Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 820
Filtrar
1.
J Food Biochem ; 45(10): e13938, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34532874

RESUMO

This study aimed to investigate the effect of hesperidin on reproductive damage caused by diabetes mellitus. A total of 24 adult male rats were divided into four groups: control group, hesperidin group, diabetes mellitus group, and diabetes mellitus + hesperidin group. The study was conducted for 4 weeks. At the end of the study, the rats were sacrificed and testicular oxidative stress markers (MDA, GSH, GSH-Px, SOD, and CAT), DNA damage in testes (8-OHdG), and routine sperm parameters were evaluated. According to the results of the study, most of the parameters were similar in the control and hesperidin groups but CAT activity in the hesperidin group was statistically higher than the control group. Also, diabetes mellitus (DM) significantly increased MDA levels and decreased enzymatic antioxidant (GSH-Px, SOD, CAT) activities and nonenzymatic (GSH) antioxidant levels. On the other hand, hesperidin supplementation significantly decreased oxidative stress and increased enzymatic antioxidant activities and nonenzymatic antioxidant levels due to the antioxidant effect. Also, DM increased DNA damage levels in testicular tissue and hesperidin supplementation significantly decreased DNA damage levels in testes of diabetic male rats. Besides, sperm motility significantly decreased while abnormal sperm rate and dead sperm rate were significantly increased in diabetic rats. Hesperidin supplementation significantly reduced these side effects in diabetic rats. In conclusion, hesperidin supplementation could be beneficial for decreasing the side effects on the male reproductive system caused by DM in rats. PRACTICAL APPLICATIONS: Diabetes is an important metabolic disease, affecting quality of life and fertility. Hesperidin has an antioxidant effect and has a potential protective effect on reproductive toxicity in diabetic male rats. Hesperidin decreased oxidative stress, and DNA damage in testis resulted from hyperglycemia and improved sperm quality in diabetic rats. The hesperidin supplementation could be a good strategy to protect male fertility in diabetic patients.


Assuntos
Diabetes Mellitus Experimental , Hesperidina , Animais , Dano ao DNA , Diabetes Mellitus Experimental/tratamento farmacológico , Hesperidina/farmacologia , Hesperidina/uso terapêutico , Humanos , Masculino , Qualidade de Vida , Ratos , Ratos Sprague-Dawley , Motilidade Espermática , Espermatozoides , Estreptozocina , Testículo
2.
Molecules ; 26(17)2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34500779

RESUMO

Up-regulated expression of programmed death-ligand 1 (PD-L1) by interferon-gamma (IFN-γ) has been associated with promotion of cancer cell survival and tumor cell escape from anti-tumor immunity. Therefore, a blockade of PD-L1 expression can potentially be used as a molecular target for cancer therapy. The aim of this study was to investigate whether suppression of IFN-γ induced PD-L1 expression in two oral cancer cell lines, HN6 and HN15, by hesperidin effectively decreased cell proliferation and migration. Further, our objective was to elucidate the involvement of the signal transducer and activator of transcription 1 (STAT1) and STAT3 in the inhibition of induced PD-L1 expression by hesperidin. Our findings indicate that IFN-γ induced expression of PD-L1 protein in HN6 and HN15 via phosphorylation of STAT1 and STAT3 and that hesperidin significantly reduced that induction through suppression of phosphorylated STAT1 and STAT3 in both cell lines. Moreover, hesperidin also significantly decreased the viability, proliferation, migration, and invasion of both cell lines. In conclusion, hesperidin exerted anticancer effects against oral cancer cells through the suppression of PD-L1 expression via inactivation of the STAT1 and STAT3 signaling molecules. The findings of this study support the use of hesperidin as a potential adjunctive treatment for oral cancer.


Assuntos
Antineoplásicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Hesperidina/farmacologia , Inibidores de Checkpoint Imunológico/farmacologia , Neoplasias Bucais/tratamento farmacológico , Antineoplásicos/química , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Hesperidina/química , Humanos , Inibidores de Checkpoint Imunológico/química , Estrutura Molecular , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Relação Estrutura-Atividade , Regulação para Cima/efeitos dos fármacos
3.
Int J Mol Sci ; 22(18)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34576189

