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1.
Int J Biol Macromol ; 253(Pt 4): 126955, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37739295

RESUMO

Apolipoprotein A4 (Apo-A4) is considered as a prospective molecular biomarker for diagnosis of depression due to its neurosynaptic toxicity. Here, we propose a neighboring hybridization induced catalyzed hairpin assembly (CHA) driven bipedal DNA walker that mediates hybridization of Ag nanoparticles (Ag NPs) with DNA probes for highly sensitive electrochemical quantitative detection of Apo-A4. Driven by CHA, this bipedal DNA walker can spread all over the surface of the sensor, induce the HP1-HP2 double chain structure, make the surface of the sensor negatively charged, and adsorb a large number of Ag ions. After chemical reduction with hydroquinone, the Ag NPs formed provide signal tracers for electrochemical dissolution analysis of the target. The Ag NPs formed by chemical reduction of hydroquinone can provide signal traces for electrochemical stripping analysis of target thrombin. The linear range of this method is from 10 pg mL-1 to 1000 ng mL-1, and the detection limit is 5.1 pg mL-1. This enzyme-free and labeling detection method provides a new strategy for rapid clinical detection of Apo-A4 and accurate identification of depression.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Hidroquinonas , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Prata/química , DNA/química , Técnicas Eletroquímicas/métodos , Limite de Detecção , Ouro/química
2.
Arch Dermatol Res ; 315(10): 2805-2812, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37568064

RESUMO

Melasma is an acquired chronic condition characterized by hyperchromic patches in photo-exposed areas. The search for new compounds for the treatment of melasma without side effects is constant. In this context, the aim of this study was to investigate the in vitro cytotoxic and antimelanogenic effects of the trace elements Zinc (Zn) and Selenium (Se). In this study, we evaluated the effects of 30 µM hydroquinone, this concentration did not alter mitochondrial function (MTT assay), but increased the percentage of necrotic cells and levels of reactive species. Furthermore, it showed no influence on tyrosinase activity and melanin content. Unlike hydroquinone, exposure for 48 h to 100 µM Zn and 1 and 5 µM Se had no significant influence on the analysis of reactive species, as well as on the percentage of necrotic cells. Still, specifically in relation to 100 µM Zn, it decreased the melanin content. Given the above, the trace elements Zn and Se did not show toxicity at the concentrations tested and Zn showed a promising effect, however, the mechanism needs to be better explored in order to contribute to new and updated research in the fight against melasma with a perspective of therapeutic use.


Assuntos
Melanose , Selênio , Oligoelementos , Humanos , Selênio/farmacologia , Selênio/análise , Zinco/análise , Zinco/farmacologia , Oligoelementos/análise , Hidroquinonas/análise , Melaninas , Melanose/tratamento farmacológico
3.
J Eur Acad Dermatol Venereol ; 37(12): 2601-2607, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37620285

RESUMO

BACKGROUND: Kligman's trio (KT), combining hydroquinone, retinoic acid and corticosteroid, is considered as the gold standard treatment of melasma. Its efficacy has never been matched before, but it is tempered by frequent adverse effects. OBJECTIVE: To assess the efficacy and tolerance of a New Trio (NT) combination with isobutylamido-thiazolyl-resorcinol, retinoic acid and cortosteroid compared to KT. METHODS: We conducted a 24-week monocentric trial, randomized, double-blind, controlled versus KT, with 40 melasma patients. NT and KT were applied for 12 weeks and associated with the same sunscreen applied for 24 weeks. The primary endpoint was the modified Melasma Area Severity Index (mMASI) at 12 weeks. Patient quality of life was investigated using MelasQoL. RESULTS: After 12 weeks, KT and NT groups both demonstrated a significant improvement in mMASI, respectively -2.84 (SE 0.69, p < 0.0002) and -4.33 (SE 0.71, p < 0.0001). The mean difference between the two groups was -1.49 (IC 95% -3.52 to 0.54, p = 0.14). MelasQoL improvement was -6.66 (SE 3.29, p = 0.0515) with KT and -12.57 (SE 3.29, p = 0.0006) with NT. CONCLUSION: The NT combination appears to be an effective treatment option for treating melasma and could be considered as a well-tolerated alternative to KT.


