Potencial dos análogos do dilapiol para uso em Doenças Negligenciadas, com ênfase para Leishmaniose Cutânea: revisão literária / Potential of dilapiol analogues for use in Neglected Diseases, with emphasis on Cutaneous Leishmaniasis: a literature review

As Doenças Tropicais Negligenciadas (DTNs) são um grupo de doenças que afetam principalmente a população de países tropicais e em desenvolvimento de baixa a média renda. Nos últimos anos, no cenário internacional, tem havido debates sobre as formas de prevenir, combater e erradicar as doenças tropicais negligenciadas, bem como pesquisas para desenvolver novos fármacos que ajudem no tratamento dessas doenças, onde através da literatura obtivemos inúmeros estudos científicos mostrando moléculas bioativas provenientes de plantas com atividades biológicas, dentre elasPiper aduncum, já que seu composto majoritário, o dilapiol, apresenta uma estrutura química natural que pode ser modificada através de semissíntese, uma alternativa de obtenção de novas moléculas ativas, esses análogos do dilapiol, testados sobre doenças negligenciadas, principalmente contra leishmaniose cutânea, inibindo as formas promastigotas e amastigotas de Leishmania de diversas espécies.

Piper aduncum against Haemonchus contortus isolates: cross resistance and the research of natural bioactive compounds

Abstract The anthelminthic activity of the essential oil (EO) of Piper aduncum L. was tested in vitro on eggs and larvae of resistant (Embrapa2010) and susceptible (McMaster) isolates of Haemonchus contortus. The EO was obtained by steam distillation and its components identified by chromatography. EO concentrations of 12.5 to 0.02 mg/mL were used in the egg hatch test (EHT) and concentrations of 3.12 to 0.01 mg/mL in the larval development test (LDT). Inhibition concentrations (IC) were determined by the SAS Probit procedure, and significant differences assessed by ANOVA followed by Tukey’s test. In the EHT, the IC50 for the susceptible isolate was 5.72 mg/mL. In the LDT, the IC50 and IC90 were, respectively, 0.10 mg/mL and 0.34 mg/mL for the susceptible isolate, and 0.22 mg/mL and 0.51 mg/mL for the resistant isolate. The EO (dillapiole 76.2%) was highly efficacious on phase L1. Due to the higher ICs obtained for the resistant isolate, it was raised the hypothesis that dillapiole may have a mechanism of action that resembles those of other anthelmintic compounds. We further review and discuss studies, especially those conducted in Brazil, that quantified the major constituents of P. aduncum-derived EO

Stability and Antioxidant Activity of Semi-synthetic Derivatives of 4-Nerolidylcatechol

4-nerolidylcatechol (4-NC) is an unstable natural product that exhibits important antioxidant, anti-inflammatory and other properties. It is readily obtainable on a multi-gram scale through straightforward solvent extraction of the roots of cultivated Piper peltatum or P. umbellatum, followed by column chromatography on the resulting extract. Semi-synthetic derivatives of 4-NC with one or two substituent groups (methyl, acetyl, benzyl, benzoyl) on the O atoms have been introduced that have increased stability compared to 4-NC and significant in vitro inhibitory activity against the human malaria parasite Plasmodium falciparum. Antioxidant and anti-inflammatory properties may be important for the antiplasmodial mode of action of 4-NC derivatives. Thus, we decided to investigate the antioxidant properties, cytotoxicity and stability of 4-NC derivatives as a means to explore the potential utility of these compounds. 4-NC showed high antioxidant activity in the DPPH and ABTS assays and in 3T3-L1 cells (mouse embryonic fibroblast), however 4-NC was more cytotoxic (IC50 = 31.4 µM) and more unstable than its derivatives and lost more than 80% of its antioxidant activity upon storage in solution at −20 °C for 30 days. DMSO solutions of mono-O-substituted derivatives of 4-NC exhibited antioxidant activity and radical scavenging activity in the DPPH and ABTS assays that was comparable to that of BHA and BHT. In the cell-based antioxidant model, most DMSO solutions of derivatives of 4-NC were less active on day 1 than 4-NC, quercetin and BHA and more active antioxidants than BHT. After storage for 30 days at −20 °C, DMSO solutions of most of the derivatives of 4-NC were more stable and exhibited more antioxidant activity than 4-NC, quercetin and BHA and exhibited comparable antioxidant activity to BHT. These findings point to the potential of derivatives of 4-NC as antioxidant compounds

Therapeutic Potential of Leaves from <i>Fridericia chica</i> (Bonpl.) L. G. Lohmann: Botanical Aspects, Phytochemical and Biological, Anti-Inflammatory, Antioxidant and Healing Action

