Search

Made available in DSpace on 2021-06-25T15:38:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-16 Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Artemisinin (ART) was initially described for the control of inflammation and pain. However, the mechanisms involved with its antinociceptive effect are still poorly understood. Thus, this present study aimed to investigate the effect of ART in both free and nanocapsulated form on postoperative pain, as well as the participation of the spinal Toll-like receptor 4 (TLR4) in this process. Postoperative pain was induced using the skin/muscle incision retraction (SMIR) model in male Swiss mice. After 3 and 28 days of SMIR, the animals received an intrathecal injection of free or nanocapsulated ART, and the nociceptive threshold was evaluated by von Frey filament test. To evaluate the involvement of the microglia, astrocytes, and TLR4, minocycline (a microglia inhibitor), fluorocitrate (an astrocyte inhibitor), andLipopolysaccharide Rhodobacter sphaeroides(LPS-RS), a TLR4 antagonist, were intrathecally injected on the third day of SMIR. The levels of spinal TLR4 protein and proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), and interleukin-1-beta (IL-1 beta) were quantified by western blot and enzyme-linked immunosorbent assay, respectively. The results showed that free ART reduced postoperative pain (P < 0.001,F-5,F-30 = 7.49, 16.66% for 1000 ng dose; andP < 0.01,F-5,F-30 = 7.49, 14.58% for 500 ng dose) on the 3rd day of SMIR; while the ART nanocapsule had this effect on both the third (P < 0.001;F-5,F-30 = 4.94; 43.75, 39.58 and 72.91% for the 250, 500 and 1000 ng doses, respectively) and 28th (P < 0.05;F-5,F-30 = 7.71; 29.16 and 33.33% for the 500 and 1000 ng doses, respectively) day. The ART nanocapsule had a more potent and longer antinociceptive effect than free ART or morphine. Postoperative pain was also reduced by minocycline and LPS-RS. The ART nanocapsule also reduced the increased levels of TLR4, TNF-alpha, and IL-1 beta induced by SMIR. These data suggest that the ART nanocapsule has a potent analgesic effect on postoperative pain at the spinal level, and this response involves the inhibition of TLR4 and the proinflammatory cytokines TNF-alpha and IL-1 beta. Univ Fed Alfenas, Fac Motr Sci, Sci Motr Inst, Jovino Fernandes Sales Ave 2600, BR-37133840 Alfenas, Brazil Univ Sao Paulo, Dept Pharmacol, Sao Paulo, Brazil Univ Estadual Campinas, Fac Pharmaceut Sci, Campinas, Brazil Sao Paulo State Univ, Inst Sci & Technol, Sorocaba, Brazil Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto, Brazil Sao Paulo State Univ, Inst Sci & Technol, Sorocaba, Brazil CAPES: 001 FAPESP: 2014/16008-3

Found in humid regions and waterways and popularly used to treat gastrointestinal problems among other applications, the present study evaluated the M. aquatica essential oil (OEMa) as a therapeutic alternative to treat gastrointestinal disorders. Produced by steam distillation, chemical composition of OEMa was determined by GC-MS analysis. The ethanol-induced ulcer and the dose-repeated acetylsalicylic acid (ASA)-induced gastrointestinal lesions models in rats evaluated, respectively, the prophylactic and curative effects of EOMa on peptic ulcers. The EOMa's effect on gastric secretion, gastric mucus and gastrointestinal motility were evaluated in in vivo models. The curative effect of EOMa on acute colitis was evaluated using the DSS-induced colitis model in mice. Obtained in 0.17% yield (w/w), with carvone (54.82 ± 1.39 g/100 g oil) as the main constituent, EOMa (at 75 mg/kg) showed potent gastroprotective effect ( 90%) mediated by non-protein sulfhydryl compounds (NPSH) and nitric oxide (NO) modulation alongside reduction in gastric secretion volume and total acidity. EOMa did not affect gastric mucus production and gastrointestinal motility. In dose-repeated ASA-induced gastrointestinal lesions model, EOMa (at 25 mg/kg) promoted the inflammatory process resolution both in gastric and duodenal walls by modulating NPSH, NO and myeloperoxidase levels. Despite delaying in 2 days the clinical symptoms worsening, EOMa (at 25 mg/kg) was not able to protect colon tissues from DSS-induced acute colitis as evidenced by macroscopic, biochemical, and histopathological parameters. This is the first report of Mentha aquatica essential oil as a promising herbal medicine for peptic ulcers treatment together with an adjuvant effect in IBD.

