RESUMO
Three undescribed solalodine-type glycoalkaloids, named solanigrinoside A-C (1-3), and six known compounds (4-9) were isolated from the whole plants of Solanum nigrum. Their structures were elucidated based on analysis of HR-ESI-MS, 1D- and 2D-NMR spectral data, and comparison with those reported in literatures. The solanigrinoside A-C (1-3), solasodine (4), and 3-acetoxysolasodine (5) exhibited cytotoxic effects against LU-1, Hep-G2, and MCF-7 cells with IC50 values in range from 4.6â µM to 56.2â µM. Compound 2 showed the significant cytotoxic activity with corresponding IC50 values of 5.7â µM, 7.9â µM, and 4.6â µM, respectively.
Assuntos
Antineoplásicos Fitogênicos , Ensaios de Seleção de Medicamentos Antitumorais , Alcaloides de Solanáceas , Solanum nigrum , Humanos , Solanum nigrum/química , Alcaloides de Solanáceas/farmacologia , Alcaloides de Solanáceas/química , Alcaloides de Solanáceas/isolamento & purificação , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Sobrevivência Celular/efeitos dos fármacos , Conformação MolecularRESUMO
Six previously unreported solanidane steroidal alkaloids, namely lyrasolanosides A-F, were isolated from Solanum lyratum. In addition, five known steroidal alkaloids were also identified. The structures of these compounds were determined through the use of NMR, HRESIMS,UV, IR and ECD analysis. To assess their bioactivities, the cytotoxic effects of the six previously unreported compounds were evaluated on A549 cells. The results revealed that lyrasolanoside B (2) exhibited the highest potency among them. Lyrasolanoside B (2) exhibited significant inhibition of cell migration, invasion, and adhesion dramatically. Mechanistically, it was found to suppress the activity of JAK2/STAT3 signaling pathway by downregulating the expression of phosphorylated JAK2/STAT3 in an exosome-dependent manner. In addition, lyrasolanoside B (2) was found to significantly upregulate the expression of E-cadherin and downregulate the expression of N-cadherin and vimentin. These findings indicate that lyrasolanoside B (2) inhibits the metastasis of A549 cells by suppressing exosome-mediated EMT. These findings suggest that lyrasolanoside B (2) may inhibit the metastasis of lung cancer by regulating A549-derived exosomes.
Assuntos
Solanum , Humanos , Células A549 , Estrutura Molecular , Solanum/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Movimento Celular/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Alcaloides de Solanáceas/farmacologia , Alcaloides de Solanáceas/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Alcaloides/farmacologia , Alcaloides/isolamento & purificação , ChinaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Fungal and bacterial infections remain a major problem worldwide, requiring the development of effective therapeutic strategies. Solanum mammosum L. (Solanaceae) ("teta de vaca") is used in traditional medicine in Peru to treat fungal infections and respiratory disorders via topical application. However, the mechanism of action remains unknown, particularly in light of its chemical composition. MATERIALS AND METHODS: The antifungal activity of TDV was determined against Trichophyton mentagrophytes and Candida albicans using bioautography-TLC-HRMS to rapidly identify the active compounds. Then, the minimum inhibitory concentration (MIC) of the fruit crude extract and the active compound was determined to precisely evaluate the antifungal activity. Additionally, the effects of the most active compound on the formation of Pseudomonas aeruginosa biofilms and pyocyanin production were evaluated. Finally, a LC-HRMS profile and a molecular network of TDV extract were created to characterize the metabolites in the fruits' ethanolic extract. RESULTS: Bioautography-TLC-HRMS followed by isolation and confirmation of the structure of the active compound by 1D and 2D NMR allowed the identification solamargine as the main compound responsible for the anti-Trichophyton mentagrophytes (MIC = 64 µg mL-1) and anti-Candida albicans (MIC = 64 µg mL-1) activities. In addition, solamargine led to a significant reduction of about 20% of the Pseudomonas aeruginosa biofilm formation. This effect was observed at a very low concentration (1.6 µg mL-1) and remained fairly consistent regardless of the concentration. In addition, solamargine reduced pyocyanin production by about 20% at concentrations of 12.5 and 50 µg mL-1. Furthermore, the LC-HRMS profiling of TDV allowed us to annotate seven known compounds that were analyzed through a molecular network. CONCLUSIONS: Solamargine has been shown to be the most active compound against T. mentoagrophytes and C. albicans in vitro. In addition, our data show that this compound affects significantly P. aeruginosa pyocyanin production and biofilm formation in our conditions. Altogether, these results might explain the traditional use of S. mammosum fruits to treat a variety of fungal infections and respiratory disorders.