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1.
Int J Mol Sci ; 22(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502045

RESUMO

Bone is a highly dynamic tissue that is constantly adapting to micro-changes to facilitate movement. When the balance between bone building and resorption shifts more towards bone resorption, the result is reduced bone density and mineralization, as seen in osteoporosis or osteopenia. Current treatment strategies aimed to improve bone homeostasis and turnover are lacking in efficacy, resulting in the search for new preventative and nutraceutical treatment options. The myokine irisin, since its discovery in 2012, has been shown to play an important role in many tissues including muscle, adipose, and bone. Evidence indicate that irisin is associated with increased bone formation and decreased bone resorption, leading to reduced risk of osteoporosis in post-menopausal women. In addition, low serum irisin levels have been found in individuals with osteoporosis and osteopenia. Irisin targets key signaling proteins, promoting osteoblastogenesis and reducing osteoclastogenesis. The present review summarizes the existing evidence regarding the effects of irisin on bone homeostasis.


Assuntos
Fibronectinas/metabolismo , Homeostase , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Animais , Humanos
2.
Endocr Connect ; 10(8): 861-872, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34319253

RESUMO

Plasma free fatty acids (FFAs) are elevated in obesity and can induce insulin resistance via endoplasmic reticulum (ER) stress. However, it is unknown whether hepatic insulin resistance caused by the elevation of plasma FFAs is alleviated by chemical chaperones. Rats received one of the following i.v. treatments for 48 h: saline, intralipid plus heparin (IH), IH plus the chemical chaperone 4-phenylbutyric acid (PBA), or PBA alone and a hyperinsulinemic-euglycemic clamp was performed during the last 2 h. PBA co-infusion normalized IH-induced peripheral insulin resistance, similar to our previous findings with an antioxidant and an IκBα kinase ß (IKKß) inhibitor. Different from our previous results with the antioxidant and IKKß inhibitor, PBA also improved IH-induced hepatic insulin resistance in parallel with activation of Akt. Unexpectedly, IH did not induce markers of ER stress in the liver, but PBA prevented IH-induced elevation of phosphorylated eukaryotic initiation factor-2α protein in adipose tissue. PBA tended to decrease circulating fetuin-A and significantly increased circulating fibroblast growth factor 21 (FGF21) without affecting markers of activation of hepatic protein kinase C-δ or p38 mitogen-activated protein kinase that we have previously involved in hepatic insulin resistance in this model. In conclusion: (i) PBA prevented hepatic insulin resistance caused by prolonged plasma FFA elevation without affecting hepatic ER stress markers; (ii) the PBA effect is likely due to increased FGF21 and/or decreased fetuin-A, which directly signal to upregulate Akt activation.

3.
Cancers (Basel) ; 13(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071869

RESUMO

Cancer is a disease associated with extreme human suffering, a huge economic cost to health systems, and is the second leading cause of death worldwide. Regular physical activity is associated with many health benefits, including reduced cancer risk. In the past two decades, exercising/contracting skeletal muscles have been found to secrete a wide range of biologically active proteins, named myokines. Myokines are delivered, via the circulation, to different cells/tissues, bind to their specific receptors and initiate signaling cascades mediating the health benefits of exercise. The present review summarizes the existing evidence of the role of the myokine irisin in cancer. In vitro studies have shown that the treatment of various cancer cells with irisin resulted in the inhibition of cell proliferation, survival, migration/ invasion and induced apoptosis by affecting key proliferative and antiapoptotic signaling pathways. However, the effects of irisin in humans remains unclear. Although the majority of the existing studies have found reduced serum irisin levels in cancer patients, a few studies have shown the opposite. Similarly, the majority of studies have found increased levels of irisin in cancer tissues, with a few studies showing the opposite trend. Clearly, further investigations are required to determine the exact role of irisin in cancer.

