RESUMO
The inadequate vascularization seen in fast-growing solid tumors gives rise to hypoxic areas, fostering specific changes in gene expression that bolster tumor cell survival and metastasis, ultimately leading to unfavorable clinical prognoses across different cancer types. Hypoxia-inducible factors (HIF-1 and HIF-2) emerge as druggable pivotal players orchestrating tumor metastasis and angiogenesis, thus positioning them as prime targets for cancer treatment. A range of HIF inhibitors, notably natural compounds originating from marine organisms, exhibit encouraging anticancer properties, underscoring their significance as promising therapeutic options. Bioprospection of the marine environment is now a well-settled approach to the discovery and development of anticancer agents that might have their medicinal chemistry developed into clinical candidates. However, despite the massive increase in the number of marine natural products classified as 'anticancer leads,' most of which correspond to general cytotoxic agents, and only a few have been characterized regarding their molecular targets and mechanisms of action. The current review presents a critical analysis of inhibitors of HIF-1 and HIF-2 and hypoxia-selective compounds that have been sourced from marine organisms and that might act as new chemotherapeutic candidates or serve as templates for the development of structurally similar derivatives with improved anticancer efficacy.
Assuntos
Antineoplásicos , Organismos Aquáticos , Produtos Biológicos , Fator 1 Induzível por Hipóxia , Neoplasias , Animais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Organismos Aquáticos/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/uso terapêutico , Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Mentha suaveolens (MS), Conyza canadensis (CC), Teucrium polium (TP) and Salvia verbenaca (SV) are used in Morocco to treat hypertension. Our aim was to characterize the composition and vasoreactivity of extracts of MS, CC, TP and SV. The chemical compositions of aqueous extracts of MS, SV and TP, and of a hydromethanolic extract of CC, were identified by HPLC-DAD. The vasoreactive effect was tested in rings of the thoracic aorta of female Wistar rats (8-14 weeks-old) pre-contracted with 10 µM noradrenaline, in the absence or presence of L-NAME 100 µM, indomethacin 10 µM or atropine 6 µM, to inhibit nitric oxide synthase, cyclooxygenase or muscarinic receptors, respectively. L-NAME and atropine decreased the vasorelaxant effect caused by low concentrations of MS. Atropine and indomethacin decreased the vasorelaxant effect of low concentrations of SV. High concentrations of MS or SV and the effect of SV and TP were not altered by any antagonist. The activation of muscarinic receptors and NO or the cyclooxygenase pathway underlie the vasorelaxant effect of MS and SV, respectively. Neither of those mechanisms underlines the vasorelaxant effect of CC and TP. These vasorelaxant effect might support the use of herbal teas from these plants as anti-hypertensives in folk medicine.
Assuntos
Conyza , Mentha , Salvia , Teucrium , Ratos , Animais , Vasodilatadores/farmacologia , Ratos Wistar , Mentha/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Salvia/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/metabolismo , Vasodilatação , Aorta/metabolismo , Aorta Torácica , Receptores Muscarínicos/metabolismo , Derivados da Atropina/metabolismo , Derivados da Atropina/farmacologiaRESUMO
The endoplasmic reticulum (ER) comprises a network of tubules and vesicles that constitutes the largest organelle of the eukaryotic cell. Being the location where most proteins are synthesized and folded, it is crucial for the upkeep of cellular homeostasis. Disturbed ER homeostasis triggers the activation of a conserved molecular machinery, termed the unfolded protein response (UPR), that comprises three major signaling branches, initiated by the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1) and the activating transcription factor 6 (ATF6). Given the impact of this intricate signaling network upon an extensive list of cellular processes, including protein turnover and autophagy, ER stress is involved in the onset and progression of multiple diseases, including cancer and neurodegenerative disorders. There is, for this reason, an increasing number of publications focused on characterizing and/or modulating ER stress, which have resulted in a wide array of techniques employed to study ER-related molecular events. This review aims to sum up the essentials on the current knowledge of the molecular biology of endoplasmic reticulum stress, while highlighting the available tools used in studies of this nature.
