Effects of Handroanthus impetiginosus (Mart. ex DC.) Mattos extract on inflammatory, immune, atherogenic profile and differentiation in THP-1 cell line.

Handroanthus impetiginosus (Mart. ex DC.) Mattos is a plant from Central-South America that possesses different pharmacological activities. Plant extract was tested in THP-1 cell model, a human cell line used to study monocyte/macrophage functions. First, the plant effects on cell viability were evaluated, demonstrating no harmful consequences even at the higher concentrations (200 µg/ml). Thus, anti-inflammatory activity was investigated in gene and protein expression by RT-qPCR and ELISA methods, resulting in a reduction of pro-inflammatory cytokines after Handroanthus impetiginosus treatment. Similarly, NF-kB nuclear translocation was decreased according to confocal images and ImageStream X -analysis. Subsequently, in macrophage differentiated THP-1, CD36 mRNA and protein expression was inhibited in a concentration-dependent manner together with cell morphology changes during treatment. In addition, modified LDL-derived cholesterol uptake by THP-1 cells was reduced after plant extract incubation. Handroanthus impetiginosus showed anti-inflammatory and immunomodulating properties that may pave the way for future characterization in higher models.

In vivo evaluation of analgesic and anti-inflammatory activity of hydroalcoholic extracts from Handroanthus impetiginosus and their chemical composition by UPLC/MS analysis.

This study demonstrates in vivo analgesic and anti-inflammatory properties of hydroalcoholic extracts of leaves, bark and flowers from the Handroanthus impetiginosus (Bignoniaceae) plant, recognized as 'Ipê roxo' in Brazil. The extracts were evaluated in male Swiss albino mice via oral administration. Moreover, results of the in vivo paw oedema test induced by carrageenan revealed that extracts of leaves and bark displayed relevant anti-inflammatory activity potential at the dosage of 100 mg/kg, 300 mg/kg, and 500 mg/kg. Likewise, the results obtained for leaves and flowers extracts suggested potent analgesic action in the conventional hot plate test. UPLC/MS analysis of the hydroalcoholic extracts samples identified metabolites belonging to several classes, mainly naphthoquinones and iridoids derivatives as well as flavonoids. Thus, the obtained results indicate that the extracts of H. impetiginosus plant parts could be considered as a complementary herbal medicine for the treatment of pain and inflammation disorders.

Beta-lapachone: Natural occurrence, physicochemical properties, biological activities, toxicity and synthesis.

ß-Lapachone is an ortho-naphthoquinone originally isolated from the heartwood of Handroanthus impetiginosus and can be obtained through synthesis from lapachol, naphthoquinones, and other aromatic compounds. ß-Lapachone is well known to inhibit topoisomerase I and to induce NAD(P)H: quinone oxidoreductase 1. Currently, phase II clinical trials are being conducted for the treatment of pancreatic cancer. In view of ever-increasing scientific interest in this naphthoquinone, herein, the authors present a review of the synthesis, physicochemical properties, biological activities, and toxicity of ß-lapachone. This natural compound has shown activity against several types of malignant tumors, such as lung and pancreatic cancers and melanoma. Furthermore, this ortho-naphthoquinone has antifungal and antibacterial activities, underscoring its action against resistant microorganisms and providing anti-inflammatory, antiobesity, antioxidant, neuroprotective, nephroprotective, and wound-healing properties. ß-Lapachone presents low toxicity, with no signs of toxicity against alveolar macrophages, dermal fibroblast cells, hepatocytes, or kidney cells.

Reduction of doxorubicin-induced genotoxicity by Handroanthus impetiginosus in mouse bone marrow revealed by micronucleus assay / Redução da genotoxicidade induzida pela doxorrubicina por Handroanthus impetiginosus na medula óssea de camundongos revelada pelo ensaio do micronúcleo

Abstract Handroanthus impetiginosus has long been used in traditional medicine and various studies have determined the presence of bioactive chemical compounds and potential phytotherapeutics. In this study, the genotoxicity of the lyophilized tincture of H. impetiginosus bark (THI) was evaluated in mouse bone marrow using micronucleus assays. The interaction between THI and genotoxic effects induced by the chemotherapeutic agent, doxorubicin (DXR), was also analyzed. Experimental groups were evaluated 24 to 48 h after treatment with N-nitroso-N-ethylurea (NEU; 50 mg/kg), DXR (5 mg/kg), sodium chloride (NaCl; 150 mM), and THI (0.5-2 g/kg). Antigenotoxic assays were carried out using THI (0.5 g/kg) in combination with NEU or DXR. Analysis of the micronucleated polychromatic erythrocytes (MNPCEs) indicated no significant differences between treatment doses of THI (0.5-2 g/kg) and NaCl. Polychromatic erythrocyte (PCE) to normochromatic erythrocyte (NCE) ratios did not indicate any statistical differences between DXR and THI or NaCl, but there were differences between THI and NaCl. A significant reduction in MNPCEs and PCE/NCE ratios was observed when THI was administered in combination with DXR. This study suggested the absence of THI genotoxicity that was dose-, time-, and gender-independent and the presence of moderate systemic toxicity that was dose-independent, but time- and gender-dependent. The combination of THI and DXR also suggested antigenotoxic effects, indicating that THI reduced genotoxic effects induced by chemotherapeutic agents.