4.
Molecules ; 26(4)2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668434

RESUMO

Cancer is a disease characterized by aberrant proliferative and apoptotic signaling pathways, leading to uncontrolled proliferation of cancer cells combined with enhanced survival and evasion of cell death. Current treatment strategies are sometimes ineffective in eradicating more aggressive, metastatic forms of cancer, indicating the need to develop novel therapeutics targeting signaling pathways which are essential for cancer progression. Historically, plant-derived compounds have been utilized in the production of pharmaceuticals and chemotherapeutic compounds for the treatment of cancer, including paclitaxel and docetaxel. Theaflavins, phenolic components present in black tea, have demonstrated anti-cancer potential in cell cultures in vitro and in animal studies in vivo. Theaflavins have been shown to inhibit proliferation, survival, and migration of many cancer cellswhile promoting apoptosis. Treatment with theaflavins has been associated with increased levels of cleaved poly (ADP-ribose) polymerase (PARP) and cleaved caspases-3, -7, -8, and -9, all markers of apoptosis, and increased expression of the proapoptotic marker Bcl-2-associated X protein (Bax) and concomitant reduction in the antiapoptotic marker B-cell lymphoma 2 (Bcl-2). Additionally, theaflavin treatment reduced phosphorylated Akt, phosphorylated mechanistic target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and c-Myc levels with increased expression of the tumour suppressor p53. This review summarizes the current in vitro and in vivo evidence available investigating the anti-cancer effects of theaflavins across various cancer cell lines and animal models.


Assuntos
Biflavonoides/uso terapêutico , Catequina/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Biflavonoides/química , Biflavonoides/farmacologia , Catequina/química , Catequina/farmacologia , Humanos , Chá/química
5.
Appl Physiol Nutr Metab ; 46(7): 819-827, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33471600

RESUMO

Impaired action of insulin in skeletal muscle, termed insulin resistance, leads to increased blood glucose levels resulting in compensatory increase in insulin levels. The elevated blood glucose and insulin levels exacerbate insulin resistance and contribute to the pathogenesis of type 2 diabetes mellitus. In previous studies we found attenuation of free fatty acid-induced muscle cell insulin resistance by rosemary extract (RE). In the present study we investigated the effects of RE on high glucose (HG) and high insulin (HI)-induced muscle cell insulin resistance. Exposure of L6 myotubes to 25 mmol/L glucose and 100 nmol/L insulin for 24 h, to mimic hyperglycemia and hyperinsulinemia, abolished the acute insulin-stimulated glucose uptake, increased the serine phosphorylation of IRS-1 and the phosphorylation/activation of mTOR and p70S6K. Treatment with RE significantly improved the insulin-stimulated glucose uptake and increased the acute insulin-stimulated tyrosine phosphorylation while reducing the HG+HI-induced serine phosphorylation of IRS-1 and phosphorylation of mTOR and p70S6K. Additionally, treatment with RE significantly increased the phosphorylation of AMPK, its downstream effector ACC and the plasma membrane GLUT4 levels. Our data indicate a potential of RE to counteract muscle cell insulin resistance and more studies are required to investigate its effectiveness in vivo. Novelty: RE phosphorylated muscle cell AMPK and ACC under both normal and HG+HI conditions. The HG+HI-induced serine phosphorylation of IRS-1 and activation of mTOR and p70S6K were attenuated by RE. RE restored the insulin-stimulated glucose uptake by enhancing GLUT4 glucose transporter translocation to plasma membrane.

