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1.
Int Immunopharmacol ; 101(Pt A): 108204, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34619497

RESUMO

Acute lung injury (ALI) is a life-threatening syndrome that possibly leads to high morbidity and mortality as no therapy exists. Several natural ingredients with negligible adverse effects have recently been investigated to possibly inhibit the inflammatory pathways associated with ALI at the molecular level. Isoflavones, as phytoestrogenic compounds, are naturally occurring bioactive compounds that represent the most abundant category of plant polyphenols (Leguminosae family). A broad range of therapeutic activities of isoflavones, including antioxidants, chemopreventive, anti-inflammatory, antiallergic and antibacterial potentials, have been extensively documented in the literature. Our review exclusively focuses on the possible anti-inflammatory, antioxidant role of botanicals'-derived isoflavones against ALI and their immunomodulatory effect in experimentally induced ALI. Despite the limited scope covering their molecular mechanisms, isoflavones substantially contributed to protecting from ALI via inhibiting toll-like receptor 4 (TLR4)/Myd88/NF-κB pathway and subsequent cytokines, chemokines, and adherent proteins. Nonetheless, future research is suggested to fill the gap in elucidating the protective roles of isoflavones to alleviate ALI concerning antioxidant potentials, inhibition of the inflammatory pathways, and associated molecular mechanisms.

2.
Integr Cancer Ther ; 20: 15347354211035450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490824

RESUMO

Doxorubicin (Dox) induces senescence in numerous cancer cell types, but these senescent cancer cells relapse again if they are not eliminated. On this principle, we investigated the apoptotic effect of thymoquinone (TQ), the active ingredient of Nigella sativa seeds and costunolide (COS), the active ingredient of Costus speciosus, on the senescent colon (Sen-HCT116) and senescent breast (Sen-MCF7) cancer cell lines in reference to their corresponding proliferative cells to rapidly eliminate the senescent cancer cells. The senescence markers of Sen-HCT116 and Sen-MCF7 were determined by a significant decrease in bromodeoxyuridine (BrdU) incorporation and significant increases in SA-ß-gal, p53, and p21 levels. Then proliferative, Sen-HCT116, and Sen-MCF7 cells were subjected to either TQ (50 µM) or COS (30 µM), the Bcl2-associated X protein (Bax), B-cell lymphoma 2 (Bcl2), caspase 3 mRNA expression and its activity were established. Results revealed that TQ significantly increased the Bax/Bcl2 ratio in HCT116 + Dox5 + TQ, MCF7 + TQ, and MCF7 + Dox5 + TQ compared with their corresponding controls. COS significantly increased the Bax/Bcl2 ratio in HCT116 + Dox5 + TQ and MCF7 + Dox5 + TQ compared with their related controls. Also, TQ and COS were significantly increased caspase 3 activity and cell proliferation of Sen-HCT116 and Sen-MCF7. The data revealed a higher sensitivity of senescent cells to TQ or COS than their corresponding proliferative cells.


Assuntos
Apoptose , Recidiva Local de Neoplasia , Benzoquinonas , Colo , Doxorrubicina/farmacologia , Humanos , Sesquiterpenos
3.
Environ Sci Pollut Res Int ; 28(36): 49447-49466, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34355314

RESUMO

Cancer, a major public health problem, is one of the world's top leading causes of death. Common treatments for cancer include cytotoxic chemotherapy, surgery, targeted drugs, endocrine therapy, and immunotherapy. However, despite the outstanding achievements in cancer therapies during the last years, resistance to conventional chemotherapeutic agents and new targeted drugs is still the major challenge. In the present review, we explain the different mechanisms involved in cancer therapy and the detailed outlines of cancer drug resistance regarding multidrug resistance-associated proteins (MRPs) and their role in treatment failures by common chemotherapeutic agents. Further, different modulators of MRPs are presented. Finally, we outlined the models used to analyze MRP transporters and proposed a future impact that may set up a base or pave the way for many researchers to investigate the cancer MRP further.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Previsões , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/farmacologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/uso terapêutico , Neoplasias/tratamento farmacológico
4.
Int J Nanomedicine ; 16: 5117-5131, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349511

