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1.
Mol Biol Rep ; 51(1): 785, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951450

RESUMO

BACKGROUND: Kaempferia parviflora Wall. ex. Baker (KP) has been reported to exhibit anti-obesity effects. However, the detailed mechanism of the anti-obesity effect of KP extract (KPE) is yet to be clarified. Here, we investigated the effect of KPE and its component polymethoxyflavones (PMFs) on the adipogenic differentiation of human mesenchymal stem cells (MSCs). METHODS AND RESULTS: KPE and PMFs fraction (2.5 µg/mL) significantly inhibited lipid and triacylglyceride accumulation in MSCs; lipid accumulation in MSCs was suppressed during the early stages of differentiation (days 0-3) but not during the mid (days 3-7) or late (days 7-14) stages. Treatment with KPE and PMFs fractions significantly suppressed peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and various adipogenic metabolic factors. Treatment with KPE and PMFs fraction induced the activation of AMP-activated protein kinase (AMPK) signaling, and pretreatment with an AMPK signaling inhibitor significantly attenuated KPE- and PMFs fraction-induced suppression of lipid formation. CONCLUSIONS: Our findings demonstrate that KPE and PMFs fraction inhibit lipid formation by inhibiting the differentiation of undifferentiated MSCs into adipocyte lineages via AMPK signaling, and this may be the mechanism underlying the anti-obesity effects of KPE and PMFs. Our study lays the foundation for the elucidation of the anti-obesity mechanism of KPE and PMFs.


Assuntos
Proteínas Quinases Ativadas por AMP , Adipogenia , Diferenciação Celular , Flavonas , Células-Tronco Mesenquimais , Extratos Vegetais , Transdução de Sinais , Zingiberaceae , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Adipogenia/efeitos dos fármacos , Extratos Vegetais/farmacologia , Zingiberaceae/química , Proteínas Quinases Ativadas por AMP/metabolismo , Flavonas/farmacologia , Diferenciação Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , PPAR gama/metabolismo , PPAR gama/genética , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adipócitos/citologia , Células Cultivadas
2.
Nutrients ; 16(13)2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38999828

RESUMO

This study aimed to investigate a synergistic anti-inflammatory effect of a citrus flavonoid nobiletin and docosahexaenoic acid (DHA), one of n-3 long-chain polyunsaturated fatty acids, in combination. Simultaneous treatment with nobiletin and DHA synergistically inhibited nitric oxide production (combination index < 0.9) by mouse macrophage-like RAW 264.7 cells stimulated with lipopolysaccharide (LPS) without cytotoxicity. On the other hand, the inhibitory effect of nobiletin and DHA in combination on proinflammatory cytokine production was not synergistic. Neither nobiletin nor DHA affected the phagocytotic activity of RAW 264.7 cells stimulated with LPS. Immunoblot analysis revealed that the inhibition potency of DHA on the phosphorylation of ERK and p38 and nuclear translocation of NF-κB is markedly enhanced by simultaneously treating with nobiletin, which may lead to the synergistic anti-inflammatory effect. Overall, our findings show the potential of the synergistic anti-inflammatory effect of nobiletin and DHA in combination.


Assuntos
Anti-Inflamatórios , Ácidos Docosa-Hexaenoicos , Sinergismo Farmacológico , Flavonas , Lipopolissacarídeos , Macrófagos , Óxido Nítrico , Animais , Camundongos , Flavonas/farmacologia , Lipopolissacarídeos/farmacologia , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Óxido Nítrico/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Citocinas/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
3.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(6): 1070-1078, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38977336

RESUMO

OBJECTIVE: To investigate the protective effect of 5-hydroxy-6,7-dimethoxyflavone (5-HDF), a compound extracted from Elsholtzia blanda Benth., against lung injury induced by H1N1 influenza virus and explore its possible mechanism of action. METHODS: 5-HDF was extracted from Elsholtzia blanda Benth. using ethanol reflux extraction and silica gel chromatography and characterized using NMR and MS analyses. In an A549 cell model of H1N1 influenza virus infection (MOI=0.1), the cytotoxicity of 5-HDF was assessed using MTT assay, and its effect on TRAIL and IL-8 expressions was examined using flow cytometry; Western blotting was used to detect the expression levels of inflammatory, apoptosis, and ferroptosis-related proteins. In a mouse model of H1N1 influenza virus infection established by nasal instillation of 50 µL H1N1 virus at the median lethal dose, the effects of 30 and 60 mg/kg 5-HDF by gavage on body weight, lung index, gross lung anatomy and lung histopathology were observed. RESULTS: 5-HDF exhibited no significant cytotoxicity in A549 cells within the concentration range of 0-200 µg/mL. In H1N1-infected A549 cells, treatment with 5-HDF effectively inhibited the activation of phospho-p38 MAPK and phospho-NF-κB p65, lowered the expressions of IL-8, enhanced the expression of anti-ferroptosis proteins (SLC7A11 and GPX4), and inhibited the expressions of apoptosis markers PARP and caspase-3 and the apoptotic factor TRAIL. In H1N1-infected mice, treatment with 5-HDF for 7 days significantly suppressed body weight loss and increment of lung index and obviously alleviated lung tissue pathologies. CONCLUSION: 5-HDF offers protection against H1N1 influenza virus infection in mice possibly by suppressing H1N1-induced ferroptosis, inflammatory responses, and apoptosis via upregulating SLC7A11 and GPX4, inhibiting the activation of phospho-NF-κB p65 and phospho-p38 MAPK, and decreasing the expression of cleaved caspase3 and cleaved PARP.