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Alcaloides de Solanáceas/farmacologia , Solanum/química , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Arthrodermataceae/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Piocianina/metabolismo , Alcaloides de Solanáceas/isolamento & purificaçãoRESUMO
BACKGROUND: Increasing evidences have revealed that solasodine, isolated from Solanum sisymbriifolium fruits, has multiple functions such as anti-oxidant, anti-tumor and anti-infection. However, its role in pancreatic cancer has not been well studied. METHODS: To explore the role of solasodine in pancreatic cancer, human pancreatic cell lines including SW1990 and PANC1 were treated with different concentrations of solasodine for 48 h, and cell viability was evaluated by MTT assay, cell invasion and migration were evaluated by Transwell assay. The effect of solasodine on the apoptosis of SW1990 and PANC1 cells was detected by flow cytometry. To further explore the antitumor effect of solasodine in vivo, an SW1990 tumor-bearing mouse model was constructed. The effects of solasodine on cytokines in the serum of SW1990 tumor-bearing mice were also evaluated by ELISA assay. RESULTS: Specifically, in vitro, solasodine could significantly inhibit the proliferation of pancreatic cancer cell lines SW1990 and PANC1 cells. Flow cytometric analysis indicated that solasodine could induce apoptosis of SW1990 and PANC1 cells. Western blot assay indicated that solasodine could significantly inhibit the activation of Cox-2/Akt/GSK3ß signal pathway. Meanwhile, the release of Cytochrome c from mitochondria to cytoplasm which can raise the caspases cascade (C-caspase 3 and C-caspase 9) was significantly enhanced by solasodine. In vivo, the results showed that solasodine had potent anti-tumor activities with a lower cytotoxicity. In addition, the serum TNF-α, IL-2 and IFN-γ levels in SW1990 tumor-bearing mice after the treatment of solasodine was significantly increased. CONCLUSION: Taken together, our results suggested that the solasodine could prevent the progression of pancreatic cancer by inhibiting proliferation and promoting apoptosis, as well as stimulating immunity, suggesting that solasodine might be a potential therapeutic strategy for pancreatic cancer.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Frutas/química , Neoplasias Pancreáticas/tratamento farmacológico , Alcaloides de Solanáceas/farmacologia , Solanum/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Conformação Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Alcaloides de Solanáceas/química , Alcaloides de Solanáceas/isolamento & purificação , Células Tumorais CultivadasRESUMO
The present research work was designed to examine the neuroprotective effect of ethanolic extract of Solanum virginianum Linn. (SV) in chronic construction injury (CCI) of sciatic nerve-induced neuropathic pain in rats. The extract was initially standardized by high-performance thin-layer chromatography using solasodine as a biomarker and was then subjected to assess the degree of mechanical allodynia, thermal allodynia, mechanical hyperalgesia, thermal hyperalgesia and biochemical evaluations. Administration of SV (100 and 200 mg/kg; p.o.) and pregabalin (10 mg/kg; p.o.) as a reference standard significantly debilitated hyperalgesia and allodynia and notably restored the altered antioxidant level and pro-inflammatory cytokine (IL-1ß and TNF-α) expression in a dose-dependent manner. Further, to appraise the mechanistic approach of solasodine, docking simulation studies were done on the 3D structure of the voltage-gated N-type calcium channel (Cav 2.2), R-type calcium channel (Cav 2.3) and sodium channel (Nav 1.7), and the results revealed that solasodine properly positioned into Phe 19, Leu 32, Met 51 and Met 71 (FLMM pocket) of Cav 2.2 and Cav 2.3 and being a competitor of Ca2+/N-lobe it may inactivate these calcium channels but did not bind into the desired binding pocket of Nav 1.7. Thus, the study confirmed the role of solasodine as a major biomarker for the observed neuroprotective nature of Solanum virginianum.
