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Made available in DSpace on 2018-11-26T17:39:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-07-25 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Context: Indigofera suffruticosa Miller (Fabaceae) and I. truxillensis Kunth produce compounds, such as isatin (ISA) and indirubin (IRN), which possess antitumour properties. Their effects in mammalian cells are still not very well understood. Objective: We evaluated the activities of ISA and/or IRN on cell viability and apoptosis in vitro, their genotoxic potentials in vitro and in vivo, and the IRN-and ISA-induced expression of ERCC1 or BAX genes. Materials and methods: HeLa and/or CHO-K1 cell lines were tested (3 or 24 h) in the MTT, Trypan blue exclusion, acridine orange/ethidium bromide, cytokinesis-blocked micronucleus (CBMN) and comet (36, 24 and 72 h) tests after treatment with IRN (0.1 to 200 mu M) or ISA (0.5 to 50 mu M). Gene expression was measured by RT-qPCR in HeLa cells. Swiss albino mice received IRN (3, 4 or 24 h) by gavage (50, 100 and 150 mg/kg determined from the LD50 - 1 g/kg b.w.) and submitted to comet assay in vivo. Results: IRN reduced the viability of CHO-K1 (24 h; 5 to 200 mu M) and HeLa cells (10 to 200 mu M), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10 mu M; HeLa: 5 and 10 mu M). The drug did not induce apoptosis, micronucleus neither altered gene expression. IRN and ISA were genotoxic for HeLa cells (3 and 24 h) at all doses tested. IRN (100 and 150 mg/kg) also induced genotoxicity in vivo (4 h). Conclusion: IRN and ISA have properties that make them candidates as chemotherapeutics for further pharmacological investigations. Univ Estadual Londrina, Ctr Biol Sci, Dept Gen Biol, Celso Garcia Cid Rd,PR 445 Km 380, BR-86057970 Londrina, Parana, Brazil Sao Paulo State Univ, Araraquara Inst Chem, Araraquara, Brazil Sao Paulo State Univ, Araraquara Fac Pharmaceut Sci, Dept Biol Sci, Araraquara, Brazil Sao Paulo State Univ, Expt Campus Paulista Coast, Sao Vicente, Brazil Yale Sch Med, Abraham Ribicoff Res Facil, New Haven, CT USA Sao Paulo State Univ, Araraquara Inst Chem, Araraquara, Brazil Sao Paulo State Univ, Araraquara Fac Pharmaceut Sci, Dept Biol Sci, Araraquara, Brazil Sao Paulo State Univ, Expt Campus Paulista Coast, Sao Vicente, Brazil

One of the major disadvantages of the current cancer therapy is the suppression of the immune system. Brazilian flora is considered one of the most diverse in the world and many plants were found to contain active constituents that can be valuable sources of new drugs. The plant Indigofera suffruticosa was studied to determine its potential to stimulate the immune system and also to be effective against tumour cells. We investigated the effects of the alkaloidal fraction and the pure alkaloid indigo obtained from I. suffruticosa on macrophage activation by measuring nitric oxide (NO) and tumour necrosis factor-α (TNF-α) production. Cytotoxic activity was also evaluated against the two tumour murine cells lines, LM2 (breast adenocarcinoma) and LP07 (lung adenocarcinoma). The alkaloidal fraction induced a high NO production and a moderated TNF-α release. The pure indigo demonstrated an elevated NO and TNF-α production. The fraction and the pure compound also exhibited cytotoxic activity against both adenocarcinoma cell lines and indigo showed the strongest cytotoxic activity with IC₅₀ value of 0.89 µg mL⁻¹ against LM2 and 1.44 µg mL⁻¹ against LP07. Our results presented the immunostimulatory and cytotoxic activity of I. suffruticosa, enhancing macrophage function and therefore contributing to the host defence against tumours.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:26:07Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:36:26Z : No. of bitstreams: 1 2-s2.0-80455131271.pdf: 3278875 bytes, checksum: cd7d0c653950fdc25c8feb76e6844ea4 (MD5) Made available in DSpace on 2014-05-27T11:26:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-11-09 Alchornea triplinervia (Spreng.) Muell. Arg (Euphorbiaceae) is a medicinal plant commonly used by people living in the Cerrado region of Brazil to treat gastrointestinal ulcers. We previously described the gastroprotective action of methanolic extract (ME) of Alchornea triplinervia and the ethyl acetate fraction (EAF) in increasing of prostaglandin