PI3K Signaling Pathways as a Molecular Target for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common type of cancer that affects the central nervous system (CNS). It currently accounts for about 2% of diagnosed malignant tumors worldwide, with 296,000 new cases reported per year. The first-choice treatment consists of surgical resection, radiotherapy, and adjuvant chemotherapy, which increases patients' survival by 15 months. New clinical and pre-clinical research aims to improve this prognosis by proposing the search for new drugs that effectively eliminate cancer cells, circumventing problems such as resistance to treatment. One of the promising therapeutic strategies in the treatment of GBM is the inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway, which is closely related to the process of tumor carcinogenesis. This review sought to address the main scientific studies of synthetic or natural drug prototypes that target specific therapy co-directed via the PI3K pathway, against human glioblastoma.

New immunodiagnostic methods for human tegumentary leishmaniasis in the last 10 years: Technological prospecting.

Leishmaniasis is a neglected disease and more than 1 billion people live in endemic areas with the risk of infection worldwide. Although it is an important epidemiological issue, the gold standard method of diagnosis requires invasive sample collection and is accompanied by a high level of sensitivity variation in results. The present study aims to conduct a patent prospection of immunodiagnostic methods for human tegumentary leishmaniasis in the last 10 years, focused on those with high sensitivity and specificity, and simple usability. We searched seven patent databases: The LENS, WIPO, EPO, USPTO, Patent Inspiration, Google patents, and INPI. Eleven patents were found that satisfy our search criteria, with six of them being registered in 2017. Most patents were registered in Brazil. The information obtained here covers the main characteristics of the immunodiagnostic methods evaluated. Moreover, our prospective study reveals the latest biotechnological advancements achieved in the immunodiagnosis of tegumentary leishmaniasis, especially in Brazil, which holds the majority of patents in this subject. However, no patent for immunodiagnostic methods was found in the last three years, which raises concerns about the present and future trends of leishmaniasis diagnosis.

Phosphate solubilization by Antarctic yeasts isolated from lichens.

Antarctica has a great diversity of microorganisms with biotechnological potential but is not very well Known about yeasts with phosphate solubilization activity. Thus, the aim of this study was to evaluate the ability of yeasts from Antarctica lichens to solubilize phosphate in vitro. In the screening, 147 yeasts were tested and 43 (29%) showed P solubilization in solid NBRIP medium at 15.0 °C, with a higher prevalence of positive genera Vishniacozyma, followed by Cystobasidium. Most of the positive yeasts were isolated from Usnea auratiacoatra, followed by Polycauliona regalis and Lecania brialmontii. Two strains with better activity after screening were selected for the solubilization in the liquid medium, Vishniacozyma victoriae 2.L15 and A.L6 (unidentified). Vishniacozyma victoriae 2.L15 exhibiting activities at 25.0 °C (29.91 mg/L of phosphate and pH 6.85) and at 30.0 °C (619.04 mg/L of phosphate and pH 3.73) and A.L6 strain at 25.0 °C (25.05 mg/L of phosphate and pH 6.69) and at 30.0 °C (31.25 mg/L of phosphate and pH 6.47). Of eight organic acids tested by HPLC, tartaric and acetic acids were detected during phosphate solubilization, with greater release in the period of 144 (2.13 mg/L) and 72 (13.72 mg/L) hours, respectively. Future studies to elucidate the presence of functional genes for P metabolism in lichens, as well as studies in the field of proteomics for the discovery of yeast proteins related to P solubilization are needed. Thus, the high prevalence of lichen-associated yeast communities probably contributed to the high frequency of phosphate-solubilizing isolates in this study.

Pre-clinical evaluation of LASSBio-1491: From in vitro pharmacokinetic study to in vivo leishmanicidal activity.