Malaria affects more than 200 million people annually around the world, killing a child every 2 min. Artemether (ART) and lumefantrine (LUM) are the gold standard choice to treat uncomplicated Plasmodium falciparum malaria; however, they are hydrophobic compounds with low oral bioavailability. Microneedle (MN) arrays consist of micron-sized needles on one side of a supporting base and have the ability to bypass the skin's stratum corneum barrier in a minimally invasive way, creating temporary channels through which drugs can diffuse, including those with poor water solubility. Herein, we report the development of dissolving MNs (DMNs) containing ART (MN-ART) and LUM (MN-LUM) as an alternative treatment regimen for malaria in low-resource settings. To incorporate the drugs into the MNs, nanosuspensions (NSs) for both molecules were developed separately to enhance drug solubility. The NSs were freeze-dried and the powder form was incorporated directly in an aqueous polymeric blend with poly-vinyl-pyrrolidone for MN-ART and a sodium hyaluronate hydrogel for MN-LUM. The in vivo bioavailability studies were performed using a MN reapplication scheme (1 × a day for 3 days), illustrating that an extended-release profile was achieved for both drugs when MNs were applied intradermally, and when compared to conventional oral treatment. The ART-LUM oral treatment was used as a positive control. For antimalarial activity, studies with animals infected with 106 Plasmodium yoelii 17XNL (12 days) were also conducted using female C57BL/6JUnib mice, demonstrating a 99.5% reduction in parasitemia by day 12 post-infection. By abolishing the infection, MN-ART and MN-LUM may serve as a promising controlled intradermal delivery device for antimalarial drugs to be explored in endemic areas.

Made available in DSpace on 2021-06-25T11:46:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-02-20 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Instituto Federal Goiano Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundacao de Amaparo a Pesquisa do Estado de Goias (FAPEG, Brazil) Artemisinin extracted from Artemisia annua L. plants has a range of properties that qualifies it to treat several diseases, such as malaria and cancer. However, it has short half-life, which requires making continuous use of it, which has motivated the association of artemisinin (ART) with polymeric nanoparticles to increase its therapeutic efficiency. However, the ecotoxicological safety of this association has been questioned, given the scarcity of studies in this area. Thus, in this work the toxicity of Poly (epsilon-Caprolactone) nanocapsules added with ART (ART-NANO) in zebrafish (Danio rerio), embryos and adults was studied. Different endpoints were analyzed in organisms exposed to ART-NANO, including those predictive of embryotoxicity and histopatoxicity. Embryotoxicity was analyzed based on Organization for Economic Co-operation and Development (OECD) test guideline (236) for fish embryo acute toxicity applied to zebrafish (Danio rerio) at 96 hpf under five nominal logarithmic concentrations (0.125 to 2.0 mg/L). Our results demonstrate, mainly, that fertilized eggs presented increased coagulation, lack of heart rate, vitelline sac displacement and lack of somite formation. On the other hand, adult individuals (exposed to the same concentrations and evaluated after 24 and 96 h of exposure) have shown increased pericarditis. Therefore, the treatment based on ART, poly (epsilon-caprolactone) nanocapsules and on their combination at different concentrations have shown toxic effects on zebrafish embryos and adult individuals. (C) 2020 Elsevier B.V. All rights reserved. Univ Sao Paulo, Biomed Sci Inst, Pharmacol Dept, Sao Paulo, SP, Brazil Fed Univ Rio Janeiro UFRJ, Biodivers & Sustainabil Inst NUPEM, Integrated Translat Biosci Lab LIBT, Macae, RJ, Brazil Univ Fed Sao Carlos, Dept Genet & Evolut, Sao Carlos, SP, Brazil Univ Estadual Campinas, Pharmaceut Sci Sch, Campinas, SP, Brazil Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil Sao Paulo State Univ, Jaboticabal, SP, Brazil Univ Fed Alfenas, Motric Sci Inst, Alfenas, MG, Brazil Livestock & Supply, Minist Agr, Sao Carlos, SP, Brazil Sao Paulo State Univ, Botucatu, SP, Brazil Goiano Fed Inst, Biol Sci Dept, Urutai, Go, Brazil Sao Paulo State Univ, Jaboticabal, SP, Brazil Sao Paulo State Univ, Botucatu, SP, Brazil CNPq: 426531/2018-3 Instituto Federal Goiano: 23219.000865.2020-78 CNPq: 307743/2018-7