RESUMO

As a crucial organ, the lung is exposed to various harmful agents that may induce inflammation and oxidative stress, which may cause chronic or acute lung injury. Nigella sativa, also known as black seed, has been widely used to treat various diseases and is one of the most extensively researched medicinal plants. Thymoquinone (TQ) is the main component of black seed volatile oil and has been proven to have antioxidant, anti-inflammatory, and antineoplastic properties. The potential therapeutic properties of TQ against various pulmonary disorders have been studied in both in vitro and in vivo studies. Furthermore, the application of nanotechnology may increase drug solubility, cellular absorption, drug release (sustained or control), and drug delivery to lung tissue target sites. As a result, fabricating TQ as nanoparticles (NPs) is a potential therapeutic approach against a variety of lung diseases. In this current review, we summarize recent findings on the efficacy of TQ and its nanotypes in lung disorders caused by immunocompromised conditions such as cancer, diabetes, gastric ulcers, and other neurodegenerative diseases. It is concluded that TQ nanoparticles with anti-inflammatory, antioxidant, antiasthma, and antitumor activity may be safely applied to treat lung disorders. However, more research is required before TQ nanoparticles can be used as pharmaceutical preparations in human studies.


Assuntos
Lesão Pulmonar , Nanopartículas , Benzoquinonas , Humanos , Nigella sativa
5.
Animals (Basel) ; 11(8)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34438756

RESUMO

Quercetin was fed to groups of broiler chickens at concentrations of 200, 400, and 800 ppm, and a control group was supplemented with a basal diet. Results revealed that quercetin dietary supplementation numerically improved the growth performance traits and significantly increased (p < 0.05) the European production efficiency factor (EPEF) in the 200 ppm group. The total coliforms and Clostridium perfringens were decreased (p < 0.05) in quercetin-supplemented groups. Conversely, Lactobacillus counts were increased (p < 0.05), due to improvement of the gut microbiota environment in quercetin-supplemented groups. Moreover, the mRNA expression of intestinal Cu/Zn-superoxide dismutase (SOD1), glutathione peroxidase (GSH-Px) and nutritional transporters, including glucose transporter 2 (GLUT2), peptide transporter 1 (PEPT1), and fatty acid synthase (FAS) genes, were significantly upregulated in quercetin-supplemented groups. Quercetin enhanced intestinal morphometry. We can suggest quercetin supplementation in broiler chickens by levels between 200 and 400 ppm to enhance their development and gut environment.

6.
Biomedicines ; 9(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34440193

RESUMO

Costunolide (COS) is a sesquiterpene lactone with anticancer properties. The present study investigated the anticancer effects of COS against the human colon (HCT116) and breast (MDA-MB-231-Luc) cancer cell lines. Inhibition of cell lines viability and IC50 of COS were assessed via an MTT assay. Furthermore, the apoptotic rate was detected by assessment of Bcl2-associated X (Bax) and B-cell lymphoma 2 (Bcl2) protein levels by flow cytometry. Xenograft mice model of HCT116 and MDA-MB-231-Luc were carried out to determine the effect of COS and its nanoparticles (COS-NPs). The results demonstrated that COS inhibited the viability of HCT116 and MDA-MB-231-Luc cells, with a half maximal inhibitory concentration value (IC50) of 39.92 µM and 100.57 µM, respectively. COS significantly increased Bax and decreased Bcl2 levels in treated cells. COS and COS-NPs, in combination with doxorubicin (DOX), significantly decreased the tumor growth of HCT116 and MDA-MB-231-Luc implants in mice. Furthermore, oral administration of COS and COS-NPs significantly decreased the viable cells and increased necrotic/apoptotic cells of HCT116 and MDA-MB-231-Luc implants. Interestingly, both COS and COS-NPs protected the cardiac muscles against DOX's cardiotoxicity. The current results indicated the promising anticancer and cardiac muscles protection of COS and COS-NPs when administered with chemotherapy.

