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1.
PLoS One ; 19(6): e0304701, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38870120

RESUMO

This paper presents the initial exploration of the free radical scavenging capabilities of peptides derived from protein hydrolysates (PPH) obtained from Zingiber cassumunar rhizomes (Phlai). To replicate the conditions of gastrointestinal digestion, a combination of pepsin and pancreatin proteolysis was employed to generate these hydrolysates. Subsequently, the hydrolysate underwent fractionation using molecular weight cut-off membranes at 10, 5, 3, and 0.65 kDa. The fraction with a molecular weight less than 0.65 kDa exhibited the highest levels ABTS, DPPH, FRAP, and NO radical scavenging activity. Following this, RP-HPLC was used to further separate the fraction with a molecular weight less than 0.65 kDa into three sub-fractions. Among these, the F5 sub-fraction displayed the most prominent radical-scavenging properties. De novo peptide sequencing via quadrupole-time-of-flight-electron spin induction-mass spectrometry identified a pair of novel peptides: Asp-Gly-Ile-Phe-Val-Leu-Asn-Tyr (DGIFVLNY or DY-8) and Ile-Pro-Thr-Asp-Glu-Lys (IPTDEK or IK-6). Database analysis confirmed various properties, including biological activity, toxicity, hydrophilicity, solubility, and potential allergy concerns. Furthermore, when tested on the human adenocarcinoma colon (Caco-2) cell line, two synthetic peptides demonstrated cellular antioxidant activity in a concentration-dependent manner. These peptides were also assessed using the FITC Annexin V apoptosis detection kit with PI, confirming the induction of apoptosis. Notably, the DY-8 peptide induced apoptosis, upregulated mRNA levels of caspase-3, -8, and -9, and downregulated Bcl-2, as confirmed by real-time quantitative polymerase chain reaction (RT-qPCR). Western blot analysis indicated increased pro-apoptotic Bax expression and decreased anti-apoptotic Bcl-2 expression in Caco-2 cells exposed to the DY-8 peptide. Molecular docking analysis revealed that the DY-8 peptide exhibited binding affinity with Bcl-2, Bcl-xL, and Mcl-1, suggesting potential utility in combating colon cancer as functional food ingredients.


Assuntos
Apoptose , Neoplasias do Colo , Peptídeos , Rizoma , Transdução de Sinais , Humanos , Apoptose/efeitos dos fármacos , Rizoma/química , Células CACO-2 , Transdução de Sinais/efeitos dos fármacos , Peptídeos/farmacologia , Peptídeos/química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Zingiberaceae/química , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química
2.
BMC Complement Med Ther ; 24(1): 241, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902620

RESUMO

Iron nanoparticles comprise a significant class of inorganic nanoparticles, which discover applications in various zones by prudence of their few exciting properties. This study achieved the green synthesis of iron oxide nanoparticles (IONPs) by black cumin seed (Nigella sativa) extract, which acts as a reducing and capping agent. The iron nanoparticles and black cumin extract were synthesized in three different concentrations: (01:01, 02:04,01:04). UV-visible spectroscopy, XRD, FTIR, and AFM characterized the synthesized iron oxide nanoparticles. UV-visible spectra show the maximum absorbance peak of 01:01 concentration at 380 nm. The other concentrations, such as 02:04, peaked at 400 nm and 01:04 at 680 nm, confirming the formation of iron oxide nanoparticles. AFM analysis reveals the spherical shape of iron oxide nanoparticles. The XRD spectra reveal the (fcc) cubic crystal structure of the iron oxide nanoparticles. The FTIR analysis's peaks at 457.13, 455.20, and 457.13 cm-1 depict the characteristic iron nanoparticle synthesis. The black cumin extract-mediated iron oxide nanoparticles show substantial antibacterial, antifungal, antioxidant and anti-inflammatory activity in a dose-dependent manner.