E 2 (PGE 2) gastric levels in the mucosa. In this work we evaluated the effect of EAF in promoting the healing process in rats with acetic acid-induced gastric ulcers. In addition, toxicity was investigated during treatment with EAF. After 14 days of treatment with EAF, the potent stimulator of gastric cell proliferation contributed to the acceleration of gastric ulcer healing. Upon immunohistochemical analysis, we observed a pronounced expression of COX-2, mainly in the submucosal layer. The 14-day EAF treatment also significantly increased the number of neutrophils in the gastric mucosa regeneration area. The EAF induced angiogenesis on gastric mucosa, observed as an increase of the number of blood vessels supplying the stomach in rats treated with EAF. Oral administration for 14 days of the ethyl acetate fraction from Alchornea triplinervia accelerated the healing of gastric ulcers in rats by promoting epithelial cell proliferation, increasing the number of neutrophils and stimulation of mucus production. This fraction, which contained mainly phenolic compounds, contributed to gastric mucosa healing. © 2011 by the authors; licensee MDPI, Basel, Switzerland. Department of Physiology Univ. Estadual Paulista-UNESP, Rubião Junior, cp 510, CEP 18618-000, Botucatu, São Paulo Institute of Chemistry Univ. Estadual Paulista-UNESP, cp 355, CEP 14801-970, Araraquara, São Paulo Department of Morphology Univ. Estadual Paulista-UNESP, cp 610, CEP 18618-000, UNESP, Botucatu, São Paulo Department of Physiology Univ. Estadual Paulista-UNESP, Rubião Junior, cp 510, CEP 18618-000, Botucatu, São Paulo Institute of Chemistry Univ. Estadual Paulista-UNESP, cp 355, CEP 14801-970, Araraquara, São Paulo Department of Morphology Univ. Estadual Paulista-UNESP, cp 610, CEP 18618-000, UNESP, Botucatu, São Paulo

Made available in DSpace on 2013-09-27T14:54:28Z (GMT). No. of bitstreams: 1 WOS000295236700022.pdf: 1054917 bytes, checksum: ade3c93db496ae9bfef43fc129742e42 (MD5) Previous issue date: 2011-09-01 Made available in DSpace on 2013-09-30T18:37:23Z (GMT). No. of bitstreams: 1 WOS000295236700022.pdf: 1054917 bytes, checksum: ade3c93db496ae9bfef43fc129742e42 (MD5) Previous issue date: 2011-09-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:49:42Z No. of bitstreams: 1 WOS000295236700022.pdf: 1054917 bytes, checksum: ade3c93db496ae9bfef43fc129742e42 (MD5) Made available in DSpace on 2014-05-20T13:49:42Z (GMT). No. of bitstreams: 1 WOS000295236700022.pdf: 1054917 bytes, checksum: ade3c93db496ae9bfef43fc129742e42 (MD5) Previous issue date: 2011-09-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Ethnopharmacological relevance: Indigofera suffruticosa is specie typical of the Cerrado or Brazilian savannah; it is a member of the Fabaceae family - in folkmedicine is used for gastric disorders, infection and inflammation.Aim of the study: Ethyl acetate fraction (AcF) and aqueous fraction (AqF) of the methanolic extract of I. suffruticosa leaves were evaluated against acute gastric ulcer. The AcF fraction was selected to assess its activity in ulcer healing and its gastroprotective effects via mucus and gastric secretion.Materials and methods: The gastroprotective action of AcF and AqF fractions were evaluated in a rodent experimental model. The action mechanisms, involvements of the antisecretory action, mucus and prostaglandin production, toxicological and healing activity of the AcF (100 mg/kg, p.o.) were evaluated. We also used histological analysis (HE and PAS) and immunohistochemical (PCNA and HSP-70) assays to evaluate the effects of I. suffruticosa.Results: AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant in 100 mg/kg group compared vehicle. AcF did not interfered with gastric secretion, significantly increased the PGE(2) and mucus production (validated in PAS technique). The gastroprotection was attenuated by pretreatment with N-ethylmaleimide, but not L-NAME. In acid-acetic-induced ulcer model AcF accelerated ulcer healing. Immunohistochemistry analysis showed induction of proliferating cell (PCNA) and heat shock protein (HSP 70).Conclusions: These results showed that AcF acted as gastroprotective agent stimulating prostaglandin, mucus and HSP70. (C) 2011 Elsevier B.V. All rights reserved. Univ Estadual Campinas, Dept Anat Biol Celular Fisiol & Biofis, Inst Biol, BR-13083970 Campinas, SP, Brazil Univ Estadual Campinas, Fac Ciencias Med, Dept Farmacol, BR-13083970 Campinas, SP, Brazil Univ Estadual Paulista, Inst Quim, Dept Quim Organ, Araraquara, SP, Brazil Univ Estadual Paulista, Dept Morfol, Inst Biociencias, Botucatu, SP, Brazil Univ Estadual Paulista, Inst Biociencias, Dept Fisiol, Botucaru, SP, Brazil Univ Estadual Paulista, Inst Quim, Dept Quim Organ, Araraquara, SP, Brazil Univ Estadual Paulista, Dept Morfol, Inst Biociencias, Botucatu, SP, Brazil Univ Estadual Paulista, Inst Biociencias, Dept Fisiol, Botucaru, SP, Brazil

