxicity and has antioxidant activity, it can be considered as a potential nutraceutical.

Cissus sicyoides (Cs) has been traditionally used to treat diabetes and belongs to the family Vitaceae, and is known as "vegetable insulin". This study aimed to evaluate the acute and chronic non-clinical toxicity of hydroalcoholic extract from the leaves of Cissus sicyoides (EHA-Cs). The acute test was performed in Wistar rats, administering a single dose of 40.5 mg/kg. Behavioral parameters for pharmacological screening were observed to detect signs of Central Nervous System activity; consumption of daily food and water, and weight evaluation. After day 14, the animals were euthanized and blood samples were collected for laboratory analyses of hematological and biochemical parameters. The chronic tests were administered in doses of 4.5, 13.5 and 40.5 mg/kg. The same parameters were observed together with body temperature, glucose, exploration activity (test on the open field), and motor activity (diagnostic tests on the Rota-rod). For the group given the highest dosage during the study, histopathological examinations of vital organs were performed. For acute toxicity, there were no CNS level effects, changes in water and food consumption, or hematologic parameters. However, there was a significant decrease in weight gain for the treated females. Biochemical analyses of the treated animals presented increased levels of AST (aspartate aminotransferase) in females, uric acid levels in females and males, and amylase in males. In the chronic toxicity tests, water consumption was higher for females (at the dosages of 13.5 and 40.5 mg/kg) and for males (at 40.5 mg/kg). At the dosages of 4.5 and 13.5 mg/kg, feed consumption increased for females, while for males it decreased along with weight gain. Blood analysis presented an increase in albumin and changes in erythrocytes and hemoglobin for males (at the dose of 13.5 mg/kg). Glycemia in females (13.5 mg/kg dose) was significantly less, presenting only slight drops at the other doses. The changes were reversible in the satellite group. EHA-Cs revealed a relatively low toxicity profile (at the popular use dose), and only small changes in hematological and biochemical parameters at the dose of 13.5 mg/kg (3x the popular use dosage). In addition, EHA-Cs did not promote histological changes in vital organs such as the heart, lungs, liver and kidneys.

By submitting this manuscript, each author certifies that they have made a direct and substantial contribution to the work reported in the manuscript. In this manuscript the conception, design, investigation, acquisition of data and analysis, interpretation of data and writing of the article were conducted by author Camila Bomfim de Sá under the guidance of professors Margareth de Fátima Formiga Melo Diniz, Hilzeth de Luna Freire Pessôa and Caliandra Maria Bezerra Luna Lima, who also approved the final version of the manuscript. Professor Damião Pergentino de Sousa and his student Mayara Castro de Morais performed the production, synthesis and chemical characterization of ethyl ferulate (EF). Professor Abrahão Alves de Oliveira Filho assessed the in silico tests. PhD student Andressa Brito Lira participated in the critical review of the text for important intellectual content and assisted in the in vitro antioxidant activity and cytotoxicity tests. Kardilandia Mendes de Oliveira participated in acute oral toxicity tests evaluating the biochemical parameters. Students, Tafaela Dias and Cinthia Rodrigues Melo also assisted in the acute oral toxicity testing and preparing of slides for histopathological analysis. Pathologist Alexandre Rolim da Paz analyzed the histopathology results. EF, a phenolic compound of the large class of phenylpropanoids, is derived from ferulic acid and is produced both naturally and synthetically. Its principal pharmacological activities are: anti-inflammatory and antioxidant activity. This study aimed to investigate the in silico, in vitro and in vivo toxicity and antioxidant activity of EF. The in silico prediction showed more than 20 biological activities as well as good absorption at the biological membranes and no theoretical toxicity. However, EF presented high environmental toxicity. EF presented low hemolytic potential and exerted protective activity for the erythrocyte membrane for only blood type O. EF presented antioxidant activity against H₂O₂ at all concentrations and all blood types, but no effect against phenylhydrazine, being unable to prevent its oxidative effects. In the acute nonclinical toxicological trial, the treated animals presented behavioral changes (e.g., sedation). Feed intake was higher for the 2000 mg/kg group, but with no significant difference in weight change. The biochemical parameters presented no differences between treated and control animals, and the organs remained intact with no change. Thus, EF presents a low toxic profile and this study provides important information about the toxicity of this compound, suggesting future safe use.