Resumo Handroanthus impetiginosus tem sido usada durante um longo período pela medicina tradicional e vários estudos têm demonstrados a presença de compostos químicos e potencial fitoterapêutico. Esta pesquisa avaliou a genotoxicidade da tintura da casca liofilizada de H. impetiginosus (THI) usando o ensaio do micronúcleo em medula óssea de camundongos. A interação entre THI e os efeitos genotóxicos induzidos pelo quimioterápico doxorrubicina (DXR) também foram analisados. Grupos experimentais foram analisados a 24-48 h após o tratamento com N-Nitroso-N-etiluréia (NEU; 50 mg/kg), DXR (5 mg/kg), NaCl (150 mM) e THI (0,5-2 g/kg). O ensaio antigenotóxico foi conduzido utilizando THI (0,5 g/kg) em combinação com NEU ou DXR. A análise de eritrócitos policromáticos micronucleados (EPCMNs) não mostrou diferenças significativas entre as doses de tratamento (0,5-2 g/kg) e NaCl. As proporções de eritrócitos policromáticos (EPC)/eritrócitos normocromáticos (ENC) não revelaram diferenças estatísticas entre DXR e THI ou NaCl, porém houve diferenças entre THI e NaCl. Uma redução significativa em EPCMNs e na razão EPC/ENC foi observada quando THI foi administrado em combinação com DXR. Essa pesquisa sugere ausência de genotoxicidade de THI, dose-, tempo- e sexo-independente, e moderada toxicidade sistêmica dose-independente, mas tempo- e sexo-dependente. A associação do THI e DXR também sugere efeitos antigenotóxicos. Por conseguinte, THI pode reduzir os efeitos genotóxicos induzidos pelo quimioterapêutico.

Growth and morphological responses of Handroanthus impetiginosus (Mart. ex DC.) Mattos seedlings to nitrogen fertilization / Crescimento e respostas morfológicas de mudas de ipê-roxo Handroanthus impetiginosus (Mart. ex DC.) Mattos à adubação nitrogenada

The use of native tree species for restoration of degraded areas is often hindered by the lack of information about the nutritional requirements of seedlings at the nursery stage. Therefore, this study aimed to evaluate the growth and morphological responses of Handroanthus impetiginosus seedlings to mineral nitrogen fertilization. The experiment was carried out from July to October 2013 in a seedling nursery under 50% shade cloth. Seeds were germinated for 15 days in low density polystyrene trays and then transplanted into 0.9-L polyethylene plastic bags. A complete randomized block design was used, with four replications and four plants per experimental unit. Treatments consisted of five nitrogen levels (0, 50, 150, 300 and 450 mg N dm-3), using ammonium sulfate as the nitrogen source. Two months after transplanting, the following variables were assessed: leaf chlorophyll content; leaf area; specific leaf area; leaf area ratio; root, stem, leaf and total dry mass; shoot dry mass/root dry mass ratio; shoot height/shoot dry mass ratio; and Dickson quality index. Mineral nitrogen fertilization improved seedling growth by promoting higher results of the leaf chlorophyll content, leaf area and shoot dry mass production. Thus, fertilized seedlings significantly expanded their leaves and invested more in shoot growth, improving their hardiness and quality. The nitrogen level of 240 mg dm-3 was considered to be the most effective for production of H. impetiginosus seedlings.

O uso de espécies arbóreas nativas para restauração de áreas degradadas é muitas vezes prejudicada pela falta de informação sobre os requerimentos nutricionais de mudas na fase de viveiro. Portanto, este trabalho objetivou avaliar o crescimento e respostas morfológicas de mudas de ipê-roxo à adubação mineral nitrogenada. O experimento foi conduzido de julho a outubro de 2013, em viveiro de mudas com tela de sombreamento de 50%. As sementes foram postas para germinar por 15 dias em bandejas de poliestireno de baixa densidade, e posteriormente transplantadas para sacos plásticos de polietileno de 0,9 L. Foi utilizado o delineamento de blocos completos ao acaso, com quatro repetições e quatro plantas por unidade experimental. Os tratamentos foram constituídos por cinco níveis de nitrogênio (0, 50, 150, 300 e 450 mg N dm-3), utilizando o sulfato de amônio como fonte. Dois meses após o transplantio, as seguintes variáveis foram avaliadas: conteúdo de clorofila foliar; área foliar; área foliar específica; razão de área foliar; matéria seca da raiz, caule, folhas e total; relação massa seca da parte aérea/massa seca da raiz; relação altura/massa seca da parte aérea; e índice de qualidade de Dickson. A adubação mineral nitrogenada otimizou o crescimento das mudas ao promover resultados mais elevados para o teor de clorofila, área foliar e produção de massa seca da parte aérea. Assim, mudas adubadas expandiram significativamente suas folhas e investiram mais no crescimento da parte aérea, melhorando sua rusticidade e qualidade. O nível de nitrogênio de 240 mg dm-3 foi considerado o mais eficiente para produção de mudas de ipê-roxo.