Assuntos
Ferroptose , Flavonas , Inflamação , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Humanos , Células A549 , Camundongos , Animais , Ferroptose/efeitos dos fármacos , Flavonas/farmacologia , Apoptose/efeitos dos fármacos , Interleucina-8/metabolismo , Pulmão/patologia , Lamiaceae/química , Infecções por Orthomyxoviridae/tratamento farmacológico , Fator de Transcrição RelA/metabolismo , Caspase 3/metabolismo
4.
Ren Fail ; 46(2): 2375033, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38967135

RESUMO

The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS). A mouse model of CKD was constructed by 5/6 nephrectomy. Renal function was assessed by creatinine and urea nitrogen. Real-time PCR and Western Blot were performed to detect the mRNA and protein changes in kidney and cells. An in vitro fibrotic cell model was constructed by TGF-ß induction in TCMK-1 cells. The results showed that thirteen active ingredients of A&P were identified by UPLC-HR-MS, nine of which were identified by analysis with standards, among which the relative percentage of NOB was high. We found that NOB treatment significantly improved renal function, pathological damage and reduced the expression level of fibrotic factors in CKD mice. The results also demonstrated that Lgals1 was overexpressed in the interstitial kidney of CKD mice, and NOB treatment significantly reduced its expression level, while inhibiting PI3K and AKT phosphorylation. Interestingly, overexpression of Lgals1 significantly increased fibrosis in TCMK1 cells and upregulated the activity of PI3K and AKT, which were strongly inhibited by NOB treatment. NOB is one of the main active components of A&P. The molecular mechanism by which NOB ameliorates renal fibrosis in CKD may be through the inhibition of Lgals1/PI3K/AKT signaling pathway.


Assuntos
Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Fibrose , Flavonas , Rim , Panax notoginseng , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Insuficiência Renal Crônica , Transdução de Sinais , Animais , Camundongos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Panax notoginseng/química , Flavonas/farmacologia , Flavonas/uso terapêutico , Rim/patologia , Rim/efeitos dos fármacos , Astrágalo/química , Camundongos Endogâmicos C57BL , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão
5.
Oncol Rep ; 52(1)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38874019

RESUMO

2',3',4'­trihydroxyflavone (2­D08), a SUMO E2 inhibitor, has several biological functions, including anticancer activity, but its effects on uterine leiomyosarcoma (Ut­LMS) are unknown. The anticancer activity of 2­D08 was explored in an in vitro model using SK­LMS­1 and SK­UT­1B cells (human Ut­LMS cells). Treatment with 2­D08 inhibited cell viability in a dose­ and time­dependent manner and significantly inhibited the colony­forming ability of Ut­LMS cells. In SK­UT­1B cells treated with 2­D08, flow cytometric analysis revealed a slight increase in apoptotic rates, while cell cycle progression remained unaffected. Western blotting revealed elevated levels of RIP1, indicating induction of necrosis, but LC3B levels remained unchanged, suggesting no effect on autophagy. A lactate dehydrogenase (LDH) assay confirmed increased LDH release, further supporting the induction of apoptosis and necrosis by 2­D08 in SK­UT­1B cells. 2­D08­induced production of reactive oxygen species and apoptosis progression were observed in SK­LMS­1 cells. Using Ki67 staining and bromodeoxyuridine assays, it was found that 2­D08 suppressed proliferation in SK­LMS­1 cells, while treatment for 48 h led to cell­cycle arrest. 2­D08 upregulated p21 protein expression in SK­LMS­1 cells and promoted apoptosis through caspase­3. Evaluation of α­SM­actin, calponin 1 and TAGLN expression indicated that 2­D08 did not directly initiate smooth muscle phenotypic switching in SK­LMS­1 cells. Transcriptome analysis on 2­D08­treated SK­LMS­1 cells identified significant differences in gene expression and suggested that 2­D08 modulates cell­cycle­ and apoptosis­related pathways. The analysis identified several differentially expressed genes and significant enrichment for biological processes related to DNA replication and molecular functions associated with the apoptotic process. It was concluded that 2­D08 exerts antitumor effects in Ut­LMS cells by modulating multiple signaling pathways and that 2­D08 may be a promising candidate for the treatment of human Ut­LMS. The present study expanded and developed knowledge regarding Ut­LMS management and indicated that 2­D08 represents a notable finding in the exploration of fresh treatment options for such cancerous tumors.


Assuntos
Apoptose , Proliferação de Células , Leiomiossarcoma , Neoplasias Uterinas , Humanos , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/patologia , Leiomiossarcoma/metabolismo , Feminino , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/patologia , Neoplasias Uterinas/metabolismo , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Flavonas/farmacologia , Antineoplásicos/farmacologia , Ciclo Celular/efeitos dos fármacos , Autofagia/efeitos dos fármacos
6.
Cell Biochem Funct ; 42(5): e4083, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38938150