RESUMO

Reactive carbonyl species (RCS) such as methylglyoxal (MGO) or glyoxal (GO) are the main precursors of the formation of advanced glycation end products (AGEs). AGEs are a major factor in the development of vascular complications in diabetes. Vasoprotectives (VPs) exhibit a wide range of activities beneficial to cardiovascular health. The present study aimed to investigate selected VPs and their structural analogs for their ability to trap MGO/GO, inhibit AGE formation, and evaluate their antioxidant potential. Ultra-high-performance liquid chromatography coupled with an electrospray ionization mass spectrometer (UHPLC-ESI-MS) and diode-array detector (UHPLC-DAD) was used to investigate direct trapping capacity and kinetics of quenching MGO/GO, respectively. Fluorimetric and colorimetric measurements were used to evaluate antiglycation and antioxidant action. All tested substances showed antiglycative effects, but hesperetin was the most effective in RCS scavenging. We demonstrated that rutin, diosmetin, hesperidin, and hesperetin could trap both MGO and GO by forming adducts, whose structures we proposed. MGO-derived AGE formation was inhibited the most by hesperetin, and GO-derived AGEs by diosmetin. High reducing and antiradical activity was confirmed for quercetin, rutin, hesperetin, and calcium dobesilate. Therefore, in addition to other therapeutic applications, some VPs could be potential candidates as antiglycative agents to prevent AGE-related complications of diabetes.


Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Animais , Antioxidantes/metabolismo , Cromatografia Líquida de Alta Pressão , Hesperidina/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Aldeído Pirúvico/farmacologia , Espectrometria de Massas por Ionização por Electrospray
4.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576198

RESUMO

Helicobacter pylori (H. pylori) is a bacterium known to infect the human stomach. It can cause various gastrointestinal diseases including gastritis and gastric cancer. Hesperetin is a major flavanone component contained in citrus fruits. It has been reported to possess antibacterial, antioxidant, and anticancer effects. However, the antibacterial mechanism of hesperetin against H. pylori has not been reported yet. Therefore, the objective of this study was to determine the inhibitory effects of hesperetin on H. pylori growth and its inhibitory mechanisms. The results of this study showed that hesperetin inhibits the growth of H. pylori reference strains and clinical isolates. Hesperetin inhibits the expression of genes in replication (dnaE, dnaN, dnaQ, and holB) and transcription (rpoA, rpoB, rpoD, and rpoN) machineries of H. pylori. Hesperetin also inhibits the expression of genes related to H. pylori motility (flhA, flaA, and flgE) and adhesion (sabA, alpA, alpB, hpaA, and hopZ). It also inhibits the expression of urease. Hespereti n downregulates major virulence factors such as cytotoxin-associated antigen A (CagA) and vacuolating cytotoxin A (VacA) and decreases the translocation of CagA and VacA proteins into gastric adenocarcinoma (AGS) cells. These results might be due to decreased expression of the type IV secretion system (T4SS) and type V secretion system (T5SS) involved in translocation of CagA and VacA, respectively. The results of this study indicate that hesperetin has antibacterial effects against H. pylori. Thus, hesperetin might be an effective natural product for the eradication of H. pylori.


Assuntos
Helicobacter pylori/efeitos dos fármacos , Hesperidina/farmacologia , Neoplasias Gástricas/metabolismo , Proteínas de Bactérias/metabolismo , Western Blotting , Flavanonas/farmacologia , Infecções por Helicobacter/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Fatores de Virulência
5.
Life Sci ; 285: 119957, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34530017

RESUMO

AIMS: Doxorubicin (Dox) is routinely used for breast cancer treatment but toxicity and drug resistance limit its use. The objective of the study was to investigate the protective effects of hesperidin alone and in combination with doxorubicin against experimentally induced breast cancer in female rats. METHODS: Breast cancer (BC) was induced by administration of 7,12-dimethylbenz(a)anthracene (DMBA) through subcutaneous injection into the 3rd right mammary gland of female Wistar rats. Hesperidin (Hes) pretreated groups were started with Hes (200 mg/kg) two weeks prior to DMBA induction. Animals were randomly divided into nine groups namely vehicle control, DMBA-induced, Dox 4 mg/kg, Dox 2 mg/kg, Hes (200 mg/kg), Hes (200 mg/kg) plus Dox 4 mg/kg treated groups and Hes pretreated groups treated with DMBA, Dox 4 mg/kg and Dox 2 mg/kg. KEY FINDINGS: Hes pretreated groups showed reduced tumor occurrence, tumor volume and increased survival rate as compared to DMBA-induced group of animals. Hes pretreated animals treated with Dox 4 mg/kg and 2 mg/kg exhibited significant reduction in malondialdehyde and improvement in levels of glutathione and inflammatory markers like IL-6, TNF-α, NF-κB, IFN-γ as compared to Dox 4 mg/kg and 2 mg/kg treated animals. Histopathology and Ki67 expression depicted better control of tumor with Hes pretreatment groups as compared to DMBA-induced. Histopathology of vital organs of Hes pretreated groups treated with Dox revealed lesser toxicity than Dox treated groups. SIGNIFICANCE: Hesperidin possesses protective effect against experimentally induced breast cancer in female rats that appears to be related to attenuation of Ki67 expression.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/prevenção & controle , Doxorrubicina/uso terapêutico , Hesperidina/uso terapêutico , Antígeno Ki-67/metabolismo , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/patologia , Carcinógenos/toxicidade , Quimioprevenção , Doxorrubicina/farmacologia , Feminino , Hesperidina/farmacologia , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/prevenção & controle , Ratos , Ratos Wistar
6.
Nutrients ; 13(8)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34444960