Assuntos
Analgésicos/farmacologia , Hiperalgesia/prevenção & controle , Simulação de Acoplamento Molecular , Neuralgia/prevenção & controle , Limiar da Dor/efeitos dos fármacos , Extratos Vegetais/farmacologia , Neuropatia Ciática/tratamento farmacológico , Alcaloides de Solanáceas/farmacologia , Solanum , Analgésicos/isolamento & purificação , Analgésicos/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Sítios de Ligação , Ligação Competitiva , Canais de Cálcio Tipo N/efeitos dos fármacos , Canais de Cálcio Tipo N/metabolismo , Modelos Animais de Doenças , Etanol/química , Feminino , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Masculino , Neuralgia/metabolismo , Neuralgia/fisiopatologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/metabolismo , Ligação Proteica , Ratos Wistar , Neuropatia Ciática/metabolismo , Neuropatia Ciática/fisiopatologia , Alcaloides de Solanáceas/isolamento & purificação , Alcaloides de Solanáceas/metabolismo , Solanum/química , Solventes/químicaRESUMO
An aqueous two-phase system was used in conjunction with ultrasonic cell disruption to extract and separate solanine (mainly solasonine and solamargine) and Solanum nigrum polysaccharide from Solanum nigrum unripe fruit. The optimized conditions of the present study were determined by a single-factor experiment and a multifactor experiment. The concentration of ethanol was set at 60% and the duration of the ultrasonic cell disruption extraction was 50â¯min. In the ethanol-K2CO3 aqueous two-phase separation system, the concentration of ethanol was 36%, the concentration of K2CO3 was 0.21â¯mg·mL-1, and the temperature was 15⯰C. The solasonine and solamargine were determined by high-performance liquid chromatography, and the Solanum nigrum polysaccharide was determined by an ultraviolet-visible spectrophotometer in accordance with the phenol-sulfuric acid method. xUnder optimized conditions, the average extraction efficiencies of solasonine, solamargine and Solanum nigrum polysaccharide were 95.86%, 95.95% and 96.95%, respectively, and the average separation efficiencies of solasonine, solamargine and Solanum nigrum polysaccharide were 2.07â¯mg·g-1, 2.05â¯mg·g-1 and 8.15â¯mg·g-1, respectively.
Assuntos
Frutas/química , Polissacarídeos/isolamento & purificação , Solanina/análise , Solanum nigrum/química , Ultrassom , Cromatografia Líquida de Alta Pressão , Polissacarídeos/análise , Alcaloides de Solanáceas/análise , Alcaloides de Solanáceas/isolamento & purificação , EspectrofotometriaRESUMO
BACKGROUND: The present study investigates the hepato- and DNA-protective effects of standardized extracts of Cleome brachycarpa (cabralealactone), Solanum incanum (solasodin), and Salvadora oleioides (salvadorin) in rats. MATERIALS AND METHODS: Hepatotoxicity was induced with intraperitoneal injection of carbon tetrachloride (CCl4) (1 mL/kg b.wt.) once a week for 12 weeks. The hepato- and DNA protective effects of the extracts in different combinations were compared with that of a standard drug Clavazin (200 mg/kg b.wt.). Tissue alanine aminotransferase, alpha-fetoprotein, tumor necrosis factor alpha (TNF-α), isoprostanes-2α, malondialdehyde, and 8-hydroxydeoxyguanosine, the significant hallmarks of oxidative stress, were studied. RESULTS: Histopathological findings of the liver sections from the rat group which received CCl4+cabralealactone, solasodin, and salvadorin demonstrated improved centrilobular hepatocyte regeneration with moderate areas of congestion and infiltration comparable with Clavazin. For in silico study, the identified compounds were subjected to molecular docking with cyclooxygenase-2 and TNF-α followed by a molecular dynamics study, which indicated their potential as anti-inflammatory agents. CONCLUSION: Cabralealactone, solasodin, and salvadorin confer some hepatoprotective and DNA-damage protective effects against CCl4-induced toxicity. They successfully restored the normal architecture of hepatocytes and have the potential to be used as inhibitor to main culprits, that is, cyclooxygenase-2 and TNF-α. They can combat oxidative stress and liver injuries both as mono and combinational therapies. However, combination therapy has more ameliorating effects.
