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1.
Molecules ; 27(16)2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-36014582

RESUMO

The Broussonetia genus (Moraceae), recognized for its value in many Chinese traditional herbs, mainly includes Broussonetia papyrifera (L.) L'Hér. ex Vent. (BP), Broussonetia kazinoki Siebold (BK), and Broussonetia luzonica (Blanco) Bureau (BL). Hitherto, researchers have found 338 compounds isolated from BP, BK, and BL, which included flavonoids, polyphenols, phenylpropanoids, alkaloids, terpenoids, steroids, and others. Moreover, its active compounds and extracts have exhibited a variety of pharmacological effects such as antitumor, antioxidant, anti-inflammatory, antidiabetic, anti-obesity, antibacterial, and antiviral properties, and its use against skin wrinkles. In this review, the phytochemistry and pharmacology of Broussonetia are updated systematically, after its applications are first summarized. In addition, this review also discusses the limitations of investigations and the potential direction of Broussonetia. This review can help to further understand the phytochemistry, pharmacology, and other applications of Broussonetia, which paves the way for future research.


Assuntos
Alcaloides , Broussonetia , Moraceae , Broussonetia/química , Etnofarmacologia , Flavonoides/farmacologia , Compostos Fitoquímicos/química , Extratos Vegetais/química
2.
Molecules ; 27(6)2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35335241

RESUMO

Broussonetia kazinoki has been used as a traditional medicine for the treatment of burns and acne, and its extracts have been found to show tyrosinase inhibitory and anticancer activities. In this study, the tyrosinase inhibitory and cytotoxic activities of B. kazinoki were explored, leading to the isolation of kazinol C (1), kazinol E (2), kazinol F (3), broussonol N (4), and kazinol X (5), of which the compounds 4 and 5 have not been previously reported. Microbial transformation has been recognized as an efficient tool to generate more active metabolites. Microbial transformation of the major compounds 1 and 3 was conducted with Mucor hiemalis, where four glucosylated metabolites (6-9) were produced from 1, while one hydroxylated (10) and one glucosylated (11) metabolites were obtained from 3. Structures of the isolated metabolites were determined by extensive spectroscopic analyses. All compounds were evaluated for their tyrosinase inhibitory and cytotoxic activities. Compound 3 and its metabolites, kazinol Y (10) and kazinol F-4″-O-ß-d-glucopyranoside (11), exhibited the most potent tyrosinase inhibitory activities with the IC50 values ranging from 0.71 to 3.36 µM. Meanwhile, none of the metabolites, except for kazinol C-2',3″-di-O-ß-d-glucopyranoside (7), showed moderate cytotoxic activities (IC50 17.80 to 24.22 µM) against A375P, B16F10 and B16F1 cell lines.


Assuntos
Broussonetia , Broussonetia/química , Flavonoides/química , Monofenol Mono-Oxigenase
3.
Molecules ; 26(11)2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34204142

RESUMO

Broussonetia papyrifera is a multifunctional deciduous tree that is both a food and a source of traditional Chinese medicine for both humans and animals. Further analysis of the UGT gene family is of great significance to the utilization of B. papyrifera. The substrates of plant UGT genes include highly diverse and complex chemicals, such as flavonoids and terpenes. In order to deepen our understanding of this family, a comprehensive analysis was performed. Phylogenetic analysis showed that 155 BpUGTs were divided into 15 subgroups. A conserved motif analysis showed that BpUGT proteins in the same subgroups possessed similar motif structures. Tandem duplication was the primary driving force for the expansion of the BpUGT gene family. The global promoter analysis indicated that they were associated with complex hormone regulatory networks and the stress response, as well as the synthesis of secondary metabolites. The expression pattern analysis showed that the expression level of BpUGTs in leaves and roots was higher than that in fruits and stems. Next, we determined the composition and content of flavonoids, the main products of the BpUGT reaction. A total of 19 compounds were isolated and analyzed by UPLC-ESI-MS/MS in 3 species of Broussonetia including B. kazinoki, B. papyrifera, and B. kazinoki × B. papyrifera, and the number of compounds was different in these 3 species. The total flavonoid content and antioxidant capacities of the three species were analyzed respectively. All assays exhibited the same trend: the hybrid paper mulberry showed a higher total flavonoid content, a higher total phenol content and higher antioxidant activity than the other two species. Overall, our study provides valuable information for understanding the function of BpUGTs in the biosynthesis of flavonoids.