Made available in DSpace on 2021-06-25T11:04:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 The guided tissue regeneration (GTR) technique can be applied in dentistry and other medical specializations, such as orthopedics. In modern dentistry, GTR has been used in periodontics and implantology to treat periodontal defects, to reconstruct lost, damaged and atrophied bone tissue in dental implant procedures, and to preserve alveolar bases after tooth extraction. In order to create and improve new therapies and to develop new biomaterials that restore, improve and prevent aggravation of compromised tissue function, poly (ϵ-caprolactone) (PCL) polymer membranes were obtained by the electrospinning process and were associated with two plant extracts: Pterodon pubescens Benth (P. pubescens) and Arrabidaea chica Verlot (A. chica) which are characterized by their pharmacological activities of anti-inflammatory and healing actions, respectively. Fiber morphology was analyzed using scanning electron microscopy (SEM), where fiber average diameter was measured from SEM images. Contact angle measurements were performed in order to evaluate the hydrophilicity of electrospun membranes containing vegetal extract. High-performance liquid chromatography was used to evaluate the ability to release active ingredients. Cytotoxicity and cell proliferation assays were performed in vitro on NIH-3T3 cells for 1, 3 and 7 d. Electrospun PCL membranes associated with plant extracts P. pubescens and/or A. chica presented a controlled release profile of the active compounds induced fibroblast formation, suggesting that they are promising and suitable for applications in GTR. Department of Manufacturing and Materials Engineering School of Mechanical Engineering University of Campinas UNICAMP School of Pharmacy Queen's University Belfast Graduate School of Bioscience and Technology of Bioactive Products Biology Institute University at Campinas Faculdade de Ciências Médicas Universidade Estadual de Campinas UNICAMP Faculty of Pharmaceutical Science University at Campinas Instituto de Biociencias Univ Estadual Paulista UNESP Instituto de Biociencias Univ Estadual Paulista UNESP

The present study evaluated whether a natural dietary additive, dried Artemisia annua leaves, may be useful to control Rhipicephalus (Boophilus) microplus on naturally infested cattle. Twenty heifers of the Canchim breed, weighing around 250 kg, were divided into two equally sized experimental groups: 1) control animals and 2) animals receiving 200 g/day of dried A. annua leaves for two months. Before treatment began, the animals were homogeneously distributed in control and treatment groups based on their pre-treatment weight and tick infestation level. Counts of engorged female ticks then occurred weekly during the two-month experimental period. We also monitored cattle weight gain and packed cell volume (PCV). Artemisinin (0.96%) was quantified in the plant material by high-performance liquid chromatography with refractive index detector (HPLC-IR). No statistical differences between the control and treatment groups were observed for engorged female counts (log averages of 1.3 ticks and 1.4 ticks per animal, respectively), daily cattle weight gain (0.910 kg and 0.888 kg, respectively) or PCV (33.5% and 33.0%, respectively). We conclude that the oral supplementation of cattle feed with dried A. annuna leaves did not control natural infestation of R. (B.) microplus. The hypothesis of artemisinin’s action on cattle ticks by ingestion through the animals’ blood was not confirmed at the evaluated dose.

The combination of chitosan (C) with alginate (A) has been explored for the production of dressings due to the positive results on wound healing. CA films can show a dense or porous flexible structure, with characteristics tunable for different applications. Porosity and flexibility can be achieved, respectively, by the addition of surfactants such as Kolliphor® P188 (P) and silicone-based compounds as Silpuran® 2130 A/B (S). Furthermore, composite matrices of these polysaccharides have potential applications as devices for releasing bioactive compounds to skin lesions. The purpose of this study was to evaluate the physicochemical and biological characteristics of flexible dense and porous CA membranes incorporating the standardized extract of Arrabidaea chica Verlot (A. chica), and also to analyze the release mechanism of the extract from different membrane formulations. The results show that the inclusion of P in the formulation allows obtaining porous matrices, promotes greater homogeneity of the mixture of the silicone gel with the suspension of polysaccharides, and increases the swelling of the polymer matrix. All formulations presented high stability, reaching a maximum mass loss of 18% after seven days. The formulations with S showed the best performance in terms of flexibility and strain at break. The presence of A. chica standardized extract did not affect negatively the characteristics of the membranes. Incorporation efficiencies of the bioactive compound above 87% were achieved, and the addition of P and S to the membrane formulation changed the release of the A. chica extract kinetics. In addition, the developed formulations did not significantly affect Vero cells proliferation.