Assuntos
Anti-Inflamatórios/farmacologia , Cumarínicos/farmacologia , Modelos Animais de Doenças , Lactonas/farmacologia , Naftalenos/farmacologia , Alcaloides de Solanáceas/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Tetracloreto de Carbono/administração & dosagem , Tetracloreto de Carbono/toxicidade , Cumarínicos/química , Cumarínicos/isolamento & purificação , Ciclo-Oxigenase 2/metabolismo , DNA/efeitos dos fármacos , Injeções Intraperitoneais , Lactonas/química , Lactonas/isolamento & purificação , Fígado/efeitos dos fármacos , Fígado/patologia , Simulação de Acoplamento Molecular , Naftalenos/química , Naftalenos/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Ratos , Alcaloides de Solanáceas/química , Alcaloides de Solanáceas/isolamento & purificação , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Solanine A is a novel steroidal alkaloid isolated from Solanum nigrum Linn., a medicinal and edible plant which is widely used for treating various inflammatory diseases. In this study, we found that solanine A markedly suppressed the production of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide/interferon-γ (LPS/IFNγ)-stimulated RAW264.7 cells, and attenuated xylene, carrageenan and agar-induced inflammation in mice. The mRNA levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and -1ß (IL-1ß), as well as C-X-C motif chemokine ligand-9 (CXCL9), were significantly decreased by solanine A. Furthermore, solanine A also suppressed LPS/IFNγ-induced protein expression of iNOS and COX2. Mechanistically, solanine A inhibited the nuclear translocation of nuclear factor-κB (NF-κB) through the prevention of NF-κB p65 and inhibitory κB-α (IκBα) phosphorylation and IκBα degradation, and it also suppressed activation of extracellular regulated protein kinases (ERK), signal transducers and activators of transcription-1 (STAT1) and serine/threonine protein kinase Akt in LPS/IFNγ-stimulated RAW264.7 macrophages and agar-induced granuloma model in mice. Taken together, solanine A exhibits a potent anti-inflammatory activity in LPS/IFNγ- activated macrophages and animal models of inflammation through inhibition of NF-κB, ERK1/2, Akt and STAT1 signaling pathways, suggesting that solanine A may be a valuable leading compound in the treatment of inflammatory diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Granuloma/tratamento farmacológico , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Alcaloides de Solanáceas/farmacologia , Solanum nigrum/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Edema/imunologia , Granuloma/imunologia , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos ICR , Alcaloides de Solanáceas/isolamento & purificação , Alcaloides de Solanáceas/uso terapêuticoRESUMO
Steroidal glycoalkaloids present in Solanaceae are toxic compounds biosynthesised for the protection of the plants. However, many health benefits of these compounds have been reported so far. One of their promising targets might be cancer, as demonstrated in a large number of studies. However, the main mechanism of action seems to be unclear. It could include the induction of apoptosis or trigger a necrosis with a subsequent inflammatory response. The relatively high systemic toxicity of steroidal compounds is another effect that must be taken into account in anticancer research. The main aim of this work was to summarise the recent progress in the investigation of the mechanisms of their antitumour action and to discuss their potential.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/farmacologia , Solanaceae/química , Alcaloides de Solanáceas/farmacologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/toxicidade , Humanos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Alcaloides de Solanáceas/isolamento & purificação , Alcaloides de Solanáceas/toxicidadeRESUMO
CONTEXT: The persistence of fascioliasis in many developing countries urges the search for simple, cheap, and effective substances. In this view, plants provide interesting molluscicidal activities thanks to the secondary metabolites they produce. The genus Solanum is known for its potent effect on vector snails. OBJECTIVE: The molluscicidal activity of Solanum elaeagnifolium Cav. (Solanaceae) seeds against Galba truncatula Müll. (Lymnaeidae), intermediate host of Fasciola hepatica L. (Fasciolidae), was evaluated. MATERIALS AND METHODS: Solanum elaeagnifolium seeds were powdered and successively extracted using n-hexane, methylene chloride, acetone, and methanol, for 20 h each. After filtration, solvents were evaporated. An acid-base treatment was conducted on seed methanolic extract to isolate total alkaloids and ß-solamarine. Total