Assuntos
Broussonetia/química , Flavonoides/isolamento & purificação , Glicosiltransferases/genética , Broussonetia/genética , Evolução Molecular , Regulação da Expressão Gênica de Plantas , Glicosiltransferases/classificação , Glicosiltransferases/metabolismo , Família Multigênica , Filogenia , Folhas de Planta/química , Folhas de Planta/genética , Proteínas de Plantas/classificação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/química , Raízes de Plantas/genética , Distribuição Tecidual
4.
Int J Biol Macromol ; 174: 61-68, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33493569

RESUMO

This study was to assess the possibility of using competitive and slow binding experiments with affinity-based ultrafiltration UPLC-QTof-MS analysis to identify potent bacterial neuraminidase (bNA) inhibitors from the Broussonetia papyrifera roots extract. To isolate unbound compounds from the enzyme-binding complex, the root bark extracts were either incubated in the absence of bNA, in the presence of bNA, or with the time-dependent bNA before the ultrafiltration was performed. Thirteen flavonoids were separated from the target extract, and their inhibitory activities were tested against bNA. The isolated flavonoids exhibited potent inhibition against NA (IC50 = 0.7-54.0 µM). Our kinetic analysis of representative active flavonoids (1, 2, and 6) showed slow and time-dependent reversible inhibition. Additionally, chalcones exhibited noncompetitive inhibition characteristics, whereas flavonols and flavans showed mixed-type behavior. The computational results supported the experimental behaviors of flavonoids 2, 6, 10, and 12, indicating that bounded to the active site, but flavonoids 6 and 10 binds near but not accurately at the active site. Although this is mixed-type inhibition, their binding can be considered competitive.


Assuntos
Broussonetia/química , Flavonoides/química , Raízes de Plantas/química , Chalcona/química , Chalconas/química , Flavonóis/química , Cinética , Neuraminidase/química , Neuraminidase/isolamento & purificação , Neuraminidase/metabolismo , Casca de Planta/química , Extratos Vegetais/química , Polifenóis/química , Prenilação/fisiologia
5.
Molecules ; 25(10)2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32429421

RESUMO

Pancreatic cancer has a high mortality rate due to poor rates of early diagnosis. One tumor suppressor gene in particular, p53, is frequently mutated in pancreatic cancer, and mutations in p53 can inactivate normal wild type p53 activity and increase expression of transcription factor forkhead box M1 (FoxM1). Overexpression of FoxM1 accelerates cellular proliferation and cancer progression. Therefore, inhibition of FoxM1 represents a therapeutic strategy for treating pancreatic cancer. Broussoflavonol B (BF-B), isolated from the stem bark of Broussonetia kazinoki Siebold has previously been shown to inhibit the growth of breast cancer cells. This study aimed to investigate whether BF-B exhibits anti-pancreatic cancer activity and if so, identify the underlying mechanism. BF-B reduced cell proliferation, induced cell cycle arrest, and inhibited cell migration and invasion of human pancreatic cancer PANC-1 cells (p53 mutated). Interestingly, BF-B down-regulated FoxM1 expression at both the mRNA and protein level. It also suppressed the expression of FoxM1 downstream target genes, such as cyclin D1, cyclin B1, and survivin. Cell cycle analysis showed that BF-B induced the arrest of G0/G1 phase. BF-B reduced the phosphorylation of extracellular signal-regulated kinase ½ (ERK½) and expression of ERK½ downstream effector c-Myc, which regulates cell proliferation. Furthermore, BF-B inhibited cell migration and invasion, which are downstream functional properties of FoxM1. These results suggested that BF-B could repress pancreatic cancer cell proliferation by inactivation of the ERK/c-Myc/FoxM1 signaling pathway. Broussoflavonol B from Broussonetia kazinoki Siebold may represent a novel chemo-therapeutic agent for pancreatic cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Broussonetia/química , Flavonóis/farmacologia , Proteína Forkhead Box M1/genética , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclina B1/genética , Ciclina B1/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Cultura em Câmaras de Difusão , Flavonóis/isolamento & purificação , Proteína Forkhead Box M1/antagonistas & inibidores , Proteína Forkhead Box M1/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Humanos , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia , Casca de Planta/química , Extratos Vegetais/química , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transdução de Sinais , Survivina/genética , Survivina/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
6.
Nutrients ; 12(3)2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32183397