This study evaluated the pharmacological effect of the association of crude extract from the fruits of Pterodon pubescens (Pp) with the essential oil of Cordia verbenacea (Cv) in antinociception and anti-inflammatory experimental models. The effective doses of each extract and the combinations used in the associations of extracts were defined by acetic acid-induced writhing test. The separate extracts were also evaluated on formalin test. Interaction between extracts was assessed by isobologram method. The effects of different concentrations of associations (A50, A100 and A200) were evaluated on formalin test, tail flick and hot plate. The anti-inflammatory activity was evaluated in paw edema induced by carrageenan and PGE2, carrageenan-induced peritonitis and mechanical allodynia induced by Complete Freund's Adjuvant (CFA). The associations were markedly synergistic, as assessed using isobolographic analyses. On formalin and on acetic acid-induced writhing tests, associations demonstrated greater efficacy when compared to extracts separately. In paw edema models, significant reductions of edema were observed. On mechanical allodynia induced by CFA, associations were effective at acute phase with pronounced effect at chronic phase. The associations were not effective in hot plate, tail flick and carrageenan-induced peritonitis tests. Phytochemical analysis by HPLC-DAD and FID showed important concentrations of α-Humulene, trans-Caryophyllene, geranylgeraniol, isomers 6α-hydroxy-7β-acetoxy-vouacapan-17βoate methyl ester and 6α-acetoxy-7β-hydroxy-vouacapan-17β-oate methyl ester (compounds m/z 404) and 6α,7β-dihydroxyvouacapan-17β-oate methyl ester (m/z 362). These findings demonstrate that the associations promote synergistic antinociceptive effect and important anti-inflammatory activities, especially on chronic inflammation conditions, at lower doses than the separate crude extracts, without demonstrating side effects, probably acting in different pharmacological receptors. The inhibition of inflammation suggests a relationship with inflammatory mediators and PGE2 pathway and might be exploited to achieve greater anti-inflammatory efficacy, being considered as a potential phytotherapy.

In the context of the cancer-inflammation relationship and the use of natural products as potential antitumor and anti-inflammatory agents, the alkaloid-enriched fraction of Boehmeriacaudata (BcAEF) aerial parts was evaluated. In vitro antiproliferative studies with human tumor cell lines showed high activity at low concentrations. Further investigation on NCI-H460 cells showed an irreversible effect on cell proliferation, with cell cycle arrest at G2/M phase and programmed cell death induction. Molecular docking studies of four alkaloids identified in BcAEF with colchicine&rsquo, s binding site on &beta, tubulin were performed, suggesting (&minus, )-C (15R)-hydroxycryptopleurine as the main inductor of the observed mitotic death. In vivo studies showed that BcAEF was able to reduce Ehrlich tumor volume progression by 30 to 40%. Checking myeloperoxidase activity, BcAEF reduced neutrophils migration towards the tumor. The in vivo anti-inflammatory activity was evaluated by chemically induced edema models. In croton oil-induced ear edema and carrageenan (CG)-induced paw edema models, BcAEF reduced edema around 70 to 80% together with inhibition of activation and/or migration of neutrophils to the inflammatory area. All together the results presented herein show BcAEF as a potent antitumor agent combining antiproliferative and anti-inflammatory properties, which could be further explored in (pre)clinical studies.