Context: Alchornea triplinervia (Spreng.) Mull. Arg. (Euphorbiaceae) is a tree widespread in many Brazilian states. This plant naturally occurs in different ecosystems including tropical Atlantic forest, Amazon rain forest, moist tropical mixed forest, savanna forest, among others. Local populations traditionally use it in tea form to treat gastric disturbances.Objective: The objective of this research was to evaluate the plant A. triplinervia as a potential inhibitor of some macrophage functions involved in the inflammatory process.Materials and methods: The effects of Alchornea triplinervia ethyl acetate fraction (AtF) on hydrogen peroxide (H2O2), nitric oxide (NO) and tumor necrosis factor-α (TNF-α) production in peritoneal macrophages were investigated using phenol red, Griess reagent and a sandwich immunoassay, respectively.Results: AtF chromatographic analyses indicate the presence of flavonoids as majority compounds. The fraction also showed an intense inhibition of H2O2 and NO production. The inhi...

Mycobacterium tuberculosis is responsible for over 8 million cases of tuberculosis (TB) annually. Natural products may play important roles in the chemotherapy of TB. The antimycobacterial activity and the innate immune response of methanol (METH) and dichloromethane (DCM) extracts of Indigofera suffruticosa Miller (Fabaceae) were evaluated. We observed that the minimum inhibitory concentrations (MICs) for METH and DCM extracts were 125 and 1000 microg/mL, respectively. However, they were able to induce the innate immune response through the production of high levels of NO and TNF-alpha (p < 0.001) by peritoneal exudate cells (PECs). These results suggest that I. suffruticosa extracts may have an important immunological role in the control of TB once macrophage activity is induced by them.

Ethanol-induced oxidative damage is commonly associated with the generation of reactive oxygen molecules, leading to oxidative stress. Considering that antioxidant activity is an important mechanism of action involved in cytoprotection, the aim of this work was to evaluate the antioxidant properties of the alkaloid indigo (1) (2 mg/kg, P. O.), obtained from the leaves of Indigofera truxillensis Kunth (Fabaceae), on rat gastric mucosa submitted to ethanol-induced (100%, 1 mL, P. O.) gastric ulcer. Enzymatic assays and DNA fragmentation analysis were performed. When ethanol was administered to the control group, the sulfhydryl content (SH) and the glutathione peroxidase (GPx) activity decreased by 41% and 50%, respectively; in contrast, superoxide dismutase (SOD) and glutathione reductase (GR) activities increased by 56% and 67%, respectively. Additionally, myeloperoxidase (MPO) activity, a marker for free radical generation caused by polymorphonuclear neutrophil (PMN) tissue infiltration, also increased 4.5-fold after ethanol treatment. Rat gastric mucosa exposed to ethanol showed DNA fragmentation. Indigo alkaloid pretreatment protected rats from ethanol-induced gastric lesions. This effect was determined by the ulcerative lesion area (ULA), indicating an inhibition of around 80% at 2 mg/kg. This alkaloid also diminished GPx activity, which was higher than that observed with ethanol alone. However, this effect was counterbalanced by increased GR activity. Indigo was unable to restore alterations in SOD activity promoted by ethanol. After indigo pretreatment, SH levels and MPO activity remained normal and gastric mucosa DNA damage caused by ethanol was also partially prevented by indigo. These results suggest that the gastroprotective mechanisms of indigo include non-enzymatic antioxidant effects and the inhibition of PMN infiltration which, in combination, partially protect the gastric mucosa against ethanol-induced DNA damage.