Assuntos
Estresse do Retículo Endoplasmático , Neoplasias/metabolismo , Doenças Neurodegenerativas/metabolismo , Animais , Autofagia , Cálcio/metabolismo , Humanos , Mitocôndrias/metabolismo , Transdução de Sinais , Resposta a Proteínas não DobradasRESUMO
Centaurium erythraea is a plant used in traditional medicine for several cardiovascular disorders, namely hypertension, but there is no scientific evidence able to provide a molecular basis for its claimed antihypertensive effects. After a preliminary screen of extracts obtained from sequential extraction of C. erythraea aerial parts, effects of the methanolic fraction (MFCE) on changes in perfusion pressure of isolated rat mesenteric vascular bed (MVB) and in rat cardiac fibroblasts proliferation were investigated, gathering information on the mechanisms involved in endothelium-dependent effects and their dependence on a pro-proliferative stimulus. The HPLC-DAD determination of the phenolics content of MFCE revealed the presence of 22 phenolic compounds. MFCE reduced (63.3 ± 3.9%; n = 4) perfusion pressure in MVB and almost completely abrogated the Ang II-induced increase in cardiac fibroblasts proliferation. Reduction of the perfusion pressure caused by MFCE was endothelium-dependent and occurred in parallel with an increase in NO release. These effects were inhibited by muscarinic receptor antagonists, by L-NAME (a NO synthase inhibitor), and by ODQ (a soluble guanylate cyclase inhibitor). Experiments revealed that effects required the involvement of K+ channels, being inhibited by tetraethylamonium (TEA; a Ca2+ activated K+ channels inhibitor) and by glibenclamide (an ATP-sensitive K+ channels inhibitor). In conclusion, extracts from C. erythraea, particularly the compounds present in the MFCE, induce endothelium-dependent vasodilation and prevent fibroblast proliferation induced by angiotensin II, which can account for the claimed antihypertensive effects of C. erythraea in traditional medicine.
Assuntos
Anti-Hipertensivos/farmacologia , Centaurium/química , Extratos Vegetais/farmacologia , Animais , Anti-Hipertensivos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Masculino , Extratos Vegetais/isolamento & purificação , Ratos , Ratos Wistar , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologiaRESUMO
Globally, the burden of neurodegenerative disorders continues to rise, and their multifactorial etiology has been regarded as among the most challenging medical issues. Bioprospecting for seaweed-derived multimodal acting products has earned increasing attention in the fight against neurodegenerative conditions. Phlorotannins (phloroglucinol-based polyphenols exclusively produced by brown seaweeds) are amongst the most promising nature-sourced compounds in terms of functionality, and though research on their neuroprotective properties is still in its infancy, phlorotannins have been found to modulate intricate events within the neuronal network. This review comprehensively covers the available literature on the neuroprotective potential of both isolated phlorotannins and phlorotannin-rich extracts/fractions, highlighting the main key findings and pointing to some potential directions for neuro research ramp-up processes on these marine-derived products.
Assuntos
Doenças Neurodegenerativas/tratamento farmacológico , Phaeophyceae/química , Polifenóis/uso terapêutico , Alga Marinha/química , Taninos/uso terapêutico , Animais , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/uso terapêutico , Humanos , Fármacos Neuroprotetores/isolamento & purificação , Fármacos Neuroprotetores/uso terapêutico , Polifenóis/isolamento & purificação , Taninos/isolamento & purificaçãoRESUMO
Commonly used to treat skin injuries in Asia, several Homalium spp. have been found to promote skin regeneration and wound healing. While ethnobotanical surveys report the use of H. bhamoense trunk bark as a wound salve, there are no studies covering bioactive properties. As impaired cutaneous healing is characterized by excessive inflammation, a series of inflammatory mediators involved in wound healing were targeted with a methanol extract obtained from H. bhamoense trunk bark. Results showed concentration-dependent inhibition of hyaluronidase and 5-lipoxygenase upon exposure to the extract, with IC50 values of 396.9 ± 25.7 and 29.0 ± 2.3 µg mL-1, respectively. H. bhamoense trunk bark extract also exerted anti-inflammatory activity by significantly suppressing the overproduction of interleukin 6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages at concentrations ranging from 125 to 1000 µg mL-1, while leading to a biphasic effect on nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) levels. The phenolic profile was elucidated by HPLC-DAD, being characterized by the occurrence of ellagic acid as the main constituent, in addition to a series of methylated derivatives, which might underlie the observed anti-inflammatory effects. Our findings provide in vitro data on anti-inflammatory ability of H. bhamoense trunk bark, disclosing also potential cutaneous toxicity as assessed in HaCaT keratinocytes.