There is no effective natural alternative control for gastrointestinal nematodes (GIN) of small ruminants, with Haemonchus contortus being the most economically important GIN. Despite frequent reports of multidrug-resistant GIN, there is no new commercial anthelmintic to substitute failing ones. Although trematocidal activity of artemisinin analogs has been reported in sheep, neither artemisinin nor its plant source (Artemisia annua) has been evaluated for anthelmintic activity in ruminants. This study evaluated the anthelmintic activity of A. annua crude extracts in vitro and compared the most effective extract with artemisinin in sheep naturally infected with H. contortus. A. annua leaves extracted with water, aqueous 0.1% sodium bicarbonate, dichloromethane, and ethanol were evaluated in vitro by the egg hatch test (EHT) and with the bicarbonate extract only for the larval development test (LDT) using H. contortus. The A. annua water, sodium bicarbonate (SBE), ethanol, and dichloromethane extracts tested in vitro contained 0.3, 0.6, 4.4, and 9.8% of artemisinin, respectively. The sodium bicarbonate extract resulted in the lowest LC99 in the EHT (1.27 μg/mL) and in a LC99 of 23.8 μg/mL in the LDT. Following in vitro results, the SBE (2 g/kg body weight (BW)) and artemisinin (100 mg/kg BW) were evaluated as a single oral dose in naturally infected Santa Inês sheep. Speciation from stool cultures established that 84-91% of GIN were H. contortus, 8.4-15.6 % were Trichostrongylus sp., and 0.3-0.7% were Oesophagostomum sp. Packed-cell volume and eggs per gram (EPG) of feces were used to test treatment efficacy. The SBE tested in vivo contained no artemisinin, but had a high antioxidant capacity of 2,295 μmol of Trolox equivalents/g. Sheep dosed with artemisinin had maximum feces concentrations 24 h after treatment (126.5 μg/g artemisinin), which sharply decreased at 36 h. By day 15, only levamisole-treated sheep had a significant decrease of 97% in EPG. Artemisinin-treated and SBE-treated sheep had nonsignificant EPG reductions of 28 and 19%, respectively, while sheep in infected/untreated group had an average EPG increase of 95%. Sheep treated with artemisinin and A. annua SBE maintained blood hematocrits throughout the experiment, while untreated/infected controls had a significant reduction in hematocrit. This is the first time oral dose of artemisinin and an aqueous extract of A. annua are evaluated as anthelmintic in sheep. Although oral dose of artemisinin and SBE, at single doses, were ineffective natural anthelmintics, artemisinin analogs with better bioavailability than artemisinin should be tested in vivo, through different routes and in multiple doses. The maintenance of hematocrit provided by artemisinin and A. annua extract and the high antioxidant capacity of the latter suggest that they could be combined with commercial anthelmintics to improve the well-being of infected animals and to evaluate potential synergism.

Purpose To develop an anesthetic mucoadhesive film containing Acmella oleracea (jambu) extract for topical use on oral mucosa. Methods Ethanolic extracts from aerial parts of jambu were prepared by maceration. Pigment removal was obtained by adsorption with activated carbon. Three mucoadhesive films were developed using a film casting method: 10 or 20% of crude jambu extract (10% JB and 20% JB), and 10% of crude jambu extract treated with activated carbon (10% JBC). The mucoadhesive films were characterized regarding their uniformity, thickness, pH, and spilanthol content, and their stability was evaluated during 120 days. Gas chromatography was used to quantify the amount of spilanthol. In vitro tests determined the permeation of spilanthol across pig esophageal epithelium mucosa in Franz diffusion cells. Topical anesthetic efficacy was assessed in vivo using a tail flick test in mice. Results The three mucoadhesive films showed physical stability and visual appearances suitable for use on oral mucosa. The permeation study revealed that the spilanthol from 10% JBC presented higher flux and permeability coefficient values, compared to 10% or 20% JB (p < 0.001). Moreover, 10% JBC showed better topical anesthetic efficacy than the other films (p < 0.01). Conclusion Mucoadhesive film containing crude extract of jambu treated with activated carbon is a potential alternative for oral, topical use, encouraging future clinical studies.