RESUMO

Hesperidin (HD) is a common flavanone glycoside isolated from citrus fruits and possesses great potential for cardiovascular protection. Hesperetin (HT) is an aglycone metabolite of HD with high bioavailability. Through the docking simulation, HD and HT have shown their potential to bind to two cellular proteins: transmembrane serine protease 2 (TMPRSS2) and angiotensin-converting enzyme 2 (ACE2), which are required for the cellular entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our results further found that HT and HD suppressed the infection of VeroE6 cells using lentiviral-based pseudo-particles with wild types and variants of SARS-CoV-2 with spike (S) proteins, by blocking the interaction between the S protein and cellular receptor ACE2 and reducing ACE2 and TMPRSS2 expression. In summary, hesperidin is a potential TMPRSS2 inhibitor for the reduction of the SARS-CoV-2 infection.


Assuntos
COVID-19/tratamento farmacológico , Hesperidina/química , Hesperidina/farmacologia , SARS-CoV-2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/metabolismo , COVID-19/virologia , Linhagem Celular Tumoral , Chlorocebus aethiops , Proteases Semelhantes à Papaína de Coronavírus/química , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , Humanos , Simulação de Acoplamento Molecular , SARS-CoV-2/metabolismo , Serina Endopeptidases/química , Serina Endopeptidases/efeitos dos fármacos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Vero
7.
J Physiol Biochem ; 77(3): 405-417, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34212313

RESUMO

Cholesterol efflux from macrophages is the first step of reverse cholesterol transport (RCT), whose increase inhibits cholesterol accumulation and foam cell formation to suppress atherogenesis. Hesperetin has been reported to exert several protective effects on cardiovascular diseases, while little is known about the role of hesperetin and its underlying mechanism in macrophage foam cell formation. In this study, we sought to investigate the potential effects of hesperetin on foam cell formation and cholesterol efflux by using human macrophages, focusing on liver X receptor alpha (LXRα) and AMPK. We found that hesperetin treatment reduced foam cell formation, intracellular cholesterol levels and the cholesterol esterification rate, and increased cholesterol efflux in THP-1 macrophages. Hesperetin increased the levels of LXRα protein and its targets, including ABCA1, ABCG1, SR-BI, and phosphorylated-AMPK. Meanwhile, the hesperetin-induced increase in LXRα expression was further increased by the AMPK agonist and inhibited by an AMPK inhibitor. Meanwhile, hesperetin increased the levels of LXRα mRNA and its target genes, all of which were decreased in cells transfected with the AMPKα1/α2 small interfering RNA (siRNA). Furthermore, the hesperetin-induced inhibition of foam cell formation and promotion of cholesterol efflux were decreased by transfection of AMPKα1/α2 siRNA. In conclusions, We are the first to report that hesperetin activate AMPK in THP-1-derived macrophages. This activation upregulats LXRα and its targets, including ABCA1, ABCG1 and SR-BI, which significantly inhibits foam cell formation and promotes cholesterol efflux. Our results highlight the therapeutic potential of hesperetin to possibly reduce foam cell formation. This new mechanism might contribute the anti-atherogenic effects of hesperetin.


Assuntos
Colesterol/metabolismo , Células Espumosas/efeitos dos fármacos , Hesperidina/farmacologia , Aterosclerose/metabolismo , Células Espumosas/patologia , Humanos , Receptores X do Fígado/metabolismo , Proteínas Quinases/metabolismo , Células THP-1
8.
Arch Oral Biol ; 129: 105208, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34298255

RESUMO

OBJECTIVE: To evaluate the action of hesperidin (HPN) at different concentrations to prevent dentin erosive wear, associated or not to abrasion. METHODS: A study with 6 experimental groups (n = 10) for erosion (experiment 1) and another 6 for erosion + abrasion (experiment 2). The treatments were: distilled water (DW), DW with collagenase (DW + Col), 0.46% epigallocatechin-3-gallate (EGCG) and 0.1%, 0.5% or 1% HPN. The specimens were submitted to a cycle (3x/day) for 5 days that consisted of immersion on 1% citric acid (5 min), artificial saliva (60 min), treatment (5 min), brushing (150 movements only in experiment 2), and artificial saliva (60 min / overnight). Collagenase was added in artificial saliva for all groups except DW-group. Dentin changes were assessed with optical profilometry and scanning electron microscopy. Data were submitted to one-way analysis of variance and Tukey tests (α = 0.05). RESULTS: For experiment 1, DW showed the lowest wear and did not significantly differ from EGCG. DW + Col showed the highest wear, being significantly different from HPN at 1%. In experiment 2, DW showed the lowest wear and DW + Col the highest. EGCG showed less wear than the three groups treated with HPN. In addition, for both cycling models, there were no significant differences among the three concentrations of HPN analyzed. In micrographs of HPN-treated groups, it could be observed the formation of a barrier on the dentin that promoted the obliteration of the tubules. CONCLUSIONS: HPN was able to preserve the demineralized organic matrix layer but did not overcome the effect of EGCG.