Leishmaniasis is a public health issue. It is among the top five parasitic illnesses worldwide and is one of the most neglected diseases. The current treatment disease includes limitations of toxicity, variable efficacy, high costs and inconvenient doses and treatment schedules. LASSBio-1736 was described as antileishmanial drug-candidate to cutaneous leishmaniasis, displaying plasma stability and with no preliminary signals of hepatic or renal toxicity. In this paper, we described the in vitro pharmacokinetic study of LASSBio-1491 (a less lipophilic isostere of LASSBio-1736) and it is in vitro and in vivo leishmanicidal activities. Our results demonstrated that LASSBio-1491 has high permeability, satisfactory aqueous solubility, long plasma and microsomal half-lives and low in vitro systemic clearance, suggesting a pharmacokinetic profile suitable for its use in a single daily dose. The antileishmanial effect of LASSBio-1491 was confirmed in vitro and in vivo. It exhibited no cytotoxic effect to mammalian cells and displayed good in -vivo effect against BALB/c mice infected with Leishmania major LV39 substrain, being 3 times more efficient than glucantime.

Can inflammasomes promote the pathophysiology of glioblastoma multiforme? A view about the potential of the anti-inflammasome therapy as pharmacological target.

Glioblastoma multiforme (GBM) is a malignant brain tumor with one of the worst general survivorship cases among the existing neoplasia. This aggressiveness is due to its complex molecular heterogeneity, immunohistochemistry and genetics. The current therapeutic approach brings little contribution to the improvement of the survival of the patients. Due to that, new forms of treatment have been explored, one of them being immunotherapy. In this aspect, the inflammasome pathway, which induces inflammation and immunosuppressive tumor response, contributing to the progression of the tumor, seems to be a new alternative to improve the treatment efficacy and the survival of the patients.

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.

Fibrinolytic Enzymes From Extremophilic Microorganisms in the Development of New Thrombolytic Therapies: Technological Prospecting.

Extremophilic microorganisms from a wide variety of extreme natural environments have been researched, and many biotechnological applications have been carried out, due to their capacity to produce biomolecules resistant to extreme conditions, such as fibrinolytic proteases. The search for new fibrinolytic enzymes is important in the development of new therapies against cardiovascular diseases. This article aimed to evaluate the patents filed about protease with fibrinolytic activity produced by extremophilic microorganisms whose use is aimed at the development of new drugs for the treatment of cardiovascular diseases. The prospecting was carried out using data on deposits and patent concessions made available on the technological bases: European Patent Office (EPO), United States Patent and Trademark Office (USPTO), World Intellectual Property Organization (WIPO), Instituto Nacional de Propriedade Industrial - Brazil (INPI), The LENS and Patent Inspiration. The International Patent Classification and subclasses and groups for each document were also evaluated. Although 382 patents were selected using terms related to extreme environments, such as "thermophile" and "acidophiles", few were related to clinical use and were mainly performed using Bacillus subtilis and Streptomyces megasporus strains. A highlight of nattokinase was produced by Bacillus subtilis GDN and actinokinase by Streptomyces megasporus SD5. The low number of patents on enzymes with this profile (extreme environments) revealed a little-explored field, promising in the development of new microbial thrombolytic drugs, such as fibrinolytic enzymes with less adverse effects.

Technological Prospecting: Mapping Patents on L-asparaginases from Extremophilic Microorganisms.

BACKGROUND: L-asparaginase (L-ASNase, L-asparagine amidohydrolase, E.C.3.5.1.1) is an enzyme with wide therapeutic applicability. Currently, the commercialized L-ASNase comes from mesophilic organisms, presenting low specificity to the substrate and limitations regarding thermostability and active pH range. Such factors prevent the maximum performance of the enzyme in different applications. Therefore, extremophilic organisms may represent important candidates for obtaining amidohydrolases with particular characteristics desired by the biotechnological market. OBJECTIVES: The present study aims to carry out a technological prospecting of patents related to the L-asparaginases derived from extremophilic organisms, contributing to pave the way for further rational investigation and application of such enzymes. METHODS: This patent literature review used six patents databases: The LENS, WIPO, EPO, USPTO, Patent Inspiration, and INPI. RESULTS: It was analyzed 2860 patents, and 14 were selected according to combinations of descriptors and study criteria. Approximately 57.14% of the patents refer to enzymes obtained from archaea, especially from the speciesPyrococcus yayanosii (35.71% of the totality). CONCLUSION: The present prospective study has singular relevance since there are no recent patent reviews for L-asparaginases, especially produced by extremophilic microorganisms. Although such enzymes have well-defined applications, corroborated by the patents compiled in this review, the most recent studies allude to new uses, such as the treatment of infections. The characterization of the catalytic profiles allows us to infer that there are potential sources still unexplored. Hence, the search for new L-ASNases with different characteristics will continue to grow in the coming years and, possibly, ramifications of the technological routes will be witnessed.