Assuntos
Anti-Inflamatórios/farmacologia , Interleucina-6/efeitos adversos , Lipopolissacarídeos/efeitos adversos , Macrófagos/efeitos dos fármacos , Medicina Tradicional/métodos , Nephropidae/química , Extratos Vegetais/farmacologia , Animais , Araquidonato 5-Lipoxigenase/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Medicina Herbária , Hialuronoglucosaminidase/efeitos dos fármacos , Hidroxibenzoatos , Mediadores da Inflamação/farmacologia , Concentração Inibidora 50 , Interleucina-6/metabolismo , Queratinócitos , Lipopolissacarídeos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7 , Fator de Necrose Tumoral alfaRESUMO
Jasonia glutinosa (L.) DC., known as rock tea (RT), is traditionally used in Spain as a digestive due to its beneficial properties in bowel disorders. The pharmacological nature of these properties has not been established yet. The aim of this work was to evaluate the therapeutic utility of RT in experimental colitis and to identify chemical constituents with anti-inflammatory and/or anti-oxidative properties. RT extract was prepared with ethanol in a Soxhlet apparatus and analysed by HPLC-DAD. Superoxide radical scavenging properties, xanthine oxidase and lipoxygenase (5-LOX) inhibitory activity, and capability to lower nitric oxide (NO) and tumor necrosis factor α (TNF-α) levels were measured in cell-free and cell-based assays. In the 2.5%-dextran-sodium sulphate (DSS) injury-repair model of ulcerative colitis (UC), mice were daily treated with sulfasalazine (SSZ, as reference drug, 100 mg/kg bw), RT (5, 25 and 50 mg/kg bw, p.o.), or vehicle over 20 days. Colitis was scored daily. Colon samples were examined macroscopically and histopathologically. Protein levels of myeloperoxidase (MPO), interleukins 6, and 10 (IL-6, IL-10), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) were studied as markers of oxidative stress and inflammatory activity. The integrity of the apical epithelial layer was assessed by immunofluorescence staining of zonula ocludens-1 (ZO-1). Finally, intestinal contractility was also evaluated by isometric myography. Fifteen phenolic compounds and three pigments were identified and quantified, of which caffeoylquinic acids, and the flavonoid, quercetin-3-O-galactoside, were the most abundant. RT extract significantly scavenged superoxide radicals, inhibited 5-LOX activity, and lowered NO and TNF-α levels. DSS-treated mice receiving RT scored clinically lower than controls during the first 3 days of DSS treatment and during the recovery period. SSZ was less effective than RT. Anatomical and histological examination of colon samples revealed that RT significantly prevented colon shortening, increased colon thickness, and lowered the macroscopic damage score. RT also significantly prevented the increase of MPO activity, IL-6 levels, iNOS and COX-2 expression, the loss of ZO-1 apical expression, and normalized contractility disturbances. In conclusion, daily administration of RT showed therapeutic properties in the DSS-model of UC. The benefits of RT can likely be attributed to its anti-inflammatory and antioxidant phenolic and flavonoid constituents.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Colo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Substâncias Protetoras/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Biomarcadores/metabolismo , Células Cultivadas , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Colo/metabolismo , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Medicina Herbária/métodos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Medicina Tradicional/métodos , Camundongos , Camundongos Endogâmicos C57BL , Fitoterapia/métodosRESUMO
While several marine natural products bearing the 2,5-diketopiperazine ring have been reported to date, the unique chemistry of dimeric frameworks appears to remain neglected. Frequently reported from marine-derived strains of fungi, many naturally occurring diketopiperazine dimers have been shown to display a wide spectrum of pharmacological properties, particularly within the field of cancer and antimicrobial therapy. While their structures illustrate the unmatched power of marine biosynthetic machinery, often exhibiting unsymmetrical connections with rare linkage frameworks, enhanced binding ability to a variety of pharmacologically relevant receptors has been also witnessed. The existence of a bifunctional linker to anchor two substrates, resulting in a higher concentration of pharmacophores in proximity to recognition sites of several receptors involved in human diseases, portrays this group of metabolites as privileged lead structures for advanced pre-clinical and clinical studies. Despite the structural novelty of various marine diketopiperazine dimers and their relevant bioactive properties in several models of disease, to our knowledge, this attractive subclass of compounds is reviewed here for the first time.