7.
Antioxidants (Basel) ; 10(6)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200190

RESUMO

Hepatocellular carcinoma (HCC) is the most common cancer in humans. Despite advances in its treatment, liver cancer remains one of the most difficult cancers to treat. This study aimed to investigate the ameliorative action and potential mechanism of Aspergillus awamori (ASP) administration against the initiation process of liver carcinogenesis induced by diethylnitrosamine (DEN) in male Wistar rats. Seventy-two male rats were divided equally into eight groups as follows, Group 1: untreated control; Group 2: DEN (200 mg/kg bw) intra-peritoneally for the initiation of HCC; Groups 3-5: DEN + ASP at a dose of 1, 0.5, and 0.25 mg/kg bw and groups 6-8: ASP at a dose of 1, 0.5, and 0.25 mg/kg bw. Supplementation of A. awamori significantly lightened the adverse impacts induced by DEN via restoring the leukogram to normal, lowering the elevated serum aspartate aminotransferase (AST), alanine transaminase (ALT), and γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Furthermore, it enhanced the hepatic antioxidant capacity through increasing the reduced glutathione (GSH) level and catalase (CAT) activity with a marked reduction in malondialdehyde (MDA) level. In addition, it decreased the positive GST-P foci. Likewise, a significant alteration of DEN-associated hepatocarcinogenesis occurred through inhibiting cytochrome P450 (Cyp19) and activating p53 gene expression. In conclusion, supplementation of A. awamori counteracts the negative effects of DEN, inhibits the early development of GST-P-positive foci and could be used as a new alternative strategy for its chemo-preventive effect in liver cancer. To the best of our knowledge, the present study is the first to report the hepato-protective effect of A. awamori in induced hepatocarcinogenesis.

8.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202112

RESUMO

D-galactose (D-gal) administration causes oxidative disorder and is widely utilized in aging animal models. Therefore, we subcutaneously injected D-gal at 200 mg/kg BW dose to assess the potential preventive effect of thymoquinone (TQ) and curcumin (Cur) against the oxidative alterations induced by D-gal. Other than the control, vehicle, and D-gal groups, the TQ and Cur treated groups were orally supplemented at 20 mg/kg BW of each alone or combined. TQ and Cur effectively suppressed the oxidative alterations induced by D-gal in brain and heart tissues. The TQ and Cur combination significantly decreased the elevated necrosis in the brain and heart by D-gal. It significantly reduced brain caspase 3, calbindin, and calcium-binding adapter molecule 1 (IBA1), heart caspase 3, and BCL2. Expression of mRNA of the brain and heart TP53, p21, Bax, and CASP-3 were significantly downregulated in the TQ and Cur combination group along with upregulation of BCL2 in comparison with the D-gal group. Data suggested that the TQ and Cur combination is a promising approach in aging prevention.


Assuntos
Benzoquinonas/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Curcumina/farmacologia , Galactose/farmacologia , Miocárdio/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Benzoquinonas/química , Curcumina/química , Imuno-Histoquímica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Especificidade de Órgãos , Ratos , Relação Estrutura-Atividade
9.
Nanomedicine (Lond) ; 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34132104

RESUMO

Aim: To investigate the anti-cancer potential of thymoquinone (TQ) and TQ nanoparticles (TQ-NPs) and their protection against doxorubicin (DOX)-induced cardiotoxicity. Methods: TQ-NPs were prepared by double emulsion method and characterized. The efficacy of TQ and TQ-DOX was studied against HCT116 and MDA-MB-231-Luc cancer cell lines in vitro and in a xenograft tumor model. Results: TQ and TQ + DOX increased Bax levels in HCT116 cells and decreased Bcl2 levels in MDA-MB-231-Luc cells. In the xenograft model, the TQ-NPs, with an average size of 218 nm, in combination with DOX, significantly reduced tumor size. The combination of TQ or TQ-NPs with DOX significantly reduced DOX-induced cardiotoxicity. Conclusion: Data suggest the promising role of TQ and TQ-NPs alone and with DOX for anti-cancer and cardiac protection benefits.

10.
Int J Mol Sci ; 22(8)2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33917107

RESUMO

Iron oxide nanoparticle (IONP) therapy has diverse health benefits but high doses or prolonged therapy might induce oxidative cellular injuries especially in the brain. Therefore, we conducted the current study to investigate the protective role of quercetin supplementation against the oxidative alterations induced in the brains of rats due to IONPs. Forty adult male albino rats were allocated into equal five groups; the control received a normal basal diet, the IONP group was intraperitoneally injected with IONPs of 50 mg/kg body weight (B.W.) and quercetin-treated groups had IONPs + Q25, IONPs + Q50 and IONPs + Q100 that were orally supplanted with quercetin by doses of 25, 50 and 100 mg quercetin/kg B.W. daily, respectively, administrated with the same dose of IONPs for 30 days. IONPs induced significant increases in malondialdehyde (MDA) and significantly decreased reduced glutathione (GSH) and oxidized glutathione (GSSG). Consequently, IONPs significantly induced severe brain tissue injuries due to the iron deposition leading to oxidative alterations with significant increases in brain creatine phosphokinase (CPK) and acetylcholinesterase (AChE). Furthermore, IONPs induced significant reductions in brain epinephrine, serotonin and melatonin with the downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitochondrial transcription factor A (mtTFA) mRNA expressions. IONPs induced apoptosis in the brain monitored by increases in caspase 3 and decreases in B-cell lymphoma 2 (Bcl2) expression levels. Quercetin supplementation notably defeated brain oxidative damages and in a dose-dependent manner. Therefore, quercetin supplementation during IONPs is highly recommended to gain the benefits of IONPs with fewer health hazards.


