RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ficus erecta, a traditional Chinese She Ethnomedicine, has been historically utilized to treat various inflammatory conditions such as arthritis, nephritis, and osteoporosis. However, the underlying mechanisms accounting for its anti-inflammatory activity, as well as its active components, largely remain elusive. AIM OF THE STUDY: The purpose of this research was to investigate the chemical constituents of F. erecta that contribute to its anti-inflammatory effects. MATERIALS AND METHODS: Coumarins and flavones were obtained from the 95% EtOH extract of F. erecta using virous column chromatography and reversed-phase semipreparative HPLC. The structures of the new compounds were elucidated by extensive analysis of spectroscopic methods, including HRESIMS, 1D and 2D NMR spectra, and CD experiments. Cultured macrophage RAW264.7 cells were utilized for the anti-inflammatory experiments. MTT cell viability assay, Griess reagent method, ELISA, and Western blot experiments were employed to evaluate the anti-inflammatory activity and investigate the related mechanism. RESULTS: Four new (1-4) and eleven previously identified (5-16) coumarins, together with one new (17) and six known flavones (18-23) were isolated from the whole plant of F. erecta. Compounds 7 and 17 significantly reduced nitric oxide (NO) and prostaglandin E2 (PGE2) production without cytotoxic effects. Furthermore, compounds 7 and 17 reduced the production of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in a concentration-dependent manner. Western blot analysis indicated that compounds 7 and 17 suppressed the expression of iNOS, COX-2, and p-IκBα in LPS-stimulated RAW264.7 macrophage cells. CONCLUSION: The current phytochemical investigations revealed that coumarins and flavones represent the primary chemical constituents of F. erecta. Compounds 7 and 17 exhibit potent anti-inflammatory properties, linked with the inhibition of NF-κB activation by preventing the degradation of IκBα phosphorylation. These compounds may serve as promising candidates for treating or preventing certain inflammatory diseases.
Assuntos
Anti-Inflamatórios , Cumarínicos , Ficus , Flavonas , Extratos Vegetais , Animais , Ficus/química , Flavonas/farmacologia , Flavonas/isolamento & purificação , Flavonas/química , Cumarínicos/farmacologia , Cumarínicos/isolamento & purificação , Cumarínicos/química , Células RAW 264.7 , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Óxido Nítrico/metabolismo , NF-kappa B/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: African wormwood (Artemisia afra Jacq. ex Willd.) has been used traditionally in southern Africa to treat illnesses causing fever and was recently shown to possess anti-tuberculosis activity. As tuberculosis is an endemic cause of fever in southern Africa, this suggests that the anti-tubercular activity of A. afra may have contributed to its traditional medicinal use. AIM OF THE STUDY: Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Given the reported activity of A. afra against Mtb, we sought to determine the mechanisms by which A. afra inhibits and kills this bacterium. MATERIALS AND METHODS: We used transcriptomics to investigate the impact of Artemisia spp. extracts on Mtb physiology. We then used chromatographic fractionation and biochemometric analyses to identify a bioactive fractions of A. afra extracts and identify an active compound. RESULTS: Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or artemisinin, suggesting that A. afra possesses other phytochemicals with unique modes of action. A biochemometric study of A. afra resulted in the isolation of an O-methylflavone (1), 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)chromen-4-one, which displayed considerable activity against Mtb strain mc26230 in both log phase growth and metabolically downshifted hypoxic cultures. CONCLUSIONS: The present study demonstrated that an O-methylflavone constituent of Artemisia afra explains part of the activity of this plant against Mtb. This result contributes to a mechanistic understanding of the reported anti-tubercular activity of A. afra and highlights the need for further study of this traditional medicinal plant and its active compounds.
Assuntos
Antituberculosos , Artemisia , Flavonas , Mycobacterium tuberculosis , Extratos Vegetais , Artemisia/química , Mycobacterium tuberculosis/efeitos dos fármacos , Antituberculosos/farmacologia , Antituberculosos/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Flavonas/farmacologia , Flavonas/isolamento & purificação , Flavonoides/farmacologia , Flavonoides/isolamento & purificaçãoRESUMO
Breast cancer presents a significant challenge due to its high rates of illness and mortality, necessitating more effective treatment approaches. While traditional treatments offer some benefits, they often lack precision in targeting cancer cells and can inadvertently harm healthy tissues. This study aims to investigate the cytotoxic effects and molecular mechanism of 5,4'-dihydroxy-6,8-dimethoxy-7-O-rhamnosyl flavone (DDR), extracted from Indigofera aspalathoides Vahl, on breast cancer cells (MDA-MB-231). Through various in vitro assays including wound healing, invasion, Western blotting, and immunofluorescence, the impact of DDR on epithelial-mesenchymal transition (EMT) and metastasis was evaluated. Treatment of MDA-MB-231 cells with different DDR concentrations (0-10 µg/mL) resulted in a significant decrease in invasion and migration, accompanied by the downregulation of metastasis-related proteins including VEGF, uPAR, uPA, and MMP-9. DDR treatment also hindered EMT by upregulating E-cadherin and downregulating N-cadherin, Slug, Twist, and Vimentin. Additionally, inhibition of the PI3K/AKT signaling pathway and downregulation of the NF-кB pathway were observed. These findings highlight the potential of DDR as a valuable source of natural compounds with promising anticancer properties, offering opportunities for the development of novel cancer therapies.