Made available in DSpace on 2015-12-07T15:39:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-10-29. Added 1 bitstream(s) on 2015-12-07T15:54:28Z : No. of bitstreams: 1 PMC4625929.pdf: 472777 bytes, checksum: dedcb2fb4fdcef28e5613e423b621389 (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Syngonanthus arthrotrichus and Syngonanthus bisulcatus, currently known for Comanthera aciphylla (Bong.) L.R.Parra & Giul. and Comanthera bisulcata (Koern.) L.R. Parra & Giul, popularly known in Brazil as sempre-vivas, are plants from the family Eriocaulaceae. They are found in the states of Minas Gerais and Bahia. The species are known to be rich in flavonoids to which their gastroprotective activity has been attributed. In this research, experimental protocols were performed to elucidate the associated mechanisms of action. The activity was evaluated using induced gastric ulcer models (acetic acid and ethanol-induced gastric lesions in NEM or L-NAME pre-treated mice, and by ischemia/reperfusion). Antioxidant enzymes, serum somatostatin, and gastrin were also evaluated. In chronic gastric ulcers, a single daily oral dose of Sa-FRF or Sb-FRF (100 mg/kg body wt.) for 14 consecutive days accelerated ulcer healing to an extent similar to that seen with an equal dose of cimetidine. The pre-treatment of mice with NEM (N-ethylmaleimide) or L-NAME (N-nitro-L-arginine) abolished the protective activity of Sa-FRF, Sa-FDF, Sb-FDF and Sb-FRF or Sa-FRF and Sb-FRF, respectively, which indicates that antioxidant compounds and nitric oxide synthase activity are involved in the gastroprotective. Sa-FRF and Sb-FRF (100 mg/kg p.o) protected the gastric mucosa against ulceration that was induced by ischemia/reperfusion (72 and 76 %, respectively). It also decreased lipid peroxidation and restored total thiols in the gastric wall of mice that had been treated with ethanol. When administered to rats submitted to ethanol-induced gastric lesions, Sa-FRF and Sb-FRF (100 mg/kg, p.o.) increased the somatostatin serum levels, while the gastrin serum levels were proportionally decreased. The results indicate significant healing effects and gastroprotective activity for the Sa-FRF and Sb-FRF, which probably involves the participation of SH groups, nitric oxide (NO), the antioxidant system, somatostatin, and gastrin. All are integral parts of the gastrointestinal mucosa's cytoprotective mechanisms against aggressive factors. Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Laboratório de Farmacologia do Trato Gastrintestinal, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, Brasil Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brasil Departamento de Morfologia, Instituto de Biociências de Botucatu (IBB), Universidade Estadual Paulista (UNESP), Botucatu, SP, Brasil Departamento de Fisiologia, Instituto de Biociências de Botucatu (IBB), Universidade Estadual Paulista (UNESP), Botucatu, SP, Brasil Departamento de Botânica, Instituto de Biociências, Universidade de São Paulo (USP), São Paulo, SP, Brasil Universidade Estadual Paulista, Departamento de Morfologia, Instituto de Biociências de Botucatu Universidade Estadual Paulista, Departamento de Fisiologia, Instituto de Biociências de Botucatu

Isatin (1H-indole-2,3-dione) is a chemical found in various medicinal plant species and responsible for a broad spectrum of pharmacological and biological properties that may be beneficial to human health, as an anticonvulsant, antibacterial, antifungal, antiviral, and anticancer agent. The aim of the present study was to determine in vitro the cytotoxic, mutagenic, and apoptotic effects of isatin on CHO-K1 and HeLa cells using the MTT viability assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide), micronucleus (MN) test, apoptosis index, and nuclear division index (NDI). The 5 isatin concentrations evaluated in the mutagenicity and apoptosis tests were 0.5, 1, 5, 10, and 50 μM, selected through a preliminary MTT assay. Positive (doxorubicin, DXR) and negative (phosphate buffered saline, PBS) control groups were also included in the analysis. Isatin did not exert a mutagenic effect on CHO-K1 after 3 and 24 h of treatment or on HeLa cells after 24 h. However, 10 and 50 μM concentrations inhibited cell proliferation and promoted apoptosis in both CHO-K1 and HeLa cells. Data indicate that the cytotoxic, apoptotic, and antiproliferative effects of isatin were concentration independent and cell line independent.