Reduction of doxorubicin-induced genotoxicity by Handroanthus impetiginosus in mouse bone marrow revealed by micronucleus assay

Abstract Handroanthus impetiginosus has long been used in traditional medicine and various studies have determined the presence of bioactive chemical compounds and potential phytotherapeutics. In this study, the genotoxicity of the lyophilized tincture of H. impetiginosus bark (THI) was evaluated in mouse bone marrow using micronucleus assays. The interaction between THI and genotoxic effects induced by the chemotherapeutic agent, doxorubicin (DXR), was also analyzed. Experimental groups were evaluated 24 to 48 h after treatment with N-nitroso-N-ethylurea (NEU; 50 mg/kg), DXR (5 mg/kg), sodium chloride (NaCl; 150 mM), and THI (0.5-2 g/kg). Antigenotoxic assays were carried out using THI (0.5 g/kg) in combination with NEU or DXR. Analysis of the micronucleated polychromatic erythrocytes (MNPCEs) indicated no significant differences between treatment doses of THI (0.5-2 g/kg) and NaCl. Polychromatic erythrocyte (PCE) to normochromatic erythrocyte (NCE) ratios did not indicate any statistical differences between DXR and THI or NaCl, but there were differences between THI and NaCl. A significant reduction in MNPCEs and PCE/NCE ratios was observed when THI was administered in combination with DXR. This study suggested the absence of THI genotoxicity that was dose-, time-, and gender-independent and the presence of moderate systemic toxicity that was dose-independent, but time- and gender-dependent. The combination of THI and DXR also suggested antigenotoxic effects, indicating that THI reduced genotoxic effects induced by chemotherapeutic agents.

Resumo Handroanthus impetiginosus tem sido usada durante um longo período pela medicina tradicional e vários estudos têm demonstrados a presença de compostos químicos e potencial fitoterapêutico. Esta pesquisa avaliou a genotoxicidade da tintura da casca liofilizada de H. impetiginosus (THI) usando o ensaio do micronúcleo em medula óssea de camundongos. A interação entre THI e os efeitos genotóxicos induzidos pelo quimioterápico doxorrubicina (DXR) também foram analisados. Grupos experimentais foram analisados a 24-48 h após o tratamento com N-Nitroso-N-etiluréia (NEU; 50 mg/kg), DXR (5 mg/kg), NaCl (150 mM) e THI (0,5-2 g/kg). O ensaio antigenotóxico foi conduzido utilizando THI (0,5 g/kg) em combinação com NEU ou DXR. A análise de eritrócitos policromáticos micronucleados (EPCMNs) não mostrou diferenças significativas entre as doses de tratamento (0,5-2 g/kg) e NaCl. As proporções de eritrócitos policromáticos (EPC)/eritrócitos normocromáticos (ENC) não revelaram diferenças estatísticas entre DXR e THI ou NaCl, porém houve diferenças entre THI e NaCl. Uma redução significativa em EPCMNs e na razão EPC/ENC foi observada quando THI foi administrado em combinação com DXR. Essa pesquisa sugere ausência de genotoxicidade de THI, dose-, tempo- e sexo-independente, e moderada toxicidade sistêmica dose-independente, mas tempo- e sexo-dependente. A associação do THI e DXR também sugere efeitos antigenotóxicos. Por conseguinte, THI pode reduzir os efeitos genotóxicos induzidos pelo quimioterapêutico.

Antiulcer effect of bark extract of Tabebuia avellanedae: activation of cell proliferation in gastric mucosa during the healing process.

Tabebuia avellanedae (syn. Handroanthus impetiginosus) is popularly known as 'ipê-roxo' and has been used in folk medicine as anti-inflammatory and in the treatment of ulcers, bacterial and fungal infections. This study evaluated the gastric ulcer healing property of the ethanolic extract (EET) of barks from Tabebuia avellanedae and investigated the mechanisms that may underlie this effect. Rats were treated with EET (twice a day for 7 days) after induction of chronic gastric ulcers by 80% acetic acid. Following treatment, histological and immunohistochemical analysis were performed in gastric ulcer tissues. Oral administration of EET (100 and 300 mg/kg) significantly reduced the gastric lesion induced by acetic acid in 44 and 36%, respectively. Histopathological evaluation demonstrated a contraction of gastric ulcer size, increase of mucus layer (periodic acid-Schiff stained mucin-like glycoproteins) and cell proliferation (proliferating cell nuclear antigen immunohistochemistry) in animals treated with EET (100 and 300 mg/kg). The results demonstrate that EET significantly accelerates healing of acetic acid induced gastric ulcer in rats through increase of mucus content and cell proliferation, indicating a potential usefulness for treatment of peptic ulcer diseases.