Assuntos
Antioxidantes/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Nanopartículas Magnéticas de Óxido de Ferro , Estresse Oxidativo/efeitos dos fármacos , Quercetina/administração & dosagem , Animais , Biomarcadores , Epinefrina/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Imuno-Histoquímica , Nanopartículas Magnéticas de Óxido de Ferro/química , Nanopartículas Magnéticas de Óxido de Ferro/ultraestrutura , Melatonina/metabolismo , Oxirredução/efeitos dos fármacos , Tamanho da Partícula , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Ratos , Serotonina/metabolismo
11.
Nutr Cancer ; 73(8): 1350-1356, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32757677

RESUMO

Pomegranate fruit extract contains many polyphenols and flavonoids of diverse biological importance including anticancer potential. In cancer, the angiogenesis process facilitates solid cancer growth and metastasis. Here, the antiangiogenic effect of pomegranate fruit extract against human pancreatic cancer (Suit-2) and colon (colo205) cell lines in the chick chorioallantoic membrane (CAM) model was studied along with the effect of pomegranate fruit extract on fibroblast growth factor (FGF2). Pomegranate fruit extract significantly reduced the tumor weight and hemoglobin content in CAM models of pancreatic Suit-2 and colon colo205.


Assuntos
Neoplasias do Colo , Romã (Fruta) , Animais , Membrana Corioalantoide , Frutas , Humanos , Extratos Vegetais/farmacologia
12.
J Therm Biol ; 93: 102683, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33077109

RESUMO

BACKGROUND: Heat stress is a condition that is due to extreme heat exposure. It occurs when the body cannot keep its temperature healthy in response to a hot climate and associated with oxidative stress. Testicular hyperthermia can induce apoptosis of sperm cells, affect sperm production and decrease sperm concentration, leading to sperm disorder, for this reason, we examined the protective impact of pycnogenol that it has a wide range of biological benefits, including antioxidant, anti-inflammatory and anti-cancer activities against the oxidative alterations that happen in testicular and brain tissues due to heat stress in rats. STUDY DESIGN: Forty-eight Wistar male rats, approximately around 6 weeks age were allocated randomly into four groups (12 in each) of control, HS (subjected to heat stress and supplemented orally with 50 mg of pycnogenol/kg b. w./day dissolved in saline for 21 days), and pycnogenol (rats supplemented orally with 50 mg of pycnogenol/kg b. w./day dissolved in saline for 21 days). RESULTS: Data revealed a promising role of pycnogenol as an antioxidant, natural product to successfully reverse the heat-induced oxidative alterations in testicular and brain tissues of rats through significant upregulation of superoxide dismutase-2, catalase, reduced glutathione, and anti-apoptotic gene, while downregulating pro-apoptotic, and heat shock protein70. Pycnogenol treatment also reversed the reproductive hormone level and spermatogenesis to their normal values. CONCLUSION: Pycnogenol as a natural protective supplement could recover these heat stress-induced oxidative changes in testes and hypothalamus.


Assuntos
Antioxidantes/farmacologia , Flavonoides/farmacologia , Transtornos de Estresse por Calor/tratamento farmacológico , Extratos Vegetais/farmacologia , Transcriptoma , Animais , Antioxidantes/uso terapêutico , Apoptose , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Flavonoides/uso terapêutico , Glutationa/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Transtornos de Estresse por Calor/prevenção & controle , Masculino , Estresse Oxidativo , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Espermatogênese , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo
13.
Molecules ; 25(11)2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32503143