Design and Synthesis In Silico Drug-like Prediction and Pharmacological Evaluation of Cyclopolymethylenic Homologous of LASSBio-1514.

Acylhydrazones are still an important framework to the design of new bioactive compounds. As treatment of chronic pain represents a clinical challenge, we decided to modify the structure of LASSBio-1514 (1), previously described as anti-inflammatory and analgesic prototype. Applying the homologation as a strategy for molecular modification, we designed a series of cyclopentyl- (2a-e), cyclobutyl- (3a-e), and cyclopropylacylhydrazones (4a-e) that were synthetized and evaluated in murine models of inflammation and pain. A comparison of their in silico physicochemical and drug-like profile was conducted, as well as their anti-inflammatory and analgesic effect. Compounds 4a (LASSBio-1755) and 4e (LASSBio-1757) displayed excellent in silico drug-like profiles and were identified as new analgesic lead-candidates in acute and chronic model of pain, through oral administration.

Pigments from Antarctic bacteria and their biotechnological applications.

Pigments from microorganisms have triggered great interest in the market, mostly by their "natural" appeal, their favorable production conditions, in addition to the potential new chemical structures or naturally overproducing strains. They have been used in: food, feed, dairy, textile, pharmaceutical, and cosmetic industries. The high rate of pigment production in microorganisms recovered from Antarctica in response to selective pressures such as: high UV radiation, low temperatures, and freezing and thawing cycles makes this a unique biome which means that much of its biological heritage cannot be found elsewhere on the planet. This vast arsenal of pigmented molecules has different functions in bacteria and may exhibit different biotechnological activities, such as: extracellular sunscreens, photoprotective function, antimicrobial activity, biodegradability, etc. However, many challenges for the commercial use of these compounds have yet to be overcome, such as: the low stability of natural pigments in cosmetic formulations, the change in color when subjected to pH variations, the low yield and the high costs in their production. This review surveys the different types of natural pigments found in Antarctic bacteria, classifying them according to their chemical structure. Finally, we give an overview of the main pigments that are used commercially today.

Schwann cell reprogramming and lung cancer progression: a meta-analysis of transcriptome data.

Schwann cells were identified in the tumor surrounding area prior to initiate the invasion process underlying connective tissue. These cells promote cancer invasion through direct contact, while paracrine signaling and matrix remodeling are not sufficient to proceed. Considering the intertwined structure of signaling, regulatory, and metabolic processes within a cell, we employed a genome-scale biomolecular network. Accordingly, a meta-analysis of Schwann cells associated transcriptomic datasets was performed, and the core information on differentially expressed genes (DEGs) was obtained by statistical analyses. Gene set over-representation analyses was performed on core DEGs to identify significantly functional and pathway enrichment analysis between Schwann cells and, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). DEGs were further integrated with genome-scale human biomolecular networks. miRNAs were proposed by the reconstruction of a transcriptional and post-transcriptional regulatory network. Moreover, microarray-based transcriptome profiling was performed, and the prognostic power of selected dedifferentiated Schwann cell biomolecules was predicted. We observed that pathways associated with Schwann cells dedifferentiation was overexpressed in lung cancer samples. However, genes associated with Schwann cells migration inhibition system were downregulated. Besides, miRNA targeting those pathways were also deregulated. In this study, we report valuable data for further experimental and clinical analysis, because the proposed biomolecules have significant potential as systems biomarkers for screening or for therapeutic purposes in perineural invasion of lung cancer.

Novel dialkylphosphorylhydrazones: Synthesis, leishmanicidal evaluation and theoretical investigation of the proposed mechanism of action.