Assuntos
Neoplasias da Mama , Movimento Celular , Transição Epitelial-Mesenquimal , Flavonas , Indigofera , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Linhagem Celular Tumoral , Flavonas/farmacologia , Flavonas/química , Flavonas/isolamento & purificação , Indigofera/química , Movimento Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-akt/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
In this study, two undescribed compounds (1 and 2), together with eight known compounds (3-10) were isolated from the aerial parts of Piper samentosum by various chromatography methods. Their chemical structures were determined to be 7'''-oxolyciumamide N (1), vitexin 2''-O-ß-D-(6'''-feruloyl)-glucopyranoside (2), 1,2-dihydro-6,8-dimethoxy-7-hydroxy-1-(3,4-dihydroxyphenyl)-N1,N2-bis-[2-(-hydroxyphenyl)ethyl]-2,3-napthalene dicarboamide (3), vitexin 6''-O-ß-D-glucopyranoside (4), vitexin 2''-O-α-L-rhamnopyranoside (5), methyl 2-hydroxybenzoate-2-O-ß-D-apiofuranosyl-(1â2)-O-ß-D-glucopyranoside (6), ficuside G (7), methyl 2-O-ß-D-glucopyranosylbenzoate (8), methyl 2,5-dihydroxybenzoate-5-O-ß-D-glucopyranoside (9), and 3,7-dimethyloct-1-ene-3,6,7-triol 6-O-ß-D-glucopyranoside (10) by spectroscopic data analysis including HR-ESI-MS, 1D-, and 2D-NMR spectra. Compoundsâ 1-5 inhibited nitric oxide production in LPS-stimulated RAW264.7 macrophages with the IC50 values of 27.62, 74.03, 38.54, 70.39, and 44.95â µM, respectively. The NMR data of 9 were firstly reported herein.
Assuntos
Flavonas , Glucosídeos , Lipopolissacarídeos , Óxido Nítrico , Piper , Componentes Aéreos da Planta , Células RAW 264.7 , Camundongos , Animais , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Componentes Aéreos da Planta/química , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Glucosídeos/química , Piper/química , Flavonas/isolamento & purificação , Flavonas/farmacologia , Flavonas/química , Amidas/química , Amidas/farmacologia , Amidas/isolamento & purificação , Estrutura MolecularRESUMO
The major bioactive components of Kaempferia parviflora (KP) rhizomes, 3,5,7,3',4'-pentamethoxyflavone (PMF), 5,7-dimethoxyflavone (DMF), and 5,7,4'-trimethoxyflavone (TMF), were chosen as the quantitative and qualitative markers for this plant material. In order to extract bioactive components (total methoxyflavones) from KP rhizomes, ultrasound-assisted extraction (UAE) was proposed as part of this study. Plackett-Burman design (PBD) and Box-Behnken design (BBD) were utilized to optimize the effects of UAE on extraction yields and total methoxyflavone contents in KP rhizomes. First, PBD was utilized to determine the effect of five independent variables on total yields and total methoxyflavone contents. The results indicated that the concentration of the extracting solvent (ethanol), the extraction time, and the ratio of solvent to solid were significant independent terms. Subsequently, BBD with three-level factorial experiments was used to optimize the crucial variables. It was discovered that the concentration of ethanol was the most influential variable on yields and total methoxyflavone contents. Optimum conditions for extraction yield were ethanol concentration (54.24% v/v), extraction time (25.25 min), and solvent-to-solid ratio (49.63 mL/g), while optimum conditions for total methoxyflavone content were ethanol concentration (95.00% v/v), extraction time (15.99 min), and solvent-to-solid ratio (50.00 mL/g). The relationship between the experimental and theoretical values was perfect, which proved that the regression models used were correct and that PBD and BBD were used to optimize the conditions in the UAE to obtain the highest yield and total methoxyflavone content in the KP rhizomes.