The crude alcoholic extracts obtained from Pterodon pubescens Benth. seeds are widely used in Brazilian folk medicine as anti-inflammatory, analgesic, anti-rheumatic tonics and depurative preparations. We previously demonstrated the antinociceptive activity on writhing capsaicin, glutamate, and hot-plate tests of two compounds isolated from P. pubescens : geranylgeraniol (C1) and 6α,7β-dihydroxyvouacapan-17β-oate methyl ester (C2). This work is a continuation of the previous study investigating the possible mechanisms of action for compounds C1 and C2, and the differences between them. The present study demonstrated that when administered intraperitoneally (i.p.): i), compounds C1 and C2 produced significant anti-allodynic activity during the acute phase of the Complete Freund's Adjuvant (CFA)-induced persistent pain model; ii) compound C1 produced significant anti-hypernociception activity in the carrageenan-induced pain model; iii) compound C2 presented a significant loss of activity after p -chlorophenylalanine methyl ester hydrochloride (PCPA) [5-HT synthesis inhibitor] treatment, suggesting that the mechanisms of action could be related to either the synthesis or release of serotonin; iv) compound C1 presented a significant loss of activity after ondansetron (5-HT 3 receptor antagonist) treatment suggesting activity upon 5-HT 3 serotonin receptors; v) compound C1 presented a significant loss of activity after efaroxan (mixed I 1 imidazoline/α 2 -adrenoceptor antagonist) treatment suggesting the participation of this compound upon imidazoline I 1 receptors; and vi) both compounds C1 and C2 did not appear to exert their activity via 5-HT 1A , 5-HT 2A , imidazoline I 2 , α 2 -adrenoceptor, nitric oxide, GABA A , acetylcholine muscarinic, and nicotinic receptors when evaluated in acetic acid-induced nociception.

Despite numerous studies with the Piper genus, there are no previous results reporting in vitro or in vivo Piper regnellii (Miq.) C. DC. var. regnellii anticancer activity. The aim of this study was to investigate P. regnellii in vitro and in vivo anticancer activity and further identify its active compounds. In vitro antiproliferative activity was evaluated in 8 human cancer cell lines: melanoma (UACC-62), breast (MCF7), kidney (786-0), lung (NCI-H460), prostate (PC-3), ovary (OVCAR-3), colon (HT29), and leukemia (K-562). Total growth inhibition (TGI) values were chosen to measure antiproliferative activity. Among the cell lines evaluated, eupomatenoid-5 demonstrated better in vitro antiproliferative activity towards prostate, ovary, kidney, and breast cancer cell lines. In vivo studies were carried out with Ehrlich solid tumor on Balb/C mice treated with 100, 300, and 1000 mg/kg of P. regnellii leaves dichloromethane crude extract (DCE), with 30 and 100 mg/kg of the active fraction (FRB), and with 30 mg/kg of eupomatenoid-5. The i. p. administration of DCE, FRB, and eupomatenoid-5 significantly inhibited tumor progression in comparison to control mice (saline). Therefore, this study showed that neolignans of Piper regnellii have promising anticancer activity. Further studies will be undertaken to determine the mechanism of action and toxicity of these compounds.

Background Pterodon pubescens Benth seeds are commercially available in the Brazilian medicinal plant street market. The crude alcoholic extracts of this plant are used in folk medicine as anti-inflammatory, analgesic, and anti-rheumatic preparations. The aim of this study was to evaluate the contribution of geranylgeraniol (C1) and 6α, 7β-dihydroxyvouacapan-17β-oate methyl ester (C2) isolated from Pterodon pubescens Benth. to the antinociceptive activity of the crude extract. Results Compounds C1 and C2 demonstrated activity against writhing with intraperitoneal (i.p.) and oral (p.o.) routes, capsaicin (i.p. and p.o.), glutamate (i.p.), and in the hot-plate (p.o.) tests, demonstrating their contribution to the antinociceptive activity of crude Pterodon pubescens Benth extracts. The observed activity of compounds C1 and C2 may be related to vanilloid receptors VR1, and/or glutamate peripheral receptors. In hot-plate model, the antinociceptive activity was maintained when naloxone chloride (opioid antagonist) was administered prior to treatment with compounds suggesting that C1 and C2 (p.o.) do not exert their antinociceptive effects in the hot-plate test via opioid receptors. The findings presented herein also suggest that compounds within the crude Pterodon pubescens Benth. extract may exert a synergistic interactive effect, since the crude extract (300 mg.kg-1) containing lower concentrations of compounds C1 (11.5%- 34.6 mg. kg-1) and C2 (1.5% - 4.7 mg.kg-1) gave statistically the same effect to the pure compounds when tested separately (C1 = C2 = 300 mg.kg-1) in writhing experimental model with p.o. administration. Further studies will be undertaken to establish more specifically the mechanisms of action for compounds C1 and C2. Possible synergistic interactions will be evaluated employing the Isobole method. Conclusion These results allowed us to establish a relationship between the popular use of Pterodon pubescens seeds for pain relief and the activity of two major compounds isolated from this species which demonstrated antinociceptive activity. Various "in vivo" experimental models corroborate the folk use of this species for different pain and inflammation disorders.

