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1.
Phytother Res ; 37(9): 4092-4101, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37253375

RESUMO

Though Honokiol was known to have anti-inflammatory, antioxidant, anticancer, antithrombotic, anti-viral, metabolic, antithrombotic, and neurotrophic activities, the underlying mechanisms of Honokiol on epithelial-mesenchymal transition (EMT) mediated liver fibrosis still remain elusive so far. Anti-EMT and antifibrotic effects of Honokiol were explored in murine AML-12 hepatocyte cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, wound healing assay, Western blotting and also in CCl4-induced liver injury mouse model by immunohistochemistry. Honokiol significantly suppressed transforming growth factor ß1 (TGF-ß1)-induced EMT and migration of AML-12 cells along with decreased EMT phenotypes such as loss of cell adhesion and formation of fibroblast like mesenchymal cells in TGF-ß1-treated AML-12 cells. Consistently, Honokiol suppressed the expression of Snail and transmembrane protease serine 4 (TMPRSS4), but not p-Smad3, and activated E-cadherin in TGF-ß1-treated AML-12 cells. Additionally, Honokiol reduced the expression of ß-catenin, p-AKT, p-ERK, p-p38 and increased phosphorylation of glycogen synthase kinase 3 beta (GSK3ß) and JNK in TGF-ß1-treated AML-12 cells via TGF-ß1/nonSmad pathway. Conversely, GSK3ß inhibitor SB216763 reversed the ability of Honokiol to reduce Snail, ß-catenin and migration and activate E-cadherin in TGF-ß1-treated AML-12 cells. Also, Honokiol suppressed hepatic steatosis and necrosis by reducing the expression of TGF-ß1 and α-SMA in liver tissues of CCl4 treated mice. These findings provide scientific evidence that Honokiol suppresses EMT and hepatic fibrosis via activation of E-cadherin/GSK3ß/JNK and inhibition of AKT/ERK/p38/ß-catenin/TMPRSS4 signaling axis.


Assuntos
Leucemia Mieloide Aguda , Fator de Crescimento Transformador beta1 , Camundongos , Animais , Fator de Crescimento Transformador beta1/metabolismo , beta Catenina/metabolismo , Proteínas Proto-Oncogênicas c-akt , Glicogênio Sintase Quinase 3 beta , Transição Epitelial-Mesenquimal , Cateninas/farmacologia , Fibrinolíticos/farmacologia , Caderinas , Cirrose Hepática
2.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638959

RESUMO

Though Morusin isolated from the root of Morus alba was known to have antioxidant, anti-inflammatory, antiangiogenic, antimigratory, and apoptotic effects, the underlying antitumor effect of Morusin is not fully understood on the glycolysis of liver cancers. Hence, in the current study, the antitumor mechanism of Morusin was explored in Hep3B and Huh7 hepatocellular carcninomas (HCC) in association with glycolysis and G1 arrest. Herein, Morusin significantly reduced the viability and the number of colonies in Hep3B and Huh7 cells. Moreover, Morusin significantly increased G1 arrest, attenuated the expression of cyclin D1, cyclin D3, cyclin E, cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), and cyclin-dependent kinase 6 (CDK6) and upregulated p21 and p27 in Hep3B and Huh7 cells. Interestingly, Morusin significantly activated phosphorylation of the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) but attenuated the expression of the p-mammalian target of protein kinase B (AKT), rapamycin (mTOR), c-Myc, hexokinase 2(HK2), pyruvate kinases type M2 (PKM2), and lactate dehydrogenase (LDH) in Hep3B and Huh7 cells. Consistently, Morusin suppressed lactate, glucose, and adenosine triphosphate (ATP) in Hep3B and Huh7 cells. Conversely, the AMPK inhibitor compound C reduced the ability of Morusin to activate AMPK and attenuate the expression of p-mTOR, HK2, PKM2, and LDH-A and suppressed G1 arrest induced by Morusin in Hep3B cells. Overall, these findings suggest that Morusin exerts an antitumor effect in HCCs via AMPK mediated G1 arrest and antiglycolysis as a potent dietary anticancer candidate.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Flavonoides/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Neoplasias Hepáticas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Hexoquinase/metabolismo , Humanos , Lactato Desidrogenase 5/metabolismo , Neoplasias Hepáticas/patologia , Proteínas de Membrana/metabolismo , Morus/química , Raízes de Plantas/química , Serina-Treonina Quinases TOR/metabolismo , Hormônios Tireóideos/metabolismo , Proteínas de Ligação a Hormônio da Tireoide
3.
Phytother Res ; 35(7): 3812-3820, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33856720