RESUMO

One of the major causes of women's death in the world is breast cancer. Consequently, numerous regimens for the control of this severe disease have been created. The chemotherapeutic agent doxorubicin (DOX) is frequently used to treat breast cancer, but DOX can also cause cardiotoxic effects that lead to heart failure. Therefore, many research studies have been done to find a natural product that effectively potentiates or does not interfere with DOX's anticancer effect and protects against its cardiotoxicity. We studied the impact of combined nanoformulated Ajwa (Phoenix dactylifera) selected bioactive compounds (BAC) rutin (R) and quercetin (Q) in nude mice breast cancer xenografts on DOX-mediated anticancer efficacy. We also studied if this Ajwa BAC could safeguard against DOX-mediated cardiomyopathies by evaluating plasma cardiac troponin-I (cTn-I) levels and cardiac histopathology. Nanoformulated Ajwa BAC effectively alleviated weight loss induced by DOX in mice and significantly decreased the elevated cTn-I. Furthermore, 5 mg RQ-NPs/kg of nude mice that subcutaneously daily injected for 11 days, attenuated the histopathological alterations induced in cardiac muscles due to DOX without any interference with the anticancer effects of DOX against breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/prevenção & controle , Doxorrubicina/farmacologia , Nanopartículas/administração & dosagem , Phoeniceae/química , Extratos Vegetais/farmacologia , Animais , Antibióticos Antineoplásicos/farmacologia , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Quimioterapia Combinada , Feminino , Humanos , Camundongos , Camundongos Nus , Nanopartículas/química , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Int J Mol Sci ; 21(12)2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32570962

RESUMO

Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging (p53, p21, IL-6, and IL-8), apoptotic (Bax, CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic (Bcl2 and Bcl2 protein), inflammatory (NF-κB, IL-1ß, and TNF-α), antioxidant (SOD1), and functional markers (GCLC and GCLM genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health.


Assuntos
Envelhecimento/genética , Galactose/administração & dosagem , Rim/química , Pâncreas/química , Quercetina/administração & dosagem , Envelhecimento/metabolismo , Animais , Relação Dose-Resposta a Droga , Galactose/efeitos adversos , Redes Reguladoras de Genes/efeitos dos fármacos , Rim/efeitos dos fármacos , Masculino , Modelos Animais , Estresse Oxidativo/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Quercetina/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar
15.
PLoS One ; 15(6): e0234076, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32520965

RESUMO

This study investigated the effects of oral administration of ß-glucan 1,3 (pharmaceutical grade 10%) on growth performance and carcass traits in two breeds of weanling rabbits adapted to survive in Egypt, New Zealand White (NZW) and Animal Production Research Institute (APRI) rabbits, with special attention to relative mRNA expression of interleukins and antioxidant enzyme genes, biochemical, and histological alterations. Oral administration of ß-glucan with doses 0.25 and 0.5 ml per one-liter of drinking water significantly accelerated body weight gain (BWG) in both rabbits' breeds, reduced total feed consumption (FC), and reduced feed conversion ratio (FCR), especially the 0.5 ml per one-liter dose in both rabbit breeds. There are remarkable differences in all the growth performance traits due to breed effect. The interaction effect between ß-glucan and breed significantly improved BWG, FC, and FCR. There were non-significant differences in all carcass traits studied due to oral administration of ß-glucan with both doses, except in dressing percentages. The highest of the dressing percentages were observed at doses 0.25 ml per one-liter (51%) and 0.5 ml per one-liter (52%) compared with control (50%). Our findings show significant variations in the final BW, total daily gain, feed consumption, and total feed conversion ratio between NZW and APRI rabbits. Absence of significant differences in the hot carcass weight and dressing percentage between the genetic groups had been reported in this study. Supplementing NZW and APRI rabbits with ß-glucan increased blood total protein and globulin. The duodenal villi dimensions, splenic lymphoid diameter, muscular fiber diameter, and muscular glycogen areas were significantly increased by ß-glucan administration. Expression of intestinal interleukin-18 (IL-18) in NZW rabbits treated with 0.25 and 0.5 doses of ß-glucan was significantly upregulated and enhanced the immune response. ß-glucan upregulated the expression of intestinal occludin mRNA particularly at dose 0.5 ß-glucan as well as upregulated intestinal superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPx1), which modulates anti-inflammatory and antioxidant properties. In conclusion, oral administration of ß-glucan at a dose of 0.25 or 0.5 ml per one-liter drinking water provided beneficial effects in the growth performance and health status of rabbits.