Ethnopharmacological relevance Arrabidaea chica Verlot. (Bignoniaceae), popularly known as Crajiru, has been traditionally used as wound healing agent. Aim of the study Investigate in vitro and in vivo healing properties of Arrabidaea chica leaves extract (AC). Materials and methods AC was evaluated in vitro in fibroblast growth stimulation (0.25–250 μg/mL) and collagen production stimulation (250 μg/mL) assays. Allantoin (0.25–250 μg/mL) and vitamin C (25 μg/mL) were used as controls respectively. DPPH and Folin-Ciocalteau assays were used for antioxidant evaluation, using trolox (0.25–250 μg/mL) as reference antioxidant. To study wound healing properties in rats, AC (100 mg/mL, 200 μL/wound/day) was topically administered during 10 days and wound area was evaluated every day. Allantoin (100 mg/mL, 200 μL/wound/day) was used as standard drug. After treatment, wound sites were removed for histopathological analysis and total collagen determination. Results AC stimulated fibroblast growth in a concentration dependent way (EC50 = 30 μg/mL), increased in vitro collagen production and demonstrated moderate antioxidant capacity. In vivo, AC reduced wound size in 96%, whereas saline group showed only 36% wound healing. Conclusion AC efficiency seems to involve fibroblast growing stimulus and collagen synthesis both in vitro and in vivo, beyond moderate scavenging activity, corroborating Crajiru folk use.

Leila Servat-Medina,1,2 Alvaro González-Gómez,2,3 Felisa Reyes-Ortega,2 Ilza Maria Oliveira Sousa,1 Nubia de Cássia Almeida Queiroz,1 Patricia Maria Wiziack Zago,1 Michelle Pedrosa Jorge,1 Karin Maia Monteiro,1,4 João Ernesto de Carvalho,1 Julio San Román,2,3 Mary Ann Foglio1 1Chemical, Biological and Agricultural Pluridisciplinary Research Center-State University of Campinas (CPQBA-UNICAMP), Campinas-SP, Brazil; 2Biomaterials Group, Polymer Science and Technology Institute-Spanish National Research Council (ICTP-CSIC), 3CIBER-BBN, Centro de Investigación Biomédica en Red, Madrid, Spain; 4Department of Medical Clinics, Faculty of Medical Sciences, University of Campinas, Campinas-SP, Brazil Abstract: Natural products using plants have received considerable attention because of their potential to treat various diseases. Arrabidaea chica (Humb. & Bonpl.) B. Verlot is a native tropical American vine with healing properties employed in folk medicine for wound healing, inflammation, and gastrointestinal colic. Applying nanotechnology to plant extracts has revealed an advantageous strategy for herbal drugs considering the numerous features that nanostructured systems offer, including solubility, bioavailability, and pharmacological activity enhancement. The present study reports the preparation and characterization of chitosan–sodium tripolyphosphate nanoparticles (NPs) charged with A. chica standardized extract (AcE). Particle size and zeta potential were measured using a Zetasizer Nano ZS. The NP morphological characteristics were observed using scanning electron microscopy. Our studies indicated that the chitosan/sodium tripolyphosphate mass ratio of 5 and volume ratio of 10 were found to be the best condition to achieve the lowest NP sizes, with an average hydrodynamic diameter of 150±13 nm and a zeta potential of +45±2 mV. Particle size decreased with AcE addition (60±10.2 nm), suggesting an interaction between the extract’s composition and polymers. The NP biocompatibility was evaluated using human skin fibroblasts. AcE-NP demonstrated capability of maintaining cell viability at the lowest concentrations tested, stimulating cell proliferation at higher concentrations. Antiulcerogenic activity of AcE-NP was also evaluated with an acute gastric ulcer experimental model induced by ethanol and indomethacin. NPs loaded with A. chica extract reduced the ulcerative lesion index using lower doses compared with the free extract, suggesting that extract encapsulation in chitosan NPs allowed for a dose reduction for a gastroprotective effect. The AcE encapsulation offers an approach for further application of the A. chica extract that could be considered a potential candidate for ulcer-healing pharmaceutical systems. Keywords: natural product, Arrabidaea chica, chitosan, nanoparticle, plant extract, herbal drug, ulcer healing