Assuntos
Hesperidina , Abrasão Dentária , Erosão Dentária , Dentina , Hesperidina/farmacologia , Humanos , Saliva Artificial , Abrasão Dentária/prevenção & controle , Erosão Dentária/prevenção & controle , Escovação Dentária
9.
Angiol Sosud Khir ; 27(2): 82-91, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34166347

RESUMO

BACKGROUND: In Russia, physicians are virtually unaware of drugs based on needle extract. However, abroad, saponins and, in particular, a combined preparation containing needle extract, hesperidin and vitamin C is one of drugs of choice, if not the leading medication in treatment of venous oedemas and other venous symptoms. AIM: The authors conducted a systematic review of the Russian-and English-language literature using the following search terms: saponins, hesperidin, needle, ruscus, ruscogenin (and their Russian equivalents), each of which was entered in a combination with the word 'venous' or its Russian equivalent, respectively. RESULTS: Ruscogenin and neoruscogenin from the root of needle possess anti-inflammatory properties and induce venous wall contraction, thus making it possible to use needle extract in treatment of chronic venous insufficiency. It was experimentally determined that needle extract stimulates vein contractility, decreasing permeability of the venous wall, influencing extracellular matrix proteins, inhibiting leukocyte migration through regulation of both proteins and matrix ribonucleic acid. Analysed herein are the results of original studies of a combination of needle extract, flavonoid hesperidin methyl chalcone and ascorbic acid, also examining in detail the mechanism of action conditioned by synergism of pharmacological effects of these components. This is followed by discussing the place of saponins in the classification of phlebotropic drugs and comparing efficacy of needle root extract with that of other phlebotonics. CONCLUSION: It was experimentally determined that a combination of needle extract, hesperidin and vitamin C possesses multiple additive phlebotropic effects. According to clinical trials, it leads to relief of most symptoms and a decrease in the ankle volume (high level of evidence 1A), being not inferior by clinical efficiency and duration of action to the best-known flavonoids, whereas by the venotonizing effect, decreased permeability of the vascular wall, and inhibition of leukocytic aggression even superior thereto. Further experimental and clinical studies of efficacy of this combination for various forms of chronic venous diseases and venous thromboses are warranted.


Assuntos
Hesperidina , Ruscus , Insuficiência Venosa , Ácido Ascórbico , Hesperidina/farmacologia , Humanos , Extratos Vegetais/farmacologia , Federação Russa , Insuficiência Venosa/tratamento farmacológico
10.
Life Sci ; 281: 119730, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34147482

RESUMO

AIM: High dose of fluoride intake is associated with toxic effects on liver and kidney tissues. One approach to tackle these toxicities is using natural antioxidants as supplements. This study evaluated the ameliorative effects of hesperidin (HSP) against sodium fluoride (NaF)-induced hepatotoxicity and nephrotoxicity in wistar albino rats. MATERIALS AND METHODS: In the present study, the rats were randomly allocated into five groups of seven male rats each group: control, NaF (600 ppm), HSP-200, NaF + HSP-100 and NaF + HSP 200. KEY FINDINGS: Hepatic and renal injuries induced by NaF were confirmed by the alteration in kidney function parameters in the serum (urea and creatinine), levels of liver enzymes (ALT, ALP and AST), activities of the antioxidant enzymes (SOD, CAT and GPx) and levels of inflammatory markers (NF-κB, IL-1ß and TNF-α). NaF also inhibited PI3K/Akt/mTOR pathway, increased levels of autophagic markers (Beclin-1, LC3A and LC3B) and expression levels of apoptotic and anti-apoptotic proteins (Bax, Bcl-2, cytochrome c, p53 and procaspase-3) in the liver and kidney tissues. Administration of HSP concurrently with NaF significantly ameliorated the deviation in the above-studied parameters. SIGNIFICANCE: The results of the current study revealed that HSP could be used as a beneficial adjuvant that confers protection against NaF-induced liver and kidney damage through antioxidant, anti-inflammatory, anti-apoptotic and anti-autophagic mechanisms.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Hesperidina/farmacologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fluoreto de Sódio/toxicidade , Animais , Biomarcadores/metabolismo , Inflamação/metabolismo , Inflamação/prevenção & controle , Rim/metabolismo , Fígado/metabolismo , Masculino , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Serina-Treonina Quinases TOR/metabolismo
11.
Am J Chin Med ; 49(5): 1251-1274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34107857