Assuntos
Anti-Infecciosos , Anti-Inflamatórios , Nigella sativa , Extratos Vegetais , Sementes , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Sementes/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Nigella sativa/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Nanopartículas Magnéticas de Óxido de Ferro/química , Compostos Férricos/química , Química Verde
3.
ACS Appl Mater Interfaces ; 16(25): 32649-32661, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38865694

RESUMO

Ultraviolet (UV) filters are the core ingredients in sunscreens and protect against UV-induced skin damage. Nevertheless, their safety and effectiveness have been questioned in terms of their poor photostability, skin penetration, and UV-induced generation of deleterious reactive oxygen species (ROS). Herein, an organic UV filter self-framed microparticle sunblock was exploited, in which quercetin (QC) and hexachlorocyclotriphosphazene (HCCP) were self-constructed into microparticles (HCCP-QC MPs) by facile precipitation polymerization without any carriers. HCCP-QC MPs could not only significantly extend the UV shielding range to the whole UV region but also remarkably reduce UV-induced ROS while avoiding direct skin contact and the resulting epidermal penetration of small-molecule QC. Meanwhile, HCCP-QC MPs possess a high QC-loading ability (697 mg g-1) by QC itself as the microparticles' building blocks. In addition, there is no leakage issue with small molecules due to its covalently cross-linked structure. In vitro and vivo experiments also demonstrated that the HCCP-QC MPs have excellent UV protection properties and effective ROS scavenging ability without toxicity. In summary, effective UV-shielding and ROS scavenging ability coupled with excellent biocompatibility and nonpenetration of small molecules make it a broad prospect in skin protection.


Assuntos
Sequestradores de Radicais Livres , Compostos Organofosforados , Polímeros , Espécies Reativas de Oxigênio , Pele , Protetores Solares , Raios Ultravioleta , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Polímeros/química , Polímeros/farmacologia , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Pele/metabolismo , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Protetores Solares/química , Protetores Solares/farmacologia , Humanos , Camundongos , Quercetina/química , Quercetina/farmacologia
4.
J Nanobiotechnology ; 22(1): 321, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849841

RESUMO

Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1ß and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.


Assuntos
Lesão Pulmonar Aguda , Cério , Indóis , Polímeros , Espécies Reativas de Oxigênio , Cério/química , Cério/farmacologia , Animais , Lesão Pulmonar Aguda/tratamento farmacológico , Polímeros/química , Polímeros/farmacologia , Indóis/química , Indóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Ratos , Camundongos , Masculino , Células RAW 264.7 , Pulmão/efeitos dos fármacos , Pulmão/patologia , Antioxidantes/farmacologia , Antioxidantes/química , Ratos Sprague-Dawley , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Raios Infravermelhos , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/uso terapêutico , Nanopartículas/química , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Citocinas/metabolismo
5.
Int J Mol Sci ; 25(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38892102

RESUMO

The synthesis, antioxidant capacity, and anti-inflammatory activity of four novel N-benzyl-2-[4-(aryl)-1H-1,2,3-triazol-1-yl]ethan-1-imine oxides 10a-d are reported herein. The nitrones 10a-d were tested for their antioxidant properties and their ability to inhibit soybean lipoxygenase (LOX). Four diverse antioxidant tests were used for in vitro antioxidant assays, namely, interaction with the stable free radical DPPH (1,1-diphenyl-2-picrylhydrazyl radical) as well as with the water-soluble azo compound AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride), competition with DMSO for hydroxyl radicals, and the scavenging of cationic radical ABTS•+ (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation). Nitrones 10b, 10c, and 10d, having the 4-fluorophenyl, 2,4-difluorophenyl, and 4-fluoro-3-methylphenyl motif, respectively, exhibited high interaction with DPPH (64.5-81% after 20 min; 79-96% after 60 min), whereas nitrone 10a with unfunctionalized phenyl group showed the lowest inhibitory potency (57% after 20 min, 78% after 60 min). Nitrones 10a and 10d, decorated with phenyl and 4-fluoro-3-methylphenyl motif, respectively, appeared the most potent inhibitors of lipid peroxidation. The results obtained from radical cation ABTS•+ were not significant, since all tested compounds 10a-d showed negligible activity (8-46%), much lower than Trolox (91%). Nitrone 10c, bearing the 2,4-difluorophenyl motif, was found to be the most potent LOX inhibitor (IC50 = 10 µM).