Made available in DSpace on 2013-08-28T14:14:05Z (GMT). No. of bitstreams: 1 WOS000311425000075.pdf: 359699 bytes, checksum: dc834e37ba779fa0c7c5ffe01de42057 (MD5) Made available in DSpace on 2013-09-30T18:37:38Z (GMT). No. of bitstreams: 2 WOS000311425000075.pdf: 359699 bytes, checksum: dc834e37ba779fa0c7c5ffe01de42057 (MD5) WOS000311425000075.pdf.txt: 48884 bytes, checksum: ef06d69e48247111c34e169cdd8280e2 (MD5) Previous issue date: 2012-11-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:50:01Z No. of bitstreams: 2 WOS000311425000075.pdf: 359699 bytes, checksum: dc834e37ba779fa0c7c5ffe01de42057 (MD5) WOS000311425000075.pdf.txt: 48884 bytes, checksum: ef06d69e48247111c34e169cdd8280e2 (MD5) Made available in DSpace on 2014-05-20T13:50:01Z (GMT). No. of bitstreams: 2 WOS000311425000075.pdf: 359699 bytes, checksum: dc834e37ba779fa0c7c5ffe01de42057 (MD5) WOS000311425000075.pdf.txt: 48884 bytes, checksum: ef06d69e48247111c34e169cdd8280e2 (MD5) Previous issue date: 2012-11-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The present study evaluated the antiulcerogenic activity and mechanisms of the aqueous (AqF 100 mg/kg) and ethyl acetate (AcF 50 mg/kg) fractions from Indigofera truxillensis leaves. This dose was selected to assess its activity on ulcer healing and its action on gastric acid and mucus secretion, prostaglandin production and antioxidant enzyme activity (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd)). Gastric ulcer was induced by absolute ethanol. Antisecretory action, mucus and prostaglandin production, healing and antioxidant enzyme activities were evaluated for both fractions. AqF and AcF significantly inhibited the gastric mucosal damage caused by ethanol. This effect was statistically significant at 100 and 50 mg/kg compared with the vehicle. Neither fraction interfered with gastric secretion. AcF increased the PGE(2) production, and both fractions increased mucus production. L-NAME did not alter the gastroprotection exerted by the fractions, but N-ethylmaleimide attenuated only AcF. In the ischemia/reperfusion model both fractions inhibited the mucosal damage. AcF increased SOD, GSH-Px and GSH-Rd activity, but AqF increased only SOD and GSH-Px. In the acetic acid-induced ulcer model AcF only accelerated ulcer healing. These results showed that Indigofera truxillensis acted as a gastroprotective agent, stimulating protective factors and antioxidants enzymes. Univ Fed Goias, Dept Biol Sci, BR-75704020 Catalao, Go, Brazil Univ Estadual Campinas, Dept Struct & Funct Biol, Inst Biol, BR-13083865 São Paulo, Brazil Univ Estadual Campinas, Dept Pharmacol, Fac Med Sci, BR-13083887 São Paulo, Brazil São Paulo State Univ, Dept Organ Chem, Inst Chem, BR-14800900 São Paulo, Brazil São Paulo State Univ, Dept Physiol, Inst Biosci, BR-18618000 São Paulo, Brazil São Paulo State Univ, Dept Organ Chem, Inst Chem, BR-14800900 São Paulo, Brazil São Paulo State Univ, Dept Physiol, Inst Biosci, BR-18618000 São Paulo, Brazil

Made available in DSpace on 2013-09-27T14:53:42Z (GMT). No. of bitstreams: 1 WOS000287055900008.pdf: 158628 bytes, checksum: 568dcc2b8f78012a539d526dedf7d3ff (MD5) Previous issue date: 2011-02-03 Made available in DSpace on 2013-09-30T18:06:19Z (GMT). No. of bitstreams: 1 WOS000287055900008.pdf: 158628 bytes, checksum: 568dcc2b8f78012a539d526dedf7d3ff (MD5) Previous issue date: 2011-02-03 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:24:20Z No. of bitstreams: 1 WOS000287055900008.pdf: 158628 bytes, checksum: 568dcc2b8f78012a539d526dedf7d3ff (MD5) Made available in DSpace on 2014-05-20T13:24:20Z (GMT). No. of bitstreams: 1 WOS000287055900008.pdf: 158628 bytes, checksum: 568dcc2b8f78012a539d526dedf7d3ff (MD5) Previous issue date: 2011-02-03 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Candido-Bacani M.B. Reis Isatin (1H-indole-2,3-dione) is a synthetically versatile substrate used for the synthesis of heterocyclic compounds and as a raw material for drug synthesis. Isatin and its derivatives demonstrate anticonvulsant, antibacterial, antifungal, antiviral, and anticancer properties. We evaluated the genotoxic and mutagenic effects of acute (24h) and repeated (14d) exposure to isatin in vivo. using the cornet assay and the micronucleus test. Three doses (50, 100, and 150 mg/kg b.w.) were administered to mice via gayage. Doses were selected according to the LD(50) of isatin, estimated in a preliminary test to be 1 g/kg b.w. To evaluate the results, parametric (ANOVA/Tukey) and non-parametric (Kruskal-Wallis/Dunn's post hoc test) tests were used, according to the nature of the data distribution. At all doses (50, 100 and 150 