RESUMO

Multidrug resistance (MDR) during clinical chemotherapy for cancer has been considered a major obstacle to treatment efficacy. The involvement of adenosine triphosphate-binding cassette (ABC) transporters in the MDR mechanism significantly reduces the efficacy of chemotherapeutics. This study investigates the potential of morin, a dietary bioflavonoid, to overcome colchicine resistance in KBChR-8-5 MDR cells. The P-gp inhibitory activity by morin was measured by calcein-AM drug efflux assay. Western blot analysis was employed to evaluate P-gp messenger RNA and protein expressions following morin treatment. Flow cytometry analysis and acridine orange/ethidium bromide fluorescence staining were utilised to investigate the induction of apoptosis and cell cycle arrest upon treatment with morin and paclitaxel in combination. Additionally, polymerase chain reaction (PCR) array analysis was conducted to study the gene expression profiles related to MDR, apoptosis and cell cycle arrest during treatment with morin, paclitaxel or their combination. Morin exhibited a strong binding interaction with human P-gp. This was corroborated by drug efflux assays, which showed a reduction in P-gp efflux function with increasing morin concentration. Furthermore, morin and paclitaxel combination potentiated the induction of apoptosis and G2/M phase cell cycle arrest. Morin treatment significantly downregulated the gene expression of ABCB1 and P-gp membrane expressions in MDR cells. Additionally, PCR array gene expression analysis revealed that the combination treatment with morin and paclitaxel upregulated proapoptotic and cell cycle arrest genes while downregulating ABCB1 gene and antiapoptotic genes. Thus, morin effectively reversed paclitaxel resistance in KBChR-8-5 drug-resistant cancer cells and concluded that morin resensitized the paclitaxel resistance in KBChR8-5 drug-resistant cancer cells.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Apoptose , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Flavonoides , Paclitaxel , Humanos , Flavonoides/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Paclitaxel/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Linhagem Celular Tumoral , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/química , Flavonas
7.
PLoS One ; 19(6): e0291531, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38924029

RESUMO

Tangeretin (Tan), a citrus flavonoid, possesses a strong anti-tumor efficacy in various human cancers. However, the precise role of Tan in the development of esophageal squamous cell carcinoma (ESCC) remains unclear. RNA sequencing (RNA-seq) analysis was performed to observe the Tan-related genes in Tan-treated TE-1 cells. The direct relationship between GLI family zinc finger 2 (GLI2) and the promoter of glycoprotein non-metastatic melanoma protein B (GPNMB) was predicted by bioinformatics analysis and validated by luciferase reporter and chromatin immunoprecipitation (ChIP) assays. Cell survival after Tan treatment was assessed by CCK8 assay. Gene expression levels were evaluated by a qRT-PCR, western blot, or immunofluorescence method. Cell migration and invasion were detected by wound-healing and transwell assays. The function of Tan in vivo was examined using xenograft studies. Our data indicated anti-migration and anti-invasion functions of Tan in ESCC cells in vitro. Tan also diminished tumor growth in vivo. Mechanistically, Tan diminished the expression and transcriptional activity of GLI2 in ESCC cells. Silencing of GLI2 resulted in decreased expression of GPNMB by inhibiting GPNMB transcription via the binding site at the GPNMB promoter at position +(1539-1550). Moreover, Tan down-regulated GPNMB expression in ESCC cells, and re-expression of GPNMB reversed anti-migration and anti-invasion functions of Tan in ESCC cells. Our findings uncover anti-migration and anti-invasion effects of Tan in ESCC cells by down-regulating GPNMB by suppressing GLI2-mediated GPNMB transcription, providing new evidence that Tan can function as a therapeutic agent against ESCC.


Assuntos
Movimento Celular , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Flavonas , Regulação Neoplásica da Expressão Gênica , Glicoproteínas de Membrana , Proteína Gli2 com Dedos de Zinco , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/metabolismo , Proteína Gli2 com Dedos de Zinco/metabolismo , Proteína Gli2 com Dedos de Zinco/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Animais , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Linhagem Celular Tumoral , Camundongos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Flavonas/farmacologia , Movimento Celular/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Transcrição Gênica/efeitos dos fármacos , Regiões Promotoras Genéticas , Proliferação de Células/efeitos dos fármacos , Proteínas do Olho/metabolismo , Proteínas do Olho/genética , Proteínas Nucleares
8.
J Agric Food Chem ; 72(26): 14678-14683, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38910321

RESUMO

Matrix metalloproteinase 9 (MMP9), an MMP isozyme, plays a crucial role in tumor progression by degrading basement membranes. It has therefore been proposed that the pharmacological inhibition of MMP9 expression or activity could inhibit tumor metastasis. We previously isolated two novel methoxylated flavones, casedulones A and B, from the leaves and/or roots of Casimiroa edulis La Llave and determined that these casedulones have antitumor activity that acts via the reduction of MMP9. Here, we examined how these casedulones suppress lipopolysaccharide (LPS)-induced MMP9 expression in human monocytic THP-1 cells. The casedulones suppressed the LPS-induced signal transducer and activator of transcription 3 (STAT3) pathway, which participates in MMP9 induction. In addition, AG490 and S3I-201, inhibitors of Janus kinase (JAK) and STAT3, suppressed LPS-mediated MMP9 induction, suggesting that the casedulones suppressed MMP9 induction through the inhibition of JAK/STAT3 pathways. Based on the findings that cycloheximide, an inhibitor of de novo protein synthesis, completely inhibited LPS-mediated MMP9 induction, the role of de novo proteins in MMP9 induction was further investigated. We found that the casedulones inhibited the induction of interleukin-6 (IL-6), a key inflammatory cytokine that participates in STAT3 activation. Moreover, tumor necrosis factor-α (TNFα)-mediated MMP9 induction was significantly suppressed in the presence of the casedulones. Taken together, these findings suggest that casedulones inhibit the IL-6/STAT3 and TNFα pathways, which all involve LPS-mediated MMP9 induction.