Assuntos
Mucosa Intestinal/efeitos dos fármacos , Ganho de Peso/efeitos dos fármacos , beta-Glucanas/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Administração Oral , Animais , Duodeno/metabolismo , Duodeno/patologia , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Interleucina-18/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Ocludina/genética , Ocludina/metabolismo , Coelhos , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Regulação para Cima/efeitos dos fármacos
16.
Int J Mol Sci ; 21(10)2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32443845

RESUMO

Interactions of the receptor for advanced glycation end product (RAGE) and its ligands in the context of their role in diabetes mellitus, inflammation, and carcinogenesis have been extensively investigated. This review focuses on the role of RAGE-ligands and anti-RAGE drugs capable of controlling cancer progression. Different studies have demonstrated interaction of RAGE with a diverse range of acidic (negatively charged) ligands such as advanced glycation end products (AGEs), high-mobility group box1 (HMGB1), and S100s, and their importance to cancer progression. Some RAGE-ligands displayed effects on anti- and pro-apoptotic proteins through upregulation of the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinases (MAPKs), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and nuclear factor kappa B (NF-κB) pathways, while downregulating p53 in cancer progression. In addition, RAGE may undergo ligand-driven multimodal dimerization or oligomerization mediated through self-association of some of its subunits. We conclude our review by proposing possible future lines of study that could result in control of cancer progression through RAGE inhibition.


Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Neoplasias/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Proteína HMGB1/antagonistas & inibidores , Proteína HMGB1/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Proteínas S100/antagonistas & inibidores , Proteínas S100/metabolismo , Transdução de Sinais
17.
Naunyn Schmiedebergs Arch Pharmacol ; 393(9): 1581-1598, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32458010

RESUMO

Cancer is a worldwide disease that causes millions of cases of mortality and morbidity. The major problem associated with the cancer is its resistance to conventional therapy and a high relapse rate. The use of chemotherapy to treat cancer began at the start of the twentieth century with attempts to control cancer. In time advance, many cancer chemotherapeutic agents have been developed for cancer treatment with different mechanisms of action including the alkylating agents, antimetabolites, antimicrotubule, topoisomerase inhibitors, and cytotoxic antibiotics, all of which have toxic effects toward normal cells in the body. Here, we reviewed chemotherapeutics' anticancer role potentiation and safety by thymoquinone (TQ) alone or in combination with the most common therapeutic drugs. Our search was done through PubMed, Science Direct, Springer Link, Taylor & Francis Online, Wiley Online Library, Nature publication group, SAGE Journals, and Web of Science databases. We recognized that TQ-chemotherapeutics combination increased chemo-modulation to the anticancer effect of different chemotherapeutics and protected the normal body cells from the toxic injuries that are induced by chemotherapeutics based on its antioxidant power. Moreover, the current study investigates the possible combinatory effect of TQ and chemotherapeutics to control cancer stem cells through molecular docking targeting of wingless/integrated (Wnt) and Hedgehog (Hh). We found that TQ modulates the Wnt and Hh pathways, by binding with tankyrase-2 and smoothened 7TM receptor, respectively, more efficiently than most chemotherapeutics drugs, while methotrexate showed high-binding affinity compared with TQ. Therefore, we encourage researchers to investigate the chemo-modulatory potential and protective effects of TQ in combination with chemotherapeutics for either cancer or cancer stem cell treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzoquinonas/uso terapêutico , Neoplasias/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzoquinonas/efeitos adversos , Proteínas Hedgehog/metabolismo , Humanos , Simulação de Acoplamento Molecular , Neoplasias/metabolismo , Neoplasias/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Domínios e Motivos de Interação entre Proteínas , Receptor Smoothened/metabolismo , Tanquirases/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt
18.
Int J Nanomedicine ; 15: 2259-2268, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280218