Assuntos
Melanose , Qualidade de Vida , Humanos , Estudos Prospectivos , Tretinoína/efeitos adversos , Resultado do Tratamento , Emolientes , Melanose/tratamento farmacológico , Hidroquinonas/efeitos adversos
4.
Free Radic Biol Med ; 205: 175-187, 2023 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-37321281

RESUMO

Mitochondria-targeted coenzyme Q10 (Mito-ubiquinone, Mito-quinone mesylate, or MitoQ) was shown to be an effective antimetastatic drug in patients with triple-negative breast cancer. MitoQ, sold as a nutritional supplement, prevents breast cancer recurrence. It potently inhibited tumor growth and tumor cell proliferation in preclinical xenograft models and in vitro breast cancer cells. The proposed mechanism of action involves the inhibition of reactive oxygen species by MitoQ via a redox-cycling mechanism between the oxidized form, MitoQ, and the fully reduced form, MitoQH2 (also called Mito-ubiquinol). To fully corroborate this antioxidant mechanism, we substituted the hydroquinone group (-OH) with the methoxy group (-OCH3). Unlike MitoQ, the modified form, dimethoxy MitoQ (DM-MitoQ), lacks redox-cycling between the quinone and hydroquinone forms. DM-MitoQ was not converted to MitoQ in MDA-MB-231 cells. We tested the antiproliferative effects of both MitoQ and DM-MitoQ in human breast cancer (MDA-MB-231), brain-homing cancer (MDA-MB-231BR), and glioma (U87MG) cells. Surprisingly, DM-MitoQ was slightly more potent than MitoQ (IC50 = 0.26 µM versus 0.38 µM) at inhibiting proliferation of these cells. Both MitoQ and DM-MitoQ potently inhibited mitochondrial complex I-dependent oxygen consumption (IC50 = 0.52 µM and 0.17 µM, respectively). This study also suggests that DM-MitoQ, which is a more hydrophobic analog of MitoQ (logP: 10.1 and 8.7) devoid of antioxidant function and reactive oxygen species scavenging ability, can inhibit cancer cell proliferation. We conclude that inhibition of mitochondrial oxidative phosphorylation by MitoQ is responsible for inhibition of breast cancer and glioma proliferation and metastasis. Blunting the antioxidant effect using the redox-crippled DM-MitoQ can serve as a useful negative control in corroborating the involvement of free radical-mediated processes (e.g., ferroptosis, protein oxidation/nitration) using MitoQ in other oxidative pathologies.


Assuntos
Neoplasias da Mama , Glioma , Humanos , Feminino , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Hidroquinonas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias da Mama/tratamento farmacológico , Ubiquinona/farmacologia , Oxirredução , Proliferação de Células , Estresse Oxidativo , Compostos Organofosforados/farmacologia
5.
Pharm Biol ; 61(1): 281-287, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36655287

RESUMO

CONTEXT: Vitiligo is a common skin disease with a complex pathogenesis, and so far, no effective treatment is available. Lycium barbarum L. (Solanaceae) polysaccharide (LBP), the main active ingredient of goji berries, has been demonstrated to protect keratinocytes and fibroblasts against oxidative stress. OBJECTIVE: This study explored the effects and mechanism of LBP on monobenzone-induced vitiligo in mice. MATERIALS AND METHODS: C57BL/6 mice were randomly divided into five groups (n = 6): negative control that received vaseline, vitiligo model group induced by monobenzone that treated with vaseline, positive control that received tacrolimus (TAC), LBP groups that received 0.3 and 0.6 g/kg LBP, respectively. We quantified the depigmentation by visual examination and scores, detected the expression of CD8+ T cells, pro-inflammatory cytokines and analysed the STAT3-Hsp70-CXCL9/CXCL10 pathway. RESULTS: LBP 0.3 and 0.6 g/kg groups can significantly reduce depigmentation scores and the infiltration of local inflammatory cells in the skin lesions. Moreover, the expression of CXCL9, CXCL3, CXCL10 and HSP70 decreased by 54.3, 20.3, 48.5 and 27.2% in 0.3 g/kg LBP group, which decreased by 62.1, 26.6, 58.2 and 34.5% in 0.6 g/kg LBP group. In addition, 0.3 and 0.6 g/kg LBP decreased the release of IL-8 (9.7%, 22.8%), IL-6 (40.8%, 42.5%), TNF-α (25.7%, 35%), IFN-γ (25.1%, 27.6%) and IL-1ß (23.7%, 33.7%) and inhibited the phosphorylation expression of STAT3 by 63.2 and 67.9%, respectively. CONCLUSION: These findings indicated LBP might be recommended as a new approach for vitiligo which provide a theoretical basis for the clinical application of LBP in treating vitiligo patients.