Assuntos
Antioxidantes , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/síntese química , Lipoxigenase/metabolismo , Glycine max/enzimologia , Glycine max/química , Inibidores de Lipoxigenase/farmacologia , Inibidores de Lipoxigenase/química , Inibidores de Lipoxigenase/síntese química , Triazóis/química , Triazóis/farmacologia , Triazóis/síntese química , Iminas/química , Iminas/farmacologia , Compostos de Bifenilo/química , Compostos de Bifenilo/antagonistas & inibidores , Picratos/química , Picratos/antagonistas & inibidores , Óxidos de Nitrogênio/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/síntese química
6.
Int J Mol Sci ; 25(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38892468

RESUMO

The biological activities and related mechanisms of curcumin, a major polyphenolic compound in turmeric, the rhizome of Curcuma longa, have been extensively investigated. Due to its poor solubility in water, the analysis of curcumin's biological activities is limited in most aqueous experimental systems. In the present study, the effects of polyvinyl alcohol (PVA), a dietary-compatible vehicle, on the solubility, stability, cellular uptake, and bioactivities of curcumin were investigated. Curcumin solubility was improved significantly by PVA; the color intensity of curcumin aqueous solution in the presence of PVA increased concentration-dependently with its peak shift to a shorter wavelength. Improved suspension stability and photostability of curcumin in an aqueous solution were also observed in the presence of PVA, even at 62.5 µg/mL. The scavenging activities of curcumin against DPPH, ABTS, AAPH radicals, and nitric oxide were enhanced significantly in the presence of PVA. PVA at 250 µg/mL also significantly enhanced the cytotoxic activity of curcumin against both HCT 116 colon cancer and INT 407 (HeLa-derived) embryonic intestinal cells by reducing the IC50 from 16 to 11 µM and 25 to 15 µM, respectively. PVA improved the cellular uptake of curcumin in a concentration-dependent manner in INT 407 cells; it increased the cellular levels more effectively at lower curcumin treatment concentrations. The present results indicate that PVA improves the solubility and stability of curcumin, and changes in these chemical behaviors of curcumin in aqueous systems by PVA could enhance the bioavailability and pharmacological efficacy of curcumin.


Assuntos
Curcumina , Álcool de Polivinil , Solubilidade , Curcumina/farmacologia , Curcumina/química , Álcool de Polivinil/química , Humanos , Estabilidade de Medicamentos , Células HCT116 , Células HeLa , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Sobrevivência Celular/efeitos dos fármacos
7.
J Mater Chem B ; 12(26): 6424-6441, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38860306

RESUMO

Gallic acid (GA), derived from land plants, possesses diverse physiological benefits, including anti-inflammatory and anticancer effects, making it valuable for biomedical applications. In this study, GA was used to modify the surface of dendritic mesoporous silica nanoparticles (DMSNs) via carbamate (DMSN-NCO-GA) or amide (DMSN-NH-GA) bonds, using a post-grafting technique. To explore GA-conjugated materials' potential in modulating cancer cell redox status, three variants of osteosarcoma cells (U2-OS) were used. These variants comprised the wild-type cells (NEO), the cells overexpressing the wild-type human Golgi anti-apoptotic protein (hGAAP), and the null mutant of hGAAP (Ct-mut), as this protein was previously demonstrated to play a role in intracellular reactive oxygen species (ROS) accumulation and cell migration. In the absence of external ROS triggers, non-modified DMSNs increased intracellular ROS in Ct-mut and NEO cells, while GA-conjugated materials, particularly DMSN-NH-GA, significantly reduced ROS levels, especially pronounced with higher GA concentrations and notably in hGAAP cells with inherently higher ROS levels. Additionaly, NH-GA conjugates were less cytotoxic, more effective in reducing cell migration, and had higher ROS buffering capacity compared to DMSN-NCO-GA materials. However, in the presence of the external stressor tert-butyl-hydroperoxide (TBHP), NCO-GA conjugates showed more efficient reduction of intracellular ROS. These findings suggest that varying chemical decoration strategies of nanomaterials, along with the accessibility of functional groups to the cellular environment, significantly influence the biological response in osteosarcoma cells. Highlighting this, GA-conjugation is a promising method for implementing antioxidant properties and inhibiting cancer cell migration, warranting further research in anticancer treatment and drug development.