RESUMO

: The chronic low-grade inflammation in adipose tissue plays a causal role in obesity-induced insulin resistance and its associated pathophysiological consequences. In this study, we investigated the effects of extracts of Broussonetia papyrifera root bark (PRE) and its bioactive components on inflammation and insulin sensitivity. PRE inhibited TNF-α-induced NF-κB transcriptional activity in the NF-κB luciferase assay and pro-inflammatory genes' expression by blocking phosphorylation of IκB and NF-κB in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-κB phosphorylation and pro-inflammatory genes' expression. Furthermore, PRE activated AMP-activated protein kinase (AMPK) and reduced lipogenic genes' expression in both adipose tissue and liver. Finally, we identified broussoflavonol B (BF) and kazinol J (KJ) as bioactive constituents to suppress pro-inflammatory responses via activating AMPK in 3T3-L1 adipocytes. Taken together, these results indicate the therapeutic potential of PRE, especially BF or KJ, in metabolic diseases such as obesity and type 2 diabetes.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo/metabolismo , Anti-Inflamatórios , Broussonetia/química , Resistência à Insulina , Casca de Planta/química , Extratos Vegetais , Raízes de Plantas/química , Transdução de Sinais/efeitos dos fármacos , Células 3T3-L1 , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Ativação Enzimática/efeitos dos fármacos , Células HEK293 , Humanos , Masculino , Camundongos , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/patologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7
7.
Sci Rep ; 10(1): 4808, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-32179776

RESUMO

Morus and Broussonetia trees are widely used as food and/or feed. Among 23 phenolics identified from leaves of five Moraceae species using UPLC-QTOF-MS/MS, 15 were screened using DPPH/ABTS-guided HPLCs, including seven weak (flavonoids with one hydroxyl on B-ring) and eight strong (four caffeoylquinic acids and four flavonoids, each with a double hydroxyl on B-ring) antioxidants. We then determined the activity and synergistic effects of individual antioxidants and a mixture of the eight strongest antioxidants using DPPH-guided HPLC. Our findings revealed that (1) flavonoid glucuronide may have a more negative effect on antioxidant activity than glucoside, and (2) other compounds in the mixture may exert a negative synergistic effect on antioxidant activity of the four flavonoids with B-ring double hydroxyls but not the four caffeoylquinic acids. In conclusion, the eight phenolics with the strongest antioxidant ability reliably represented the bioactivity of the five extracts examined in this study. Moreover, the Morus alba hybrid had more phenolic biosynthesis machinery than its cross-parent M. alba, whereas the Broussonetia papyrifera hybrid had significantly less phenolic machinery than B. papyrifera. This difference is probably the main reason for livestock preference for the hybrid of B. papyrifera over B. papyrifera in feed.


Assuntos
Antioxidantes , Broussonetia/química , Flavonoides/análise , Flavonoides/farmacologia , Moraceae/química , Fenóis/análise , Fenóis/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Árvores/química , Benzotiazóis , Compostos de Bifenilo , Cromatografia Líquida de Alta Pressão/métodos , Radicais Livres , Picratos , Relação Estrutura-Atividade , Ácidos Sulfônicos , Espectrometria de Massas em Tandem/métodos
8.
Bioorg Chem ; 92: 103233, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31518759