6.
Appl Physiol Nutr Metab ; 46(2): 141-147, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32791009

RESUMO

Glucose is the primary metabolic substrate of neurons and is responsible for supporting many vital functions including neuronal signalling. Decreases in glucose uptake and utilization are common characteristics of dementia, particularly Alzheimer's disease, and thus agents that can restore neuronal glucose availability may be especially valuable to the field. Diets rich in antioxidants and polyphenols have been associated with reductions in the risk of chronic disease that are associated with aging. In previous studies, rosemary extract (RE) has been reported to have antioxidant, anti-inflammatory, anticancer, and antidiabetic properties. The purpose of the present study was to explore the effects of RE on neuronal glucose uptake. Human SH-SY5Y neuroblastoma cells exposed to varied concentrations of RE showed a dose-dependent increase in glucose uptake, with a significant increase observed following treatment with 5 µg/mL RE for 2 h (159% ± 20.81% of control) that was comparable to maximum insulin stimulation (135.6% ± 3.2% of control). This increase in glucose uptake was paralleled by increases in AMP-activated protein kinase (AMPK), but not Akt, phosphorylation/activation. The present study is the first to report that treatment with rosemary extract can stimulate glucose uptake in a neuronal cell line. These results demonstrate the potential of RE to be used as an agent to regulate neuronal glucose homeostasis. Novelty: RE increases neuronal glucose uptake. RE activates AMPK in neurons. RE increases neuronal glucose uptake independently of insulin signalling.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Glucose/metabolismo , Neurônios/metabolismo , Extratos Vegetais/farmacologia , Rosmarinus , Acetil-CoA Carboxilase/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Proteínas Ativadoras de GTPase/metabolismo , Humanos , Neuroblastoma , Fosforilação , Extratos Vegetais/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Rosmarinus/química , Células Tumorais Cultivadas
7.
Biomed Pharmacother ; 131: 110717, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152908

RESUMO

Prostate cancer is the most commonly diagnosed type of cancer in North American men and is typically classified as either androgen receptor positive or negative depending on the expression of the androgen receptor (AR). AR positive prostate cancer can be treated with hormone therapy while AR negative prostate cancer is aggressive and does not respond to hormone therapy. It has been previously reported that rosemary extract (RE) has antioxidant, anti-inflammatory and anti-cancer properties. In the present study, we found that treatment of the androgen-insensitive PC-3 prostate cancer cells with RE resulted in a significant inhibition of proliferation, survival, migration, Akt, and mTOR signaling. In addition, treatment of the androgen-sensitive 22RV1 prostate cancer cells with RE resulted in a significant inhibition of proliferation and survival while RE had no effect on normal prostate epithelial PNT1A cells. These findings suggest that RE has potent effects against prostate cancer and warrants further investigation.


Assuntos
Extratos Vegetais/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Rosmarinus , Serina-Treonina Quinases TOR/antagonistas & inibidores , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Masculino , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/fisiologia
8.
Biomolecules ; 10(11)2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33182828

RESUMO

Cancer is a condition characterized by remarkably enhanced rates of cell proliferation paired with evasion of cell death. These deregulated cellular processes take place following genetic mutations leading to the activation of oncogenes, the loss of tumor suppressor genes, and the disruption of key signaling pathways that control and promote homeostasis. Plant extracts and plant-derived compounds have historically been utilized as medicinal remedies in different cultures due to their anti-inflammatory, antioxidant, and antimicrobial properties. Many chemotherapeutic agents used in the treatment of cancer are derived from plants, and the scientific interest in discovering plant-derived chemicals with anticancer potential continues today. Curcumin, a turmeric-derived polyphenol, has been reported to possess antiproliferative and proapoptotic properties. In the present review, we summarize all the in vitro and in vivo studies examining the effects of curcumin in prostate cancer.


Assuntos
Antineoplásicos/farmacologia , Curcumina/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Curcumina/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/fisiopatologia
9.
Antioxidants (Basel) ; 9(10)2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33049974

RESUMO

Cancer is characterized by unrestricted cell proliferation, inhibition of apoptosis, enhanced invasion and migration, and deregulation of signalling cascades. These properties lead to uncontrolled growth, enhanced survival, and the formation of tumours. Carnosol, a naturally occurring phyto-polyphenol (diterpene) found in rosemary, has been studied for its extensive antioxidant, anti-inflammatory, and anticancer effects. In cancer cells, carnosol has been demonstrated to inhibit cell proliferation and survival, reduce migration and invasion, and significantly enhance apoptosis. These anticancer effects of carnosol are mediated by the inhibition of several signalling molecules including extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK), Akt, mechanistic target of rapamycin (mTOR) and cyclooxygenase-2 (COX-2). Additionally, carnosol prevents the nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and promotes apoptosis, as indicated by increased levels of cleaved caspase-3, -8, -9, increased levels of the pro-apoptotic marker Bcl-2-associated X (BAX), and reduced levels of the anti-apoptotic marker B-cell lymphoma 2 (Bcl-2). The current review summarizes the existing in vitro and in vivo evidence examining the anticancer effects of carnosol across various tissues.