Assuntos
Organismos Aquáticos/química , Produtos Biológicos/química , Dicetopiperazinas/química , Fungos/química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Dicetopiperazinas/farmacologia , Dimerização , Humanos , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
The role of the marine environment in the development of anticancer drugs has been widely reviewed, particularly in recent years. However, the innovation in terms of clinical benefits has not been duly emphasized, although there are important breakthroughs associated with the use of marine-derived anticancer agents that have altered the current paradigm in chemotherapy. In addition, the discovery and development of marine drugs has been extremely rewarding with significant scientific gains, such as the discovery of new anticancer mechanisms of action as well as novel molecular targets. Approximately 50 years since the approval of cytarabine, the marine-derived anticancer pharmaceutical pipeline includes four approved drugs and eighteen agents in clinical trials, six of which are in late development. Thus, the dynamic pharmaceutical pipeline consisting of approved and developmental marine-derived anticancer agents offers new hopes and new tools in the treatment of patients afflicted with previously intractable types of cancer.
Assuntos
Antineoplásicos/química , Organismos Aquáticos/química , Descoberta de Drogas/tendências , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Neoplasias/tratamento farmacológicoRESUMO
Sea hares of Aplysia genus are recognized as a source of a diverse range of metabolites. 5α,8α-Endoperoxides belong to a group of oxidized sterols commonly found in marine organisms and display several bioactivities, including antimicrobial, anti-tumor, and immunomodulatory properties. Herein we report the isolation of 5α,8α-epidioxycholest-6-en-3ß-ol (EnP(5,8)) from Aplysia depilans Gmelin, based on bioguided fractionation and nuclear magnetic resonance (NMR) analysis, as well as the first disclosure of its anti-inflammatory properties. EnP(5,8) revealed capacity to decrease cellular nitric oxide (NO) levels in RAW 264.7 macrophages treated with lipopolysaccharide (LPS) by downregulation of the Nos2 (inducible nitric oxide synthase, iNOS) gene. Moreover, EnP(5,8) also inhibited the LPS-induced expression of cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) at the mRNA and protein levels. Mild selective inhibition of COX-2 enzyme activity was also evidenced. Our findings provide evidence of EnP(5,8) as a potential lead drug molecule for the development of new anti-inflammatory agents.
Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Aplysia/química , Ésteres do Colesterol/química , Ésteres do Colesterol/farmacologia , Ergosterol/análogos & derivados , Macrófagos/efeitos dos fármacos , Adjuvantes Imunológicos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Fracionamento Químico , Ésteres do Colesterol/isolamento & purificação , Regulação para Baixo/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Ergosterol/química , Ergosterol/isolamento & purificação , Ergosterol/farmacologia , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Óxido Nítrico Sintase Tipo II/genética , Células RAW 264.7RESUMO
INTRODUCTION: Nowadays several plant species, such as Echinacea angustifolia L., can be considered natural important sources for therapeutic applications. Echinacea angustifolia is one of the most known medicinal plants, it shows protective and preventive effects against many chronic diseases, thanks to immunostimulant properties, mostly due to its polysaccharides and antioxidants. However, the optimisation of green extraction techniques to respect the environment is, currently, a hard challenge for the recovery of secondary metabolites. METHODOLOGY: Hydro-enzymatic extraction has been performed for the first time, it was compared with other different extraction techniques, for their efficacy in bioactive compound recovery. Phytochemical characterisation has been carried out through high-performance liquid chromatography diode array detector (HPLC-DAD) analysis and the antioxidant activity has been also measured. RESULTS: The highest extractive yields and the strongest antioxidant activity was obtained by cellulase and xylanase enzyme extraction. The enzymatic extraction with pectinase enzyme led to a higher polysaccharide content in comparison with the literature. The hydro-enzymatic extraction method and analytical conditions allowed the identification and quantification of two compounds, to the best of our knowledge, for the first time in E. angustifolia root extract. CONCLUSION: The optimised extraction methods discussed in this work led to a higher polysaccharides content, in comparison to previous literature results. The enzymatic extraction seems to be the best extraction technique, in terms of antioxidant yield and efficacy in bioactive compound recovery.