RESUMO

Broussonetia papyrifera has been used as a diuretic, tonic and suppressor of edema. Bioactivity-guided fractionation and metabolite investigation of root bark extracts of this plant resulted in the isolation and identification of six 1,3-diphenylpropanes (1, 2, 8, 10, 17, 20), flavanone (3), two chalcones (4, 5), five flavans (6, 11, 14-16), dihydroflavonol (7) and five flavonols (9, 12, 13, 18, 19), including five new compounds (5, 7, 8, 19, 20) that inhibit NO production in LPS-induced RAW264.7 cells. The structures of compounds 1-20 were elucidated on the basis of spectroscopic data (1D and 2D NMR, MS, MS/MS, and HRMS). In particular, compounds 3, 5, 7, 12, and 20 exhibited significant inhibitory effects on the NO, iNOS, and pro-inflammatory cytokine (TNF-α and IL-6) production. Therefore, this study suggests that the flavonoid-rich products of B. papyrifera, including the new compounds, could be valuable candidates for the development of pharmaceuticals or functional foods in the prevention and treatment of anti-inflammatory disease.


Assuntos
Anti-Inflamatórios/farmacologia , Broussonetia/química , Flavonoides/farmacologia , Casca de Planta/química , Animais , Anti-Inflamatórios/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Relação Dose-Resposta a Droga , Flavonoides/isolamento & purificação , Expressão Gênica/efeitos dos fármacos , Interleucina-6/antagonistas & inibidores , Lipopolissacarídeos , Medicina Tradicional Coreana , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/genética , Células RAW 264.7 , Fator de Necrose Tumoral alfa/antagonistas & inibidores
9.
Environ Sci Pollut Res Int ; 26(26): 27353-27361, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31325092

RESUMO

The objective of this study was to investigate whether δ13C values can be used to identify pollen specie in the atmosphere. A Burkard 7-day recording volumetric spore trap was used to collected pollens in the atmosphere in Tainan City, Taiwan, from January 2 to December 28, 2006, and a light microscope was used to identify the pollen species and concentrations. A Burkard cyclone sampler was used to collect particulate matter and an elemental analyzer with an isotope ratio mass spectrometer was used to analyze the δ13C values. Our data showed that the predominate pollen specie in the atmosphere was Broussonetia papyrifera pollen and that the annual average concentration was 27 grains/m3 (pollen season, 36; nonpollen season, 9 grains/m3). The average δ13C value was - 26.19‰ for particulate matter in the atmosphere (pollen season, - 26.00‰; nonpollen season, - 26.28‰). No significant association was observed between δ13C values and Broussonetia papyrifera pollen concentrations. However, the δ13C value in the atmosphere was associated with the levels of Broussonetia papyrifera pollen among the samples with a diameter of particulate matter smaller than 10 µm at a level lower than 40 µg/m3. In addition, the relative contribution of Broussonetia papyrifera pollen to the carbon in the atmosphere using a two end-member mixing models was found to be associated with the Broussonetia papyrifera pollen concentration. In summary, our study suggested that δ13C values can be applied in the assessment of Broussonetia papyrifera pollen specie under specific conditions in the atmosphere.


Assuntos
Poluentes Atmosféricos/análise , Ar/análise , Broussonetia/química , Isótopos de Carbono/análise , Pólen/química , Monitoramento Biológico/instrumentação , Monitoramento Biológico/métodos , Material Particulado/análise , Estações do Ano , Taiwan
10.
Zhongguo Zhong Yao Za Zhi ; 44(1): 88-94, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-30868817

RESUMO

Eleven flavonoids were isolated from the twigs of Broussonetia papyrifera by column chromatography over silica gel,ODS,MCI gel,and Sephadex LH-20,as well as RP-HPLC.Their structures were identified by spectroscopic methods including NMR,MS,UV,and IR as broupapyrin A(1),5,7,3',4'-tetrahydroxy-3-methoxy-8-geranylflavone(2),8-prenylquercetin-3-methyl ether(3),broussonol D(4),broussoflavonol B(5),uralenol(6),broussonol E(7),8-(1,1-dimethylallyl)-5'-(3-methylbut-2-enyl)-3',4',5,7-tetrahydroxyflanvonol(8),broussoflavonol E(9),4,2',4'-trihydroxychalcone(10),and butein(11).Compound 1 is a new isoprenylated flavonol.Compounds 3,6,10,and 11 were obtained from the genus Broussonetia for the first time,and 4 and 7 were firstly discovered in B.papyrifera.Compounds 1-5 and 7-9 showed significant inhibitory effects on PTP1 B with IC50 values ranging from(0.83±0.30) to(4.66±0.83) µmol·L-1.