Assuntos
Sequestradores de Radicais Livres , Ácido Gálico , Nanopartículas , Osteossarcoma , Dióxido de Silício , Humanos , Ácido Gálico/química , Ácido Gálico/farmacologia , Nanopartículas/química , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Dióxido de Silício/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Propriedades de Superfície , Tamanho da Partícula , Ensaios de Seleção de Medicamentos Antitumorais , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral
8.
Molecules ; 29(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38930835

RESUMO

Ginseng (Panax ginseng C.A. Mey) is known for its rich saponin compounds and tonic effects. To better utilize the medicinal value of ginseng, this study investigated the extraction process, components, free radical scavenging ability, and immunomodulatory activity of total saponins of ginseng fibrous roots. The response surface methodology was employed to optimize the extraction process of total saponins, and Q-Orbitrap high-resolution liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical constituents in the total saponins extract of ginseng fibrous roots (GRS). The results showed that the optimal extraction process was achieved with an ethanol concentration of 68%, a material-solvent ratio of 1:25 mL/g, and an extraction time of 20 min, yielding a total saponin content of 6.34% under these conditions. The extract contained four terpenoid compounds and four polyphenolic compounds. GRS exhibited considerable scavenging activity against DPPH and ABTS radicals, with IC50 values of 0.893 and 0.210 mg/mL, respectively. Moreover, GRS restored immune suppression in mice by increasing white blood cell, red blood cell, and neutrophil counts, and improving the lymphocyte. It also promoted immune system recovery, as evidenced by elevated serum levels of IL-2, IFN-γ, TNF-α, and IL-1ß in mice. GRS is a natural compound with promising potential for developing antioxidants and immunomodulatory foods.


Assuntos
Sequestradores de Radicais Livres , Panax , Extratos Vegetais , Raízes de Plantas , Saponinas , Panax/química , Saponinas/farmacologia , Saponinas/química , Saponinas/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Raízes de Plantas/química , Animais , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Antioxidantes/farmacologia , Antioxidantes/química
9.
ACS Appl Mater Interfaces ; 16(26): 33106-33120, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38906850

RESUMO

The scavenging ability of cerium oxide nanoparticles (CeNPs) for reactive oxygen species has been intensively studied in the field of catalysis. However, the immunological impact of these particles has not yet been thoroughly investigated, despite intensive research indicating that modulation of the reactive oxygen species could potentially regulate cell fate and adaptive immune responses. In this study, we examined the intrinsic capability of CeNPs to induce tolerogenic dendritic cells via their reactive oxygen species-scavenging effect when the autoantigenic peptides were simply mixed with CeNPs. CeNPs effectively reduced the intracellular reactive oxygen species levels in dendritic cells in vitro, leading to the suppression of costimulatory molecules as well as NLRP3 inflammasome activation, even in the presence of pro-inflammatory stimuli. Subcutaneously administrated PEGylated CeNPs were predominantly taken up by antigen-presenting cells in lymph nodes and to suppress cell maturation in vivo. The administration of a mixture of PEGylated CeNPs and myelin oligodendrocyte glycoprotein peptides, a well-identified autoantigen associated with antimyelin autoimmunity, resulted in the generation of antigen-specific Foxp3+ regulatory T cells in mouse spleens. The induced peripheral regulatory T cells actively inhibited the infiltration of autoreactive T cells and antigen-presenting cells into the central nervous system, ultimately protecting animals from experimental autoimmune encephalomyelitis when tested using a mouse model mimicking human multiple sclerosis. Overall, our findings reveal the potential of CeNPs for generating antigen-specific immune tolerance to prevent multiple sclerosis, opening an avenue to restore immune tolerance against specific antigens by simply mixing the well-identified autoantigens with the immunosuppressive CeNPs.