Assuntos
Medicamentos de Ervas Chinesas , Lycium , Vitiligo , Animais , Camundongos , Vitiligo/tratamento farmacológico , Vitiligo/prevenção & controle , Vitiligo/induzido quimicamente , Camundongos Endogâmicos C57BL , Hidroquinonas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico
6.
Int J Dermatol ; 62(2): 260-268, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36083295

RESUMO

Melasma is acquired hyperpigmentation that mainly affects the face, can cause negative changes in self-esteem, and mostly affects women. Treatment is difficult, and different drugs can be used in mono or combination therapy. In this article, we present a brief overview of melasma, how to evaluate it, and a synthesis of the most commonly used topical therapies and their indications, including sunscreens, pharmacological agents, and plant extracts. Hydroquinone (4%) in monotherapy or combined with corticosteroids (dexamethasone and fluocinolone acetonide) and retinoids (tretinoin); arbutin (1%); methimazole (5%); kojic (2%), azelaic (20%), and tranexamic (5%) acids are the pharmacological agents that stand out. Correct application of these substances determines a variable improvement in melasma but often causes adverse reactions such as erythema, itching, and burning at the application site. Vitamin C can contribute to the reduction of melasma and have little or no adverse effects while sunscreens are normally used as coadjuvant therapies. In conclusion, we have compiled specific topical therapies for treating melasma and discussed those that are the most used currently. We consider it important that prescribers and researchers evaluate the best cost-benefit ratio of topical therapeutic options and develop new formulations, enabling efficacy in the treatment with safety and comfort during application, through the reduction of adverse effects.


Assuntos
Melanose , Protetores Solares , Feminino , Humanos , Protetores Solares/uso terapêutico , Melanose/etiologia , Tretinoína/efeitos adversos , Retinoides/uso terapêutico , Fluocinolona Acetonida/efeitos adversos , Hidroquinonas/uso terapêutico , Resultado do Tratamento
7.
Molecules ; 27(24)2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36558059

RESUMO

The use of biolubricants as a replacement for petroleum-based products is becoming more and more important, due to the current global energy and crude oil scenario. Thus, the production of biolubricants (which could take place in biorefineries) should be as efficient as possible, obtaining high-quality products with suitable viscosity or oxidation stability values to compete with oil refineries. One of the ways to produce biolubricants is through double transesterification from vegetable oils, where the role of catalysts (usually homogeneous) is vital, as they can improve the yield of the process. However, they should be removed after the chemical reaction, which is difficult once the biolubricant is obtained. Otherwise, they could act as catalysts during oxidation, contributing to a further decrease in oxidation stability and provoking significant changes. To avoid this, antioxidant addition could be an interesting choice. The aim of this work was to assess TBHQ addition in frying oil biolubricants, monitoring properties such as viscosity, acid number, absorbance or TBHQ content (through voltammetry) during oxidation. TBHQ addition (2114 mg·L-1) kept the main quality parameters during oxidation compared to control samples. In contrast, TBHQ content decreased during oxidation (to 160 mg·L-1), which proved its antioxidant effect.


Assuntos
Antioxidantes , Hidroquinonas , Oxirredução , Antioxidantes/química , Hidroquinonas/química , Esterificação , Óleos de Plantas
8.
Acta Ophthalmol ; 100 Suppl 273: 3-59, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36343937