Assuntos
Broussonetia/química , Flavonoides/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Cromatografia Líquida de Alta Pressão , Flavonoides/isolamento & purificação , Espectroscopia de Ressonância Magnética , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
11.
Environ Sci Pollut Res Int ; 26(7): 6565-6575, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30623334

RESUMO

In this study, Broussonetia papyrifera leaves collected from land near a restored manganese mine in the Hunan Province of China were converted into biochar under high-temperature anaerobic conditions, regeneration and utilization of agricultural and forest waste, and applied to the prevention of eutrophication. The physicochemical properties of the B. papyrifera biochar were characterized using Micromeritics 3Flex analyzer, scanning electron microscope (SEM), Fourier transform infrared spectrometer (FT-IR), thermogravimetric analyzer (TGA), X-ray photoelectron spectrometer (XPS), zeta potential meter (zeta), and X-ray diffraction (XRD). The effects of pH, ionic strength, coexisting ions, time, initial concentration, and temperature on the decontamination process of phosphate in water were studied. The results indicated that adsorption was enhanced under alkaline conditions. The pseudo-second-order model of adsorption kinetics was applied to illustrate the adsorption processes. The chemical adsorption reaction was the main rate-limiting step in the adsorption process. Isotherm experimental data were best fitted by the Freundlich model at 25 °C and by the Langmuir model at 35 °C. The phosphate combined with B. papyrifera biochar mainly in the forms of exchangeable phosphorus (Ex-P), Al-bound phosphorus (Al-P), and Fe-bound phosphorus (Fe-P). These results indicate that B. papyrifera biochar is a suitable candidate for the treatment of a eutrophic body of water.


Assuntos
Carvão Vegetal/química , Fosfatos/química , Poluentes Químicos da Água/química , Adsorção , Broussonetia/química , China , Cinética , Concentração Osmolar , Fosfatos/análise , Fósforo , Espectroscopia Fotoeletrônica , Pirólise , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Poluentes Químicos da Água/análise , Difração de Raios X
12.
Fitoterapia ; 130: 37-42, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30086333

RESUMO

Three new (1a/1b and 2b) and five known flavans (2a, 6a/6b, 7, and 8), one new flavan glycoside (3), and two new (4 and 5) and six known 1,3-diphenylpropanes (9-14) were isolated from the twigs of Broussonetia kazinoki. Compounds 1, 2, and 6 are scalemic mixtures, and were resolved by chiral HPLC to provide 1a/1b, 2a/2b, and 6a/6b. The structures of these compounds were elucidated by extensive spectroscopic methods, including NMR, MS, and ECD analyses. Compounds 1, 2, 5, 8, 9, 11, and 12 showed in vitro inhibition of protein tyrosine phosphatase 1B (PTP1B).


Assuntos
Broussonetia/química , Flavonoides/isolamento & purificação , Glicosídeos/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , China , Flavonoides/farmacologia , Glicosídeos/farmacologia , Estrutura Molecular , Compostos Fitoquímicos/farmacologia , Relação Estrutura-Atividade
13.
Molecules ; 23(3)2018 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-29534539

RESUMO

Excessive nitric oxide (NO) production by macrophages has been involved in inflammatory diseases. Seven polyphenols (1-7) were isolated from Broussonetia kazinoki (B. kazinoki) and investigated as potential inhibitors of NO overproduction in lipopolysaccharide (LPS)-activated RAW 264.7 cells. Among them, four prenylated polyphenols (2-4 and 6) with a catechol moiety efficiently suppressed the LPS-induced high level of NO with IC50 values of less than 6 µM. The compounds 2-4 and 6 also attenuated protein and mRNA levels of inducible nitric oxide synthase (iNOS). Moreover, they suppressed the nuclear factor κB (NF-κB) activity by inhibiting the degradation of inhibitory-κB-α (I-κB-α) and the translocation of NF-κB into the nucleus in LPS-activated macrophages. Taken together, these findings suggest that polyphenols from B. kazinoki might be beneficial for treatment of inflammatory diseases.