Assuntos
Cério , Células Dendríticas , Encefalomielite Autoimune Experimental , Tolerância Imunológica , Nanopartículas , Peptídeos , Espécies Reativas de Oxigênio , Cério/química , Cério/farmacologia , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/tratamento farmacológico , Nanopartículas/química , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Tolerância Imunológica/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/imunologia , Camundongos Endogâmicos C57BL , Autoantígenos/imunologia , Autoantígenos/química , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Feminino , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia
10.
ACS Appl Mater Interfaces ; 16(26): 33205-33222, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38915205

RESUMO

In diabetic patients with skin injuries, bacterial proliferation, accumulation of reactive oxygen species (ROS) in the tissues, and impaired angiogenesis make wound healing difficult. Therefore, eliminating bacteria, removing ROS, and promoting angiogenesis are necessary for treating acute diabetic wounds. In this study, benefiting from the ability of polyphenols to form a metal-phenolic network (MPN) with metal ions, TA-Eu MPN nanoparticles (TM NPs) were synthesized. The prepared photothermal agent CuS NPs and TM NPs were then loaded onto the supporting base and needle tips of PVA/HA (PH) microneedles, respectively, to obtain PH/CuS/TM microneedles. Antibacterial experiments showed that microneedles loaded with CuS NPs could remove bacteria by the photothermal effect. In vitro experiments showed that the microneedles could effectively scavenge ROS, inhibit macrophage polarization to the M1 type, and induce polarization to the M2 type as well as have the ability to promote vascular endothelial cell migration and angiogenesis. Furthermore, in vivo experiments showed that PH/CuS/TM microneedles accelerated wound healing by inhibiting pro-inflammatory cytokines and promoting angiogenesis in a diabetic rat wound model. Therefore, PH/CuS/TM microneedles have efficient antibacterial, ROS scavenging, anti-inflammatory, immunomodulatory, and angiogenic abilities and hold promise as wound dressings for treating acute diabetic wounds.


Assuntos
Antibacterianos , Diabetes Mellitus Experimental , Espécies Reativas de Oxigênio , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Espécies Reativas de Oxigênio/metabolismo , Ratos , Antibacterianos/farmacologia , Antibacterianos/química , Diabetes Mellitus Experimental/tratamento farmacológico , Camundongos , Neovascularização Fisiológica/efeitos dos fármacos , Agulhas , Ratos Sprague-Dawley , Humanos , Masculino , Células Endoteliais da Veia Umbilical Humana , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Células RAW 264.7 , Angiogênese
11.
Neuromolecular Med ; 26(1): 26, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907170

RESUMO

Spinal cord injury (SCI) causes irreversible cell loss and neurological dysfunctions. Presently, there is no an effective clinical treatment for SCI. It can be the only intervention measure by relieving the symptoms of patients such as pain and fever. Free radical-induced damage is one of the validated mechanisms in the complex secondary injury following primary SCI. Hydrogen sulfide (H2S) as an antioxidant can effectively scavenge free radicals, protect neurons, and improve SCI by inhibiting the p38MAPK/mTOR/NF-κB signaling pathway. In this report, we analyze the pathological mechanism of SCI, the role of free radical-mediated the p38MAPK/mTOR/NF-κB signaling pathway in SCI, and the role of H2S in scavenging free radicals and improving SCI.


Assuntos
Sequestradores de Radicais Livres , Sulfeto de Hidrogênio , NF-kappa B , Transdução de Sinais , Traumatismos da Medula Espinal , Serina-Treonina Quinases TOR , Proteínas Quinases p38 Ativadas por Mitógeno , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Sulfeto de Hidrogênio/uso terapêutico , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/metabolismo , Animais , Sequestradores de Radicais Livres/uso terapêutico , Sequestradores de Radicais Livres/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ratos , Camundongos , Radicais Livres/metabolismo , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Humanos
12.
Biomolecules ; 14(6)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38927041