Assuntos
Flavonas , Extratos Vegetais , Ultrassom , Zingiberaceae , Cromatografia Líquida de Alta Pressão/métodos , Flavonas/química , Flavonas/isolamento & purificação , Extratos Vegetais/química , Rizoma/química , Tailândia , Ultrassom/métodos , Zingiberaceae/químicaRESUMO
Brown planthopper (BPH, Nilaparvata lugens Stal.) is the most damaging rice pest affecting stable rice yields worldwide. Currently, methods for controlling BPH include breeding a BPH-resistant cultivar and using synthetic pesticides. Nevertheless, the continuous cultivation of resistant cultivars allows for the emergence of various resistant races, and the use of synthetic pesticides can induce environmental pollution as well as the emergence of unpredictable new pest species. As plants cannot migrate to other locations on their own to combat various stresses, the production of secondary metabolites allows plants to protect themselves from stress and tolerate their reproduction. Pesticides using natural products are currently being developed to prevent environmental pollution and ecosystem disturbance caused by synthetic pesticides. In this study, after BPH infection in rice, chrysoeriol7 (C7), a secondary metabolite that induces resistance against BPH, was assessed. After C7 treatment and BPH infection, relative expression levels of the flavonoid-related genes were elevated, suggesting that in plants subjected to BPH, compounds related to flavonoids, among the secondary metabolites, play an important role in inducing resistance. The plant-derived natural compound chrysoeriol7 can potentially thus be used to develop environmentally friendly pesticides. The suggested control of BPH can be effectively used to alleviate concerns regarding environmental pollution and to construct a relatively safe rice breeding environment.
Assuntos
Resistência à Doença , Flavonas/isolamento & purificação , Hemípteros/crescimento & desenvolvimento , Repelentes de Insetos/isolamento & purificação , Oryza/crescimento & desenvolvimento , Animais , Vias Biossintéticas , Flavonas/química , Flavonas/farmacologia , Regulação da Expressão Gênica de Plantas , Química Verde , Hemípteros/efeitos dos fármacos , Repelentes de Insetos/química , Repelentes de Insetos/farmacologia , Oryza/química , Oryza/parasitologia , Proteínas de Plantas/genética , Metabolismo SecundárioRESUMO
The total flavone of Abelmoschus manihot (TFA), a compound extracted from the flowers of Abelmoschus manihot (L.) Medic, has been widely used for the treatment of Crohn's disease, chronic glomerulonephritis and other diseases. The aim of this study was to investigate the effect of TFA on the gut microbiota and intestinal barrier in dextran sulfate sodium (DSS)-induced experimental colitis. C57BL/6J mice were treated with 2.5% DSS in drinking water to induce colitis. Mice were orally administered TFA (62.5 mg/kg, 125 mg/kg) or prednisone acetate (PAT, 2.5 mg/kg) once daily for 7 days. Biological samples were collected for analysis of inflammatory cytokines, gut microbiota and intestinal barrier integrity. TFA-H (125 mg/kg) markedly attenuated DSS-induced colon shortening and histological injury in experimental colitis. The therapeutic effect was similar to that of PAT administration. TFA-H notably modulated the dysbiosis of gut microbiota induced by DSS and greatly enriched Akkermansia muciniphila (A. muciniphila). Moreover, TFA-H remarkably ameliorated the colonic inflammatory response and intestinal epithelial barrier dysfunction. Interestingly, TFA directly promotes the growth of A. muciniphila in vitro. Taken together, the results revealed for the first time that TFA, as a prebiotic of A. muciniphila, improved DSS-induced experimental colitis, at least partly by modulating the gut microflora profile to maintain colonic integrity and inhibit the inflammatory response.
Assuntos
Abelmoschus/química , Colite/tratamento farmacológico , Flavonas/uso terapêutico , Prebióticos , Akkermansia/crescimento & desenvolvimento , Animais , Colite/microbiologia , Citocinas/biossíntese , Flavonas/administração & dosagem , Flavonas/isolamento & purificação , Microbioma Gastrointestinal , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Prednisona/administração & dosagemRESUMO
Three new flavone glycosides, one known flavone glycoside, and the phenolic derivative apiopaenonside were isolated and identified from the ethyl acetate fraction of the aerial parts of Scleranthus perennis. The planar structures were elucidated through extensive analysis of UV-Vis, IR, and 1H NMR and 13C NMR spectral data, including the 2D techniques COSY, HSQC, and HMBC, as well as ESI mass spectrometry. The isolated compounds were established as 5,7,3'-trihydroxy-4'-acetoxyflavone-8-C-ß-d-xylopyranoside-2''-O-glucoside (1), 5,7,3'-trihydroxy-4'-methoxyflavone-8-C-ß-d-xylopyranoside-2''-O-glucoside (2), 5,7-dihydroxy-3'-methoxy-4'-acetoxyflavone-8-C-ß-d-xylopyranoside-2''-O-glucoside (3), 5,7-dihydroxy-3'-methoxy-4'-acetoxyflavone-8-C-ß-d-xylopyranoside-2''-O-(4'''-acetoxy)-glucoside (4), and apiopaenonside (5). Moreover, all isolated compounds were evaluated for anti-collagenase activity. All compounds exhibited moderate inhibitory activity with IC50 values ranging from 36.06 to 70.24 µM.