Assuntos
Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Broussonetia/química , Óxido Nítrico/metabolismo , Polifenóis/isolamento & purificação , Polifenóis/farmacologia , Animais , Antioxidantes/química , Regulação para Baixo , Lipopolissacarídeos/efeitos adversos , Camundongos , Estrutura Molecular , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Polifenóis/química , Prenilação , Transporte Proteico/efeitos dos fármacos , Células RAW 264.7
14.
Phytomedicine ; 23(12): 1462-1468, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27765366

RESUMO

BACKGROUND: Broussonetia papyrifera (B. papyrifera), also known as paper mulberry, has been used as a traditional medicine for the treatment of several diseases, including ophthalmic disorders and impotency. However, the biological activity of kazinol A (1) among flavonols isolated from B. papyrifera has not been identified. PURPOSE: We identified a candidate metabolite for anti-human bladder cancer treatment from B. papyrifera and investigated the possible molecular mechanisms underlying its cytotoxic effects in T24 and cisplatin-resistant T24R2 human bladder cancer cells. METHODS: T24 and T24R2 cells were treated with five flavonols from B. papyrifera and their cytotoxic effects were determined using MTT assay, cell cycle analysis, mitochondrial membrane potential, and propidium iodide staining. Autophagy rate was calculated by counting LC3-GFP dots in the cells. All related protein expressions were analyzed by immunoblotting. RESULTS: Compound 1 showed relatively higher cytotoxicity in the human bladder cancer cells, T24 and T24R2, rather than other tissues-originated cancer cells. Compound 1 significantly attenuated cell growth through G0/1 arrest mediated by a decrease in cyclin D1 and an increase of p21. Apoptosis and autophagy induced by compound 1 treatment was accompanied by a modulation of the AKT-BAD pathway and AMPK-mTOR pathway, respectively. CONCLUSIONS: Our results suggest that compound 1 induces cytotoxic effects in human bladder cancer cells, including the cisplatin-resistant T24R2. Compound 1 may be a candidate for the development of effective anti-cancer drug on human urinary bladder cancer.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Broussonetia/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Bexiga Urinária/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Humanos , Extratos Vegetais/farmacologia , Bexiga Urinária/patologia
15.
Fitoterapia ; 112: 90-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27223849

RESUMO

In this study, we evaluated the insulin-sensitizing effect of flavans purified from Broussonetia kazinoki Siebold (BK) on 3T3-L1 adipocytes. Among the tested compounds, kazinol B enhanced intracellular lipid accumulation, gene expression of proliferator-activated receptorγ (PPARγ) and CCAAT/enhancer binding protein-alpha (C/EBPα), and consistently induced PPARγ transcriptional activation. To further investigate the insulin-sensitizing effect of kazinol B, we measured glucose analogue uptake by fully differentiated adipocytes and myotubes. Kazinol B increased 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG) uptake by cells by upregulating the gene expression and translocation of glucose transporter 4 (GLUT-4) into the plasma membrane in adipocytes. Kazinol B stimulated the gene expression and secretion of adiponectin, which is associated with a low risk of types 1 and 2 diabetes mellitus. We also suggested the mechanism of the antidiabetic effect of kazinol B by assaying Akt and AMP-activated protein kinase (AMPK) phosphorylation. In conclusion, kazinol B isolated from BK improved insulin sensitivity by enhancing glucose uptake via the insulin-Akt signaling pathway and AMPK activation. These results suggest that kazinol B might be a therapeutic candidate for diabetes mellitus.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Broussonetia/química , Flavonoides/farmacologia , Resistência à Insulina , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células 3T3-L1 , 4-Cloro-7-nitrobenzofurazano/análogos & derivados , 4-Cloro-7-nitrobenzofurazano/metabolismo , Adipócitos/efeitos dos fármacos , Adiponectina/metabolismo , Animais , Desoxiglucose/análogos & derivados , Desoxiglucose/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Hipoglicemiantes/farmacologia , Camundongos , PPAR gama/metabolismo , Fosforilação , Transdução de Sinais/efeitos dos fármacos
16.
Oncol Rep ; 33(1): 223-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25394483