Assuntos
Antioxidantes/farmacologia , Echinacea/química , Química Verde/métodos , Compostos Fitoquímicos/análise , Extratos Vegetais/química , Antioxidantes/análise , Cromatografia Líquida de Alta Pressão/métodos , Raízes de Plantas/químicaRESUMO
Predominantly spread in West Tropical Africa, the shrub Salacia senegalensis (Lam.) DC. is known because of its medicinal properties, the leaves being used in the treatment of skin diseases. Prompted by the ethnomedicinal use, a hydroethanolic extract obtained from the leaves of the plant was screened against a panel of microbial strains, the majority of which involved in superficial infections. The extract was found to be active against the dermatophytes Trichophyton rubrum and Epidermophyton floccosum. Notable results were also recorded regarding the attenuation of the inflammatory response, namely the inhibitory effects observed against soybean 5-lipoxygenase (IC50 = 71.14 µg mL-1), no interference being recorded in the cellular viability of RAW 264.7 macrophages and NO levels. Relevantly, the extract did not lead to detrimental effects against the keratinocyte cell line HaCaT, at concentrations displaying antidermatophytic and anti-inflammatory effects. Flavonoid profiling of S. senegalensis leaves was achieved for the first time, allowing the identification and quantitation of myricitrin, three 3-O-substituted quercetin derivatives, and three other flavonoid derivatives, which may contribute, at least partially, to the observed antidermatophytic and anti-inflammatory effects. In the current study, the plant S. senegalensis is assessed concerning its antidermatophytic and anti-inflammatory properties.
Assuntos
Anti-Inflamatórios/farmacologia , Antifúngicos/farmacologia , Arthrodermataceae/efeitos dos fármacos , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Salacia/química , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Antifúngicos/química , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Flavonoides/química , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Fitoquímicos/química , Extratos Vegetais/química , Células RAW 264.7 , Análise EspectralRESUMO
In the worldwide search for new strategies in sustainable weed management, the use of allelopathic plants incorporated into the soil as green manure can help control weeds by releasing allelochemicals into the environment. In previous experiments, Eucalyptus globulus leaves incorporated into the soil as green manure were shown to have a notable potential for weed control. But, 'what was exactly happening at chemical level?' and 'which were the compounds potentially responsible for the phytotoxic effects observed during those greenhouse assays?' In the present study, in-vitro phytotoxicity bioassays and chemical analysis of eucalyptus leaves were carried out in order to explore the relationship between the temporal phytotoxic effects and the dynamics of chemical composition. For that, eucalyptus leaves were removed from soil at different sampling times during 30 days and analyzed for phenolic and volatile organic compounds (VOCs) by HPLC and HS-SPME/GC-MS, respectively. The phytotoxic potential of the aqueous extract and the volatile fraction was tested on the germination and early growth of Lactuca sativa. Eucalyptus leaves incorporated into the soil as green manure showed a continuous release of different phenolic and volatile compounds during a 30-day period of decomposition. Both fractions had phytotoxic effects during the time assayed; however, the target process of phytotoxicity was different: phenolic compounds being the factor causing germination inhibition and VOCs responsible for growth reduction. The dynamics of release of this cocktail of allelochemicals into the soil environment may be the responsible for the phytotoxicity observed in our previous works.
Assuntos
Eucalyptus/fisiologia , Feromônios/metabolismo , Folhas de Planta/fisiologia , Alelopatia , Eucalyptus/química , Germinação/efeitos dos fármacos , Lactuca/efeitos dos fármacos , Lactuca/crescimento & desenvolvimento , Fenóis/análise , Fenóis/metabolismo , Feromônios/análise , Feromônios/toxicidade , Folhas de Planta/química , Solo/química , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/toxicidade , Controle de Plantas Daninhas/métodosRESUMO
BACKGROUND: We have recently demonstrated that palmitoleic acid (16:1n7) increases lipolysis, glucose uptake and glucose utilization for energy production in white adipose cells. In the present study, we tested the hypothesis that palmitoleic acid modulates bioenergetic activity in white adipocytes. METHODS: For this, 3 T3-L1 pre-adipocytes were differentiated into mature adipocytes in the presence (or absence) of palmitic (16:0) or palmitoleic (16:1n7) acid at 100 or 200 µM. The following parameters were evaluated: lipolysis, lipogenesis, fatty acid (FA) oxidation, ATP content, oxygen consumption, mitochondrial mass, citrate synthase activity and protein content of mitochondrial oxidative phosphorylation (OXPHOS) complexes. RESULTS: Treatment with 16:1n7 during 9 days raised basal and isoproterenol-stimulated lipolysis, FA incorporation into triacylglycerol (TAG), FA oxidation, oxygen consumption, protein expression of subunits representing OXPHOS complex II, III, and V and intracellular ATP content. These effects were not observed in adipocytes treated with 16:0. CONCLUSIONS: Palmitoleic acid, by concerted action on lipolysis, FA esterification, mitochondrial FA oxidation, oxygen consumption and ATP content, does enhance white adipocyte energy expenditure and may act as local hormone.