RESUMO

Age-related macular degeneration (AMD) is an eye disease, which causes impaired vision that can lead to blindness. The incidence of AMD increases with age. Retinal pigment epithelial (RPE) cells maintain retinal homeostasis and support the functionality of photoreceptors. In the pathogenesis of AMD, the degeneration of the RPE cells precedes photoreceptor cell death. RPE cells are susceptible to oxidative stress, and chronic inflammation involving nucleotide-binding domain, leucine-rich repeat and pyrin domain 3 (NLRP3) inflammasome activation and impaired autophagy are challenges faced by aged RPE cells in AMD. There are two types of AMD, dry (85-90%) and wet (10-15%) disease forms. Choroidal neovascularization is typical for wet AMD, and anti-vascular endothelial growth factor (anti-VEGF) injections are used to prevent the progression of the disease but there is no curative treatment. There is no cure for the dry disease form, but antioxidants have been proposed as a potential treatment option. Ageing is the most important risk factor of AMD, and tobacco smoke is the most important environmental risk factor that can be controlled. Hydroquinone is a cytotoxic, immunotoxic, carcinogenic and pro-oxidative component of tobacco smoke. The aim of this PhD thesis was to study hydroquinone-induced oxidative stress and NLRP3 inflammasome activation in human RPE cells (ARPE-19 cells). An age-related eye disease study (AREDS) formulation (incl. omega-3 fatty acids, vitamin C and E, copper, zinc, lutein and zeaxanthin), which is clinically investigated p.o. dosing combination of dietary supplements for AMD patients, has been evaluated as a possible treatment and restraining option for AMD. Resvega (4.1.1, Table 2) is a similar kind of product to AREDS with added resveratrol, and many of the components incorporated within Resvega can be considered as belonging to the normal antioxidative defence system of the retina. Another aim was to evaluate the effects of Resvega on hydroquinone-induced oxidative stress or NLRP3 inflammasome activation induced by impaired protein clearance. The results of this study reveal that hydroquinone elevated the activity of NADPH oxidase which subsequently mediated the production of reactive oxygen species (ROS) and predisposed RPE cells to degeneration by reducing levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). Hydroquinone induced an NLRP3-independent IL-18 release and NLRP3 accumulation inside the IL-1α-primed cells. Resvega treatment reduced the extent of hydroquinone-induced ROS production and NLRP3 inflammasome activation evoked by impaired protein clearance. Thus, Resvega alleviated hydroquinone- and impaired protein clearance-induced stress in human RPE cells, but more studies are needed, for example, to reveal the most optimal route of administration for targeting the cells in the retina, since both oxidative stress and NLRP3 inflammasome activation are important contributors to the development of AMD and represent significant treatment targets.


Assuntos
Células Epiteliais , Estresse Oxidativo , Poluição por Fumaça de Tabaco , Degeneração Macular Exsudativa , Humanos , Antioxidantes/metabolismo , Fatores de Crescimento Endotelial/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Hidroquinonas , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/patologia , Poluição por Fumaça de Tabaco/efeitos adversos , Degeneração Macular Exsudativa/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-36231404

RESUMO

Melasma is a chronic skin condition that involves the overproduction of melanin in areas exposed to ultraviolet radiation. Melasma treatment is long-term and complicated with recurrence and resistance to treatment. The pathogenesis of melasma is highly complex with multiple pathologies occurring outside of the skin pigment cells. It includes photoaging, excessive melanogenesis, an increased number of mast cells, increased vascularization, and basement membrane damage. In addition, skin lesions related to melasma and their surrounding skin have nearly 300 genes differentially expressed from healthy skin. Traditionally, melasma was treated with topical agents, including hydroquinone, tretinoin, glucocorticosteroids and various formulations; however, the current approach includes the topical application of a variety of substances, chemical peels, laser and light treatments, mesotherapy, microneedling and/or the use of systemic therapy. The treatment plan for patients with melasma begins with the elimination of risk factors, strict protection against ultraviolet radiation, and the topical use of lightening agents. Hyperpigmentation treatment alone can be ineffective unless combined with regenerative methods and photoprotection. In this review, we show that in-depth knowledge associated with proper communication and the establishment of a relationship with the patient help to achieve good adherence and compliance in this long-term, time-consuming and difficult procedure.


Assuntos
Hidroquinonas , Melanose , Humanos , Hidroquinonas/uso terapêutico , Melaninas/uso terapêutico , Melanose/terapia , Resultado do Tratamento , Tretinoína/uso terapêutico , Raios Ultravioleta
10.
Food Res Int ; 161: 111861, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36192984

RESUMO

Linusorbs (LOs, cyclolinopeptides) are a class of naturally occurring cyclic hydrophobic peptides found in flaxseed oil, whose oxidation states indicate the oxidative stability and bitterness of flaxseed oil. Subjected to 63 °C accelerated oxidation, most Met-containing LOs in cold-pressed flaxseed oil entirely depleted by the 6th day except CLP, and MetO2-containing LOs became the dominant ones. However, no MetO2 form of Trp-containing LOs, such as CLD, CLF and CLG, were detected. Given their oxidative kinetics, methionine sulfoxide (MetO) residue in some LOs was less sensitive toward oxidation in the presence of Trp (Tryptophan) group, and the oxidative stability of Met-containing LOs was CLP < CLB < CLL ≈ CLM < CLO, as compared to MetO-containing LOs: CLD < CLE < CLC < CLF ≈ CLG. When antioxidant was added into cold-pressed flaxseed oil to assess the additives' antioxidant effect, no significant difference was observed on oil oxidative indices in early stage except α-tocopherol, where they vary dramatically in suppressing Met oxidation of LOs: L-AP (L-ascorbyl palmitate) > TBHQ (tert-butyl hydroquinone) > Î³-tocopherol > carnosic acid > α-tocopherol. Besides its ability to suppress oxidation of Trp-containing LOs, L-AP also exhibits superior antioxidant effect on non-Trp-containing LOs due to its amphiphilic property. Due to the prooxidative effects of both α- and γ-tocopherol on LOs that contain Trp, it has been suggested that tocopherols may repair Trp residue on LOs, leading to increased tendency of MetO residues to oxidize. The findings of this research are critical for elucidating the antioxidative mechanism of LOs, which can further lead to the establishment of strategies in suppressing bitter after taste to produce high-quality flaxseed oil.