RESUMO

Kazinol C is a 1,3-diphenylpropane, obtained from Broussonetia kazinoki, that has been employed in folk medicine as an edema suppressant. It exerts beneficial effects in oxidative stress-related diseases, such as cancer. However, the molecular mechanism involved in the anticancer effects remains to be determined. AMP-activated protein kinase (AMPK) has emerged as a possible anticancer target molecule. The present study investigated the effect of kazinol C on AMPK activation as well as subsequent HT-29 colon cancer cell viability, apoptosis and migration. Kazinol C markedly induced AMPK phosphorylation and significantly attenuated HT-29 colon cancer cell growth and viability. Compound C, as a well­known AMPK inhibitor, blocked the kazinol C-induced cell death, and stable transduction of dominant-negative (DN) AMPK in colon cancer cells also inhibited kazinol C-induced cell apoptosis. In addition, kazinol C inhibited HT-29 cell migration and anchorage-independent growth. AMPK inhibition using stable transduction with DN AMPK significantly abrogated the kazinol C-induced inhibition of cancer cell migration. Thus, AMPK is a critical and novel regulator of kazinol C-mediated cancer cell apoptosis and inhibition of migration, suggesting that AMPK is a prime cancer target.


Assuntos
Adenilato Quinase/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Ativadores de Enzimas/farmacologia , Hemiterpenos/farmacologia , Resorcinóis/farmacologia , Apoptose , Broussonetia/química , Adesão Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ativação Enzimática , Células HT29 , Humanos
17.
Biochem Biophys Res Commun ; 456(1): 471-5, 2015 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-25482443

RESUMO

The activation of MyoD family transcription factors is critical for myogenic differentiation, which is fundamental to the regeneration of skeletal muscle after injury. Kazinol-P (KP) from Broussonetia kazinoki (B. kazinoki), a natural compound, has been reported to possess an anti-oxidant function. In a screen of natural compounds for agonists of the MyoD activity, we identified KP and examined its effect on myoblast differentiation. Consistently, KP enhanced the myotube formation, accompanied with upregulation of myogenic markers such as MHC, Myogenin and Troponin-T. KP treatment in C2C12 myoblasts led to strong activation of a key promyogenic kinase p38MAPK in a dose, and time-dependent manner. Furthermore, KP treatment enhanced the MyoD-mediated trans-differentiation of 10T1/2 fibroblasts into myoblasts. Taken together, KP promotes myogenic differentiation through activation of p38MAPK and MyoD transcription activities. Thus KP may be a potential therapeutic candidate to prevent fibrosis and improve muscle regeneration and repair.


Assuntos
Antioxidantes/farmacologia , Broussonetia/química , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Músculo Esquelético/efeitos dos fármacos , Proteína MyoD/metabolismo , Extratos Vegetais/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Diferenciação Celular , Linhagem Celular , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibrose/tratamento farmacológico , Camundongos , Desenvolvimento Muscular , Mioblastos/efeitos dos fármacos , Miogenina , Regeneração , Transdução de Sinais
18.
PLoS One ; 9(4): e94198, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24714659

RESUMO

Broussonetia papyrifera leaves (BPL) as a traditional Chinese medicine are also used in livestock feed for stimulating reproduction, adipose tissue and muscle development; however, the mechanism of their action is still unknown. Through estrogen biosynthesis-guided fractionation in human ovarian granulosa-like KGN cells, five new phenolic glycosides, broussoside A-E(1-5), along with fifteen known dietary phenolic compounds, were isolated from the n-butanol extract of BPL, and their structures were elucidated on the basis of NMR spectra analysis and chemical evidence. New compounds 3, 4, 5 and the known compounds 9 and 10 were found to potently inhibit estrogen biosynthesis in KGN cells. In addition, compounds 9, 17, 18, and 20 showed strong antioxidant activity against ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) and DPPH (1, 1'-diphenyl -2-picryl-hydrazyl radical) assays. These findings suggest that BPL may improve meat quality through the regulation of estrogen biosynthesis. Furthermore, they may be useful for the discovery of potential aromatase modulators from natural products. Finally, they could be considered as a new source for natural antioxidants.