RESUMO

Neohesperidin has anti-oxidative and anti-inflammatory properties and exerts extensive therapeutic effects on various cancers. In this study, the osteosarcoma cell lines were exposed to different concentrations of neohesperidin. Cell proliferation and viability were assessed by CCK-8 and colony-formation assays. The role of neohesperidin in cell cycle progression and apoptosis were analyzed by flow cytometry and western blotting. To identify autophagosomes and autolysosomes, we used a tandem GFP-mRFP-LC3B lentiviral construct. In addition, autophagy was evaluated by examining autophagosome formation using transmission electron microscopy. Intracellular reactive oxygen species (ROS) production was detected by fluorescence microscopy and flow cytometry. Subsequently, the activation of the ROS/JNK signaling pathway was investigated. Neohesperidin could inhibit proliferation and induce apoptosis in SJSA and HOS cells. The formation of autophagosomes indicated that autophagy occurred in neohesperidin-treated cells and the apoptotic effect of neohesperidin was significantly increased after the use of autophagy inhibitors. Subsequently, we found that neohesperidin-induced apoptosis and autophagy were related to the increase in ROS generation and were significantly inhibited by GSH. Moreover, neohesperidin induced activation of the c-Jun N-terminal kinase (JNK) signaling pathway and inhibition of JNK with SP600125 attenuated neohesperidin-induced apoptosis and autophagy simultaneously. Our data indicated that neohesperidin caused G2/M phase arrest and induced apoptosis and autophagy by activating the ROS/JNK pathway in human osteosarcoma cells, suggesting that neohesperidin is a potential drug candidate for the treatment of osteosarcomas.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Hesperidina/análogos & derivados , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Osteossarcoma/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Hesperidina/farmacologia , Humanos
12.
J Food Biochem ; 45(7): e13800, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34047379

RESUMO

Plant flavonoids have been emerged as a potent anticancerous agent by exhibiting significant growth inhibitory potential and apoptotic induction in several carcinomas via targeting several oncoproteins. However, inverse association of hesperidin with Jab1 oncoprotein in cervical cancer has rarely been reported. Thus, we have intended our research study towards establishing this unexplored inverse correlation of hesperidin with Jab1 which could further prevent cervical cancer progression. Our research findings clearly demonstrated that hesperidin treatment resulted in Jab1 gene down-regulation and p27 up-regulation in a dose-dependent manner in HeLa cancer cells. These gene modulations might occur via excessive reactive oxygen species (ROS) generation and caspase-3 activation which further resulted in apoptotic induction. Increase in apoptotic cells was confirmed through Hoechst staining and cell cycle analysis. Thus, these results strongly suggested that Jab1 is a potent therapeutic target of hesperidin to suppress cell growth and trigger apoptosis in HeLa cells. PRACTICAL APPLICATIONS: Dietary flavonoids play a crucial role in the management of numerous malignancies via targeting several mutated oncogenes. Our study strongly exhibited that hesperidin treatment suppressed the HeLa cancer cell proliferation via increased ROS generation and reduced Jab1 mRNA expression. Thus, the inference of Jab1-mediated intracellular signals by hesperidin might be a novel approach to control cervical cancer.


Assuntos
Hesperidina , Neoplasias do Colo do Útero , Apoptose , Proliferação de Células , Feminino , Células HeLa , Hesperidina/farmacologia , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética
13.
Int J Biol Macromol ; 183: 908-917, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33965489

RESUMO

The biological activity of neohesperidin (NH, a flavanone glycoside) is limited due to instability in the physiological environment. Thus, the current study aimed to explore the protective effect of NH-loaded pectin-chitosan decorated liposomes (P-CH-NH-NL) against palmitic acid (PA)-induced hepatic oxidative injury in L02 cells. The particles were characterized using DLS, TEM, HPLC, DSC, and cellular uptake study. Then, the protective effect of NH-loaded liposomal systems (NH-NLs) against PA-induced oxidative injury was evaluated in terms of cell viability study, intracellular ROS, superoxide ions (O2-), MMP, and cellular GSH determination. Our results exhibited that NH-NLs significantly lessened the PA-induced hepatic oxidative injury in L02 cells via decreasing ROS and O2- generation, reducing MMP collapse, and attenuating GSH reduction, whereas the free NH samples were ineffective. Furthermore, the coated NH-NLs were more effective than that of uncoated nanoliposome. Overall, our study confirmed that P-CH-NH-NL was capable of reducing PA-induced hepatic oxidative injury. Therefore, the pectin-chitosan decorated nanoliposome can be considered as an efficient delivery system for enhancing cellular uptake of lipophilic compound with controlled release and greater biological activity.