saponins fraction was obtained after successive macerations and evaporations. The molluscicidal activity was evaluated by subjecting snails, in groups of 10, for 48 h to 500 mL of extracts, fractions, and pure product aqueous solutions, each containing amounts, ranging from 1 to 50 mg of plant material in 5 mg increments. RESULTS: The methanolic extract of seeds, ß-solamarine isolated for the first time from this plant and total saponins fraction showed very potent activities on snails, giving respective median lethal concentrations (LC50) of 1.18, 0.49, and 0.94 mg/L. Total alkaloids fraction obtained from the methanolic extract was less active giving an LC50 value of 14.67 mg/L. DISCUSSION AND CONCLUSION: This study emphasizes that glycoalkaloids and saponins of Solanum elaeagnifolium are potent molluscicidal agents. Seed methanolic extract, ß-solamarine, and total saponins fraction may be used as molluscicides.
Assuntos
Fasciola hepatica/efeitos dos fármacos , Lymnaea/efeitos dos fármacos , Moluscocidas/farmacologia , Extratos Vegetais/farmacologia , Sementes , Alcaloides de Solanáceas/farmacologia , Solanum , Animais , Fasciola hepatica/metabolismo , Lymnaea/metabolismo , Moluscocidas/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Caramujos , Alcaloides de Solanáceas/isolamento & purificaçãoRESUMO
Candida albicans undergoes yeast-to-hyphal transition that has been recognized as a virulence factor as well as the key point for the development of mature biofilm. In this study, we found that a natural product, solasodine-3-O-ß-D-glucopyranoside (SG), a steroidal alkaloid glycoside, isolated from Solanum. nigrum L., could attenuate the virulence of C. albicans by inhibiting the adhesion and morphological transition. Moreover, SG dramatically inhibited the biofilm formation and displayed killing activity against the mature biofilm. In vivo study using Caenorhabditis elegans showed that SG prolonged the survival time of C. albicans infected worms. The mechanism investigation revealed that SG could inhibit the expression of adhesions and hyphae-specific genes by regulating Ras-cAMP-PKA signaling pathway. The inhibitory effects on yeast-to-hyphal conversion and biofilm formation caused by SG could be rescued by addition of exogenerous cAMP, suggesting that the retarded cAMP synthesis is responsible for these actions. Taken together, our work uncovers the underlying mechanism of SG-dependent inhibition of the yeast-to-hyphal switch and biofilm formation and provides a potential application in treating relevant fungal infections.
Assuntos
Antifúngicos/metabolismo , Biofilmes/efeitos dos fármacos , Produtos Biológicos/metabolismo , Candida albicans/efeitos dos fármacos , Hifas/efeitos dos fármacos , Alcaloides de Solanáceas/metabolismo , Fatores de Virulência/antagonistas & inibidores , Animais , Antifúngicos/isolamento & purificação , Biofilmes/crescimento & desenvolvimento , Produtos Biológicos/isolamento & purificação , Caenorhabditis elegans/microbiologia , Candida albicans/fisiologia , AMP Cíclico/metabolismo , Modelos Animais de Doenças , Glicosídeos/isolamento & purificação , Glicosídeos/metabolismo , Hifas/crescimento & desenvolvimento , Viabilidade Microbiana/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Alcaloides de Solanáceas/isolamento & purificação , Solanum/química , Análise de SobrevidaRESUMO
Optimization based on central composite design (CCD) for enantioseparation of anisodamine (AN), atenolol (AT), and metoprolol (ME) in human urine was developed using a microfluidic chip-CE device. Coupling the flexible and wide working range of microfluidic chip-CE device to CCD for chiral separation of AN, AT, and ME in human urine, a total of 15 experiments is needed for the optimization procedure as compared to 75 experiments using the normal one variable at a time optimization. The optimum conditions obtained are found to be more robust as shown by the curvature effects of the interaction factors. The developed microfluidic chip-CE-ECL system with adjustable dilution ratios has been validated by satisfactory recoveries (89.5-99% for six enanotiomers) in urine sample analysis. The working range (0.3-600 µM), repeatability (3.1-4.9% RSD for peak height and 4.0-5.2% RSD for peak area), and detection limit (0.3-0.6 µM) of the method developed are found to meet the requirements for bedside monitoring of AN, AT, and ME in patients under critical conditions. In summary, the hyphenation of CCD with the microfluidic chip-CE device is shown to offer a rapid means for optimizing the working conditions on simultaneous separation of three racemic drugs using the microfluidic chip-CE device developed.