Assuntos
Trifosfato de Adenosina/metabolismo , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/metabolismo , Ácidos Graxos Monoinsaturados/farmacologia , Ácidos Graxos/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Lipólise/efeitos dos fármacos , Camundongos , Oxirredução/efeitos dos fármacos , Triglicerídeos/metabolismoRESUMO
Pyrrolizidine alkaloids (PA) are widely distributed in plants throughout the world, frequently in species relevant for human consumption. Apart from the toxicity that these molecules can cause in humans and livestock, PA are also known for their wide range of pharmacological properties, which can be exploited in drug discovery programs. In this work we review the current body of knowledge regarding the chemistry, toxicology, pharmacology and food safety of PA.
Assuntos
Inocuidade dos Alimentos , Plantas/química , Alcaloides de Pirrolizidina/química , Alcaloides de Pirrolizidina/farmacologia , Animais , Descoberta de Drogas , Humanos , Plantas/toxicidade , Alcaloides de Pirrolizidina/toxicidadeRESUMO
Sclerocarya birrea (A.Rich.) Hochst (Anacardiaceae) is a savannah tree that has long been used in sub-Saharan Africa as a medicinal remedy for numerous ailments. The purpose of this study was to increase the scientific knowledge about this plant by evaluating the total content of polyphenols, flavonoids, and tannins in the methanol extracts of the leaves and bark (MLE and MBE, respectively), as well as the in vitro antioxidant activity and biological activities of these extracts. Reported results show that MLE is rich in flavonoids (132.7 ± 10.4 mg of quercetin equivalents/g), whereas MBE has the highest content of tannins (949.5 ± 29.7 mg of tannic acid equivalents/g). The antioxidant activity was measured using four different in vitro tests: ß-carotene bleaching (BCB), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), O2-â¢, and nitric oxide (NOâ¢) assays. In all cases, MBE was the most active compared to MLE and the standards used (Trolox and ascorbic acid). Furthermore, MBE and MLE were tested to evaluate their activity in HepG2 and fibroblast cell lines. A higher cytotoxic activity of MBE was evidenced and confirmed by more pronounced alterations in cell morphology. MBE induced cell death, triggering the intrinsic apoptotic pathway by reactive oxygen species (ROS) generation, which led to a loss of mitochondrial membrane potential with subsequent cytochrome c release from the mitochondria into the cytosol. Moreover, MBE showed lower cytotoxicity in normal human dermal fibroblasts, suggesting its potential as a selective anticancer agent.
Assuntos
Anacardiaceae/química , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Antioxidantes/química , Apoptose , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Células Hep G2 , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Oxirredução , Casca de Planta/química , Extratos Vegetais/química , Folhas de Planta/química , Polifenóis/análise , Espécies Reativas de Oxigênio/metabolismo , Taninos/análiseRESUMO
Bioprospection of marine invertebrates has been predominantly biased by the biological richness of tropical regions, thus neglecting macro-organisms from temperate ecosystems. Species that were not the object of studies on their biochemical composition include the Heterobranchia gastropods Armina maculata, Armina tigrina and Aglaja tricolorata, inhabitants of the Portuguese Atlantic coastal waters. Here, we present for the first time the fatty acid profile of neutral lipids and homarine content of these three species. Qualitative and quantitative differences in the fatty acid content among species points to the existence of a fatty acid profile of neutral lipids, particularly of each genus. The results from cytotoxicity assays, using the acetonic extracts of the gastropods on human gastric adenocarcinoma (AGS) and human lung adenocarcinoma (A549) cell lines, revealed a pronounced cytotoxic effect of the A. tigrina extract on both cell lines (IC50 values of 68.75 and 69.77 µg mL−1 for AGS and A549, respectively). It is worth noting the significant reduction of NO levels in LPS-challenged RAW 264.7 macrophages exposed to A. tricolorata extract, at concentrations as low as 125 µg mL−1.