Assuntos
Flavonas , Janus Quinases , Metaloproteinase 9 da Matriz , Extratos Vegetais , Fator de Transcrição STAT3 , Transdução de Sinais , Fator de Necrose Tumoral alfa , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Flavonas/farmacologia , Flavonas/química , Janus Quinases/metabolismo , Janus Quinases/genética , Transdução de Sinais/efeitos dos fármacos
9.
Eur J Pharmacol ; 977: 176705, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38830457

RESUMO

Obesity is a major health issue that contributes significantly to increased mortality and morbidity worldwide. Obesity is caused by uncontrolled adipogenesis and lipogenesis, leading to several metabolism-associated problems. Pancreatic lipase, an enzyme that breaks down dietary lipids, is a prominent target for obesity. Orlistat, a known inhibitor of pancreatic lipase, is commonly employed for the management of obesity. However, its side effects, such as diarrhoea, nausea and bladder pain, urge to look out for safer alternatives. Morin is a pentahydroxyflavone, exerts a broad spectrum of pharmacological effects including antioxidant, anti-inflammatory, lipid lowering, anti-diabetic, anti-fibrotic, anti-cancer, etc. This study investigated the effect of morin on pancreatic lipase activity, in vitro and in vivo adipogenesis. Molecular docking and simulation studies showed morin to have a higher binding affinity towards pancreatic lipase compared with orlistat, which also inhibited its activity in vitro. Morin also reduced lipid droplet accretion and downregulated the expression of adipogenic and lipogenic genes. The acute oral toxicity of morin was determined in C57BL/6 mice, where morin did not show toxicity up to 2000 mg/kg body weight dose. Oral administration of morin to high fat diet fed mice reduced body weight, glucose and insulin levels. Also, the histopathological examination revealed reduction in adipocyte size and decreased mRNA expression of adipogenesis markers in white adipose tissue of morin administered group compared to high fat diet group. Overall, the results suggested morin inhibited pancreatic lipase activity, adipogenesis and further studies are warranted to explore its therapeutic potential for obesity.


Assuntos
Adipogenia , Flavonoides , Lipase , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Animais , Adipogenia/efeitos dos fármacos , Flavonoides/farmacologia , Camundongos , Lipase/antagonistas & inibidores , Lipase/metabolismo , Masculino , Células 3T3-L1 , Dieta Hiperlipídica/efeitos adversos , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Fármacos Antiobesidade/farmacologia , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Humanos , Orlistate/farmacologia , Flavonas
10.
Anal Chem ; 96(26): 10835-10840, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38889097

RESUMO

G-quadruplex (G4) DNA is considered as a prospective therapeutic target due to its potential biological significance. To understand G4 biological roles and function, a G4-specific fluorescent probe is necessary. However, it is difficult for versatile G4 to precisely recognize without perturbing their folding dynamics. Herein, we reported that flavone P0 can be a fluorescent probe for G4 DNA-specific recognition and have developed a highly selective detection of K+ ion by dimeric G4/P0 system. When comparing various nucleic acid structures, including G4, i-motif, ss/ds-DNA, and triplex, an apparent fluorescence enhancement is observed in the presence of G4 DNA for 85-fold, but only 8-fold for non-G4 DNA. Furthermore, based on fluorescent probe of flavone P0 for G4 DNA screening, the noncovalent dimeric G4/P0 system is exploited as a K+ sensor, that selectively responds to K+ with a 513-fold fluorescence enhancement and a detection range for K+ ion concentration from 0 to 500 mM. This K+ sensor also has a remarkably anti-interference ability for other metal cations, especially for a high concentration of Na+. These results have demonstrated that flavone P0 is an efficient tool for monitoring G-quadruplex DNA and endows flavone P0 with bioanalytical and medicinal applications.


Assuntos
DNA , Flavonas , Corantes Fluorescentes , Quadruplex G , Potássio , Flavonas/química , Corantes Fluorescentes/química , Potássio/química , Potássio/análise , DNA/química , Espectrometria de Fluorescência
11.
Mol Nutr Food Res ; 68(12): e2300833, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38850176

RESUMO

SCOPE: Alcoholic liver disease (ALD) is a global public health concern. Nobiletin, a polymethoxyflavone abundant in citrus fruits, enhances circadian rhythms and ameliorates diet-induced hepatic steatosis, but its influences on ALD are unknown. This study investigates the role of brain and muscle Arnt-like protein-1 (Bmal1), a key regulator of the circadian clock, in nobiletin-alleviated ALD. METHODS AND RESULTS: This study uses chronic ethanol feeding plus an ethanol binge to establish ALD models in Bmal1flox/flox and Bmal1 liver-specific knockout (Bmal1LKO) mice. Nobiletin mitigates ethanol-induced liver injury (alanine aminotransferase [ALT]), glucose intolerance, hepatic apoptosis, and lipid deposition (triglyceride [TG], total cholesterol [TC]) in Bmal1flox/flox mice. Nobiletin fails to modulated liver injury (ALT, aspartate aminotransferase [AST]), apoptosis, and TG accumulation in Bmal1LKO mice. The expression of lipogenic genes (acetyl-CoA carboxylase alpha [Acaca], fatty acid synthase [Fasn]) and fatty acid oxidative genes (carnitine pamitoyltransferase [Cpt1a], cytochrome P450, family 4, subfamily a, polypeptide 10 [Cyp4a10], and cytochrome P450, family4, subfamily a, polypeptide 14 [Cyp4a14]) is inhibited, and the expression of proapoptotic genes (Bcl2 inteacting mediator of cell death [Bim]) is enhanced by ethanol in Bmal1flox/flox mice. Nobiletin antagonizes the expression of these genes in Bmal1flox/flox mice and not in Bmal1LKO mice. Nobiletin activates protein kinase B (PKB, also known as AKT) phosphorylation, increases the levels of the carbohydrate response element binding protein (ChREBP), ACC1, and FASN, and reduces the level of sterol-regulatory element binding protein 1 (SREBP1) and phosphorylation of ACC1 in a Bmal1-dependent manner. CONCLUSION: Nobiletin alleviates ALD by increasing the expression of genes involved in fatty acid oxidation by increasing AKT phosphorylation and lipogenesis in a Bmal1-dependent manner.