mg/kg b.w.), after acute treatment with isatin, alterations in DNA migration (comet assay) were not observed and mutagenic effects were not seen (micronucleus test on peripheral blood cells). After repeated doses, only the highest dose of isatin (150 mg/kg b.w.) induced alterations in the DNA that gave rise to micronuclei in the bone marrow and peripheral blood cells of the mice. Our results show that the mutagenic and genotoxic effects of isatin depend on dose and on period of exposure. (C) 2010 Elsevier B.V. All rights reserved. Universidade Estadual de Londrina (UEL), Dept Gen Biol, Ctr Biol Sci, Uel, PR, Brazil São Paulo State Univ, Chem Inst Araraquara, UNESP, São Carlos, SP, Brazil São Paulo State Univ, Dept Biol Sci, UNESP, Fac Pharmaceut Sci Araraquara, São Carlos, SP, Brazil São Paulo State Univ, Chem Inst Araraquara, UNESP, São Carlos, SP, Brazil São Paulo State Univ, Dept Biol Sci, UNESP, Fac Pharmaceut Sci Araraquara, São Carlos, SP, Brazil

Made available in DSpace on 2022-04-28T21:24:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-01-01 Phenolic compounds are produced by secretory idioblasts and hypodermis, and by specialized cells of the epidermis and chlorenchyma of leaves of Alchornea triplinervia. Phytochemical investigation of these leaves led to the isolation of the known substances quercetin, quercetin-7-O-β-D-glucopyranoside, quercetin-3-O-β-D-glucopyranoside, quercetin-3-O-β-Dgalactopyranoside, quercetin-3-O-α-L-arabinopyranoside, amentoflavone, brevifolin carboxylic acid, gallic acid, and methyl gallate from the methanolic extract, and stigmasterol, campesterol, sitosterol, lupeol, friedelan-3-ol, and friedelan-3-one from the chloroform extract. In studies of antibacterial activity and mutagenicity, the methanolic extract showed promising activity against Staphylococcus aureus (MIC=62.5 μg/mL) and was slightly mutagenic in vitro and in vivo at the highest concentrations tested (1335 mg/kg b.w.). UNESP - São Paulo State University Instituto de Química de Araraquara Departamento de Química Orgânica, c.p. 355, CEP 14800-900, Araraquara, SP FATEC - Faculty of Technology of Capão Bonito, CEP 18304-750, Capão Bonito, SP UNESP - São Paulo State University Faculdade de Ciências Farmacêuticas Departamento de Ciências Biológicas, CEP 14801-902, Araraquara, SP UEL - Universidade Estadual de Londrina Centro de Ciências Biológicas Departamento de Biologia Geral, CEP 86051-990, Londrina, PR UNESP - São Paulo State University Instituto de Química de Araraquara Departamento de Química Orgânica, c.p. 355, CEP 14800-900, Araraquara, SP UNESP - São Paulo State University Faculdade de Ciências Farmacêuticas Departamento de Ciências Biológicas, CEP 14801-902, Araraquara, SP

Among the current treatment strategies for the peptic ulcer patient with Helicobacter pylori infection, the method of choice is triple therapy based on the concurrent use of proton inhibitors and two antibiotics. Alchornea triplinervia is a medicinal plant commonly used by people living in the Cerrado region of Brazil to treat gastrointestinal ulcers. In the present work we proposed therapy based on this medicinal plant that presents effective gastroprotective action with antibiotic effects. Oral pretreatment with methanolic extract (ME) of A. triplinervia in rats and mice decreased the gastric injuries induced by ethanol and HCl/ethanol. Increasing the dose reduced the gastroprotective effects of ME on the gastric lesions induced by nonsteroidal anti-inflammatory drug. After pylorus ligature of mice, oral administration of ME induced a decrease not only in total acid but also in the ulcer index. We also observed that ME displayed antibacterial activity against H. pylori. Liquid-liquid separation of ME indicated that active constituents responsible for the gastroprotective action are concentrated in the ethyl acetate fraction (EAF) (50% protection) rather than in the aqueous fraction, which did not induce significant gastroprotection at the same dose (100 mg/kg). EAF induced an increase of gastric mucosa prostaglandin (PG) E(2) levels, which remained high even after previous administration of indomethacin. The phytochemical profile of ME revealed that EAF contains mainly flavonoids. In conclusion, all these results suggest that ME did not show acute toxicity, but exhibited an antisecretory property, anti-H. pylori effect, and gastroprotective action. The observed effect did not involve the participation of nitric oxide or endogenous sulfhydryl groups. However, EAF showed a more efficient gastroprotective effect than ME at a lower dose and protected the gastric mucosa by increasing PGE(2).