Assuntos
Antiarrítmicos/urina , Atenolol/urina , Eletroforese em Microchip/instrumentação , Metoprolol/urina , Alcaloides de Solanáceas/urina , Antiarrítmicos/isolamento & purificação , Atenolol/isolamento & purificação , Desenho de Equipamento , Humanos , Limite de Detecção , Medições Luminescentes/instrumentação , Metoprolol/isolamento & purificação , Reprodutibilidade dos Testes , Alcaloides de Solanáceas/isolamento & purificação , EstereoisomerismoRESUMO
Steroidal glycoalkaloids (SGAs) constitute one of the main groups of secondary metabolites in tomato fruit. However, the detailed composition of SGAs other than α-tomatine, dehydrotomatine and esculeoside A, remains unclear. Comparative SGA profiling was performed in eight tomato accessions, including wild tomato species by HPLC-Fourier transform ion cyclotron resonance mass spectrometry (HPLC-FTICR/MS). On the basis of molecular formulae obtained from accurate m/z and fragmentation patterns by multistage MS/ MS (MS(n)), 123 glycoalkaloids in total were screened. Detailed MS(n) analysis showed that the observed structural diversity was derived from various chemical modifications, such as glycosylation, acetylation, hydroxylation and isomerization. Total SGA content in each tomato accession was in the range of 121-1986 nmol/gfr.wt. Furthermore, the compositional variety of SGA structures was distinctive in some tomato accessions. While most tomato accessions were basically categorized as α-tomatine-rich or esculeoside A-rich group, other specific SGAs also accumulated at high levels in wild tomato. Here, five such SGAs were isolated and their structures were determined by NMR spectroscopic analysis, indicating three of them were presumably synthesized during α-tomatine metabolism.
Assuntos
Frutas/química , Glicosídeos/isolamento & purificação , Fitosteróis/isolamento & purificação , Extratos Vegetais/química , Alcaloides de Solanáceas/isolamento & purificação , Solanum lycopersicum/química , Glicosídeos/química , Estrutura Molecular , Fitosteróis/química , Alcaloides de Solanáceas/químicaRESUMO
Six steroidal glycoalkaloids (1-6) were isolated and purified from Solanum nigrum L. (SNL) by acid extraction and alkaline precipitation, various chromatographic techniques, and their structures were elucidated by spectroscopic data. Antitumor activity, structure-activity and its molecular mechanism were investigated by methyl thiazolyl tetrazolium (MTT) method, flow cytometry, colorimetric assay and an immunocytochemical method. Experimental results showed that compounds 1 (solasonine), 2 (ß1-solasonine), 3 (solamargine) and 6 (solanigroside P) have cytotoxicity to MGC-803 cells. Compounds with three sugar units and a-l-rhamnopyranose at C-2 or a hydroxyl group on the steroidal backbone may be potential candidates for the treatment of gastric cancer. The mechanism of action may be related to the decrease of mutation p53, the increase of the ratio of Bax to Bcl-2 and the activation of caspase-3 to induce apoptosis.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Alcaloides de Solanáceas/isolamento & purificação , Alcaloides de Solanáceas/farmacologia , Solanum nigrum/química , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Humanos , Estrutura Molecular , Extratos Vegetais/química , Alcaloides de Solanáceas/química , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismoRESUMO
Leishmaniasis is an infection caused by a protozoan parasite of the genus Leishmania and is the second most prevalent parasitic protozoal disease after malaria in the world. We report the in vitro leishmanicidal activity on promastigote forms of Leishmania amazonensis and cytotoxicity, using LLCMK2 cells, of the glycoalkaloids from the fruits of Solanum lycocarpum, determined by colorimetric methods. The alkaloidic extract was obtained by acid-base extraction; solamargine and solasonine were isolated by silica-gel chromatography, followed by reversed-phase HPLC final purification. The alkaloidic extract, solamargine, solasonine, as well as the equimolar mixture of the glycoalkaloids solamargine and solasonine displayed leishmanicidal activity against promastigote forms of L. amazonensis, whereas the aglycone solasodine was inactive. After 24 and 72â h of incubation, most of the samples showed lower cytotoxicities (IC50 6.5 to 124â µM) as compared to leishmanicidal activity (IC50 1.1 to 23.6â µM). The equimolar mixture solamargine/solasonine was the most active with an IC50 value of 1.1â µM, after 72â h. Likewise, solamargine was the most active after 24â h with an IC50 value of 14.4â µM, both in comparison with the positive control amphotericin B.