RESUMO

Purpose: This study was designed to determine the potential effect of nanoencapsulated bioactive compounds from different natural sources on human pancreatic cancer. Background: Pancreatic cancer carries the highest fatality rate among all human cancers because of its high metastatic potential and late presentation at the time of diagnosis. Hence there is a need for improved methods to prevent and treat it. Natural products, such as 3, 3'-diindolylmethane (DIM) and ellagic acid (EA) demonstrated anticancer efficacy against various cancer types. However, DIM is insoluble. Hence, using nanotechnology to encapsulate these compounds in combination with EA might improve their physical and chemical properties and their delivery to the cancer cells. Methods: Human pancreatic cancer cells, namely SUIT2-luciferase transfected, were used to examine the effects of DIM or EA and their nanoformulation in poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) [PLGA-PEG] nanoparticles (NPs) on SUIT2-luciferase cell viability/proliferation over 24 hrs. Additionally, effects on tumor weight and angiogenesis were determined using the chick chorioallantoic membrane (CAM) tumor implant model. Results: Both DIM and EA PLGA-PEG NPs resulted in rapid suppression of pancreatic cancer cell viability/proliferation within 24 hrs (P < 0.01), while the non-encapsulated DIM and EA did not show any significant effect on SUIT2 cancer cell viability or cell proliferation (MTT assay). In the CAM pancreatic cancer cell (SUIT2) implant model, results showed a greater suppression of tumor weight (P < 0.01), tumor cell viability, and tumor angiogenesis (P < 0.01) for DIM NPs and EA NPs and their combinations versus DIM or EA alone. Conclusion: Nanoformulation of DIM and EA resulted in a more effective suppression of pancreatic cancer cell viability, pancreatic tumor weight, implanted cancer cell viability, and tumor angiogenesis as compared with these bioactive compounds alone.


Assuntos
Antineoplásicos/farmacologia , Produtos Biológicos/química , Ácido Elágico/farmacologia , Indóis/farmacologia , Nanopartículas/química , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Ácido Elágico/administração & dosagem , Humanos , Indóis/administração & dosagem , Nanopartículas/uso terapêutico , Neoplasias Pancreáticas/patologia , Poliésteres/química , Polietilenoglicóis/química
19.
Molecules ; 25(6)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32244860

RESUMO

Cancer is a multifactorial disorder that induces mortality worldwide, and the colorectal type is the third most common cancer globally. Resveratrol (RSV) is a natural compound with an effective anticancer effect, especially against colorectal cancer, and therefore numerous studies recommended its use in colorectal cancer prevention and treatment. The current study investigated the effect of either RSV or its nanoformulation (NP-RSV) on the growth and vascularity of xenograft and orthotopic mice models in colon cancer (COLO205-luc). Both RSV and NP-RSV induced significant reductions in tumor growth and the hemoglobin percentages of the tumor mass, but NP-RSV showed greater bioavailability and efficacy than RSV. Generally, we recommend using NP-RSV as a therapeutic to control colon cancer.


Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Composição de Medicamentos , Resveratrol/farmacologia , Nanomedicina Teranóstica , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacocinética , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacocinética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Camundongos , Resveratrol/química , Resveratrol/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Integr Cancer Ther ; 19: 1534735419901160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32054357

RESUMO

Cellular senescence is a process of physiological growth arrest that can be induced by intrinsic or extrinsic stress signals. Some cancer therapies are associated with senescence of cancer cells with a typical cell cycle arrest. Doxorubicin (Dox) induces senescence by a p53-dependent pathway and telomere dysfunction of numerous cancers. However, cellular senescence induces suppression in proliferation activity, and these cells will remain metabolically active and play an important role in tumor relapse and development of drug resistance. In the current study, we investigated the apoptotic effect of curcumin (Cur), caffeine (Caff), and thymoquinone (TQ) on senescent colon cancer HCT116 and breast cancer MCF7 cell lines treated with Dox. Results showed typical senescence markers including decreased bromodeoxyuridine incorporation, increased accumulation of senescence-associated ß-galactosidase (SA-ß-gal), cell cycle arrest, and upregulation of p53, P-p53, and p21 proteins. Annexin-V analysis by flow cytometry revealed 2- to 6-fold increases in annexin-V-positive cells in Dox-treated MCF7 and HCT116 cells by Cur (15 µM), Caff (10 mM), and TQ (50 µM; P < .001). In comparison between proliferative and senescent of either HCT116 or MCF7 cells, Caff at 15 mM and TQ at 25 µM induced significant increases in apoptosis of Dox-treated cells compared with proliferative cells (P < .001). Data revealed that Cur, Caff, and TQ potentially induced apoptosis of both proliferative and senescent HCT116 and MCF7 cells. In vivo and clinical trials are of great importance to validate this result.


Assuntos
Benzoquinonas/farmacologia , Neoplasias da Mama , Cafeína/farmacologia , Senescência Celular , Neoplasias do Colo , Curcumina/farmacologia , Doxorrubicina/farmacologia , beta-Galactosidase/metabolismo , Antimetabólitos Antineoplásicos/análise , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Bromodesoxiuridina/análise , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Senescência Celular/efeitos dos fármacos , Senescência Celular/fisiologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Humanos
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