Assuntos
Fatores de Transcrição ARNTL , Flavonas , Lipogênese , Hepatopatias Alcoólicas , Camundongos Knockout , Proteínas Proto-Oncogênicas c-akt , Animais , Flavonas/farmacologia , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Hepatopatias Alcoólicas/prevenção & controle , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/tratamento farmacológico , Lipogênese/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Masculino , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Camundongos , Substâncias Protetoras/farmacologia , Etanol , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos
12.
Biochem Biophys Res Commun ; 724: 150217, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38865809

RESUMO

Neuropathy is a disturbance of function or a pathological change in nerves causing poor health and quality of life. A proportion of chronic pain patients in the community suffer persistent neuropathic pain symptoms because current drug therapies may be suboptimal so there is a need for new therapeutic modalities. This study investigated the neuroprotective flavonoid, 6-methoxyflavone (6MF), as a potential therapeutic agent and gabapentin as the standard comparator, against neuropathic models. Thus, neuropathic-like states were induced in Sprague-Dawley rats using sciatic nerve chronic constriction injury (CCI) mononeuropathy and systemic administration of streptozotocin (STZ) to induce polyneuropathy. Subsequent behaviors reflecting allodynia, hyperalgesia, and vulvodynia were assessed and any possible motoric side-effects were evaluated including locomotor activity, as well as rotarod discoordination and gait disruption. 6MF (25-75 mg/kg) antagonized neuropathic-like nociceptive behaviors including static- (pressure) and dynamic- (light brushing) hindpaw allodynia plus heat/cold and pressure hyperalgesia in the CCI and STZ models. 6MF also reduced static and dynamic components of vulvodynia in the STZ induced polyneuropathy model. Additionally, 6MF reversed CCI and STZ suppression of locomotor activity and rotarod discoordination, suggesting a beneficial activity on motor side effects, in contrast to gabapentin. Hence, 6MF possesses anti-neuropathic-like activity not only against different nociceptive modalities but also impairment of motoric side effects.


Assuntos
Flavonas , Hiperalgesia , Neuralgia , Ratos Sprague-Dawley , Animais , Ratos , Neuralgia/tratamento farmacológico , Neuralgia/etiologia , Flavonas/farmacologia , Flavonas/uso terapêutico , Hiperalgesia/tratamento farmacológico , Masculino , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Gabapentina/farmacologia , Gabapentina/uso terapêutico , Nociceptividade/efeitos dos fármacos , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/metabolismo , Feminino , Ácido gama-Aminobutírico/metabolismo , Aminas/farmacologia , Aminas/uso terapêutico , Nervo Isquiático/lesões , Nervo Isquiático/efeitos dos fármacos , Vulvodinia/tratamento farmacológico , Constrição , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico
13.
Food Chem Toxicol ; 190: 114842, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38942164

RESUMO

High levels of reactive oxygen species (ROS) have been associated with the progression of neurodegenerative diseases such as Alzheimer's disease. The activation of the NFE2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway may restore the neuron's redox balance and provide a therapeutic impact. Hydroxygenkwanin (HGK), a dominant flavone from Genkwa Flos, has received expanding attention due to its medicinal activities. Our investigation results demonstrated the ability of HGK to protect the PC12 cells from oxidative damage caused by an excessive hydrogen peroxide load. HGK also showed the ability to upregulate a panel of endogenous antioxidant proteins. Further investigations have demonstrated that the neuroprotection mechanism of HGK is dependent on the activation of the Nrf2/ARE signaling pathway. Activating the Nrf2/ARE pathway by HGK reveals a novel mechanism for understanding the pharmacological functions of HGK. These findings suggest that HGK could be considered for further development as an oxidative stress-related neurological pathologies potential therapeutic drug.


Assuntos
Elementos de Resposta Antioxidante , Fator 2 Relacionado a NF-E2 , Fármacos Neuroprotetores , Estresse Oxidativo , Transdução de Sinais , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células PC12 , Ratos , Elementos de Resposta Antioxidante/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Peróxido de Hidrogênio , Flavonas/farmacologia , Espécies Reativas de Oxigênio/metabolismo
14.
J Inorg Biochem ; 258: 112635, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38852294