Assuntos
Quitosana/química , Hesperidina/análogos & derivados , Lipossomos/química , Ácido Palmítico/toxicidade , Pectinas/química , Hesperidina/química , Hesperidina/farmacologia , Humanos , Fígado/metabolismo , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos
14.
Food Funct ; 12(9): 3898-3918, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33977953

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease. Dietary supplementation has become a promising strategy for managing NAFLD. Hesperetin, a citrus flavonoid, is mainly found in citrus fruits (oranges, grapefruit, and lemons) and possesses multiple pharmacological properties, including anti-cancer, anti-Alzheimer and anti-diabetic effects. However, the anti-NAFLD effect and mechanisms of hesperetin remain unclear. In this study, we investigated the therapeutic effect of hesperetin against NAFLD and the underlying mechanism in vitro and in vivo. In oleic acid (OA)-induced HepG2 cells, hesperetin upregulated antioxidant levels (SOD/GPx/GR/GCLC/HO-1) by triggering the PI3 K/AKT-Nrf2 pathway, alleviating OA-induced reactive oxygen species (ROS) overproduction and hepatotoxicity. Furthermore, hesperetin suppressed NF-κB activation and reduced inflammatory cytokine secretion (TNF-α and IL-6). More importantly, we revealed that this anti-inflammatory effect is attributed to reduced ROS overproduction by the Nrf2 pathway, as pre-treatment with Nrf2 siRNA or an inhibitor of superoxide dismutase (SOD) or/and glutathione peroxidase (GPx) abolished hesperetin-induced NF-κB inactivation and reductions in inflammatory cytokine secretion. In a rat model of high-fat diet (HFD)-induced NAFLD, we confirmed that hesperetin relieved hepatic steatosis, oxidative stress, inflammatory cell infiltration and fibrosis. Moreover, hesperetin activated the PI3 K/AKT-Nrf2 pathway in the liver, increasing antioxidant expression and inhibiting NF-κB activation and inflammatory cytokine secretion. In summary, our results demonstrate that hesperetin ameliorates hepatic oxidative stress through the PI3 K/AKT-Nrf2 pathway and that this antioxidative effect further suppresses NF-κB-mediated inflammation during NAFLD progression. Thus, our study suggests that hesperetin may be an effective dietary supplement for improving NAFLD by suppressing hepatic oxidative stress and inflammation.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Hepatócitos/efeitos dos fármacos , Hesperidina/farmacologia , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Elementos de Resposta Antioxidante , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Interleucina-6/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Ácido Oleico/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Fator de Transcrição RelA/metabolismo , Ativação Transcricional , Fator de Necrose Tumoral alfa/metabolismo
15.
J Orthop Surg Res ; 16(1): 334, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34020675

RESUMO

BACKGROUND: Osteoporosis is a common disease in aging populations. However, osteoporosis treatment is still challenging. Here, we aimed to investigate the role of neohesperidin (NEO) in osteoporosis progression and the potential mechanism. METHODS: Bone mesenchymal stem cells (BMSCs) were isolated and treated with different concentrations of NEO (0, 10, 30, 100 µM). Cell proliferation was analyzed by cell count kit-8 (CCK-8) assay. RNA-sequencing was performed on the isolated BMSCs with control and NEO treatment. Differentially expressed genes were obtained by R software. Alkaline phosphatase (ALP) staining and Alizarin red staining (ARS) were performed to assess the osteogenic capacity of the NEO. qRT-PCR was used to detect the expression of osteoblast markers. Western blot was used to evaluate the protein levels in BMSCs. RESULTS: NEO treatment significantly improved hBMSC proliferation at different time points, particularly when cells were incubated with 30 µM NEO (P < 0.05). NEO dose-dependently increased the ALP activity and calcium deposition than the control group (P < 0.05). A total of 855 differentially expressed genes were identified according to the significance criteria of log2 (fold change) > 1 and adj P < 0.05. DKK1 partially reversed the promotion effects of NEO on osteogenic differentiation of BMSCs. NEO increased levels of the ß-catenin protein in BMSCs. CONCLUSION: NEO plays a positive role in promoting osteogenic differentiation of BMSCs, which was related with activation of Wnt/ß-catenin pathway.