Assuntos
Antioxidantes , Óleo de Semente do Linho , Antioxidantes/química , Hidroquinonas , Óleo de Semente do Linho/química , Peptídeos Cíclicos , Tocoferóis , Triptofano , alfa-Tocoferol , gama-Tocoferol
11.
Biol Pharm Bull ; 45(9): 1389-1393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36047210

RESUMO

Thymoquinone is a popular health-promoting antioxidant supplement, but it may induce toxicity to cells and organs because of its propensity to promote oxidation of biomolecules under some conditions. Furthermore, as hydroquinones have been found to exhibit more potent antioxidant and prooxidant activities than their parent quinones, the reduced metabolite thymohydroquinone may have stronger effects than thymoquinone. In this study, the antioxidant and prooxidant activities of thymoquinone and thymohydroquinone were assessed to determine whether they both act as antioxidants and induce oxidative damage to biomolecules as do other quinones. Using ESR spectroscopy, we demonstrated that thymohydroquinone exhibits more potent antioxidant activity than does thymoquinone. In addition, thymohydroquinone was found to act as a prooxidant to induce oxidative damage of isolated plasmid DNA in the presence of free Cu2+ or Fe2+-ethylenediaminetetraacetic acid (EDTA). Interestingly, the prooxidant effect of thymohydroquinone in the presence of Fe2+ was not observed in the absence of EDTA. Thymohydroquinone thus was demonstrated to have two biologically relevant activities: as an antioxidant and a prooxidant.


Assuntos
Antioxidantes , Hidroquinonas , Antioxidantes/química , Benzoquinonas/farmacologia , Cobre , Ácido Edético , Hidroquinonas/farmacologia , Oxirredução , Espécies Reativas de Oxigênio/metabolismo
12.
Environ Res ; 214(Pt 4): 114107, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35995230

RESUMO

Chlorella vulgaris (C. vulgaris) and Scenedesmus obliquus (S. obliquus) were compared to remove toxicity under conditions of sludge extract cultivation for 30 days. The toxicity of sludge extract, the growth characteristics, photosynthetic pigment, superoxide dismutase (SOD) enzyme and catalase (CAT) enzyme activities of the two microalgae were studied by contrast. The results showed that small molecular organic matter (<500 Da) was more easily utilized by microalgae. The toxicity in the toxic group of C. vulgaris and S. obliquus on the 30th day decreased to 56.8 ± 1.2% and 60.7 ± 2.8%, respectively. In the toxic group, the maximal SOD enzyme activity of C. vulgaris and S. obliquus were 2.02 U/mg proteins and 8.21 U/mg proteins, respectively, demonstrating that toxicity caused more oxidative damage to S. obliquus than to C. vulgaris. Proteomics analysis revealed that C. vulgaris mainly regulates energy synthesis and distribution primarily through sugar metabolism, and biomass synthesis primarily through carbon metabolism, whereas S. obliquus mainly regulates energy synthesis and distribution primarily through sugar metabolism and oxidative phosphorylation, resulting in sludge toxicity stress regulation.


Assuntos
Chlorella vulgaris , Microalgas , Scenedesmus , Autocontrole , Chlorella vulgaris/metabolismo , Hidroquinonas , Microalgas/metabolismo , Extratos Vegetais , Scenedesmus/metabolismo , Esgotos , Açúcares/metabolismo , Superóxido Dismutase/metabolismo
13.
J Cosmet Dermatol ; 21(11): 5739-5746, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35708506