RESUMO

Morin (MRN), an intriguing bioflavonol, has received increasing interest for its antioxidant properties, as have its metal complexes (Mz+-MRN). Understanding their antioxidant behavior is critical to assess their pharmaceutical, nutraceutical potential, and therapeutic impact in the design of advanced antioxidant drugs. To this end, knowing the speciation of different H+-MRN and Mz+-MRN is pivotal to understand and compare their antioxidant ability. In this work, the protonation constant values of MRN under physiological ionic strength and temperature conditions (I = 0.15 mol L-1 and t = 37 °C), determined by UV-vis spectrophotometric titrations, are introduced. Thus, a reliable speciation model on H+-MRN species in aqueous solution is presented, which exhibits five stable forms depending on pH, supplemented by quantum-mechanical calculations useful to determine the proton affinities of each functional group and corresponding deprotonation order. Furthermore, potentiometry and UV-vis spectrophotometry have been exploited to determine the thermodynamic interaction parameters of MRN with different metal cations (Mg2+, Mn2+, Zn2+, Al3+). The antioxidant ability of H+-MRN and Mz+-MRN has been evaluated by the 2,2'-diphenyl-1-benzopyran-4-one (DPPH) method, and the Zn2+-MRN system has proven to afford the most potent antioxidant effect. Ab initio molecular dynamics simulations of Mz+-MRN species at all possible chelation sites and under explicit water solvation allowed for the fine characterization not only of the metal chelation modalities of MRN in explicit water, but also of the role played by the local water environment around the metal cations. Those microscopic patterns reveal to be informative on the different antioxidant capabilities recorded experimentally.


Assuntos
Antioxidantes , Complexos de Coordenação , Flavonoides , Zinco , Flavonoides/química , Antioxidantes/química , Complexos de Coordenação/química , Zinco/química , Magnésio/química , Alumínio/química , Manganês/química , Termodinâmica , Flavonas
15.
Int J Food Microbiol ; 420: 110769, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-38823189

RESUMO

The study prepared and used eugenol nanoemulsion loaded with nobiletin as fungistat to study its antifungal activity and potential mechanism of Penicillium italicum (P. italicum). The results showed that the minimum inhibitory concentration (MIC) of eugenol nanoemulsion loaded with nobiletin (EGN) was lower than that of pure eugenol nanoemulsion (EG), which were 160 µg/mL and 320 µg/mL, respectively. At the same time, the mycelial growth inhibition rate of EGN nanoemulsion (54.68 %) was also higher than that of EG nanoemulsion (9.92 %). This indicates that EGN nanoemulsion is more effective than EG nanoemulsion. Compared with EG nanoemulsion, the treatment of EGN nanoemulsion caused more serious damage to the cell structure of P. italicum. At the same time, in vitro inoculation experiments found that EGN nanoemulsion has better control and delay the growth and reproduction of P. italicum in citrus fruits. And the results reflected that EGN nanoemulsion may be considered as potential resouces of natural antiseptic to inhibit blue mold disease of citrus fruits, because it has good antifungal activity.


Assuntos
Antifúngicos , Citrus , Emulsões , Eugenol , Flavonas , Testes de Sensibilidade Microbiana , Penicillium , Penicillium/efeitos dos fármacos , Penicillium/crescimento & desenvolvimento , Eugenol/farmacologia , Antifúngicos/farmacologia , Emulsões/farmacologia , Flavonas/farmacologia , Nanopartículas/química
16.
Elife ; 132024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856179

RESUMO

Vitamin B6 deficiency has been linked to cognitive impairment in human brain disorders for decades. Still, the molecular mechanisms linking vitamin B6 to these pathologies remain poorly understood, and whether vitamin B6 supplementation improves cognition is unclear as well. Pyridoxal 5'-phosphate phosphatase (PDXP), an enzyme that controls levels of pyridoxal 5'-phosphate (PLP), the co-enzymatically active form of vitamin B6, may represent an alternative therapeutic entry point into vitamin B6-associated pathologies. However, pharmacological PDXP inhibitors to test this concept are lacking. We now identify a PDXP and age-dependent decline of PLP levels in the murine hippocampus that provides a rationale for the development of PDXP inhibitors. Using a combination of small-molecule screening, protein crystallography, and biolayer interferometry, we discover, visualize, and analyze 7,8-dihydroxyflavone (7,8-DHF) as a direct and potent PDXP inhibitor. 7,8-DHF binds and reversibly inhibits PDXP with low micromolar affinity and sub-micromolar potency. In mouse hippocampal neurons, 7,8-DHF increases PLP in a PDXP-dependent manner. These findings validate PDXP as a druggable target. Of note, 7,8-DHF is a well-studied molecule in brain disorder models, although its mechanism of action is actively debated. Our discovery of 7,8-DHF as a PDXP inhibitor offers novel mechanistic insights into the controversy surrounding 7,8-DHF-mediated effects in the brain.


Vitamin B6 is an important nutrient for optimal brain function, with deficiencies linked to impaired memory, learning and mood in various mental disorders. In older people, vitamin B6 deficiency is also associated with declining memory and dementia. Although this has been known for years, the precise role of vitamin B6 in these disorders and whether supplements can be used to treat or prevent them remained unclear. This is partly because vitamin B6 is actually an umbrella term for a small number of very similar and interchangeable molecules. Only one of these is 'bioactive', meaning it has a biological role in cells. However, therapeutic strategies aimed at increasing only the bioactive form of vitamin B6 are lacking. Previous work showed that disrupting the gene for an enzyme called pyridoxal phosphatase, which breaks down vitamin B6, improves memory and learning in mice. To investigate whether these effects could be mimicked by drug-like compounds, Brenner, Zink, Witzinger et al. used several biochemical and structural biology approaches to search for molecules that bind to and inhibit pyridoxal phosphatase. The experiments showed that a molecule called 7,8-dihydroxyflavone ­ which was previously found to improve memory and learning in laboratory animals with brain disorders ­ binds to pyridoxal phosphatase and inhibits its activity. This led to increased bioactive vitamin B6 levels in mouse brain cells involved in memory and learning. The findings of Brenner et al. suggest that inhibiting pyridoxal phosphatase to increase vitamin B6 levels in the brain could be used together with supplements. The identification of 7,8-dihydroxyflavone as a promising candidate drug is a first step in the discovery of more efficient pyridoxal phosphatase inhibitors. These will be useful experimental tools to directly study whether increasing the levels of bioactive vitamin B6 in the brain may help those with mental health conditions associated with impaired memory, learning and mood.