Assuntos
Anti-Inflamatórios/análise , Antineoplásicos/análise , Ácidos Graxos/análise , Gastrópodes/metabolismo , Macrófagos/efeitos dos fármacos , Ácidos Picolínicos/análise , Células A549 , Animais , Anti-Inflamatórios/metabolismo , Antineoplásicos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ácidos Graxos/metabolismo , Humanos , Lipopolissacarídeos/efeitos adversos , Macrófagos/citologia , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Ácidos Picolínicos/metabolismo , Células RAW 264.7RESUMO
Quercus species have a plethora of applications, either in wine and wood industries, in human and animal nutrition or in human health. In order to improve the knowledge on this genus, the aim of the present study was to correlate, for the first time, the phenolic composition of different Quercus ilex L. plant tissues (leaves in two maturation stages, acorns, teguments and cotyledons) and different extraction procedures with scavenging and anticholinesterase activities. The hydromethanolic and aqueous extracts obtained showed strong radical scavenging activity against DPPH, superoxide anion radical and nitric oxide radical, leaves exhibiting higher total phenolic content and revealing the best antioxidant properties, followed by tegument and acorns. Concerning the phenolic profile, fifteen compounds were identified and quantified by HPLC-DAD, ranging from 1568.43 to 45,803.16 mg/kg dried extract. The results indicate that Q. ilex can be a source of strong antioxidant phenolic compounds with possible interest for food and pharmaceutical industries.
Assuntos
Antioxidantes/isolamento & purificação , Fenóis/isolamento & purificação , Quercus/química , Animais , Antioxidantes/farmacologia , Humanos , Métodos , Fenóis/farmacologia , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Estações do AnoRESUMO
The need of new anti-inflammatory drugs has led to the search for safer and more potent molecules in distinct sources, such as natural products. This work aimed to explore the anti-inflammatory potential of aqueous extracts from two herbal teas (Annona muricata L. and Jasminum grandiflorum L.) in RAW 264.7 macrophages cells and in cell-free assays. Furthermore, the phenolic composition of both extracts and of their hydrolysates was characterized by HPLC-DAD, in order to establish possible relationships with the biological activity. In a general way, A. muricata displayed a stronger capacity to inhibit nitric oxide (NO) production and the activity of phospholipase A2 (PLA2 ), displaying an IC50 value of 142 µg/ml against this enzyme. A deeper look at phenolic compounds revealed that aglycones had more capacity to inhibit NO and PLA2 than their corresponding glycosides, quercetin being clearly the most potent one (IC50 = 7.47 and 1.36 µm, respectively). In addition, 5-O-caffeoylquinic acid, at 1.56 µm, could also inhibit PLA2 (ca. 35%). Our findings suggest that the consumption of both herbal teas may be a preventive approach to inflammatory disorders.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Chás de Ervas , Animais , Annona/química , Anti-Inflamatórios/farmacologia , Sistema Livre de Células/efeitos dos fármacos , Jasminum/química , Camundongos , Óxido Nítrico/antagonistas & inibidores , Fenóis/análise , Fenóis/farmacologia , Inibidores de Fosfolipase A2 , Extratos Vegetais , Células RAW 264.7RESUMO
The antioxidant and enzyme inhibitory properties of methanolic extracts from four aromatic plants used in traditional medicine and food [Calamintha nepeta (L.) Savi subsp. nepeta, Helichrysum italicum subsp. picardii Franco, Mentha spicata L. and Origanum vulgare subsp. virens (Hoffmanns. & Link) Bonnier & Layens] were evaluated. The extract from O. vulgare exhibited the strongest DPPH (IC50 of 4.65 ± 0.12 µg/ml) and ABTS (1479.56 ± 12.29 µmolTE/gextract) scavenging capacities, as well as the largest ferric reducing ability (1746.76 ± 45.11 µmolAAE/gextract). This extract also showed the highest total phenolic content (1597.20 ± 24.10 µmolGAE/gextract) and although HPLC-DAD analysis revealed rosmarinic acid as the main compound of the extract, other compounds seem to be involved in the antioxidant activity. Furthermore, the extract from H. italicum, which was found to be rich in caffeoylquinic and dicaffeoylquinic acids and in pinocembrin, showed the highest inhibitory potential against acetylcholinesterase, tyrosinase and α-glucosidase. Overall, the results obtained validate the usefulness of the studied plants as valuable sources of natural agents beneficial for human health.