Assuntos
Antiprotozoários/química , Alcaloides de Solanáceas/química , Solanum/química , Animais , Antiprotozoários/isolamento & purificação , Antiprotozoários/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Frutas/química , Leishmania/efeitos dos fármacos , Macaca mulatta , Alcaloides de Solanáceas/isolamento & purificação , Alcaloides de Solanáceas/toxicidadeRESUMO
Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma; it accounts for more than 280,000 deaths annually. In this work we investigated the effect of the alkaloidic extract obtained by acid-base extraction of the dried fruits of Solanum lycocarpum on schistosomiasis. We used this extract at concentrations of 10, 20, and 40 mg/kg to treat mice infected with Schistosoma mansoni in different phases of the parasite cycle, and we compared its effect with that of the positive control praziquantel (60 mg/kg). We evaluated the results on the basis of the number of macrophages, eggs, and granulomas; we also assessed nitric oxide (NO) and interferon-gamma (IFN-γ) production. Animals treated with a daily dose of 10 or 20 mg/kg alkaloidic extract between the 37th and 41st day of infection showed increased number of macrophages, elevated NO and IFN-γ concentrations, and reduced number of eggs and granulomas in the liver. The alkaloidic extract of S. lycocarpum fruits displayed an immunomodulatory effect on mice infected with S. mansoni, so its potential to treat schistosomiasis deserves further studies.
Assuntos
Frutas/química , Fatores Imunológicos/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Alcaloides de Solanáceas/farmacologia , Solanum/química , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Contagem de Células , Feminino , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/uso terapêutico , Interferon gama/sangue , Interferon gama/metabolismo , Fígado/parasitologia , Fígado/patologia , Macrófagos Peritoneais/citologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Contagem de Ovos de Parasitas , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Praziquantel/farmacologia , Praziquantel/uso terapêutico , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Alcaloides de Solanáceas/isolamento & purificação , Alcaloides de Solanáceas/uso terapêuticoRESUMO
The normal levels and types of glycoalkaloids found in commercial varieties of potato (Solanum tuberosum) appear to present no hazard to human health. However when wild Solanum species are used in breeding endeavors, new and untested glycoalkaloids may be introduced. Recent studies of domestic crosses with a wild Solanum oplocense accession indicated that the levels of a non-indigenous glycoalkaloid appeared associated with reduced defoliation by the Colorado potato beetle. The non-indigenous glycoalkaloid was isolated from foliage of the wild S. oplocense accession and unambiguously characterized by high-resolution electrospray ionization mass spectrometry and NM analysis as the glycoalkaloid dehydrocommersonine.