Assuntos
Osso e Ossos/citologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Hesperidina/análogos & derivados , Células-Tronco Mesenquimais/fisiologia , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genética , beta Catenina/metabolismo , Fosfatase Alcalina/metabolismo , Cálcio/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Células Cultivadas , Relação Dose-Resposta a Droga , Hesperidina/farmacologia , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteoporose/genética , Osteoporose/metabolismo , Osteoporose/patologia
16.
Biomed Pharmacother ; 139: 111552, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33839495

RESUMO

Hesperetin (HSP) is a natural flavonoid that offers useful curative effects for cardiovascular diseases, but its effect on myocardial ischemia and its precise mechanism remains unclear. The aim of this study is to explore the potential cardioprotective mechanism of HSP on myocardial ischemia caused by isoproterenol (ISO). Adult male Kunming mice were randomly divided into five groups: control, ISO, low-dose HSP (L-HSP, 25 mg/kg/d), high-dose HSP (H-HSP, 50 mg/kg/d), and verapamil (VER) group. Treatment groups of mice received HSP or VER for seven days, and the groups other than the control group were injected with ISO (100 mg/kg/d) subcutaneously for two consecutive days to establish a model of myocardial ischemia. Electrocardiogram and heart-histology changes were used to assess changes in myocardial architecture. The activities and the content of oxidative stress markers and inflammatory cytokines were determined and assayed using kits respectively. The expressions of proteins associated with apoptosis and the Sirt1/Nrf2 pathway were evaluated by Western blotting. The results demonstrate that VER, L-HSP and H-HSP significantly reduced the J-point displacement, heart rate, cardiac pathomorphological changes, and the levels of creatine kinase, lactated dehydrogenase, malonaldehyde, interleukin-6, and tumor necrosis factor-α in serum while promoting the activation of superoxide dismutase, catalase, glutathione in serum in the ISO-treated animals. Furthermore, L-HSP and H-HSP also reversed the ISO-induced apoptosis and the changes in the Sirt1/Nrf2 signaling pathway, as evident from the levels of proteins Bax, Bcl-2, caspase-3, Sirt1, Nrf2, NQO-1, and HO-1. In conclusion, HSP plays a protective role in ISO-induced myocardial ischemia by modulating oxidative stress, inflammation, and apoptosis via Sirt1/Nrf2 pathway activation.


Assuntos
Apoptose/efeitos dos fármacos , Hesperidina/farmacologia , Inflamação/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Relação Dose-Resposta a Droga , Eletrocardiografia/efeitos dos fármacos , Testes de Função Cardíaca , Masculino , Camundongos , Miocárdio/patologia , Vasodilatadores/uso terapêutico , Verapamil/uso terapêutico
17.
Environ Toxicol ; 36(8): 1600-1617, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33908150

RESUMO

In this study, we investigated the effects of hesperidin (HSP) on oxidants/antioxidants status, inflammation, apoptotic, and autophagic activity in hepato-renal toxicity induced by chronic chlorpyrifos (CPF) exposure in rats. We used a total of 35 male albino rats in five groups of seven: control, HSP 100, CPF, CPF + HSP50, and CPF + HSP100. After rats were sacrificed, blood, liver, and kidney samples were collected. Serum levels of aspartate aminotransferases (ALT and AST), alkaline phosphatase (ALP), creatinine, and urea were tested. Then, contents of the superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GPx), and glutathione (GSH) were measured to detect the level of oxidative stress in rat liver and renal tissues. We measured inflammatory and autophagy markers of chlorpyrifos induced oxidative stress in the liver and kidney tissues including TNF-α, iNOS, IL-1 ß, COX-2, NF-κB, MAPK14, and Beclin-1 using ELISA. Histopathological findings were also examined followed by immunohistochemical determination of 8-OHdG expression. Real-time PCR (RT-PCR) was used to examine Cas-3, Bax, Bcl-2, PARP-1, and VEGF, which are associated with apoptosis, autophagy, DNA, and endothelial damage, respectively. In addition, PARP-1 activity was supported by western blot and immunofluorescence, VEGF activity was supported by western blot methods. Treatment with HSP reduced the effect of CPF on ALT, AST, ALP, and total proteins, and increased its effect on tissue antioxidants. PARP/VEGF, apoptotic, pro-apoptotic, anti-apoptotic, and autophagic gene expressions were regulated, and Caspase-3 and Bax expressions were decreased; Bcl-2 expression increased in both the liver and kidney samples, and positivity of 8-OHdG and PARP-1 were reduced in the CPF plus HSP-treated group. Overall, the study demonstrates that HSP may reduce the effects of hepato-renal toxicity caused by CPF by regulating oxidative stress, inflammation, apoptosis, autophagy, and PARP/VEGF genes at biochemical, cellular, and molecular levels.