Plants of the species Fridericia chica (Bonpl.) L. G. Lohmann (Bignoniaceae), which are widely distributed in Brazil and named crajiru in the state of Amazonas, are known in folk medicine as a traditional medicine in the form of a tea for the treatment of intestinal colic, diarrhea, and anemia, among other diseases. The chemical analysis of extracts of the leaves has identified phenolic compounds, a class of secondary metabolites that provide defense for plants and benefits to the health of humans. Several studies have shown the therapeutic efficacy of F. chica extracts, with antitumor, antiviral, wound healing, anti-inflammatory, and antioxidant activities being among the therapeutic applications already proven. The healing action of F. chica leaf extract has been demonstrated in several experimental models, and shows the ability to favor the proliferation of fibroblasts, which is essential for tissue repair. The anti-inflammatory activity of F. chica has been clearly demonstrated by several authors, who suggest that it is related to the presence of 3-deoxyanthocyanidins, which is capable of inhibiting pro-inflammatory pathways such as the kappa B (NF-kB) nuclear transcription factor pathway. Another important effect attributed to this species is the antioxidant effect, attributed to phenolic compounds interrupting chain reactions caused by free radicals and donating hydrogen atoms or electrons. In conclusion, the species Fridericia chica has great therapeutic potential, which is detailed in this paper with the objective of encouraging new research and promoting the sum of efforts for the inclusion of herbal medicines in health systems around the world

Physicochemical characterization and cosmetic applications of Passiflora nitida Kunth leaf extract

Passiflora nitida&nbsp;Kunth, an Amazonian&nbsp;Passiflora&nbsp;species, is little studied, although the specie’s high biological potential. Herein the plant’s pharmacognostic characterization, extract production, antioxidant potential evaluation, and application of this extract in cosmetic products is reported. The physical chemical parameters analyzed were particle size by sieve analysis, loss through drying, extractive yield, total ash content, laser granulometry, specific surface area and pore diameter (SBET), differential scanning calorimetry, thermogravimetry (TG), and wave dispersive X-Ray fluorescence (WDXRF). Total phenol/flavonoid content, LC-MS/MS analysis, DPPH and ABTS antioxidant radical assays, cytotoxicity, melanin, and tyrosinase inhibition in melanocytes test provided evidence to determine the content of the major constituent.&nbsp;P. nitida&nbsp;dry extract provided a fine powder with mesopores determined by SBET, with the TG curve showing five stages of mass loss. The antioxidant potential ranged between 23.5-31.5 mg∙mL-1&nbsp;and tyrosinase inhibition between 400-654 μg∙mL-1. The species presented an antimelanogenic effect and an inhibitory activity of cellular tyrosinase (26.6%) at 25 µg/mL. The LC-MS/MS analysis of the spray-dried extract displayed the main and minor phenolic compounds constituting this sample. The results indicate that&nbsp;P. nitida&nbsp;extract has promising features for the development of cosmetic formulations

