Abstract Leishmaniasis is a disease of public health relevance that demands new therapeutic alternatives due to the toxicity of conventional treatments. In this study, 27 plants of interest to the Unified Health System (SUS) were evaluated for cytotoxicity in macrophages, leishmanicidal activity and production of nitric oxide (NO). None of the species demonstrated cytotoxicity to macrophages (CC50 >100 μg/mL). Extracts from Chenopodium ambrosioides, Equisetum arvense, Maytenus ilicifolia showed greater efficacy in inducing the death of Leishmania amazonensis amastigotes with IC50 of 68.4, 82.3, 75.7 μg/mL, respectively. The species Cynara scolymus, Punica granatum and Passiflora alata were the most effective in inducing an increase in the indirect concentration of NO (41.31, 29.30 and 28.86 µM, respectively) in cultures of macrophages infected with L. amazonensis. Furthermore, Punica granatum was also the most effective species in inducing an increase in NO in macrophages infected by Leishmania chagasi (19.90 µM). The results obtained so far support the continuation of studies, with the possibility of developing safer and more effective treatments for leishmaniasis, using natural products. The identification of plants that stimulate the production of NO in macrophages infected by Leishmania opens doors for more detailed investigations of the mechanism of action of these natural products. study 2 SUS (SUS NO. . (NO) CC50 CC (CC5 100 >10 μg/mL. μgmL μg/mL μg mL μg/mL) ambrosioides arvense IC IC5 684 68 4 68.4 823 82 3 82.3 757 75 7 75. respectively scolymus 41.31, 4131 41 31 (41.31 2930 29 30 29.3 2886 28 86 28.8 µM L Furthermore 19.90 1990 19 90 (19.9 µM. µM) studies leishmaniasis products (NO CC5 (CC 10 >1 6 68. 8 82. 41.31 413 (41.3 293 29. 288 28. 19.9 199 1 9 (19. > 41.3 (41. 19. (19 41. (41 (1 (4 (

Abstract Cereus jamacaru DC. (Cactaceae) is used in folk medicine for treating pain and inflammation. However, the therapeutic potential of C. jamacaru extracts has not been assessed experimentally. This study aimed to characterize the effect of both aqueous (CAECJ) and ethanolic (CEECJ) extracts of C. jamacaru in mouse models of pain and inflammation. CAECJ and CEECJ were chemically characterized by qualitative methods. Toxicity of extracts was evaluated in vitro against J774.A1 macrophages and in vivo by monitoring mice for 14 days following a single oral treatment at 2000 mg/kg. The antinociceptive activity of the extracts was assessed in models of pain in mice: acetic acid-induced writhing test, formalin test, hot plate test, and glutamate-induced nociception assay. The anti-inflammatory activity of the extracts was assessed following zymosan-induced peritonitis and in the model of arthritis induced by Complete Freund’s Adjuvant (CFA). Phytochemical analyses revealed alkaloids, condensed tannins, flavonoids, and anthraquinones in both extracts; saponins were present in CEECJ only. Neither extract was cytotoxic in vitro or induced toxicity in mice. Both extracts reduced nociception in all models of nociception without impairing motor function. Both extracts reduced leucocyte migration during experimental peritonitis and reduced paw edema during experimental arthritis. The effects of the extracts can be both due to anti-inflammatory and centrally-mediated mechanisms. This paper corroborates the traditional use of C. jamacaru extracts and demonstrates their therapeutic potential in the development of new analgesic and anti-inflammatory drugs with a good safety profile. DC Cactaceae (Cactaceae inflammation However C experimentally (CAECJ (CEECJ methods J774A1 JA J774 A1 J A J774.A 1 200 mgkg mg kg mg/kg acidinduced acid test glutamateinduced glutamate assay antiinflammatory anti inflammatory zymosaninduced zymosan Freunds Freund s CFA. CFA . (CFA) alkaloids tannins flavonoids only function centrallymediated centrally mediated mechanisms profile J774A J77 20 (CFA J7 2

Abstract The Pyroligneous extract is a product from the combustion of plant biomass with applications in the fields of health, industrial chemistry, and agriculture. The discovery of new molecules with therapeutic potential and of natural origin continues to be one of the great challenges for research centres around the world. The following work aims to analyze, through a technological prospection, the use of pyroligneous extracts for therapeutic purposes. To carry out the study, searches were carried out in documents deposited in Brazil, Europe, and the United States and searched on platforms specialized in patents. The number of inventions using pyroligneous extract with therapeutic applications is still quite small, however, innovations have been observed for the treatment of diseases of great clinical relevance such as cancer and hypertension. The systematic mapping of innovations is of great importance for the development of new technologies. health chemistry agriculture world analyze prospection purposes study Brazil Europe patents small however hypertension technologies