RESUMO

The genus Brassica is an important source of food in the Mediterranean diet with documented nutritional and medicinal properties. However, few studies have investigated the phytochemical composition and the biological activity of wild Sicilian taxa. Thus, we aimed to study the chemical profile and the antioxidant potential, in vitro and in LPS-stimulated RAW 264.7 cells, of a methanolic extract of leaves of wild Brassica macrocarpa Guss (B. macrocarpa) (Egadi Islands; Sicily-Italy). B. macrocarpa methanolic extract showed a large amount of glucosinolates and different phenolic compounds. It exhibited antioxidant activity in the DPPH assay and in LPS-stimulated RAW 264.7 cells, being able to reduce NO and ROS levels and NOS2 mRNA expression. Our study demonstrated that Sicilian B. macrocarpa methanolic extract, in LPS-stimulated macrophages, efficiently counteracts oxidative stress and displays radical scavenging activity. Future studies are required to identify the contribution of the single phytocomponents, to characterize the action mechanism, and to reveal possible applications in human health.


Assuntos
Antioxidantes , Brassica , Sequestradores de Radicais Livres , Extratos Vegetais , Folhas de Planta , Células RAW 264.7 , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Camundongos , Folhas de Planta/química , Animais , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Brassica/química , Antioxidantes/farmacologia , Antioxidantes/química , Óxido Nítrico/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Lipopolissacarídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Fenóis/química , Sicília , Glucosinolatos/farmacologia , Glucosinolatos/química
13.
Int J Nanomedicine ; 19: 5995-6014, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895150

RESUMO

Introduction: To improve the bioavailability of trans-resveratrol (trans-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging. Methods: A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading trans-Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in trans-Res release. Results: Under protection of Ngel, trans-Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of trans-Res in the intestine. Ngel and Ngel@Res increased the lifespan of Caenorhabditis elegans to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of daf-16, sod-5 and skn-1, while downregulating the expression of daf-2 and age-1. Conclusion: This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of trans-Res.


Assuntos
Alginatos , Caenorhabditis elegans , Nanogéis , Espécies Reativas de Oxigênio , Resveratrol , Animais , Caenorhabditis elegans/efeitos dos fármacos , Resveratrol/farmacologia , Resveratrol/química , Resveratrol/farmacocinética , Resveratrol/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Alginatos/química , Alginatos/farmacologia , Nanogéis/química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/farmacocinética , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polietilenoimina/química , Polietilenoimina/farmacologia , Polietilenoimina/farmacocinética , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/farmacocinética , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética
14.
J Nanobiotechnology ; 22(1): 252, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750509

RESUMO

With increasing proportion of the elderly in the population, age-related diseases (ARD) lead to a considerable healthcare burden to society. Prevention and treatment of ARD can decrease the negative impact of aging and the burden of disease. The aging rate is closely associated with the production of high levels of reactive oxygen species (ROS). ROS-mediated oxidative stress in aging triggers aging-related changes through lipid peroxidation, protein oxidation, and DNA oxidation. Antioxidants can control autoxidation by scavenging free radicals or inhibiting their formation, thereby reducing oxidative stress. Benefiting from significant advances in nanotechnology, a large number of nanomaterials with ROS-scavenging capabilities have been developed. ROS-scavenging nanomaterials can be divided into two categories: nanomaterials as carriers for delivering ROS-scavenging drugs, and nanomaterials themselves with ROS-scavenging activity. This study summarizes the current advances in ROS-scavenging nanomaterials for prevention and treatment of ARD, highlights the potential mechanisms of the nanomaterials used and discusses the challenges and prospects for their applications.