Assuntos
Inibidores Enzimáticos , Monoéster Fosfórico Hidrolases , Animais , Camundongos , Humanos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Monoéster Fosfórico Hidrolases/metabolismo , Monoéster Fosfórico Hidrolases/antagonistas & inibidores , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosfato de Piridoxal/metabolismo , Flavonas/farmacologia , Flavonas/metabolismo , Flavonas/química , Camundongos Endogâmicos C57BL
17.
Molecules ; 29(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38893369

RESUMO

Spinach (Spinacia oleracea) is one of the most famous vegetables worldwide, rich in essential metabolites for various health benefits. It is a valuable plant source that has the potential to be a nutraceutical. This study aimed to evaluate the single characteristic marker compound to establish the validation of HPLC-DAD methods applied to the development of a nutraceutical using spinach samples. Six metabolites (1-6) were identified from the spinach samples such as freeze-dried spinach (FDS) and spinach extract concentrate (SEC) by LC-Q-TOF/MS analysis. Among the six metabolites, 3',4',5-trihydroxy-3-methoxy-6,7-methylenedioxyflavone 4'-glucuronide (TMG) was selected as a marker compound due to its highest abundance and high selectivity. The specificity, accuracy, linearity, precision, repeatability, limit of detection (LOD), and limit of quantification (LOQ) of TMG in the spinach samples (FDS and SEC) were validated according to AOAC international guideline. The specificity was confirmed by monitoring the well separation of the marker compound from other compounds of spinach samples in the base peak intensity (BPI) and ultraviolet (UV) chromatogram. The calibration curve of TMG (15.625~500 µg/mL) had reasonable linearity (R2 = 0.999) considered with LOD and LOQ values, respectively. Recovery rate of TMG was 93-101% for FDS and 90-95% for SEC. The precision was less than 3 and 6% in the intraday and interday. As a result, the HPLC-DAD validation method of TMG in the spinach samples (FDS and SEC) was first established with AOAC and KFDA regulations for approving functional ingredients in functional foods.


Assuntos
Spinacia oleracea , Spinacia oleracea/química , Cromatografia Líquida de Alta Pressão/métodos , Glucuronídeos/análise , Glucuronídeos/química , Limite de Detecção , Reprodutibilidade dos Testes , Flavonoides/análise , Flavonoides/química , Extratos Vegetais/química , Extratos Vegetais/análise , Flavonas/análise , Flavonas/química , Padrões de Referência
18.
J Pharm Biomed Anal ; 245: 116186, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38692216

RESUMO

The inflorescences of the Mexican gordolobo are used as a folk medicine to treat various respiratory diseases. Currently, the botanical species that bear the name Mexican gordolobo belong to the genera Gnaphalium and Pseudognaphalium. Despite a long history of traditional use, most Mexican gordolobo species have never been fully chemically characterized, and the range of constituents in the species has not been comprehensively reported. To establish a quality control and chemical characterization method, a total of 49 samples belonging to 18 species of Pseudognaphalium and four species of Gnaphalium were studied. Nine flavones were quantified using a UPLC-PDA method. The method was validated in terms of linearity (R2 > 0.99), precision (intra- and inter-day: 0.1-3.9%), accuracy (96-103%), detection limit (10 ng/mL), limit of quantification (25 ng/mL) and robustness. 3-Methylquercetin, luteolin, quercetin, 3,5-dihydroxy-6,7,8-trimethoxyflavone, apigenin and gnaphaliin A were present at relatively high levels in most of the samples analyzed. The samples of P. oxyphyllum and P. liebmannii showed the highest content of the 9 compounds analyzed. Whereas the samples of the 5 species of Gnaphalium showed the lowest levels, including non-detectable, of the 9 compounds quantified. This marks an important difference with Pseudognaphalium species. Furthermore, using UHPLC-ESI-QToF data with targeted and non-targeted approaches, 57 compounds, were identified in Mexican gordolobo samples. Flavonoids were the main group of compounds found in Mexican gordolobo.


Assuntos
Flavonas , Gnaphalium , Extratos Vegetais , Cromatografia Líquida de Alta Pressão/métodos , Flavonas/análise , Flavonas/química , Gnaphalium/química , Extratos Vegetais/química , Extratos Vegetais/análise , Limite de Detecção , Reprodutibilidade dos Testes , México , Controle de Qualidade , Medicina Tradicional/métodos , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massas/métodos
19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(2): 236-246, 2024 Feb 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38755719