Abstract Microbial therapeutic enzymes are the protagonists in the pharmacological treatment of different human diseases. The intrinsic enzymatic characteristics, such as high affinity and specificity to the corresponding substrate, enable effective therapies, with minimal adverse effects and complete remission. However, immunogenicity, short half-life, low enzymatic yield, and low selectivity regarding available enzyme drugs are currently the main obstacles to their development and the broad adherence to therapeutic protocols. By harboring adapted and still unexplored microbial life, environments of extreme conditions, such as Antarctica, become especially important in the prospecting and development of new enzymatic compounds that present higher yields and the possibility of genetic improvement. Antarctic microorganisms have adaptation mechanisms, such as more fluid cell membranes, production of antifreeze proteins and enzymes with more malleable structures, more robust, stable, selective catalytic sites for their respective substrates, and high antioxidant capacity. In this context, this review aims to explore enzymes synthesized by bacteria and fungi from Antarctica as potential drug producers, capable of providing therapeutic efficacy, less adverse effects, and lower production costs with highlight to L-Asparaginase, collagenase, superoxide dismutase and ribonucleases. In addition, this review highlights the unique biotechnological profile of these Antarctic extremophile microorganisms.

Abstract Currently, antimicrobial resistance has become a global public health problem, which has made the need for new antimicrobial compounds to deal with resistant infections an emergency. However, environments that once offered so many innovative molecules, now already exhaustively exploited, do not meet this need. In this context, a geographically isolated, under-explored and extreme environment, such as Antarctica, which holds organisms with unique physiological and biochemical characteristics, assumes great importance as a potential source of new compounds with antimicrobial activity. In this patent review, we investigate the state of technological development in the field of antimicrobial compounds obtained from Antarctic organisms, highlighting the main countries and researchers active in the field, the species utilized, the compounds obtained, and their possible therapeutic applications. As results, few patent documents were found, however they encompass a wide diversity of compounds and species, indicating a great antimicrobial potential present in Antarctic biota, including compounds active against the most important human pathogenic microorganisms, such as including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp. and multi-resistant Mycobacterium tuberculosis. Furthermore, due to the increasing trend in patent applications, a significant rise in the number of patents in this area is expected in the coming years.

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.

ABSTRACT N-acylhydrazone is an interesting privileged structure that has been used in the molecular design of a myriad of bioactive compounds. In order to identify new antinociceptive drug candidates, we described herein the design, synthesis, X-ray diffraction study and the pharmacological evaluation of a series of 3-amino-4-methylthiophene-2-acylcarbohydrazone derivatives (8a-t). Compounds were prepared in good overall yields through divergent synthesis from a common key intermediate and were characterized by classical spectroscopy methods. X-ray diffraction study was employed for unequivocal determination of the imine double bond stereochemistry. 8a-t were evaluated in vivo through oral administration using the classical writhing test in mice. N-acylhydrazone derivatives 8j and 8l displayed relative potency similar to dipyrone, highlighting them as promising analgesic lead-candidates for further investigation.

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.

AbstractSidastrum paniculatum (L.) Fryxell, Malvaceae, is popularly known in Brazil as “malva-roxa” or “malvavisco”. The species is found mainly in Northeast region where it is used by locals to treat spider bites and bee stings. Aiming to identify the chemical compounds from S. paniculatum secondary metabolism and to contribute to the chemotaxonomic knowledge of Malvaceae family, a phytochemical study of S. paniculatum was carried out. Besides that, the isolated compounds were evaluated for antileishmanial activity against promastigotes of Leishmania braziliensis. By using chromatographic techniques the study resulted the isolation of eight compounds: 3-oxo-21β-H-hop-22(29)-ene; sebiferic acid; sitosterol 3-O-β-d-glucopyranoside/stigmasterol 3-O-β-d-glucopyranoside; phaeophytin a; 132(S)-hydroxyphaeophytin a; 132(S)-hydroxy-(173)-ethoxyphaeophorbide a and 7,4′-di-O-methylisoescutellarein. The structure of all isolated compounds was elucidated by spectroscopic analysis, including two-dimensional NMR techniques. In addition, the isolated compounds phaeophytin a; 132(S)-hydroxyphaeophytin a; 132(S)-hydroxy-(173)-ethoxyphaeophorbide a and 7,4′-di-O-methylisoescutellarein exhibited antileishmanial activity against promastigotes of L. braziliensis.