Alchornea glandulosa (Euphorbiaceae) is a plant used in folk medicine as an antiulcer agent. Rats pretreated with methanolic extract obtained from the leaves of A. glandulosa (AG) showed a dose-dependent effect and significant reduction of gastric ulcers induced by absolute ethanol at the doses of 500 (57%) and 1000 mg/kg (85%) in relation to the control group. Pretreatment of mice with AG (500, 1000 mg/kg, p.o.) showed dose-dependent activity and significantly decreased the severity of lesions caused by HCl/ethanol and by non steroidal anti inflammatory drug-induced gastric lesions. Pretreatment with AG also induced antisecretory action via local and systemic routes and a significant decrease in the total gastric acid content. The gastroprotective effects of AG involved the participation of nitric oxide and increased levels of endogenous sulfhydryl compounds, which are defensive mechanisms of the gastrointestinal mucosa against aggressive factors. The ability of AG to heal gastric ulcers was evaluated after 14 consecutive days of treatment. The results showed that single oral administrations of AG (250 mg/kg/once daily) potently stimulates gastric epithelial cell proliferation that contributes to the accelerated healing of gastric ulcers induced by acetic acid. In addition, no subacute toxicity (body weight gain, vital organs, and serum biochemical parameters) was observed during treatment with AG. Phytochemical investigation of AG led to the isolation of myricetin-3-O-alpha-L-rhamnopyranoside, quercetin-3-O-alpha-L-arabinopyranoside, quercetin-3-O-beta-D-galactopyranoside, quercetin, amentoflavone, methyl gallate, gallic acid, and pterogynidine. We also established the phytochemical profile of AG with the quantification of total phenolic compounds. These compounds may contribute to the observed antiulcerogenic effects of AG.

The effects of Alchornea glandulosa ethyl acetate fraction (AGF) on hydrogen peroxide (H2O2), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production in peritoneal macrophages activated with lipopolysaccharide (LPS) or phorbol myristate acetate (PMA) were investigated. Analysis by thin layer chromatography (TLC) of AGF showed several constituents, including flavonoids, which may have anti-inflammatory activity. Inhibitory effects of the fraction in H2O2 and NO production ranged from 8.59+/-7.84% to 70.56+/-4.16% and from 16.06+/-3.65% to 38.73+/-3.90%, respectively. The TNF-alpha production was only partially inhibited in the tested concentrations (12.21+/-6.23% - 15.16+/-0.96%). According to these results, it is suggested that AGF has anti-inflammatory activity. This medicinal plant may have therapeutic potential in the control of inflammatory disorders.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:57:42Z No. of bitstreams: 1 S0102-695X2005000100010.pdf: 967176 bytes, checksum: dd4317582637407777d9933f0819c20a (MD5) Made available in DSpace on 2013-08-22T18:57:42Z (GMT). No. of bitstreams: 1 S0102-695X2005000100010.pdf: 967176 bytes, checksum: dd4317582637407777d9933f0819c20a (MD5) Previous issue date: 2005-03-01 Made available in DSpace on 2013-09-30T19:52:45Z (GMT). No. of bitstreams: 2 S0102-695X2005000100010.pdf: 967176 bytes, checksum: dd4317582637407777d9933f0819c20a (MD5) S0102-695X2005000100010.pdf.txt: 30042 bytes, checksum: 8c15e576393666bf36b0df38e42d6bc5 (MD5) Previous issue date: 2005-03-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T13:23:48Z No. of bitstreams: 2 S0102-695X2005000100010.pdf: 967176 bytes, checksum: dd4317582637407777d9933f0819c20a (MD5) S0102-695X2005000100010.pdf.txt: 30042 bytes, checksum: 8c15e576393666bf36b0df38e42d6bc5 (MD5) Made available in DSpace on 2014-05-20T13:23:48Z (GMT). No. of bitstreams: 2 S0102-695X2005000100010.pdf: 967176 bytes, checksum: dd4317582637407777d9933f0819c20a (MD5) S0102-695X2005000100010.pdf.txt: 30042 bytes, checksum: 8c15e576393666bf36b0df38e42d6bc5 (MD5) Previous issue date: 2005-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Plantas têm contribuído no tratamento da maioria das doenças. Considerando a importância terapêutica das plantas medicinais, foi avaliada a atividade imunológica dos extratos metanólico e etanólico de Davilla elliptica. Macrófagos estão envolvidos em todos estágios da resposta imune, podendo liberar componentes como: peróxido de hidrogênio (H2O2), óxido nítrico (NO) e fator de necrose tumoral-alfa (TNF-alfa). A estimulação dos macrófagos foi avaliada pela determinação de H2O2, NO e TNF-alfa em culturas de macrófagos peritoneais de camundongos na presença dos extratos da D. elliptica. IC50 foi determinado através de ensaio utilizando MTT. Os estudos fitoquímicos realizados mostraram a presença de flavonóides derivados da quercetina e miricetina entre outros compostos. A produção de H2O2 não foi muito expressiva em ambos extratos, contudo a de NO foi significativa. Os dois