10.
J Vasc Res ; 57(6): 325-340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32777783

RESUMO

We have shown that both insulin and resveratrol (RSV) decrease neointimal hyperplasia in chow-fed rodents via mechanisms that are in part overlapping and involve the activation of endothelial nitric oxide synthase (eNOS). However, this vasculoprotective effect of insulin is abolished in high-fat-fed insulin-resistant rats. Since RSV, in addition to increasing insulin sensitivity, can activate eNOS via pathways that are independent of insulin signaling, such as the activation of sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK), we speculated that unlike insulin, the vasculoprotective effect of RSV would be retained in high-fat-fed rats. We found that high-fat feeding decreased insulin sensitivity and increased neointimal area and that RSV improved insulin sensitivity (p < 0.05) and decreased neointimal area in high-fat-fed rats (p < 0.05). We investigated the role of SIRT1 in the effect of RSV using two genetic mouse models. We found that RSV decreased neointimal area in high-fat-fed wild-type mice (p < 0.05), an effect that was retained in mice with catalytically inactive SIRT1 (p < 0.05) and in heterozygous SIRT1-null mice. In contrast, the effect of RSV was abolished in AMKPα2-null mice. Thus, RSV decreased neointimal hyperplasia after arterial injury in both high-fat-fed rats and mice, an effect likely not mediated by SIRT1 but by AMPKα2.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Lesões das Artérias Carótidas/tratamento farmacológico , Artéria Carótida Primitiva/efeitos dos fármacos , Dieta Hiperlipídica , Artéria Femoral/efeitos dos fármacos , Neointima , Resveratrol/farmacologia , Sirtuína 1/metabolismo , Lesões do Sistema Vascular/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/genética , Animais , Lesões das Artérias Carótidas/enzimologia , Lesões das Artérias Carótidas/patologia , Artéria Carótida Primitiva/enzimologia , Artéria Carótida Primitiva/patologia , Modelos Animais de Doenças , Artéria Femoral/enzimologia , Artéria Femoral/lesões , Artéria Femoral/patologia , Resistência à Insulina , Camundongos Knockout , Ratos Sprague-Dawley , Transdução de Sinais , Sirtuína 1/genética , Lesões do Sistema Vascular/enzimologia , Lesões do Sistema Vascular/patologia
11.
Int J Mol Sci ; 21(14)2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32664532

RESUMO

Insulin resistance, a main characteristic of type 2 diabetes mellitus (T2DM), is linked to obesity and excessive levels of plasma free fatty acids (FFA). Studies indicated that significantly elevated levels of FFAs lead to skeletal muscle insulin resistance, by dysregulating the steps in the insulin signaling cascade. The polyphenol resveratrol (RSV) was shown to have antidiabetic properties but the exact mechanism(s) involved are not clearly understood. In the present study, we examined the effect of RSV on FFA-induced insulin resistance in skeletal muscle cells in vitro and investigated the mechanisms involved. Parental and GLUT4myc-overexpressing L6 rat skeletal myotubes were used. [3H]2-deoxyglucose (2DG) uptake was measured, and total and phosphorylated levels of specific proteins were examined by immunoblotting. Exposure of L6 cells to FFA palmitate decreased the insulin-stimulated glucose uptake, indicating insulin resistance. Palmitate increased ser307 (131% ± 1.84% of control, p < 0.001) and ser636/639 (148% ± 10.1% of control, p < 0.01) phosphorylation of IRS-1, and increased the phosphorylation levels of mTOR (174% ± 15.4% of control, p < 0.01) and p70 S6K (162% ± 20.2% of control, p < 0.05). Treatment with RSV completely abolished these palmitate-induced responses. In addition, RSV increased the activation of AMPK and restored the insulin-mediated increase in (a) plasma membrane GLUT4 glucose transporter levels and (b) glucose uptake. These data suggest that RSV has the potential to counteract the FFA-induced muscle insulin resistance.