Assuntos
Caryophyllaceae/química , Flavonas/química , Flavonas/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Inibidores de Metaloproteinases de Matriz/química , Inibidores de Metaloproteinases de Matriz/farmacologia , Colagenases/metabolismo , Ensaios Enzimáticos , Flavonas/isolamento & purificação , Glicosídeos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Inibidores de Metaloproteinases de Matriz/isolamento & purificação , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Artocarpus hirsutus Lam., or wild jack, a perennial tree of the Western Ghats of peninsular India, serves as a rich source of flavonoids. The indigenous knowledge of this multipurpose flora chronicles the efficient property of its bark as a natural treatment for various skin infections. Herein, we describe a rational explanation of this traditional knowledge via a broader evaluation of inhibitory activity of one of its phytoconstituents, cudraflavone C (Cud C), a prenyl flavone isolated from stem bark against diverse multidrug-resistant Staphylococcus aureus along with decidedly potent synergy combinations with a standard drug, gentamycin, especially against gentamycin-resistant S. aureus NRS 10119. Cud C exhibited equipotent MIC (4 µg/mL) against a varied array of MDR strains comprising MRSA, VRSA, and VRE and was nontoxic toward eukaryotic cells with a sizable selectivity index (SI 25-50). Cud C displayed concentration-dependent bactericidal activity against planktonic cells, an excellent biofilm disruption property exceeding that of levofloxacin and vancomycin against preformed S. aureus biofilm, and an enhanced capability to kill intracellular S. aureus more potently than vancomycin, thus exemplifying its position as an antibacterial lead candidate. In addition, S. aureus was unable to generate resistance to Cud C even after exposure for more than 40 days, whereas it generated resistance to levofloxacin within â¼20 days of exposure. Therefore, the naturally occurring prenylflavone Cud C can be accounted for as one of the reasons for the reported antibacterial properties of the bark of A. hirsutus. Taken together, detailed biological studies propose that Cud C can be considered as an effective antibacterial drug candidate against MDR S. aureus, which is fast becoming a significant threat to public health worldwide.
Assuntos
Antibacterianos/farmacologia , Artocarpus/química , Biofilmes/efeitos dos fármacos , Flavonas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Animais , Antibacterianos/isolamento & purificação , Chlorocebus aethiops , Flavonas/isolamento & purificação , Índia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Casca de Planta/química , Células VeroRESUMO
Even today, weeds continue to be a considerable problem for agriculture. The application of synthetic herbicides produces serious environmental consequences, and crops suffer loss of their activity due to the appearance of new resistant weed biotypes. Our aim is to develop new effective natural herbicides that improve the problem of resistance and do not harm the environment. This work is focused on a bioassay-guided isolation and the characterization of natural products present in Moquiniastrum pulchrum leaves with phytotoxic activity and its preliminary application in weeds. Moquiniastrum pulchrum was selected for two reasons: it is an abundant species in the Cerrado region (the second most important ecosystem in Brazil, after the Amazon)-the explanation behind its being a dominant species is a major focus of interest-and it has traditional employment in folk medicine. Six major compounds were isolated in this plant: one flavone and five diterpenes, two of which are described for the first time in the literature. Four of the six compounds exhibited phytotoxic activity in the bioassays performed. The results confirmed the phytotoxic potential of this plant, which had not been investigated until now.