RESUMO

BACKGROUND: Melasma is an acquired disorder that results in irregular brown patches on the skin that can occur due to hormonal changes. Although pregnancy-induced melasma is usually temporary, it can become a chronic condition, with significant negative impact on quality of life (QoL). AIMS: Determine the efficacy and tolerability of a topical, non-hydroquinone, non-retinol pigment-correcting serum (LYT2) for the treatment of pregnancy-induced melasma. METHODS: This 12-week, single-center clinical trial enrolled 34 non-pregnant women who developed mild to severe facial melasma following a previous pregnancy (mean age, 42 years). LYT2 was applied twice daily to facial skin for 12 weeks in addition to a basic skincare regimen. Outcomes included changes from baseline in skin physiology parameters, such as brightness (L*), using objective digital image analysis, investigator-rated Overall Hyperpigmentation scale, Global Improvement, and Melasma Area and Severity Index (MASI), as well as subject-assessed Melasma Quality of Life Scale. Subjects also completed a questionnaire on self-perceived efficacy and attributes of the study product. Tolerability was assessed by the investigators (erythema, scaling, and edema) and subjects (burning/stinging and itching). Clinical assessments were conducted at baseline and Weeks 4, 8, and 12. RESULTS: LYT2 provided statistically significant reductions in overall hyperpigmentation scores as early as Week 4 (-5.8% change from baseline) and continued through Week 12 (-14.6% change from baseline; all p < 0.001). Significant improvements in MASI scores and QoL were also achieved following LYT2 treatment, which was well tolerated. CONCLUSIONS: LYT2 represents a new efficacious alternative to hydroquinone-based treatments for pregnancy-induced melasma.


Assuntos
Hiperpigmentação , Melanose , Feminino , Humanos , Gravidez , Adulto , Qualidade de Vida , Resultado do Tratamento , Melanose/diagnóstico , Melanose/tratamento farmacológico , Hiperpigmentação/tratamento farmacológico , Administração Cutânea , Hidroquinonas/efeitos adversos
14.
Drug Des Devel Ther ; 16: 1495-1514, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35611357

RESUMO

Background: Alzheimer's disease (AD) belongs to neurodegenerative disease, and the increasing number of AD patients has placed a heavy burden on society, which needs to be addressed urgently. ChEs/MAOs dual-target inhibitor has potential to treat AD according to reports. Purpose: To obtain effective multi-targeted agents for the treatment of AD, a novel series of hybrid compounds were designed and synthesized by fusing the pharmacophoric features of 3,4-dihydro-2 (1H)-quinolinone and dithiocarbamate. Methods: All compounds were evaluated for their inhibitory abilities of ChEs and MAOs. Then, further biological activities of the most promising candidate 3e were determined, including the ability to cross the blood-brain barrier (BBB), kinetics and molecular model analysis, cytotoxicity in vitro and acute toxicity studies in vivo. Results: Most compounds showed potent and clear inhibition to AChE and MAOs. Among them, compound 3e was considered to be the most effective and balanced inhibitor to both AChE and MAOs (IC50=0.28 µM to eeAChE; IC50=0.34 µM to hAChE; IC50=2.81 µM to hMAO-B; IC50=0.91 µM to hMAO-A). In addition, 3e showed mixed inhibition of hAChE and competitive inhibition of hMAO-B in the enzyme kinetic studies. Further studies indicated that 3e could penetrate the BBB and showed no toxicity on PC12 cells and HT-22 cells when the concentration of 3e was lower than 12.5 µM. More importantly, 3e lacked acute toxicity in mice even at high dose (2500 mg/kg, P.O.). Conclusion: This work indicated that compound 3e with a six-carbon atom linker and a piperidine moiety at terminal position was a promising candidate and was worthy of further study.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Quinolonas , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Animais , Inibidores da Colinesterase/farmacologia , Desenho de Fármacos , Humanos , Hidroquinonas , Cinética , Camundongos , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase , Doenças Neurodegenerativas/tratamento farmacológico , Quinolonas/farmacologia , Quinolonas/uso terapêutico , Ratos , Relação Estrutura-Atividade
15.
J Cosmet Dermatol ; 21(7): 2871-2878, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35510765