RESUMO

OBJECTIVES: Hypoxia is a common pathological phenomenon, usually caused by insufficient oxygen supply or inability to use oxygen effectively. Hydroxylated and methoxylated flavonoids have significant anti-hypoxia activity. This study aims to explore the synthesis, antioxidant and anti-hypoxia activities of 6-hydroxygenistein (6-OHG) and its methoxylated derivatives. METHODS: The 6-OHG and its methoxylated derivatives, including 4',6,7-trimethoxy-5-hydroxyisoflavone (compound 3), 4',5,6,7-tetramethoxyisoflavone (compound 4), 4',6-imethoxy-5,7-dihydroxyisoflavone (compound 6), and 4'-methoxy-5,6,7-trihydroxyisoflavone (compound 7), were synthesized by methylation, bromination, methoxylation, and demethylation using biochanin A as raw material. The structure of these products were characterized by 1hydrogen-nuclear magnetic resonance spectroscopy (1H-NMR) and mass spectrometry (MS). The purity of these compounds was detected by high pressure chromatography (HPLC). The antioxidant activity in vitro was investigated by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) free radical scavenging assay. PC12 cells were divided into a normal group, a hypoxia model group, rutin (1×10-9-1×10-5 mol/L) groups, and target compounds (1×10-9-1×10-5 mol/L) groups under normal and hypoxic conditions. Cell viability was detected by cell counting kit-8 (CCK-8) assay, the target compounds with excellent anti-hypoxia activity and the drug concentration at the maximum anti-hypoxia activity were screened. PC12 cells were treated with the optimal concentration of the target compound or rutin with excellent anti-hypoxia activity, and the cell morphology was observed under light microscope. The apoptotic rate was determined by flow cytometry, and the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were detected by Western blotting. RESULTS: The structure of 6-OHG and its 4 methylated derivatives were correct, and the purity was all more than 97%. When the concentration was 4 mmol/L, the DPPH free radical removal rates of chemical compounds 7 and 6-OHG were 81.16% and 86.94%, respectively, which were higher than those of rutin, the positive control. The removal rates of chemical compounds 3, 4, and 6 were all lower than 20%. Compared with the normal group, the cell viability of the hypoxia model group was significantly decreased (P<0.01). Compared with the hypoxia model group, compounds 3, 4, and 6 had no significant effect on cell viability under hypoxic conditions. At all experimental concentrations, the cell viability of the 6-OHG group was significantly higher than that of the hypoxia model group (all P<0.05). The cell viability of compound 7 group at 1×10-7 and 1×10-6 mol/L was significantly higher than that of the hypoxia model group (both P<0.05). The anti-hypoxia activity of 6-OHG and compound 7 was excellent, and the optimal drug concentration was 1×10-6 and 1×10-7 mol/L. After PC12 cells was treated with 6-OHG (1×10-6 mol/L) and compound 7 (1×10-7 mol/L), the cell damage was reduced, the apoptotic rate was significantly decreased (P<0.01), and the protein expression levels of HIF-1α and VEGF were significantly decreased in comparison with the hypoxia model group (both P<0.01). CONCLUSIONS: The optimized synthesis route can increase the yield of 6-OHG and obtain 4 derivatives by methylation and selective demethylation. 6-OHG and compound 7 have excellent antioxidant and anti-hypoxia activities, which are related to the structure of the A-ring ortho-triphenol hydroxyl group in the molecule.


Assuntos
Antioxidantes , Antioxidantes/farmacologia , Antioxidantes/síntese química , Ratos , Animais , Células PC12 , Metilação , Hipóxia Celular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Isoflavonas/farmacologia , Isoflavonas/síntese química , Isoflavonas/química , Flavonas/farmacologia
20.
Microb Genom ; 10(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38785231

RESUMO

The genus Catenibacillus (family Lachnospiraceae, phylum Bacillota) includes only one cultivated species so far, Catenibacillus scindens, isolated from human faeces and capable of deglycosylating dietary polyphenols and degrading flavonoid aglycones. Another human intestinal Catenibacillus strain not taxonomically resolved at that time was recently genome-sequenced. We analysed the genome of this novel isolate, designated Catenibacillus decagia, and showed its ability to deglycosylate C-coupled flavone and xanthone glucosides and O-coupled flavonoid glycosides. Most of the resulting aglycones were further degraded to the corresponding phenolic acids. Including the recently sequenced genome of C. scindens and ten faecal metagenome-assembled genomes assigned to the genus Catenibacillus, we performed a comparative genome analysis and searched for genes encoding potential C-glycosidases and other polyphenol-converting enzymes. According to genome data and physiological characterization, the core metabolism of Catenibacillus strains is based on a fermentative lifestyle with butyrate production and hydrogen evolution. Both C. scindens and C. decagia encode a flavonoid O-glycosidase, a flavone reductase, a flavanone/flavanonol-cleaving reductase and a phloretin hydrolase. Several gene clusters encode enzymes similar to those of the flavonoid C-deglycosylation system of Dorea strain PUE (DgpBC), while separately located genes encode putative polyphenol-glucoside oxidases (DgpA) required for C-deglycosylation. The diversity of dgpA and dgpBC gene clusters might explain the broad C-glycoside substrate spectrum of C. scindens and C. decagia. The other Catenibacillus genomes encode only a few potential flavonoid-converting enzymes. Our results indicate that several Catenibacillus species are well-equipped to deglycosylate and degrade dietary plant polyphenols and might inhabit a corresponding, specific niche in the gut.


Assuntos
Flavonoides , Microbioma Gastrointestinal , Polifenóis , Humanos , Polifenóis/metabolismo , Flavonoides/metabolismo , Genoma Bacteriano , Genômica , Flavonas/metabolismo , Glicosídeos/metabolismo , Filogenia , Fezes/microbiologia , Glicosilação , Xantonas/metabolismo
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