LASSBio-596: a New Pre-clinical Candidate for Rheumatoid Arthritis?

Pain and inflammatory disorders are significant health problems because of prevalence and associated disabilities. In this context, LASSBio-596 is a hybrid compound able to modulate TNF-α and phosphodiesterases 4 and 5, exhibiting an anti-inflammatory effect in the pulmonary inflammatory model. Aiming at a better description of the activities of LASSBio-596, we initially conducted nociception tests (acetic acid-induced abdominal writhing, glutamate, and formalin-induced nociception and hot plate test) and later inflammatory tests (acute, peritonitis; and chronic, arthritis) that directed us to this last one. In the abdominal writhing test, there was a dose-dependent inhibition, whose response occurred at the maximum dose (50 mg/kg, p.o.), used in the subsequent tests. LASSBio-596 also inhibited nociception induced by chemical (glutamate by 31.9%; and formalin, in both phases, 1st phase: 25.7%; 2nd phase: 23.9%) and thermal agents (hotplate, by increased latency for pain at two different times). These effects were independent of the motor function, legitimated in rotarod. As there was a response in the inflammatory component of nociception, we performed the peritonitis test, in which migration was inhibited by LASSBio-596 by 39.9%. As the inflammatory process is present in autoimmune diseases, we also performed the arthritis test. LASSBio-596 reduced paw edema from the 15th day to the 21st day of treatment (no liver changes and with fewer paw injuries). In addition, LASSBio-596 decreased serum levels of TNF-α by 67.1%. These data demonstrated the antinociceptive effect of LASSBio-596 and reinforces its anti-inflammatory property (i.e., RA), amplifying the therapeutic potential of this molecule.

Costus spiralis (Jacq.) Roscoe leaves fractions have potential to reduce effects of inflammatory diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Since drugs currently used to manage pain and inflammatory conditions present several side effects, the investigation of new anti-inflammatory and antinociceptive agents from folk-medicine plants is an important approach. Costus spiralis (Costaceae) has been used in Brazilian medicinal teas to treat urinary infection, cough, inflammation, arthritis, among others. AIM OF THE STUDY: The current study focused on investigating anti-inflammatory and antinociceptive effects of fractions from C. spiralis leaves using animal models. MATERIALS AND METHODS: Adults Swiss mice were used in the following experimental models: acetic acid-induced abdominal writhing, formalin-induced nociception, hot plate, zymosan-induced peritonitis, and arthritis induced by complete Freund's adjuvant. RESULTS: The presence of steroids was confirmed in all fractions. Flavonoids, condensed tannins and saponins were observed in EFL. In methanolic fraction leaves (MFL), the presence of flavonoids and pentacyclic triterpenoids was confirmed. Orally administered leaf fractions significantly reduced abdominal writhing. Fractions were ineffective in the neurogenic stage of the formalin test, but in the inflammatory stage, ethyl acetate fraction levaes (AcFL), ethanolic fraction leaves (EFL), and MFL significantly reduced paw licking time by 69.6 ± 11.9%, 58.2 ± 9.4%, and 79.6 ± 8.3%, respectively. In the hot plate test, the reaction latency was similar for treated animals and controls. However, in the peritonitis test, cell migration was significantly reduced in animals treated with chloroform fractions leaves ClFL (61.8 ± 11.4%), AcFL (58.7 ± 8.3%), EFL (39.2 ± 5.0%), and MFL (64.8 ± 4.4%). This was similar to the result observed in the chronic inflammation model, this time only the chloroform fraction was able to reduce paw edema. CONCLUSION: Our results show that leaf fractions of Costus spiralis are capable of modulating peripheral nociceptive and inflammatory responses without effects on central nervous system being potential substrates for phytochemical purification, structural and mechanistic studies.

Citrus limon (L.) Burm f. Essential Oil Has Anxiolytic and Sedative Properties by Modulating GABAA-Receptors

Abstract The high prevalence of anxiety disorders associated with pharmacotherapy side effects have motivated the search for new pharmacological agents. Species from Citrus genus, such as Citrus limon (sicilian lemon), have been used in folk medicine as a potential therapy to minimize emotional disorders. In order to searching for new effective treatments with fewer side effects, the present study evaluated the anxiolytic mechanism of action and the hypnotic-sedative activity from the Citrus limon fruit's peels essential oil (CLEO). Adults male Swiss mice were submitted to barbiturate-induced sleep test; elevated plus-maze (EPM) and light-dark box (LDB) (evaluation of the mechanism of action); rotarod; and catalepsy tests. CLEO oral treatment decreased latency and increased the sleep total time; moreover it induced in animals an increased the number of entries and percentage of time spent into open arms of the EPM; an increased the number of transitions and the percentage of time into light compartment in the LDB; which were only antagonized by flumazenil pretreatment, with no injury at motor function. Thus, results suggest that CLEO treatment induced an anxiolytic behavior suggestively modulated by the benzodiazepine binding site of the GABAA receptor or by an increase of GABAergic neurotransmission, without cause impairment in the motor coordination.