extratos induziram a produção de TNF-alfa, sendo que a liberação dessa citocina pelo extrato metanólico foi quase cinco vezes maior do que pelo extrato etanólico. Uma relação entre as sínteses de NO e TNF-alfa foi observada. O aumento na produção de NO está relacionado com a indução de citocinas pró-inflamatórias como TNF-alfa. Analisando os resultados, sugere-se que os extratos metanólico e etanólico de D. elliptica podem modular a ativação de macrófagos. Plants have contributed in a significant way to the treatment of most of the diseases. Considering the therapeutic importance of the medicinal plants, the immunological activity of the methanolic and ethanolic extract of Davilla elliptica was evaluated. In every stage of the immune response macrophages are involved and they can release many compounds such as hydrogen peroxide (H2O2), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). Macrophages stimulation was evaluated by the determination of H2O2, NO and TNF-alpha in peritoneal macrophages cultures of mice in the presence of the D. elliptica extracts. IC50 was determined by MTT assay. The phytochemical study showed flavonoids derived from quercetin and myricetin and other compounds. The production of H2O2 was not very expressive in both extracts, but they presented a significant effect on NO production. The two extracts induced TNF-alpha production, although the methanolic liberated almost five times more TNF-alpha than the ethanolic one. A relationship among the synthesis of NO and TNF-alpha was observed. The increase of NO production is related with the induction of proinflammatory cytokines like TNF-alpha. Analyzing the results, it is suggested that methanolic and ethanolic extract of D. elliptica can modulate macrophage activation. Universidade Estadual Paulista Faculdade de Ciências Farmacêuticas Departamento de Análises Clínicas Universidade Estadual Paulista Faculdade de Ciências Farmacêuticas Departamento de Ciências Biológicas Universidade Estadual Paulista Instituto de Química Departamento de Química Orgânica Universidade Estadual Paulista Faculdade de Ciências Farmacêuticas Departamento de Análises Clínicas Universidade Estadual Paulista Faculdade de Ciências Farmacêuticas Departamento de Ciências Biológicas Universidade Estadual Paulista Instituto de Química Departamento de Química Orgânica

Some species of the plant genus Alchornea (family Euphorbiaceae) are widely used in popular medicine, mainly in South America and in Africa. Several kinds of biological activity have been seen in the species: antioxidant, antifungal, anti-inflammatory, antibacterial, cytotoxic against tumor cell lines and inhibitory to the replication of HIV-1 and HIV-2. In Brazil, the species Alchornea castaneaefolia Willd. A. Juss. and Alchornea glandulosa Poepp. & Endl. are used by the local population to treat rheumatism, arthritis and muscular pains. In view of the popular use of these plants as medicines and the potential risks from their consumption, we assessed the mutagenic potential of chloroform and methanol extracts of the leaves of these plant species, employing the in vivo micronucleus test and the Ames assay. The data obtained showed that the chloroform extracts were not mutagenic. The methanol extract of A. castaneaefolia was mutagenic to strain TA98 of Salmonella typhimurium and the methanol extract of A. glandulosa to strains TA98 and TA97a. The methanol extracts of both species of Alchornea were mutagenic in vivo at the largest dose employed. The probable mutagenic agents involved were the aglycone quercetin and amentoflavone, present in both species. Algumas espécies de plantas do gênero Alchornea (Euphorbiaceae) são conhecidas por apresentarem as atividades biológicas: antioxidante, antifúngica, antiinflamatória, antibacteriana, citotóxica para células tumorais e inibidoras da replicação dos vírus HIV-1 e HIV-2. São também amplamente usadas na medicina popular na America do Sul e África. No Brasil, Alchornea castaneaefolia Willd. A. Juss. e Alchornea glandulosa Poepp. & Endl. são usadas para tratamento do reumatismo, artrite e dores musculares. Devido ao uso medicinal dessas plantas e o potencial risco do seu consumo indiscriminado, no presente trabalho foi avaliada a atividade mutagênica dos extratos metanólico e clorofórmico das folhas, empregando o teste do micronúcleo in vivo e o teste de Ames. Os resultados mostraram que o extrato clorofórmico não apresentou mutagenicidade, porém, o extrato metanólico de A. castaneaefolia foi mutagênico para a linhagem TA98 de Salmonella typhimurium e o extrato metanólico de A. glandulosa para as linhagens TA98 e TA97a. O extrato metanólico de ambas as espécies também apresentaram mutagenicidade positiva nos ensaios in vivo na maior concentração usada. Os prováveis agentes mutagênicos envolvidos foram a quercetina aglicona e amentoflavona presentes em ambas as espécies.