Assuntos
Asteraceae/química , Agentes de Controle Biológico/toxicidade , Diterpenos/toxicidade , Flavonas/toxicidade , Herbicidas/toxicidade , Plantas Daninhas/efeitos dos fármacos , Controle de Plantas Daninhas/métodos , Bioensaio , Agentes de Controle Biológico/química , Agentes de Controle Biológico/isolamento & purificação , Produtos Agrícolas/crescimento & desenvolvimento , Diterpenos/química , Diterpenos/isolamento & purificação , Flavonas/química , Flavonas/isolamento & purificação , Herbicidas/química , Herbicidas/isolamento & purificação , Humanos , Estrutura Molecular , Extratos Vegetais/química , Folhas de Planta/química , Plantas Daninhas/crescimento & desenvolvimentoRESUMO
PURPOSE: Total flavone of Abelmoschus manihot (TFA), the effective constituents extracted from Flos Abelmoschus Manihot, has been reported to inhibit inflammation. However, the effect of TFA on ulcerative colitis (UC) progression in patients with depression is unknown. The purpose of our research was to explore the anti-UC effects of TFA in the context of depression in mice with UC by regulating the gut microbiota to drive the intestinal barrier. METHODS: In this study, chronic stress (CS) and dextran sodium sulfate (DSS) were used to induce depression and UC, respectively, in C57BL/6J mice. Fecal microbiota transplantation (FMT) was used to evaluate how treating mice modeling UC and depression with TFA effected their gut microbiota. RESULTS: Our results showed that TFA effectively improved UC aggravated by CS. In addition, TFA treatment improved the depression-like phenotype, the disturbed gut microbiota, and the intestinal barrier function in CS mice. It is worth noting that FMT from the CS mice to the receptor group further aggravated the damage of the intestinal barrier and the disturbance of the gut microbiota in the recipient DSS mice, thus further aggravating UC, however, treatment of the intervention of TFA in the CS fecal microbiota transplant with TFA also played its therapeutic outcome. CONCLUSION: Taken together, our results show that CS disrupts the gut microbiota, triggers intestinal barrier injury and aggravates DSS colitis, while TFA is a promising drug for the treatment of UC in patients with depression.
Assuntos
Abelmoschus/química , Colite Ulcerativa/tratamento farmacológico , Depressão/tratamento farmacológico , Flavonas/farmacologia , Animais , Colite Ulcerativa/fisiopatologia , Sulfato de Dextrana , Modelos Animais de Doenças , Transplante de Microbiota Fecal , Flavonas/isolamento & purificação , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológicoRESUMO
We measured and studied the growth parameters and the qualitative and quantitative composition of the flavones of hairy roots of the Scutellaria genus: S. lateriflora, S. przewalskii and S. pycnoclada. Hairy roots were obtained using wild-type Agrobacterium rhizogenes A4 by co-cultivation of explants (cotyledons) in a suspension of Agrobacterium. The presence of the rol-genes was confirmed by PCR analysis. The hairy roots of the most studied plant from the Scutellaria genus, S. baicalensis, were obtained earlier and used as a reference sample. HPLC-MS showed the predominance of four main flavones (baicalin, baicalein, wogonin and wogonoside) in the methanol extracts of the studied hairy roots. In addition to the four main flavones, the other substances which are typical to the aerial part of plants were found in all the extracts: apigenin, apigetrin, scutellarin and chrysin-7-O-ß-d-glucuronide. According to the total content of flavones, the hairy roots of the studied skullcaps form the following series: S. przewalskii (33 mg/g dry weight) > S. baicalensis (17.04 mg/g dry weight) > S. pycnoclada (12.9 mg/g dry weight) > S. lateriflora (4.57 mg/g dry weight). Therefore, the most promising producer of anti-coronavirus flavones is S. przewalskii.
Assuntos
Antivirais/química , Flavonas/química , Scutellaria/química , Agrobacterium/crescimento & desenvolvimento , Agrobacterium/metabolismo , Antivirais/isolamento & purificação , Antivirais/farmacologia , Cromatografia Líquida de Alta Pressão , Flavonas/isolamento & purificação , Flavonas/farmacologia , Células Vegetais/metabolismo , Extratos Vegetais/química , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Scutellaria/crescimento & desenvolvimento , Scutellaria/metabolismo , Espectrometria de Massas em TandemRESUMO
Soapberry (Sapindus mukorossi Gaertn.) is a multi-functional tree with widespread application in toiletries, biomedicine, biomass energy, and landscaping. The pericarp of soapberry can be used as a medicine or detergent. However, there is currently no systematic study on the chemical constituents of soapberry pericarp during fruit development and ripening, and the dynamic changes in these constituents still unclear. In this study, a non-targeted metabolomics approach using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was used to comprehensively profile the variations in metabolites in the soapberry pericarp at eight fruit growth stages. The metabolome coverage of UHPLC-HRMS on a HILIC column was higher than that of a C18 column. A total of 111 metabolites were putatively annotated. Principal component analysis and hierarchical clustering analysis of pericarp metabolic composition revealed clear metabolic shifts from early (S1-S2) to late (S3-S5) development stages to fruit ripening stages (S6-S8). Furthermore, pairwise comparison identified 57 differential metabolites that were involved in 18 KEGG pathways. Early fruit development stages (S1-S2) were characterized by high levels of key fatty acids, nucleotides, organic acids, and phosphorylated intermediates, whereas fruit ripening stages (S6-S8) were characterized by high contents of bioactive and valuable metabolites, such as troxipide, vorinostat, furamizole, alpha-tocopherol quinone, luteolin, and sucrose. S8 (fully developed and mature stage) was the most suitable stage for fruit harvesting to utilize the pericarp. To the best of our knowledge, this was the first metabolomics study of the soapberry pericarp during whole fruit growth. The results could offer valuable information for harvesting, processing, and application of soapberry pericarp, as well as highlight the metabolites that could mediate the biological activity or properties of this medicinal plant.