Assuntos
Adenilato Quinase/fisiologia , Ácidos Graxos não Esterificados/toxicidade , Resistência à Insulina/fisiologia , Músculo Esquelético/efeitos dos fármacos , Resveratrol/farmacologia , Proteínas Quinases S6 Ribossômicas 70-kDa/fisiologia , Serina-Treonina Quinases TOR/fisiologia , Animais , Linhagem Celular , Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/metabolismo , Células Musculares/efeitos dos fármacos , Células Musculares/metabolismo , Músculo Esquelético/metabolismo , Palmitatos/farmacologia , Palmitatos/toxicidade , Fosforilação , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos
12.
Cells ; 9(5)2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32365859

RESUMO

Interleukin-6 (IL-6) is a pleiotropic cytokine that can be released from the brain during prolonged exercise. In peripheral tissues, exercise induced IL-6 can result in GLUT4 translocation and increased glucose uptake through AMPK activation. GLUT4 is expressed in the brain and can be recruited to axonal plasma membranes with neuronal activity through AMPK activation. The aim of this study is to examine if IL-6 treatment: (1) results in AMPK activation in neuronal cells, (2) increases the activation of proteins involved in GLUT4 translocation, and (3) increases neuronal glucose uptake. Retinoic acid was used to differentiate SH-SY5Y neuronal cells. Treatment with 100 nM of insulin increased the phosphorylation of Akt and AS160 (p < 0.05). Treatment with 20 ng/mL of IL-6 resulted in the phosphorylation of STAT3 at Tyr705 (p ≤ 0.05) as well as AS160 (p < 0.05). Fluorescent Glut4GFP imaging revealed treatment with 20ng/mL of IL-6 resulted in a significant mobilization towards the plasma membrane after 5 min until 30 min. There was no difference in GLUT4 mobilization between the insulin and IL-6 treated groups. Importantly, IL-6 treatment increased glucose uptake. Our findings demonstrate that IL-6 and insulin can phosphorylate AS160 via different signaling pathways (AMPK and PI3K/Akt, respectively) and promote GLUT4 translocation towards the neuronal plasma membrane, resulting in increased neuronal glucose uptake in SH-SY5Y cells.


Assuntos
Adenilato Quinase/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Interleucina-6/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Adenilato Quinase/fisiologia , Transporte Biológico , Linhagem Celular , Glucose/metabolismo , Transportador de Glucose Tipo 4/fisiologia , Humanos , Insulina/metabolismo , Interleucina-6/metabolismo , Neurônios/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Transporte Proteico/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
13.
Nutrients ; 12(4)2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32230718

RESUMO

Insulin resistance, the hallmark of type 2 diabetes mellitus (T2DM), is linked to hyperinsulinemia, which develops to counterbalance initial peripheral hormone resistance. Studies indicate that chronically elevated levels of insulin lead to skeletal muscle insulin resistance by deregulating steps within the insulin signaling cascade. The polyphenol resveratrol (RSV) has been shown to have antidiabetic properties in vitro and in vivo. In the present study, we examined the effect of RSV on high insulin (HI)-induced insulin resistance in skeletal muscle cells in vitro and investigated the mechanisms involved. Parental and GLUT4myc-overexpressing L6 rat skeletal muscle cells were used. [3H]2-deoxyglucose (2DG) uptake was measured, and total and phosphorylated levels of specific proteins were examined by immunoblotting. Exposure of L6 cells to HI levels (100 nM) for 24 h decreased the acute-insulin-stimulated 2DG uptake, indicating insulin resistance. HI increased ser307 and ser636/639 phosphorylation of IRS-1 (to 184% ± 12% and 225% ± 28.9% of control, with p < 0.001 and p < 0.01, respectively) and increased the phosphorylation levels of mTOR (174% ± 6.7% of control, p < 0.01) and p70 S6K (228% ± 33.5% of control, p < 0.01). Treatment with RSV abolished these HI-induced responses. Furthermore, RSV increased the activation of AMPK and restored the insulin-mediated increase in plasma membrane GLUT4 glucose transporter levels. These data suggest that RSV has a potential to counteract the HI-induced muscle insulin resistance.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Resistência à Insulina/fisiologia , Músculo Esquelético/citologia , Resveratrol/farmacologia , Animais , Linhagem Celular , Insulina/farmacologia , Proteínas Substratos do Receptor de Insulina/metabolismo , Ratos , Serina-Treonina Quinases TOR/metabolismo
14.
J Leukoc Biol ; 107(5): 843-857, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32202360