RESUMO

BACKGROUND: Few safe and effective treatments are available for melasma. Cysteamine, a non-melanocytotoxic molecule is a safer alternative to hydroquinone and usable for long-term use. AIM: To evaluate the effect of cysteamine 5% cream in the treatment of melasma. METHODS: Sixty-five of 80 patients completed this single-blind, randomized, controlled trial. The patients received cysteamine 5% or hydroquinone 4%/ascorbic acid 3% (HC) cream. The therapeutic response was evaluated by modified MASI (mMASI) and melanin index (SkinColorCatch) after 2 and 4 months of treatment. The effect of treatment on the quality of life was also assessed. RESULTS: The decrease in mMASI score was from 6.69 ± 2.96 to 4.47 ± 2.16 in the cysteamine group and from 6.26 ± 3.25 to 3.87 ± 2.00 in the HC group after 4 months (p values < 0.001). The melanin index decreased from 37.72 ± 10.17 to 31.47 ± 11.90 in the cysteamine group and from 36.37 ± 10.80 to 23.16 ± 8.83 in the HC group after 4 months (p-value = 0.003 and <0.001, respectively). The difference between mMASI score at baseline and month 4 was not significant between both groups (p-value > 0.05). The difference between the melanin index at baseline and month 4 was significantly more pronounced in the HC group (p-value = 0.002). Quality of life improved in both groups (p-value < 0.05), but was not significantly different between groups (p-value > 0.05). CONCLUSION: Cysteamine was confirmed to be an effective treatment for melasma, with equivalent results to HC in reducing mMASI score and improving quality of life, despite lesser melanin index reduction observed. Cysteamine and HC efficacy was confirmed in patients recalcitrant to previous treatments, by a significant reduction of mMASI and melanin index.


Assuntos
Hidroquinonas , Melanose , Ácido Ascórbico/efeitos adversos , Cisteamina/efeitos adversos , Emolientes/uso terapêutico , Humanos , Hidroquinonas/efeitos adversos , Melaninas , Melanose/diagnóstico , Melanose/tratamento farmacológico , Qualidade de Vida , Método Simples-Cego , Resultado do Tratamento
16.
Food Chem ; 388: 132898, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35436634

RESUMO

This study constructed a novel biomimetic enzyme electrochemical biosensor based on tetraphenyl metalloporphyrins functionalized multi-walled carbon nanotubes (MWCNTs). The effect of central metal ions on the catalytic activity of tetraphenyl metalloporphyrin biomimetic enzyme was investigated. It was found that the change of central metal ions had a significant effect on the catalytic performance of metalloporphyrin and Zinc(II) tetraphenylporphyrin (ZnTPP) had the most excellent catalytic property. The electrochemical behaviors of tert-butylhydroquinone (TBHQ) on ZnTPP/MWCNTs modified electrode were investigated. It was found that the redox peak current was increased significantly, which was attributed to the redox peak current to the electrocatalytic activity of ZnTPP and the synergistic effect between ZnTPP and MWCNTs. A strong linear relationship was shown in the concentration range of 0.01 to 1000 µM. This electrochemical sensor also had excellent repeatability, storage, and interference resistance. This work provided a simple and sensitive method for the determination of TBHQ.


Assuntos
Metaloporfirinas , Nanotubos de Carbono , Antioxidantes , Biomimética , Técnicas Eletroquímicas , Eletrodos , Hidroquinonas , Nanotubos de Carbono/química , Oxirredutases , Óleos de Plantas
17.
Analyst ; 147(9): 1906-1914, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35352722

RESUMO

tert-Butylhydroquinone (TBHQ) residues in foods pose a threat to human health. Therefore, it is necessary to develop a rapid method for TBHQ detection. In this study, a sensitive monoclonal antibody 5C3 (IgG2a subclass) against TBHQ was produced. It possessed a half maximal inhibitory concentration of 7.43 ng mL-1. A gold nanoparticle-based immunochromatographic assay (ICA) was established for the rapid and sensitive screening of TBHQ in soybean oil. Qualitative analysis results were obtained within 10 min and observed with the naked eye. The visual limit of detection (LOD) was 50 ng g-1 and the cut-off value was 1000 ng g-1. A hand-held strip reader was used for quantitative analysis, in which the calculated LOD was defined as 18.68 ng g-1. The average recoveries of TBHQ ranged from 89.55% ± 2.70% to 100.66% ± 3.02% for soybean oil, with a coefficient of variation of 2.89%-7.05%. Therefore, our developed ICA is a useful tool for the rapid and on-site detection of TBHQ in real food samples.


Assuntos
Ouro , Nanopartículas Metálicas , Cromatografia de Afinidade/métodos , Ouro/química , Humanos , Hidroquinonas , Limite de Detecção , Óleo de Soja
18.
J Ethnopharmacol ; 289: 115092, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35143933