Assuntos
Frutas/química , Redes e Vias Metabólicas/fisiologia , Metaboloma , Metabolômica/métodos , Sapindus/química , Ácidos Carboxílicos/classificação , Ácidos Carboxílicos/isolamento & purificação , Ácidos Carboxílicos/metabolismo , Cromatografia Líquida de Alta Pressão , Ácidos Graxos/classificação , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/metabolismo , Flavonas/classificação , Flavonas/isolamento & purificação , Flavonas/metabolismo , Frutas/metabolismo , Nucleotídeos/classificação , Nucleotídeos/isolamento & purificação , Nucleotídeos/metabolismo , Análise de Componente Principal , Quinonas/classificação , Quinonas/isolamento & purificação , Quinonas/metabolismo , Sapindus/metabolismo , Saponinas/classificação , Saponinas/isolamento & purificação , Saponinas/metabolismoRESUMO
Centaurothamnus maximus (family Asteraceae), is a leafy shrub indigenous to the southwestern Arabian Peninsula. With a paucity of phytochemical data on this species, we set out to chemically characterize the plant. From the aerial parts, two newly identified guaianolides were isolated: 3ß-hydroxy-4α(acetoxy)-4ß(hydroxymethyl)-8α-(4-hydroxy methacrylate)-1αH,5αH, 6αH-gual-10(14),11(13)-dien-6,12-olide (1) and 15-descarboxy picrolide A (2). Seven previously reported compounds were also isolated: 3ß, 4α, 8α-trihydroxy-4-(hydroxymethyl)-lαH, 5αH, 6ßH, 7αH-guai-10(14),11(13)-dien-6,12-olide (3), chlorohyssopifolin B (4), cynaropikrin (5), hydroxyjanerin (6), chlorojanerin (7), isorhamnetin (8), and quercetagetin-3,6-dimethyl ether-4'-O-ß-d-pyranoglucoside (9). Chemical structures were elucidated using spectroscopic techniques, including High Resolution Fast Atom Bombardment Mass Spectrometry (HR-FAB-MS), 1D NMR; 1H, 13C NMR, Distortionless Enhancement by Polarization Transfer (DEPT), and 2D NMR (1H-1H COSY, HMQC, HMBC) analyses. In addition, a biosynthetic pathway for compounds 1-9 is proposed. The chemotaxonomic significance of the reported sesquiterpenoids and flavonoids considering reports from other Centaurea species is examined.
Assuntos
Asteraceae/química , Lactonas/isolamento & purificação , Sesquiterpenos de Guaiano/isolamento & purificação , Vias Biossintéticas , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Flavonas/química , Flavonas/isolamento & purificação , Lactonas/química , Conformação Molecular , Espectroscopia de Prótons por Ressonância Magnética , Sesquiterpenos de Guaiano/químicaRESUMO
The bioassay-guided fractionation of a CHCl3-MeOH extract from the stems of Cissus trifoliata identified an active fraction against PC3 prostate cancer cells. The treatment for 24 h showed an 80% reduction in cell viability (p ≤ 0.05) by a WST-1 assay at a concentration of 100 µg/mL. The HPLC-QTOF-MS analysis of the fraction showed the presence of coumaric and isoferulic acids, apigenin, kaempferol, chrysoeriol, naringenin, ursolic and betulinic acids, hexadecadienoic and octadecadienoic fatty acids, and the stilbene resveratrol. The exposure of PC3 cells to resveratrol (IC25 = 23 µg/mL) for 24 h induced significant changes in 847 genes (Z-score ≥ ±2). The functional classification tool of the DAVID v6.8 platform indicates that the underlying molecular mechanisms against the proliferation of PC3 cells were associated (p ≤ 0.05) with the process of differentiation and metabolism. These findings provide experimental evidence suggesting the potential of C. trifoliata as a promising natural source of anticancer compounds.