RESUMO

Mast cells are immune sentinels and a driving force in both normal and pathological contexts of inflammation, with a prominent role in allergic hypersensitivities. Crosslinking of FcεRI by allergen-bound IgE Abs leads to mast cell degranulation, resulting in an early-phase response and release of newly synthesized pro-inflammatory mediators in the late-phase. The MAPK and NF-κB pathways are established as critical intracellular mechanisms directing mast cell-induced inflammation. Rosemary extract (RE) has been shown to modulate the MAPK and NF-κB pathways in other cellular contexts in vitro and in vivo. However, the effect of RE on mast cell activation has not been explored, and thus we aim to evaluate the potential of RE in modulating mast cell activation and FcεRI/c-kit signaling, potentially via these key pathways. Primary murine mast cells were sensitized with anti-TNP IgE and stimulated with cognate allergen (TNP-BSA) under stem cell factor (SCF) potentiation while treated with 0-25 µg/ml RE. RE treatment inhibited phosphorylation of p38 and JNK MAPKs while also impairing NF-кB transcription factor activity. Gene expression and mediator secretion analysis showed that RE treatment decreased IL-6, TNF, IL-13, CCL1, and CCL3, but major component polyphenols do not contribute to these effects. Importantly, RE treatment significantly inhibited early phase mast cell degranulation (down to 15% of control), with carnosic acid and carnosol contributing. These findings indicate that RE is capable of modulating mast cell functional outcomes and that further investigation of the underlying mechanisms and its potential therapeutic properties in allergic inflammatory conditions is warranted.


Assuntos
Degranulação Celular/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Extratos Vegetais/farmacologia , Alérgenos/imunologia , Animais , Degranulação Celular/imunologia , Camundongos , Rosmarinus/imunologia
15.
Int J Mol Sci ; 21(3)2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32012648

RESUMO

Breast cancer is the most commonly diagnosed cancer in women. Triple-negative (TN) breast cancer lacks expression of estrogen receptor (ER), progesterone receptor (PR) as well as the expression and/or gene amplification of human epidermal growth factor receptor 2 (HER2). TN breast cancer is aggressive and does not respond to hormone therapy, therefore new treatments are urgently needed. Plant-derived chemicals have contributed to the establishment of chemotherapy agents. In previous studies, rosemary extract (RE) has been found to reduce cell proliferation and increase apoptosis in some cancer cell lines. However, there are very few studies examining the effects of RE in TN breast cancer. In the present study, we examined the effects of RE on TN MDA-MB-231 breast cancer cell proliferation, survival/apoptosis, Akt, and mTOR signaling. RE inhibited MDA-MB-231 cell proliferation and survival in a dose-dependent manner. Furthermore, RE inhibited the phosphorylation/activation of Akt and mTOR and enhanced the cleavage of PARP, a marker of apoptosis. Our findings indicate that RE has potent anticancer properties against TN breast cancer and modulates key signaling molecules involved in cell proliferation and survival.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Rosmarinus/química , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Extratos Vegetais/química
16.
Nutrients ; 12(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31906278

RESUMO

Type 2 diabetes mellitus (T2DM) is a growing metabolic disease characterized by insulin resistance and hyperglycemia. Current preventative and treatment strategies for T2DM and insulin resistance lack in efficacy resulting in the need for new approaches to prevent and manage/treat the disease better. In recent years, epidemiological studies have suggested that diets rich in fruits and vegetables have beneficial health effects including protection against insulin resistance and T2DM. Curcumin, a polyphenol found in turmeric, and curcuminoids have been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, neuroprotective, immunomodulatory and antidiabetic properties. The current review (I of II) summarizes the existing in vitro studies examining the antidiabetic effects of curcumin, while a second (II of II) review summarizes evidence from existing in vivo animal studies and clinical trials focusing on curcumin's antidiabetic properties.