RESUMO

Since the AKT/mammalian target of rapamycin (mTOR)/c-Myc signaling plays a pivotal role in the modulation of aerobic glycolysis and tumor growth, in the present study, the role of AKT/mTOR/c-Myc signaling in the apoptotic effect of Compound K (CK), an active ginseng saponin metabolite, was explored in HepG2 and Huh7 human hepatocellular carcinoma cells (HCCs). Here, CK exerted significant cytotoxicity, increased sub-G1, and attenuated the expression of pro-Poly (ADP-ribose) polymerase (pro-PARP) and Pro-cysteine aspartyl-specific protease (pro-caspase3) in HepG2 and Huh7 cells. Consistently, CK suppressed AKT/mTOR/c-Myc and their downstreams such as Hexokinase 2 (HK2) and pyruvate kinase isozymes M2 (PKM2) in HepG2 and Huh7 cells. Additionally, CK reduced c-Myc stability in the presence or absence of cycloheximide in HepG2 cells. Furthermore, AKT inhibitor LY294002 blocked the expression of p-AKT, c-Myc, HK2, PKM2, and pro-cas3 in HepG2 cells. Pyruvate blocked the ability of CK to inhibit p-AKT, p-mTOR, HK2, and pro-Cas3 in treated HepG2 cells. Overall, these findings provide evidence that CK induces apoptosis via inhibition of glycolysis and AKT/mTOR/c-Myc signaling in HCC cells as a potent anticancer candidate for liver cancer clinical translation.


Assuntos
Carcinoma Hepatocelular , Ginsenosídeos/farmacologia , Neoplasias Hepáticas , Transdução de Sinais , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Linhagem Celular Tumoral , Glicólise , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
4.
Sci Rep ; 11(1): 758, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436876

RESUMO

The purpose of this research was to identify metabolite change during barley (Hordeum vulgare) germination and reveal active principles for the anti-wrinkle activity. Barley was germinated with deionized water (DW) and mineral-rich water (MRW) for the comparison of the effect of mineral contents on the metabolites changes during germination. The effects of germinated barley extracts (GBEs) on collagen production and collagenase inhibition were evaluated in vitro using human dermal fibroblasts (HDFs). A pronounced anti-wrinkle activity was observed in the test group treated with the MRW-GBEs. In order to find out the active components related to the anti-wrinkle activity, an orthogonal projection to latent structure-discriminant analysis (OPLS-DA) was performed, using the data from secondary metabolites profiling conducted by UPLC-PDA-ESI-MS. The anti-wrinkle activity of MRW-GBEs was revealed to be associated with the increase of oligomeric compounds of procyanidin and prodelphinidin, indicating that it can be used as an active ingredient for anti-wrinkle agents.