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Arctostaphylos uva-ursi (L.) Spreng. (bearberry) is a well-known traditional herbal plant used as a urinary tract disinfectant. Its antiseptic and diuretic properties can be attributed to hydroquinone, obtained by hydrolysis of arbutin. AIM OF THE STUDY: This study aimed to determine the toxic profile of free hydroquinone on urinary bladder cells (T24) as a target of therapeutic action. MATERIALS AND METHODS: Quantitative and qualitative analysis of the extract and the digestive stability and bioavailability of arbutin and hydroquinone were performed by HPLC assay and simulated in vitro digestion, respectively. Cytotoxic effect, reactive oxygen species induction and proteome changes in T24 cells after hydroquinone treatment were determined using Neutral red assay, 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assay and mass spectrometry, respectively. RESULTS: Through in vitro digestion, arbutin was stable, but hydroquinone increased after pepsin treatment (109.6%) and then decreased after the small intestine phase (65.38%). The recommended doses of Uva-ursi had a cytotoxic effect on T24 cells only when all hydroquinone conjugates were converted to free hydroquinone (320 and 900 µg/mL) and the toxic effect was enhanced by recovery. One cup of the therapeutic dose had a prooxidative effect after 4 h of incubation. Shorter time of cell exposure (2 h) to hydroquinone did not have any impact on reactive oxygen species induction. Proteomic analysis found 17 significantly up-regulated proteins compared to control. Hydroquinone activated proteins related to oxidative stress response, stress-adaptive signalling, heat shock response and initiation of translation. CONCLUSIONS: Despite the therapeutic properties of bearberry, up-regulated T24 cell proteins are evidence that plant compounds, although from a natural source, may exhibit negative properties.


Assuntos
Arctostaphylos/química , Hidroquinonas/toxicidade , Extratos Vegetais/toxicidade , Bexiga Urinária/efeitos dos fármacos , Arbutina/química , Arbutina/isolamento & purificação , Células CACO-2 , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Humanos , Hidroquinonas/isolamento & purificação , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Proteoma , Proteômica , Bexiga Urinária/citologia
19.
Food Chem ; 377: 131946, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34979403

RESUMO

Synthetic antioxidant tert-butylhydroquinone (TBHQ) is easily oxidized to tert-butylquinone (TQ) during the storage of edible oils, resulting in an obvious decrease in the content of TBHQ in edible oils. Therefore, it is quite desirable to develop a simple analytical method for accurately tracking the original content of TBHQ in edible oils. In this work, deep eutectic solvents (DESs) have been successfully used in room temperature vortex-assisted liquid-liquid microextraction (VALLME) of TBHQ from edible oils. The DES composed of ethylene glycol and choline chloride (ChCl) could selectively extract TBHQ from edible oils containing both TBHQ and TQ. The DES composed of sesamol and ChCl (molar ratio of 3:1) could efficiently reduce TQ to TBHQ and extract TBHQ from edible oils. The whole VALLME process only required 5 min at room temperature. This switchable DESs-based VALLME with common RP-HPLC analysis showed high efficiency and good performance with linearity (R2 = 0.9999) in 5-500 mg/kg range, detection limit of 0.02 mg/kg, recoveries of 96.1-106.0% and intra-/inter-day precision below 2.0%. This analytical method is suitable for detecting the current content of TBHQ and tracking the original content of TBHQ during the storage of edible oils at room temperature, respectively.


Assuntos
Microextração em Fase Líquida , Antioxidantes , Cromatografia Líquida de Alta Pressão , Solventes Eutéticos Profundos , Hidroquinonas , Limite de Detecção , Óleos de Plantas , Solventes
20.
Food Chem ; 377: 131867, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34974409

RESUMO

It is pivotal to precisely detect food preservatives to ascertain food quality and safety. In this work, we report the sensitive electrochemical detection of widely used cytotoxic food preservative tert-butylhydroquinone (TBHQ). A novel nanocomposite was sonochemically prepared by embedding ternary metal oxide (TMO) comprising ZnO, CuO, and MgO in ß-cyclodextrin (ß-CD) functionalized carbon black (CB). The properties of the prepared nanocomposite were evaluated by employing multiple characterization methods. The nanocomposite fabricated on a screen printed carbon electrode exhibited exceptional electrocatalytic activity towards TBHQ detection, evident from the resultant very low detection limit of 1 nM and high sensitivity of 22.67 µA µM-1 cm-2. Moreover, the developed TBHQ sensor evinced all the important traits of a good electrochemical sensor including excellent selectivity, stability, reproducibility, and repeatability. Furthermore, for validating practical feasibility of TBHQ detection, we successfully determined this food additive in edible oils.


Assuntos
Aditivos Alimentares , beta-Ciclodextrinas , Carbono , Técnicas Eletroquímicas , Eletrodos , Hidroquinonas , Óxidos , Óleos de Plantas , Reprodutibilidade dos Testes , Fuligem
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