Assuntos
Antineoplásicos Fitogênicos/química , Proliferação de Células/efeitos dos fármacos , Cissus/química , Proteínas de Neoplasias/genética , Transcriptoma , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apigenina/química , Apigenina/isolamento & purificação , Apigenina/farmacologia , Bioensaio , Sobrevivência Celular/efeitos dos fármacos , Flavanonas/química , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Flavonas/química , Flavonas/isolamento & purificação , Flavonas/farmacologia , Perfilação da Expressão Gênica , Humanos , Quempferóis/química , Quempferóis/isolamento & purificação , Quempferóis/farmacologia , Masculino , Análise em Microsséries , Proteínas de Neoplasias/classificação , Proteínas de Neoplasias/metabolismo , Células PC-3 , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/química , Resveratrol/química , Resveratrol/isolamento & purificação , Resveratrol/farmacologia , Ácido BetulínicoRESUMO
Combretum quadrangulare Kurz is widely used in folk medicine in Eastern Asia and is associated with various ethnopharmacological properties including hepatoprotective, antipyretic, analgesic, antidysenteric, and anthelmintic activities. Previous phytochemical investigations reported the presence of numerous triterpenes (mostly cycloartanes, ursanes, lupanes, and oleananes) along with dozens of flavonoids. However, the extracts of C. quadrangulare and isolated flavonoids have not been evaluated for their alpha-glucosidase inhibition. In the frame of our efforts dedicated to the chemical investigation of Vietnamese medicinal plants and their biological activities, a phytochemical study of the MeOH extract of the leaves of C. quadrangulare using bioactive guided isolation was undertaken. In this paper, the isolation and structure elucidation of twelve known compounds, 5-hydroxy-3,7,4'-trimethoxyflavone (1), ayanin (2), kumatakenin (3), rhamnocitrin (4), ombuin (5), myricetin-3,7,3',5'-tetramethyl ether (6), gardenin D (7), luteolin (12), apigenin (13), mearnsetin (14), isoorientin (15), and vitexin (16) were reported. Bromination was applied to compounds 2 and 3 to provide four new synthetic analogues 8-11. All isolated and synthesized compounds were evaluated for alpha-glucosidase inhibition and antibacterial activity. Compounds 4 and 5 showed moderate antibacterial activity against methicillin-resistant Staphylococcus aureus while others were inactive. All compounds failed to reveal any activity toward extended spectrum beta-lactamase-producing Escherichia coli. Compounds 2, 4, 6-9, and 11-14 showed good alpha-glucosidase inhibition with IC50 values in the range of 30.5-282.0 µM. The kinetic of enzyme inhibition showed that 8 and 11 were noncompetitive type inhibition against alpha-glucosidase. In silico molecular docking model indicated that compounds 8 and 11 were potential inhibitors against enzyme α-glucosidase.
Assuntos
Combretum/química , Flavonas/química , Flavonas/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Relação Dose-Resposta a Droga , Flavonas/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Ligação de Hidrogênio , Ligantes , Modelos Moleculares , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Compostos Fitoquímicos/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Six flavonoids were identified and isolated from the ethanolic extract of Alternanthera tenella Colla (Amaranthaceae) whole plant (EEAT) including 2â³-O-ß-D-glucopyranosyl-vitexin (A19). Flavonoids have anti-inflammatory activity; however, the 2â³-O-ß-D-glucopyranosyl-vitexin anti-inflammatory property was not totally explored. The aim of the present study was to investigate the anti-inflammatory effects of ethanolic extract from A. tenella whole plant and isolated flavone C-glycoside A19 in models of inflammation. The oral administration (p.o.) of EEAT (30, 100, and 300 mg/kg), A19 (0.1, 1, and 10 mg/kg), and prednisolone (3 mg/kg) were tested against the carrageenan-induced paw edema in Swiss mice. The EEAT (100 mg/kg, p.o.), A19 (1 mg/kg, p.o.), and prednisolone (3 mg/kg, p.o.) were tested in the zymosan-articular inflammation, carrageenan-pleurisy, and complete Freund's adjuvant (CFA) models in Swiss mice. In silico analysis and search for structural relationships between vitexin derivatives flavones present in the EEAT and TNF-α inhibitors were performed. EEAT, A19, and prednisolone significantly inhibited (i) edema, mechanical hyperalgesia in carrageenan-induced paw inflammation; (ii) leukocyte migration and protein extravasation in carrageenan-induced pleurisy; (iii) knee edema, mechanical hyperalgesia, and leukocyte migration in articular inflammation induced by zymosan. Still the CFA induced the increase in myeloperoxidase and N-acetylglucosaminidase activities, EEAT, A19, and prednisolone significantly inhibited these enzymes. The in silico analysis showed that molecules with similar structure to apigenin and vitexin have a potential inhibition on the TNF system. This study confirms the anti-inflammatory properties of EEAT and A19. The C-glycosylated flavone A19 could be responsible for the EEAT anti-edematogenic and anti-hyperalgesic effects and a potential TNF-α inhibitor.