In vitro and in vivo anti‑malarial activity of plants from the Brazilian Amazon

Submitted by Nuzia Santos ([email protected]) on 2016-07-08T18:45:22Z No. of bitstreams: 1 ve_Lima_Renata_INVitro_CPqRR_2015.pdf: 1203610 bytes, checksum: 9964e837e33fd7a374e0dfede7b35a3c (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2016-07-08T19:00:53Z (GMT) No. of bitstreams: 1 ve_Lima_Renata_INVitro_CPqRR_2015.pdf: 1203610 bytes, checksum: 9964e837e33fd7a374e0dfede7b35a3c (MD5)Made available in DSpace on 2016-07-08T19:00:53Z (GMT). No. of bitstreams: 1 ve_Lima_Renata_INVitro_CPqRR_2015.pdf: 1203610 bytes, checksum: 9964e837e33fd7a374e0dfede7b35a3c (MD5) Previous issue date: 2015Made available in DSpace on 2016-07-22T13:23:06Z (GMT). No. of bitstreams: 3 ve_Lima_Renata_INVitro_CPqRR_2015.pdf.txt: 78136 bytes, checksum: 163d252edb75adfcdde79e41ea296080 (MD5) ve_Lima_Renata_INVitro_CPqRR_2015.pdf: 1203610 bytes, checksum: 9964e837e33fd7a374e0dfede7b35a3c (MD5) license.txt: 2991 bytes, checksum: 5a560609d32a3863062d77ff32785d58 (MD5) Previous issue date: 2015Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil / Universidade Federal do Amazonas. Programa de Pós‑graduação em Biotecnologia. Manaus, AM, Brasil / Centro Universitário Lima do Norte. Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil / Universidade Federal do Amazonas. Programa de Pós‑graduação em Biotecnologia. Manaus, AM, Brasil / Centro Universitário Lima do Norte. Manaus, AM, Brasil.Universidade Estadual do Amazonas. Escola Superior de Ciências da Saúde. Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil / Universidade Federal do Amazonas. Programa de Pós‑graduação em Biotecnologia. Manaus, AM, Brasil.Universidade Federal do Amazonas. Faculdade de Ciências Farmacêuticas. Manaus, AM, Brasil.Universidade Federal do Amazonas. Faculdade de Ciências Farmacêuticas. Manaus, AM, Brasil.Universidade Federal do Amazonas. Faculdade de Ciências Farmacêuticas. Manaus, AM, Brasil.Universidade Federal do Amazonas. Faculdade de Ciências Farmacêuticas. Manaus, AM, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil.Embrapa Amazônia Ocidental. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.Instituto Nacional de Pesquisas da Amazônia Laboratório de Malária e Dengue, Coordenação de Sociedade, Ambiente. Manaus, AM, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.Instituto Nacional de Pesquisas da Amazônia. Coordenação de Tecnologia e Inovação. Laboratório de Princípios Ativos da Amazônia. Manaus, AM, Brasil.BACKGROUND: The anti-malarials quinine and artemisinin were isolated from traditionally used plants (Cinchona spp. and Artemisia annua, respectively). The synthetic quinoline anti-malarials (e.g. chloroquine) and semi-synthetic artemisinin derivatives (e.g. artesunate) were developed based on these natural products. Malaria is endemic to the Amazon region where Plasmodium falciparum and Plasmodium vivax drug-resistance is of concern. There is an urgent need for new anti-malarials. Traditionally used Amazonian plants may provide new treatments for drug-resistant P. vivax and P. falciparum. Herein, the in vitro and in vivo antiplasmodial activity and cytotoxicity of medicinal plant extracts were investigated. METHODS: Sixty-nine extracts from 11 plant species were prepared and screened for in vitro activity against P. falciparum K1 strain and for cytotoxicity against human fibroblasts and two melanoma cell lines. Median inhibitory concentrations (IC50) were established against chloroquine-resistant P. falciparum W2 clone using monoclonal anti-HRPII (histidine-rich protein II) antibodies in an enzyme-linked immunosorbent assay. Extracts were evaluated for toxicity against murine macrophages (IC50) and selectivity indices (SI) were determined. Three extracts were also evaluated orally in Plasmodium berghei-infected mice. RESULTS: High in vitro antiplasmodial activity (IC50 = 6.4-9.9 µg/mL) was observed for Andropogon leucostachyus aerial part methanol extracts, Croton cajucara red variety leaf chloroform extracts, Miconia nervosa leaf methanol extracts, and Xylopia amazonica leaf chloroform and branch ethanol extracts. Paullinia cupana branch chloroform extracts and Croton cajucara red variety leaf ethanol extracts were toxic to fibroblasts and or melanoma cells. Xylopia amazonica branch ethanol extracts and Zanthoxylum djalma-batistae branch chloroform extracts were toxic to macrophages (IC50 = 6.9 and 24.7 µg/mL, respectively). Andropogon leucostachyus extracts were the most selective (SI >28.2) and the most active in vivo (at doses of 250 mg/kg, 71% suppression of P. berghei parasitaemia versus untreated controls). CONCLUSIONS: Ethnobotanical or ethnopharmacological reports describe the anti-malarial use of these plants or the antiplasmodial activity of congeneric species. No antiplasmodial activity has been demonstrated previously for the extracts of these plants. Seven plants exhibit in vivo and or in vitro anti-malarial potential. Future work should aim to discover the anti-malarial substances present

Control of Hysterothylacium sp . (Nematoda: Anisakidae) in juvenile pirarucu ( Arapaima gigas ) by the oral application of essential oil of Piper aduncum

The nematode Hysterothylacium sp. (Nematoda, Anisakidae) may cause significant economic losses in fish production. In order to control the nematode larvae in juvenile pirarucu (52 ± 3.2 g), the efficacy of essential oil (EO) of Piper aduncum when added to feed was evaluated. Chemical analysis of the EO composition had been performed previously, showing that 92% of the substance was dillapiole. After the palatability test, the efficacy of the EO was evaluated (0, 32, 48, 56, and 64 mL/kg) at 7 and 15 days, based on the blood parameters and the parasite load of the fish. The results showed significant differences for hematocrit and corpuscular constants at 7 days and for total proteins at 15 days between the treatment groups and the control group (without EO). The parasitic indices showed a prevalence of 100% for stage L3 larva of the nematode Hysterothylacium sp. At 7 and 15 days, the values of average intensity, average abundance, and intensity of parasites decreased with increasing EO concentration, and at 15 days, these were significantly lower between the treatment group and the control group, with an efficacy of 76.21% for 64 mL/kg. Thus, the EO of P. aduncum demonstrates anthelmintic potential in the control of nematode larvae in pirarucu without affecting fish homeostasis. © 2018 Elsevier B.V