Assuntos
Clorpirifos , Hesperidina , Animais , Antioxidantes/metabolismo , Apoptose , Autofagia , Hesperidina/farmacologia , Inflamação/metabolismo , Fígado , Masculino , Estresse Oxidativo , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Ratos , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Environ Sci Pollut Res Int ; 28(34): 47046-47055, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33886055

RESUMO

Nephrotoxicity is a very important complication of 5-fluorouracil (5-FU)-treated cancer patients. Increased oxidative stress, kidney damage, and apoptosis play an important role in the pathogenesis of nephrotoxicity caused by 5-FU. In this study, protective effects of two natural compounds, hesperidin and curcumin, on experimentally induced kidney damage in mice with 5-FU were determined. Application of 5-FU resulted in severe histopathological changes and severe renal failure with increased serum urea and creatinine levels. Also, 5-FU-induced kidney damage, increased levels of malondialdehyde (MDA), decreased superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) activity, and glutathione (GSH) level have been demonstrated. Also, where 5-FU is in the concentration of caspase-3 and 8-OHdG immune-positive cells and therefore causes apoptosis and DNA damage in kidney tissue cells. However, especially high doses of hesperidin and curcumin treatment significantly improved 5-FU-induced oxidative stress/lipid peroxidation, apoptosis/DNA damage, and renal dysfunction. Based on these data, our results suggest that hesperidin and curcumin may be used as new and promising agents against 5-FU-induced nephrotoxicity.


Assuntos
Curcumina , Hesperidina , Insuficiência Renal , Animais , Antioxidantes/metabolismo , Curcumina/metabolismo , Curcumina/farmacologia , Fluoruracila/toxicidade , Glutationa/metabolismo , Hesperidina/farmacologia , Humanos , Rim/metabolismo , Malondialdeído/metabolismo , Camundongos , Estresse Oxidativo , Superóxido Dismutase/metabolismo
19.
J Biochem Mol Toxicol ; 35(7): e22787, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33830595

RESUMO

Local anesthetic with bupivacaine (BV) administration may cause severe neurotoxicity and neurological complications in developing neurons. Any substances that can mitigate the toxic effects of BV are of great importance in surgical procedures and pain management. The present study attempted to investigate if hesperidin (HN) could inhibit or prevent BV-induced neurotoxicity in SH-SY5Y cells. Exposure of BV at 5 mM resulted in a significant decrease of cell viability and a remarkable increase of lactate dehydrogenase release via the induction of apoptosis and production of reactive oxygen species. Moreover, a loss of mitochondrial membrane potential, decreased Bcl-2 protein expression, as well as increased expression of cytoplasmic cytochrome c, Bax, and cleaved caspase-3 protein was also observed in BV-stimulated SH-SY5Y cells. In addition, BV stimulation impaired the balance of oxidation-reduction and inflammation system, as evidenced by the increased malondialdehyde content, decreased superoxide dismutase and catalase activity, and reduced level of reduced glutathione, interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α. However, these iatrogenic changes were all reversed by the HN (5, 10, and 20 µM) supplement for 48 h in a concentration-dependent manner. In conclusion, HN can protect SH-SY5Y cells against BV-stimulated neurotoxicity via the inhibition of apoptosis, oxidative stress, and inflammation response. The present findings suggested that HN may be an effective alternative agent to inhibit or prevent BV-induced neurotoxicity in human patients.


Assuntos
Anestésicos Locais/efeitos adversos , Apoptose/efeitos dos fármacos , Bupivacaína/efeitos adversos , Hesperidina/farmacologia , Síndromes Neurotóxicas , Estresse Oxidativo/efeitos dos fármacos , Anestésicos Locais/farmacologia , Bupivacaína/farmacologia , Linhagem Celular Tumoral , Humanos , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia
20.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33810030

RESUMO

This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin's influence in mineralized tissue formation and regeneration. Hesperidin was added to a culture of MC3T3-E1 cells at various concentrations. Cell proliferation, viability, osteogenic gene expression and deposited collagen matrix analyses were performed. Treatment with hesperidin showed significant upregulation of osteogenic markers, particularly with lower doses. Mature and compact collagen fibrils in hesperidin-treated cultures were observed by picrosirius red staining (PSR), although a thinner matrix layer was present for the higher dose of hesperidin compared to osteogenic media alone. Fourier-transform infrared spectroscopy indicated a better mineral-to-matrix ratio and matrix distribution in cultures exposed to hesperidin and confirmed less collagen deposited with the 100-µM dose of hesperidin. In vivo, hesperidin combined with a suboptimal dose of bone morphogenetic protein 2 (BMP2) (dose unable to promote healing of a rat mandible critical-sized bone defect) in a collagenous scaffold promoted a well-controlled (not ectopic) pattern of bone formation as compared to a large dose of BMP2 (previously defined as optimal in healing the critical-sized defect, although of ectopic nature). PSR staining of newly formed bone demonstrated that hesperidin can promote maturation of bone organic matrix. Our findings show, for the first time, that hesperidin has a modulatory role in mineralized tissue formation via not only osteoblast cell differentiation but also matrix organization and matrix-to-mineral ratio and could be a potential adjunct in regenerative bone therapies.


Assuntos
Calcificação Fisiológica/efeitos dos fármacos , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Hesperidina/farmacologia , Osteogênese/efeitos dos fármacos , Animais , Proteína Morfogenética Óssea 2/farmacologia , Regeneração Óssea , Linhagem Celular , Células Cultivadas , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Ratos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...