Assuntos
Envelhecimento , Sequestradores de Radicais Livres , Nanoestruturas , Estresse Oxidativo , Espécies Reativas de Oxigênio , Espécies Reativas de Oxigênio/metabolismo , Humanos , Nanoestruturas/química , Envelhecimento/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/química
15.
J Org Chem ; 89(11): 8168-8177, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38810117

RESUMO

Marine algae are a rich source of aromatic secondary metabolites, with bromophenols (BPs) receiving particular attention due to their health benefits. Despite extensive research on BPs, the understanding of their antioxidant potential, as well as their mechanisms of action at the molecular level, remains incomplete. This study utilized density functional theory (DFT) to systematically elucidate the antioxidant and pro-oxidant mechanisms of the main BP scaffolds under physiological conditions. It was found that BPs exhibit potent antioxidant capacity in both polar and lipid environments. In lipid media, the formal hydrogen transfer mechanism has been identified as the exclusive antiradical pathway. The position of bromine atoms significantly influenced the activity, particularly in scaffolds containing one hydroxyl group. However, no significant effect was observed in scaffolds with two hydroxyl groups. In water, monodeprotonated BPs showed key radical scavenging activity, with different mechanisms favored depending on the configuration of the hydroxyl groups. Additionally, BPs, particularly those bearing a catechol moiety, exhibit secondary antioxidant activity by reducing the production of hydroxyl radicals via the ascorbic acid anion pathway. These findings provide further validation of the potent antioxidant properties of BPs and shed light on their mechanism of action in physiological environments.


Assuntos
Antioxidantes , Teoria da Densidade Funcional , Fenóis , Antioxidantes/química , Antioxidantes/farmacologia , Fenóis/química , Fenóis/farmacologia , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia
16.
Colloids Surf B Biointerfaces ; 239: 113956, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38733647

RESUMO

The early stages of osteoarthritis (OA) in the joints are typically characterized by two key factors: the dysfunction of articular cartilage lubrication and inflammation resulting from the excessive production of reactive oxygen species (ROS). Synthetic injectable macromolecular materials present great potential for preventing the progression of early OA. In this study, to mimic the excellent lubricity of brush-like aggregates found in natural synovial fluid, we develop a novel macromolecular biolubricant (CS-PS-DA) by integrating adhesion and hydration groups onto backbone of natural biomacromolecules. CS-PS-DA exhibits a strong affinity for cartilage surfaces, enabling the formation of a stable lubrication layer at the sliding interface of degraded cartilages to restore joint lubrication performance. In vitro results from ROS scavenging and anti-inflammatory experiments indicate the great advantage of CS-PS-DA to decrease the levels of proinflammatory cytokines by inhibiting ROS overproduction. Finally, in vivo rats OA model demonstrates that intra-cavitary injection of CS-PS-DA could effectively resist cartilage wear and mitigated inflammation in the joints. This novel biolubricant provides a new and timely strategy for the treatment of OA.


Assuntos
Osteoartrite , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Animais , Espécies Reativas de Oxigênio/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoartrite/patologia , Ratos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Lubrificação , Masculino , Cartilagem Articular/metabolismo , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química , Propriedades de Superfície , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química
17.
ACS Appl Mater Interfaces ; 16(22): 28991-29002, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38769310

RESUMO

Triphenylphosphine functionalized carbon dots (TPP-CDs) showcase robust mitochondria targeting capacity owing to their positive electrical properties. However, TPP-CDs typically involve complicated synthesis steps and time-consuming postmodification procedures. Especially, the one-step target-oriented synthesis of TPP-CDs and the regulation of TPP linkage modes remain challenges. Herein, we propose a free-radical-initiated random copolymerization in combination with hydrothermal carbonation to regulate the TPP backbone linkage for target-oriented synthesis of triphenylphosphine copolymerization carbon dots (TPPcopoly-CDs). The linkage mechanism of random copolymerization reactions is directional, straightforward, and controllable. The TPP content and IC50 of hydroxyl radicals scavenging ability of TPPcopoly-CDs are 53 wt % and 0.52 mg/mL, respectively. TPP serves as a charge control agent to elevate the negatively charged CDs by 20 mV. TPPcopoly-CDs with negative charge can target mitochondria, and in the corresponding mechanism the TPP moiety plays a crucial role in targeting mitochondria. This discovery provides a new perspective on the controlled synthesis, TPP linkage modes, and mitochondrial targeting design of TPP-CDs.