Assuntos
Antioxidantes/farmacologia , Vias Biossintéticas/efeitos dos fármacos , Broussonetia/química , Estrogênios/metabolismo , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Antioxidantes/química , Feminino , Sequestradores de Radicais Livres , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Fenóis/química , Extratos Vegetais/química
19.
Chin J Nat Med ; 11(3): 269-73, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23725840

RESUMO

AIM: To investigate the chemical constituents from the leaves of Broussonetia papyrifera. METHODS: The chemical constituents were isolated and purified by macroporous adsorptive resin D101, silica gel, and ODS column chromatography and preparative HPLC. Their structures were elucidated on the basis of 1D and 2D NMR analyses. In addition, their cytotoxic activity against human hepatoma carcinoma cells (HepG-2) were evaluated by the MTT method. Furthermore, RP-HPLC and colorimetric methods were used for the analysis of cosmosiin and total flavonoids. RESULTS: A new lignan, together with five known compounds were obtained, and their structures were characterized as (+)-pinoresinol-4'-O-ß-D-glucopyranosyl-4″-O-ß-D-apiofuranoside (1), cosmosiin (2), luteolin-7-O-ß-D-glucopyranoside (3), liriodendrin (4), 3, 5, 4'-trihydroxy-bibenzyl-3-O-ß-D-glucoside (5), and apigenin-6-C-ß-D-glucopyranside (6). Furthermore, RP-HPLC and colorimetric methods were established for the analysis of cosmosiin and total flavonoids. CONCLUSION: Compound 1 was a new lignan, and compounds 5 and 6 were isolated for the first time from the title plant. Compounds 1, 4 and 6 showed definite activities against HepG-2, while the other compounds didn't show inhibitory effects. The optimal harvest time of B. papyrifera (L.) Vent. is September.


Assuntos
Broussonetia/química , Citotoxinas/toxicidade , Extratos Vegetais/toxicidade , Folhas de Planta/química , Proliferação de Células/efeitos dos fármacos , Citotoxinas/química , Citotoxinas/isolamento & purificação , Células Hep G2 , Humanos , Lignanas/química , Lignanas/toxicidade , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação
20.
PLoS One ; 7(2): e32021, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22389678

RESUMO

Fruits of Broussonetia papyrifera from South China were analyzed for their total chemical composition, and antioxidant activities in ethanol and aqueous extracts. In the fruit of this plant, the crude protein, crude fat and carbohydrates was 7.08%, 3.72% and 64.73% of dry weight, respectively. The crude protein, crude fat and carbohydrates were 15.71%, 20.51% and 36.09% of dry weight, respectively. Fatty acid and amino acid composition of the fruit were analyzed. Unsaturated fatty acid concentration was 70.6% of the total fatty acids. The percentage of the essential amino acids (EAAs) was 40.60% of the total amino acids. Furthermore, B. papyrifera fruit are rich in many mineral elements and vitamins. Total phenolic content was assessed using the Folin-Ciocalteau assay, whereas antioxidant activities were assessed by measuring the ability of the two extracts to scavenge DPPH radicals, inhibit peroxidation, and chelate ferric ions. Their reducing power was also assessed. Results indicated that the aqueous extract of B. papyrifera was a more potent reducing agent and radical-scavenger than the ethanol extract. GC-MS analysis of the ethanol extract showed the presence of some acid-containing compounds. The changes in total phenolic content and antioxidant capacity in B. papyrifera from four different regions grown under normal conditions were assessed. The antioxidant activity of different extracts was positively associated with their total phenolic content. These results suggest that the fruit of B. papyrifera could be used in dietary supplement preparations, or as a food additive, for nutritional gain, or to prevent oxidation in food products.


Assuntos
Antioxidantes/química , Broussonetia/química , Frutas/química , Carboidratos/química , Ácidos Graxos/química , Sequestradores de Radicais Livres/química , Oxirredução , Fenóis/química , Proteínas de Plantas/química
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