As part of a program to develop new drugs for the treatment of neglected diseases, new dialkylphosphorylhydrazones were synthesized and evaluated against the trypanosomatid parasites Leishmania braziliensis and Leishmania amazonensis. The synthesis of these compounds proved satisfactory with yields ranging from moderate to good. The most active compounds against L. braziliensis presented IC50 values in the 10(-2) µM range, similar to that of the reference drug pentamidine. Two compounds, 4m and 4n, showed a significant dose dependent decrease in the infection index of L. amazonensis infected macrophages and caused a complete healing of nodules and ulcers when tested in vivo against L. amazonensis-infected mice, but the control of parasite burden at the inoculation site was statistically significant only in the case of treatment with 4n. A target fishing (reverse docking) approach using molecular docking with 15 enzymes of L. braziliensis indicated that the probable target of the active compounds was hexokinase, the first enzyme of the glycolytic pathway.

Antileishmanial activity of medicinal plants used in endemic areas in northeastern Brazil.

This study investigates the leishmanicidal activity of five species of plants used in folk medicine in endemic areas of the state of Alagoas, Brazil. Data were collected in the cities of Colonia Leopoldina, Novo Lino, and União dos Palmares, Alagoas state, from patients with cutaneous leishmaniasis (Leishmania amazonensis) who use medicinal plants to treat this disease. Plants extracts were tested at a concentration of 1-100 µg/mL in all experiments, except in an assay to evaluate activity against amastigotes, when 10 µg/mL was used. All plants extracts did not show deleterious activity to the host cell evidenced by LDH assay at 100, 10, and 1 µg/mL after 48 h of incubation. The plants extracts Hyptis pectinata (L.) Poit, Aloe vera L., Ruta graveolens L., Pfaffia glomerata (Spreng.) Pedersen, and Chenopodium ambrosioides L. exhibited direct activity against extracellular forms at 100 µg/mL; these extracts inhibited growth by 81.9%, 82.9%, 74.4%, 88.7%, and 87.4%, respectively, when compared with promastigotes. The plants extracts H. pectinata, A. vera, and R. graveolens also significantly diminished the number of amastigotes at 10 µg/mL, inhibiting growth by 85.0%, 40.4%, 94.2%, and 97.4%, respectively, when compared with control. Based on these data, we conclude that the five plants exhibited considerable leishmanicidal activity.

Antinociceptive and anti-inflammatory effects of flavonoids PMT1 and PMT2 isolated from Piper montealegreanum Yuncker (Piperaceae) in mice.

In this study, we identified the antinociceptive and anti-inflammatory effects of two flavonoids (PMT1 and PMT2) from Piper montealegreanum. The antinociceptive effect was evaluated using the classical tests: acetic acid-induced writhing, formalin and hot plate test. PMT1 and PMT2 (0.1, 1, 30 and 100 µmol/kg, i.p.) reduced the writhings, with an ID50 of 0.58 and 0.44 µmol/kg, respectively. Moreover, these flavonoids (100 µmol/kg, i.p.) inhibited paw-licking time in the neurogenic phase of the formalin test, but only PMT2 was active in the inflammatory phase. However, PMT1 and PMT2 (100 µmol/kg, i.p.) did not increase the latency time of the animals in the hot plate. In order to evaluate the anti-inflammatory effect of these flavonoids, capsaicin-induced ear oedema was carried out. Both flavonoids (100 µmol/kg, i.p.) were active in this model. These results suggest that PMT1 and PMT2 have antinociceptive and anti-inflammatory activities.

Leishmanicidal activity of the crude extract, fractions and major piperidine alkaloids from the flowers of Senna spectabilis.