Assuntos
Carbono , Mitocôndrias , Compostos Organofosforados , Pontos Quânticos , Compostos Organofosforados/química , Carbono/química , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Pontos Quânticos/química , Humanos , Espécies Reativas de Oxigênio/metabolismo , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/farmacologia , Células HeLa
18.
Toxicol In Vitro ; 98: 105839, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723978

RESUMO

Vitamin K possesses efficacy as a topical dermatological agent. However, vitamin K is phototoxic and susceptible to photodegradation. Herein, we investigated the mechanisms underlying the phototoxicity of phylloquinone (PK, vitamin K1) and menaquinone-4 (MK-4, vitamin K2) under ultraviolet A (UVA) irradiation using various reactive oxygen species (ROS) scavengers. This resulted in the production of superoxide anion radicals via type I and singlet oxygen via type II photodynamic reactions, which were quenched by the ROS scavengers: superoxide dismutase and sodium azide (NaN3). In HaCaT cells, MK-4 and PK induced the production of intracellular ROS, particularly hydrogen peroxide, in response to UVA irradiation. Furthermore, the addition of catalase successfully decreased maximum ROS levels by approximately 30%. NaN3 and catalase decreased the maximum reduction in cell viability induced by UVA-irradiated PK and MK-4 in cell viability by approximately 2-7-fold. Additionally, ROS scavengers had no effect on the photodegradation of PK or MK-4 at 373 nm. Therefore, the phototoxicities of PK and MK-4 were attributed to the generation of singlet oxygen and hydrogen peroxide, underscoring the importance of photoshielding in circumventing phototoxicity.


Assuntos
Sobrevivência Celular , Sequestradores de Radicais Livres , Espécies Reativas de Oxigênio , Raios Ultravioleta , Espécies Reativas de Oxigênio/metabolismo , Humanos , Sequestradores de Radicais Livres/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Azida Sódica/farmacologia , Azida Sódica/toxicidade , Linhagem Celular , Vitamina K 2/análogos & derivados , Vitamina K 2/farmacologia , Vitamina K 1/farmacologia , Dermatite Fototóxica , Catalase/metabolismo , Células HaCaT , Superóxido Dismutase/metabolismo
19.
J Nanobiotechnology ; 22(1): 229, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720321

RESUMO

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings.


Assuntos
Síndromes do Olho Seco , Soluções Oftálmicas , Espécies Reativas de Oxigênio , Soluções Oftálmicas/química , Soluções Oftálmicas/farmacologia , Síndromes do Olho Seco/tratamento farmacológico , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Córnea/efeitos dos fármacos , Córnea/metabolismo , Álcool de Polivinil/química , Humanos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Boratos/química , Nanopartículas/química , Masculino
20.
Sci Rep ; 14(1): 10145, 2024 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698070

RESUMO

For centuries, medicinal plants have served as the cornerstone for traditional health care systems and same practice is still prevalent today. In the Himalayan region, Saussurea heteromalla holds a significant place in traditional medicine and is used to address various health issues. Despite its historical use, little exploration has focused on its potential for scavenging free radicals and reducing inflammation. Hence, our current study aims to investigate the free radical scavenging capabilities of S. heteromalla extracts. The n-hexane extract of entire plant revealed promising activity. This extract underwent extensive extraction on a larger scale. Subsequent purification, employing column chromatography, HPLC-DAD techniques, led to the identification of active compounds, confirmed via GC-MS and the NIST database as 1-O-butyl 2-O-octyl benzene-1,2-dicarboxylate and 2,4-ditert-butylphenol. Assessing the free radical scavenging properties involved utilizing RAW-264.7 macrophages activated by lipopolysaccharides. Notably, the compound 2,4-di-tert-butylphenol exhibited remarkable scavenging abilities, demonstrating over 80% inhibition of Nitric oxide. This study stands as the inaugural report on the isolation of these compounds from S. heteromalla.


Assuntos
Antioxidantes , Cromatografia Gasosa-Espectrometria de Massas , Macrófagos , Óxido Nítrico , Extratos Vegetais , Saussurea , Saussurea/química , Camundongos , Óxido Nítrico/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Células RAW 264.7 , Antioxidantes/farmacologia , Antioxidantes/química , Lipopolissacarídeos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/química
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