The antinociceptive activity of the Maytenus rigida Mart. (Celastraceae) ethanol extract and its ethyl acetate fraction as well as of (-)-4'-methylepigallocatechin (1), a previously isolated compound, was demonstrated in vivo. ED50 for 1 in the writhing test was 14.14 mg/kg. The acetic acid-induced writhing was inhibited by 98.4, 84.4, and 58.3%, respectively, when mice were treated with the ethanol extract, ethyl acetate fraction, and 1. In the hot plate test, mice pretreated with 1 showed significantly increased reaction times (60-89%). Oral administration of 1 significantly inhibited first and second phases of the formalin-induced pain (50 and 26.5%, respectively), whereas indomethacin inhibited only the second phase of the test (41.2%). Ethanol extract and its fraction showed effects on inflammatory pain, while neurogenic and inflammatory pain suppression by 1 is a strong indication of the presence of both central and peripheral effects and suggests its analgesic and anti-inflammatory potential.

Erythrina mulungu Mart. ex Benth., Fabaceae, popularly known as mulungu, is used for the treatment of insomnia and disorders of the central nervous system. This study examined the antinociceptive effects of the hydroalcoholic extracts (HAE), the ethyl acetate and chloroformic fractions from E. mulungu in four experimental models of nociception using laboratory mice. The extracts and fractions were administered orally to mice at doses of 100 mg/kg. Inhibition of abdominal contractions were observed for all the extracts and fractions tested, as compared to controls. All extracts and fractions from E. mulungu reduced the nociception activity produced by formalin in the 2nd phase. In the hot plate test no significant effect was observed for any extract or fraction. In the peritonitis test induced by Zymosan, all of the tested extracts and the chloroformic fraction, except for the ethyl acetate phase, reduced cell migration of the peritoneal cavity. We concluded that E. mulungu shows antinociceptive effects, which are independent of the opioid system.

Neste estudo, tentamos identificar a atividade antinociceptiva do extrato metanólico bruto e das fases n-butanólica, clorofórmica e acetato de etila provenientes da alga Caulerpa racemosa. Esta alga é cosmopolita no mundo, principalmente em regiões tropicais. O extrato metanólico bruto e as fases n-butanólica, clorofórmica e acetato de etila foram administrados por via oral, na concentração de 100 mg/kg. Estes foram capazes de reduzir a nocicepção produzida pelo ácido acético, sendo 47,39%, 70,51%, 76,11% e 72,24%, respectivamente. No ensaio da placa quente as fases clorofórmica e acetato de etila foram ativas neste modelo. Na fase neurogênica do teste de formalina, foi observado que o extrato metanólico bruto (51,77%), fase n-butanólica (35,12%), fase clorofórmica (32,70%) e indometacina (32,06%) foram eficazes em inibir a resposta nociceptiva. Na fase inflamatória, apenas a fase acetato de etila (75,43%) e indometacina (47,83%) foram capazes de inibir significativamente a resposta nociceptiva. Com base nestes dados, podemos sugerir que o a fase acetato de etila apresenta um significativo efeito anti-inflamatório, cuja potência ainda não foi determinada. No entanto, estudos farmacológicos e químicos serão necessários, a fim de caracterizar o mecanismo responsável pela ação antinociceptiva e também para identificar outros princípios ativos presentes na alga Caulerpa racemosa.

In this study, we attempted to identify the possible antinociceptive actions of n-butanolic phase, chloroformic phase, ethyl acetate phase and crude methanolic extract obtained from Caulerpa racemosa. This seaweed is cosmopolitan in world, mainly in tropical regions. The n-butanolic, chloroformic, ethyl acetate phases and crude methanolic extract, all administered orally in the concentration of 100 mg/kg, reduced the nociception produced by acetic acid by 47.39%, 70.51%, 76.11% and 72.24%, respectively. In the hotplate test the chloroformic and ethyl acetate phase were activite in this models. In the neurogenic phase on formalin test, were observed that crude methanolic extract (51.77%), n-butanolic phase (35.12%), chloroformic phase (32.70%) and indomethacin (32.06%) were effective in inhibit the nociceptive response. In the inflammatory phase, only the ethyl acetate phase (75.43%) and indomethacin (47.83%) inhibited significantly the nociceptive response. Based on these data, we can infer that the ethyl acetate phase shows a significant anti-inflammatory profile, whose power has not yet been determined. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive action and also to identify other active principles present in Caulerpa racemosa.

Species of Cassia are widely distributed in tropical and subtropical regions throughout the world, and have been extensively investigated chemically and pharmacologically.They are known to be a rich source of phenolic derivatives, most of them with important biological and pharmacological properties. Some Asian, African and Indian tribes use these species as a laxative, purgative, antimicrobial, antipyretic, antiviral and anti-inflammatory agent. Among a number of other classes of secondary metabolites, such as anthracene derivatives, antraquinones, steroids and stilbenoids, biologically active piperidine alkaloids are an especially important bioactive class of compounds that showed to be restricted to a small group of Cassia species. In this paper we present an overview of the chemical, biological and ethnopharmacological data on Cassia piblished in the literature.