Assuntos
Curcuma/química , Curcumina/farmacologia , Hipoglicemiantes/farmacologia , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hiperglicemia/tratamento farmacológico , Resistência à Insulina
17.
Nutrients ; 12(1)2019 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-31881654

RESUMO

Type 2 diabetes mellitus (T2DM) is a growing metabolic disease characterized by insulin resistance and hyperglycemia. Current preventative and treatment approaches to insulin resistance and T2DM lack in efficacy, resulting in the need for new approaches to prevent and treat the disease. In recent years, epidemiological studies have suggested that diets rich in fruits and vegetables have beneficial health effects, including protection against insulin resistance and T2DM. Curcumin, a polyphenol found in turmeric, and curcuminoids have been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, neuroprotective, immunomodulatory and antidiabetic properties. The current review (II of II) summarizes the existing in vivo studies examining the antidiabetic effects of curcumin.


Assuntos
Curcumina , Hipoglicemiantes , Animais , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Progressão da Doença , Feminino , Humanos , Resistência à Insulina , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Ratos
18.
Nutrients ; 11(7)2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31319485

RESUMO

Different diseases and disorders that affect the kidneys include, but are not limited to, glomerulonephritis, diabetic nephropathy, polycystic kidney disease, kidney stones, renal fibrosis, sepsis, and renal cell carcinoma. Kidney disease tends to develop over many years, making it difficult to identify until much later when kidney function is severely impaired and undergoing kidney failure. Although conservative care, symptom management, medication, dialysis, transplantation, and aggressive renal cancer therapy are some of the current strategies/approaches to kidney disease treatment, new preventative targeted therapies are needed. Epidemiological studies have suggested that a diet rich in fruits and vegetables is associated with health benefits including protection against kidney disease and renal cancer. Resveratrol, a polyphenol found in grapes and berries, has been reported to have antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective, and anti-cancer properties. The current review summarizes the existing in vitro and in vivo animal and human studies examining the nephroprotective effects of resveratrol.


Assuntos
Antioxidantes/uso terapêutico , Nefropatias/tratamento farmacológico , Resveratrol/uso terapêutico , Humanos
19.
Antioxidants (Basel) ; 8(6)2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31234300

RESUMO

Insulin resistance, a pathological condition characterized by defects in insulin action leads to the development of Type 2 diabetes mellitus (T2DM), a disease which is currently on the rise that pose an enormous economic burden to healthcare systems worldwide. The current treatment and prevention strategies are considerably lacking in number and efficacy and therefore new targeted therapies and preventative strategies are urgently needed. Plant-derived chemicals such as metformin, derived from the French lilac, have been used to treat/manage insulin resistance and T2DM. Other plant-derived chemicals which are not yet discovered, may have superior properties to prevent and manage T2DM and thus research into this area is highly justifiable. Hydroxytyrosol is a phenolic phytochemical found in olive leaves and olive oil reported to have antioxidant, anti-inflammatory, anticancer and antidiabetic properties. The present review summarizes the current in vitro and in vivo studies examining the antidiabetic properties of hydroxytyrosol and investigating the mechanisms of its action.

20.
Biomolecules ; 9(3)2019 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-30871083

RESUMO

Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by insulin resistance and hyperglycemia and is associated with personal health and global economic burdens. Current strategies/approaches of insulin resistance and T2DM prevention and treatment are lacking in efficacy resulting in the need for new preventative and targeted therapies. In recent years, epidemiological studies have suggested that diets rich in vegetables and fruits are associated with health benefits including protection against insulin resistance and T2DM. Naringenin, a citrus flavanone, has been reported to have antioxidant, anti-inflammatory, hepatoprotective, nephroprotective, immunomodulatory and antidiabetic properties. The current review summarizes the existing in vitro and in vivo animal studies examining the anti-diabetic effects of naringenin.


Assuntos
Citrus/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Flavanonas/farmacologia , Hipoglicemiantes/farmacologia , Animais , Flavanonas/química , Humanos , Hipoglicemiantes/química
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