Senna spectabilis (sin. Cassia excelsa, C. spectabilis) is an endemic tree of South America and Africa, very common in Brazil, where it is known as "canafistula-de-besouro" and "cassia-do-nordeste". In folk medicine, this plant is indicated for the treatment of constipation, insomnia, anxiety, epilepsy, malaria, dysentery and headache. Phytopharmacological studies have also confirmed anticonvulsive, sedative, anti-malarial, antimicrobial and cytotoxic properties of many parts of S. spectabilis. In this communication, we present a comparative study of the leishmanicidal activity of the crude ethanolic extract, its fractions and also the two major alkaloidal metabolites (-)-cassine/(-)-spectaline, trying to establish a relationship between the presence of piperidine alkaloidal constituents and leishmanicidal activity. The growth inhibitory effect of promastigote forms of Leishmania major was determined for the crude extract, fractions of the flowers of S. spectabilis and a mixture of (-)-cassine/(-)-spectaline in comparison to pentamidine used as standard drug. The cytotoxic effects were assessed on macrophage strain J774 by lactate dehydrogenase assay. Fractions dichloromethane (FL-DCM) and n-butanol (FL-Bu) and a mixture of (-)-cassine/(-)-spectaline (∼7:3) exhibited significant activity against the parasite Leishmania major (IC50 values of 0.6±0.1 µg/ml, 1.6±0.9 µg/ml and 24.9±1.4 µg/ml, respectively), without toxic effects on murine macrophages. Due to the promising results elicited, further studies in vivo need to be performed to confirm the therapeutic potential of Senna spectabilis.

Antinociceptive and anti-inflammatory activity from algae of the genus Caulerpa.

Marine natural products have been the focus of discovery for new products of chemical and pharmacological interest. The aim of this study was to evaluate the antinociceptive activity of the methanolic (ME), acetate (AE), hexanic (HE) and chloroform (CE) extracts obtained from Caulerpa mexicana, and ME, CE and HE obtained from Caulerpa sertularioides. These marine algae are found all over the world, mainly in tropical regions. Models such as the writhing test, the hot plate test and formalin-induced nociception test were used to evaluate antinociceptive activity in laboratory mice. In the writhing test, all the extracts were administered orally at a concentration of 100 mg/kg, and induced high peripheral antinociceptive activity, with a reduction in the nociception induced by acetic acid above 65%. In the hot plate test, treatment with extracts from C. sertularioides (100 mg/kg, p.o.) did not significantly increase the latency of response, although the ME, AE and HE from C. mexicana showed activity in this model. This result suggests that these extracts exhibit antinociceptive activity. In the formalin test, it was observed that ME, AE and HE obtained from C. mexicana reduced the effects of formalin in both phases. On the other hand only CE from C. sertularioides induced significant inhibition of the nociceptive response in the first phase. To better assess the potential anti-inflammatory activity of the extracts, the carrageenan-induced peritonitis test was used to test Caulerpa spp. extracts on cell migration into the peritoneal cavity. In this assay, all extracts evaluated were able to significantly inhibit leukocyte migration into the peritoneal cavity in comparison with carrageenan. These data demonstrate that extracts from Caulerpa species elicit pronounced antinociceptive and anti-inflamatory activity against several nociception models. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive action and also to identify the active principles present in the Caulerpa species.

Synthesis and pharmacological evaluation of pyrazine N-acylhydrazone derivatives designed as novel analgesic and anti-inflammatory drug candidates.

In this paper, we report the synthesis and pharmacological evaluation of pyrazine N-acylhydrazone (NAH) derivatives (2a-s) designed as novel analgesic and anti-inflammatory drug candidates. This series was planned by molecular simplification of prototype 1 (LASSBio-1018), previously described as a non-selective cyclooxygenase inhibitor. Derivatives 2a-s were evaluated in several animal models of pain and inflammation, standing-out compound 2o (2-N'-[(E)-(3,4,5-trimethoxyphenyl) methylidene]-2-pyrazinecarbohydrazide; LASSBio-1181), that was also active in a murine model of chronic inflammation (i.e., adjuvant-induced arthritis test in rats) and can be considered a new analgesic and anti-inflammatory lead for drug development.

The antinociceptive and anti-inflammatory activities of Piptadenia stipulacea Benth. (Fabaceae).