Assuntos
Fibroblastos/efeitos dos fármacos , Germinação , Hordeum/metabolismo , Metaboloma , Extratos Vegetais/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Células Cultivadas , Colágeno Tipo I/metabolismo , Derme/citologia , Derme/efeitos dos fármacos , Derme/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Hordeum/crescimento & desenvolvimento , Humanos , Metaloproteinase 1 da Matriz/química
5.
Int J Med Sci ; 17(16): 2496-2504, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029092

RESUMO

Background: To maintain the normal pregnancy, suppression of inflammatory signaling pathway is a crucial physiologic response. Dexmedetomidine has been used for labor analgesia or supplement of inadequate regional analgesia during delivery. And it has been reported that dexmedetomidine has an anti-inflammatory effect. In this study, we examined the influence of dexmedetomidine on the expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and inflammatory cytokines in lipopolysaccharide (LPS)-stimulated human amnion-derived WISH cells. In addition, we evaluated the association of mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathway in anti-inflammatory effect of dexmedetomidine. Methods: Human amnion-derived WISH cells were pretreated with various concentrations of dexmedetomidine (0.001-1 µg/ml) for 1 h and after then treated with LPS (1 µg/ml) for 24 h. MTT assay was conducted to evaluate the cytotoxicity. Nitric oxide (NO) production was analyzed using Griess-reaction microassay. RT-PCR was performed for analysis of mRNA expressions of COX-2, PGE2, tumor necrosis factor (TNF)-α and interlukin (IL)-1ß. Protein expressions of COX-2, PGE2, p38 and NF-κB were analyzed by western blotting. Results: LPS and dexmedetomidine had no cytotoxic effect on WISH cells. There was no difference in NO production after dexmedetomidine pretreatment. The mRNA and protein expressions of COX-2 and PGE2 were decreased by dexmedetomidine pretreatment in LPS-treated WISH cells. Dexmedetomidine also attenuated the LPS-induced mRNA expression of TNF-α and IL-1ß. The activation of p38 and NF-κB was suppressed by dexmedetomidine pretreatment in LPS-treated WISH cells. Conclusion: We demonstrated that dexmedetomidine pretreatment suppressed the expressions of inflammatory mediators increased by LPS. In addition, this study suggests that anti-inflammatory effect of dexmedetomidine on WISH cells was mediated by the inhibitions of p38 and NF-κB activation.


Assuntos
Âmnio/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Dexmedetomidina/farmacologia , Inflamação/tratamento farmacológico , Âmnio/citologia , Âmnio/imunologia , Anti-Inflamatórios/uso terapêutico , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Dexmedetomidina/uso terapêutico , Dinoprostona/metabolismo , Avaliação Pré-Clínica de Medicamentos , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Meat Sci ; 93(3): 715-22, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23273483

RESUMO

In this study, we assessed the antioxidant efficacy and nutritional value of 10 leafy edible plants and evaluated their potential as natural antioxidants for meat preservation. We measured total phenolic content, 2,2-diphenyl-1-picryl-hydrazil (DPPH) radical scavenging activity, and vitamin C, chlorophyll, and carotenoid contents of 70% ethanol and water extracts of the edible plants. Based on these results, we investigated the effects of butterbur and broccoli extracts on lipid oxidation in ground beef patties. Plant extracts and butylated hydroxytoluene (BHT) were individually added to patties at both 0.1% and 0.5% (w/w) concentrations. Thiobarbituric acid reactive substance (TBARS) values and color parameters were tested periodically during 12 days of refrigerated storage. TBARS levels were significantly lower (p≤0.05) in the samples containing plant extracts or BHT than the non-treated control. In addition, the beef patties formulated with the selected plant extracts showed significantly (p≤0.05) better color stability than those without antioxidants. These results indicate that edible plant extracts are promising sources of natural antioxidants and can potentially be used as functional preservatives in meat products.


Assuntos
Antioxidantes , Brassica , Conservação de Alimentos/métodos , Peroxidação de Lipídeos/efeitos dos fármacos , Carne/análise , Petasites , Extratos Vegetais , Animais , Hidroxitolueno Butilado/farmacologia , Bovinos , Cor , Conservantes de Alimentos , Armazenamento de Alimentos , Valor Nutritivo , Plantas Comestíveis , Substâncias Reativas com Ácido Tiobarbitúrico
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