Assuntos
Amaranthaceae , Anti-Inflamatórios/uso terapêutico , Etanol/uso terapêutico , Flavonas/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Relação Dose-Resposta a Droga , Edema/tratamento farmacológico , Edema/patologia , Feminino , Flavonas/química , Flavonas/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Componentes Aéreos da Planta , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificaçãoRESUMO
Three new guaianolide lactones (1-3) and four new 9-oxonerolidol glucosides (5-8) together with 20 known compounds were isolated from the MeOH extract of the flowers of Chrysanthemum indicum. Their structures were elucidated based on the interpretation of NMR, HRESIMS, and electronic circular dichroism (ECD) data along with acid hydrolysis. Of the isolates, sesquiterpenoids 1-4 and 15 and flavones 17 and 18 exhibited inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 cells with IC50 values in the range 0.2-27.0 µM.
Assuntos
Anti-Inflamatórios/farmacologia , Chrysanthemum/química , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Flavonas/isolamento & purificação , Flavonas/farmacologia , Flores/química , Glucosídeos/isolamento & purificação , Lactonas/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Células RAW 264.7 , República da Coreia , Sesquiterpenos/isolamento & purificaçãoRESUMO
Phellinus Quél is one of the largest genera of Hymenochaetaceae, which is comprised of about 220 species. Most Phellinus macro-fungi are perennial lignicolous mushrooms, which are widely distributed on Earth. Some Phellinus fungi are historically recorded as traditional medicines used to treat various diseases in eastern Asian countries, especially China, Japan and Korean. Previous phytochemical studies have revealed that Phellinus fungi produce diverse secondary metabolites, which mainly contain polysaccharides, flavones, coumarins, terpenes, steroids, and styrylpyranones. Pharmacological documents have demonstrated that Phellinus mushrooms and their compounds have a variety of bioactivities, such as anti-tumor, immunomodulation, anti-oxidative and anti-inflammation, anti-diabetes, neuro-protection, and anti-viral effects. This review surveys the literature reporting the isolation, characterization, and bioactivities of secondary metabolites from the fungi of the genus Phellinus, focusing on studies published in the literature up to April 2020. Herein, a total of more than 300 compounds from 13 Phellinus species and their isolation, characterization, chemistry, pharmacological activities, and relevant molecular mechanisms are comprehensively summarized.
Assuntos
Flavonas , Phellinus/química , Polifenóis , Polissacarídeos , Esteroides , Terpenos , Anti-Inflamatórios , Antineoplásicos , Antioxidantes , Antivirais , Flavonas/química , Flavonas/isolamento & purificação , Flavonas/farmacologia , Carpóforos/química , Hipoglicemiantes , Medicina Tradicional , Estrutura Molecular , Phellinus/metabolismo , Polifenóis/química , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Polissacarídeos/farmacologia , Esteroides/química , Esteroides/isolamento & purificação , Esteroides/farmacologia , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
Retinal pigment epithelium (RPE) cell dysfunction caused by excessive oxidative damage is partly involved in age-related macular degeneration, which is among the leading causes of visual impairment in elderly people. Here, we investigated the protective role of chrysoeriol against hydrogen peroxide (H2O2)-induced oxidative stress in RPE cells. The cellular viability, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were monitored under oxidative stress or pre-treatment with chrysoeriol. The expression levels of mitochondrial-related genes and associated transcription factors were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Moreover, the protein expression of antioxidant signal molecules was characterized by Western blot analysis. Chrysoeriol significantly increased cell viability, reduced ROS generation, and increased the occurrence of antioxidant molecules in H2O2-treated ARPE-19 cells. Additionally, mitochondrial dysfunction caused by H2O2-induced oxidative stress was also considerably diminished by chrysoeriol treatment, which reduced the mitochondrial membrane potential (MMP) and upregulated mitochondrial-associated genes and proteins. Chrysoeriol also markedly enhanced key transcription factors (Nrf2) and antioxidant-associated genes (particularly HO-1 and NQO-1). Therefore, our study confirms the protective effect of chrysoeriol against H2O2-induced oxidative stress in RPE cells, thus confirming that it may prevent mitochondrial dysfunction by upregulating antioxidant-related molecules.