AIM: In this study, we attempted to identify the possible antinociceptive and anti-inflammatory actions of the aqueous phase, the ethyl acetate phase and one unknown flavonoid obtained from aerial parts of Piptadenia stipulacea, known in Brazil as "jurema-branca", "carcará" and "rasga-beiço". MATERIALS AND METHODS: Aerial parts of Piptadenia stipulacea were used and after fractionation, the flavonoid FGAL was obtained. Experiments were conducted on Swiss mice using the acetic acid-induced writhing test, the hot plate test, the formalin-induced pain test and zymosan A-induced peritonitis test. RESULTS: The aqueous and ethyl acetate phases (p.o., 100mg/kg); and the flavonoid FGAL (p.o. and i.p. at 100 micromol/kg), reduced the nociception produced by acetic acid, by 49.92%, 54.62%, 38.97% and 64.79%, respectively. In vivo inhibition of nociception by the ethyl acetate phase (100mg/kg, p.o.) in the hot plate test was favorable, indicating that this fraction exhibited central activity. The ethyl acetate phase (100mg/kg, p.o.) reduced the formalin effects in both phases by 28.51% and 55.72%, respectively. Treatment with the aqueous phase (100mg/kg, p.o.) and FGAL (100 micromol/kg, i.p.) only protected the second phase by 69.76% and 68.78%, respectively. In addition, it was observed in the zymosan A-induced peritonitis test that the aqueous phase, the ethyl acetate phase and the FGAL exhibited anti-inflammatory activity, reducing significantly the number of recruit cells by 35.84%, 37.70% and FGAL (1), respectively. CONCLUSIONS: These data demonstrate that the FGAL elicits pronounced antinociceptive activity against several pain models. The actions of this flavonoid probably are due to antioxidative properties. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for this antinociceptive action and also to identify other active substances present in Piptadenia stipulacea.

Synthesis and pharmacological evaluation of N-phenyl-acetamide sulfonamides designed as novel non-hepatotoxic analgesic candidates.

In this paper we report the design, synthesis and pharmacological evaluation of a series of N-phenyl-acetamide sulfonamide derivatives (5a-g), planned by structural modification on the prototype paracetamol (1). In this series (5a-g), compound LASSBio-1300 (5e; ID(50)=5.81 micromol/kg) stands out as a new non-hepatotoxic analgesic drug candidate. The increase of area, volume and electrostatic potential of paracetamol's analogues seems to be beneficial to the analgesic activity. Unlike paracetamol (1) and the other analogues (5a, 5d-g), compounds 5b and 5c presented an important anti-hypernociceptive activity associated to inflammatory pain.

The antinociceptive and anti-inflammatory activities of caulerpin, a bisindole alkaloid isolated from seaweeds of the genus Caulerpa.

The antinociceptive and anti-inflammatory activity of caulerpin was investigated. This bisindole alkaloid was isolated from the lipoid extract of Caulerpa racemosa and its structure was identified by spectroscopic methods, including IR and NMR techniques. The pharmacological assays used were the writhing and the hot plate tests, the formalin-induced pain, the capsaicin-induced ear edema and the carrageenan-induced peritonitis. Caulerpin was given orally at a concentration of 100 micromol/kg. In the abdominal constriction test caulerpin showed reduction in the acetic acid-induced nociception at 0.0945 micromol (0.0103-1.0984) and for dypirone it was 0.0426 micromol (0.0092-0.1972). In the hot plate test in vivo the inhibition of nociception by caulerpin (100 micromol/kg, p.o.) was also favorable. This result suggests that this compound exhibits a central activity, without changing the motor activity (seen in the rotarod test). Caulerpin (100 micromol/kg, p.o.) reduced the formalin effects in both phases by 35.4% and 45.6%, respectively. The possible anti-inflammatory activity observed in the second phase in the formalin test of caulerpin (100 micromol/kg, p.o.) was confirmed on the capsaicin-induced ear edema model, where an inhibition of 55.8% was presented. Indeed, it was also observed in the carrageenan-induced peritonitis that caulerpin (100 micromol/kg, p.o.) exhibited anti-inflammatory activity, reducing significantly the number of recruit cells by 48.3%. Pharmacological studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive and anti-inflammatory actions and also to identify other active principles present in Caulerpa racemosa.