The Antinociceptive Effect of the Leaves and Flowers Ethanolic Extracts of Tabebuia aurea (Silva Manso) Benth & Hook. F. ex S. Moore

ABSTRACT In view of the traditional use of Tabebuia aurea for treating pain and inflammation, the antinociceptive pharmacological potential of T. aurea ethanolic extracts (TAEE) was investigated through in vivo experimental models. First, the MTT assay was conducted to determine the potential cytotoxicity of the TAEEs. Afterwards, the acetic acid-induced writhing test and the formalin-, and glutamate-induced nociception tests were performed on Swiss adult mice treated with TAEEs (100 and 200 mg/kg doses, p.o.), or saline solution (control groups, 10mL/kg, p.o.), or standard drugs: dipyrone 40 mg/kg (p.o.), and morphine 5,7 mg/kg (i.p). In the MTT assay, none of the tested concentrations demonstrated signals of cytotoxicity. In the in vivo experimental models of acetic acid-induced writhing and glutamate-induced nociception, all TAEEs doses were able to statistically reduce the nociceptive response. However, the TAEEs did not show significant decrease in the amount of time that the animals spent licking the stimulated paw in the neurogenic phase of formalin-induced nociception test, differently of what was observed in the inflammatory phase. The results showed that T. aurea species induce an antinociceptive effect in rodents, which encourages the study of new drugs and contributes to the research on natural products.

Potencial ansiolítico do gênero citrus: revisão integrativa da literatura / Anxiolytic potential of the citrus genus: an integrative literature review

A alta prevalência de pessoas acometidas por algum distúrbio de ansiedade associada aos efeitos colaterais da farmacoterapia a longo prazo tem motivado a procura por novas terapias. Como terapia complementar e alternativa, óleos essenciais e infusos obtidos de folhas, cascas e flores de muitas espécies do gênero Citrus têm sido utilizadas pela população para minimizar distúrbios emocionais e tem sido recomendado no tratamento da ansiedade. O presente estudo buscou analisar a literatura publicada referente ao potencial ansiolítico do gênero Citrus, por meio de uma revisão integrativa nas bases de dados: MEDLINE, PubMed, SciELO e LILACS, no período de Janeiro a Abril de 2014, utilizando os descritores ansiedade e Citrus e selecionados 12 artigos que compuseram a amostra do estudo. Em todos os artigos selecionados foi demonstrado o potencial ansiolítico do gênero Citrus, o qual se atribui à atividade sinérgica ou isolada dos metabólitos presentes nestes extratos e/ou óleos essenciais estudados, que se assemelham. Diante dos resultados satisfatórios já realizados em humanos, observa-se a importância e a necessidade de maiores estudos e investimentos no sentido de tornar possível a utilização desses compostos de origem natural e de fácil acesso à população na terapêutica.

The high prevalence of people suffering from anxiety disorders associated with side effects of long-term pharmacotherapy has motivated the search for new therapies. As a complementary and alternative therapy, essential oils and infusions obtained from leaves, skins and flowers of many species of the Citrus genus have been used by the population to minimize emotional disorders, as well as being recommended in the anxiety treatment. The present study aimed to analyze the published literature regarding the anxiolytic potential of the Citrus genus, through an integrative review in the MEDLINE, PubMed, SciELO and LILACS databases, from January to April 2014, using the keywords anxiety and Citrus. A total of 12 articles were selected, which composed the study sample. All papers demonstrated the anxiolytic potential of the Citrus genus, which is attributed to the synergistic or isolated activity from the metabolites present in these extracts and/or essential oils studied, which are similar among themselves. Given the satisfactory results already achieved in humans, the importance and the need for further studies and investments is observed, in order to make it possible to use such compounds occurring naturally, which are easily accessible to the population in the therapy.