Assuntos
Alcaloides de Solanáceas/química , Solanum/química , Isótopos de Carbono , Espectroscopia de Ressonância Magnética/normas , Estrutura Molecular , Folhas de Planta/química , Prótons , Padrões de Referência , Alcaloides de Solanáceas/isolamento & purificação , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
A new spirostanol saponin (1), along with four known saponins, dioscin (2), protodioscin (3), methyl-protodioscin (4), and indioside D (5), and one known steroid glycoalkaloid solamargine (6) were isolated from the two synonymous species, Solanum incanum and S. heteracanthum. The structure of the new saponin was established as (23S,25R)-spirost-5-en-3ß,23-diol 3-O-{ß-D-xylopyranosyl-(1â2)-O-α-L-rhamnopyranosyl-(1â4)-[O-α-L-rhamnopyranosyl-(1â2)]-ß-D-glucopyranoside}, by using a combination of 1D and 2D NMR techniques including (1)H, (13)C, COSY, TOCSY, NOESY, HSQC and HMBC experiments and by mass spectrometry. The compounds 1, 3, 4 and 5 were evaluated for cytotoxicity against five cancer cell lines and for antioxidant and cytoprotective activity.
Assuntos
Antioxidantes/farmacologia , Diosgenina/análogos & derivados , Glicosídeos/farmacologia , Neoplasias/tratamento farmacológico , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Solanum/química , Espirostanos/farmacologia , Esteroides/farmacologia , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , Linhagem Celular Tumoral , Diosgenina/isolamento & purificação , Diosgenina/farmacologia , Diosgenina/uso terapêutico , Glicosídeos/isolamento & purificação , Glicosídeos/uso terapêutico , Humanos , Camundongos , Estrutura Molecular , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/uso terapêutico , Alcaloides de Solanáceas/química , Alcaloides de Solanáceas/isolamento & purificação , Solanum/classificação , Especificidade da Espécie , Espirostanos/química , Espirostanos/isolamento & purificação , Esteroides/isolamento & purificação , Esteroides/uso terapêuticoRESUMO
From the leaves of Solanum campaniforme, two new spirosolane alkaloids ß-acetoxyl-(25S)-22ßN-spirosol-4-en-3-one (1) and ß-hydroxyl-(25S)-22ßN-spirosol-4-en-3-one (4) were isolated along with two other known alkaloids of the same class (25S)-22ßN-spirosol-1,4-dien-3-one (2) and (25S)-22ßN-spirosol-4-en-3-one (3), which are reported for the first time as natural products. The structures of all alkaloids were established after an extensive analysis by 1D and 2D NMR spectroscopy (COSY, HSQC, HMBC and NOESY) as well as HRESIMS.
Assuntos
Alcaloides/química , Solanum/química , Alcaloides/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Fitosteróis/química , Fitosteróis/isolamento & purificação , Folhas de Planta/química , Padrões de Referência , Alcaloides de Solanáceas/química , Alcaloides de Solanáceas/isolamento & purificaçãoRESUMO
Solanum lycocarpum (Solanaceae), a Brazilian medicinal plant known as "wolf fruit," contains about 1.5% of glycoalkaloids in its dried fruits, consisting mainly of solamargine and solasonine. The present work reports the obtainment of the alkaloidic extract of the S. lycocarpum fruit by acid-base extraction and the isolation of the major alkaloid heterosides by chromatographic means, as well as the evaluation of their in vitro schistosomicidal activities. The in vitro schistosomicidal activities of the alkaloidic extract of S. lycocarpum fruits and its isolated steroidal alkaloids were undertaken against adult worms of Schistosoma mansoni. The alkaloidic extract (20, 32, and 50 µg mL(-1)), solasonine (50 µM), solamargine (32 and 50 µM), and equimolar mixture of glycoalkaloids (20, 32, and 50 µM) lead to the separation of all couple worms and extensive disruption on their teguments, such as sloughing, as well as their deaths within 24 h of incubation. In addition, the alkaloidic extract (10 and 15 µg mL(-1)), solasonine (50 µM), solamargine (10, 15, and 20 µM), and equimolar mixtures of glycoalkaloids (10 and 15 µM) reduced the development of eggs produced by the adult worms. Solamargine, containing the sugar chain moiety chacotriose, was more active than the solasonine, which contains solatriose sugar chain moiety. A synergistic effect was also observed for a mixture of solamargine and solasonine. Therefore, the alkaloidic extract of S. lycocarpum, and its major components, solamargine and solasonine, showed promising schistosomicidal activity.