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1.
Molecules ; 29(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474563

RESUMO

Aeginetia indica L., a parasitic root in the Orobanchaceae family, is used as a food colorant in traditional Thai desserts. However, scant information is available on its food applications as well as medicinal properties, while overharvesting by the local people has severely depleted wild plant populations. This research, thus, aimed to extract optimized total phenolic content (TPC) in varying extraction conditions using response surface methodology (RSM) and the Box-Behnken design (BBD). Results indicated that an extraction temperature of 90 °C, 80% (v/v) aqueous ethanol, and 0.5% (w/v) solid-to-liquid ratio yielded the highest TPC at 129.39 mg gallic acid equivalent (GAE)/g dry weight (DW). Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) identified the predominant phenolics as apigenin (109.06 mg/100 g extract) and luteolin (35.32 mg/100 g extract) with trace amounts of naringenin and rutin. Under the optimal extraction condition, the plant extract exhibited antioxidant activities of 5620.58 and 641.52 µmol Trolox equivalent (TE)/g DW determined by oxygen radical absorbance capacity (ORAC) and ferric ion reducing antioxidant power (FRAP) assay, while the scavenging capacity of total radicals at 50% (SC50) was determined to be 135.50 µg/mL using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The plant extract also exhibited inhibitory activities against the key enzymes relevant to type II diabetes, obesity, and Alzheimer's disease, suggesting the potential for medicinal applications.


Assuntos
Antioxidantes , Diabetes Mellitus Tipo 2 , Humanos , Antioxidantes/química , Espectrometria de Massas em Tandem , Extratos Vegetais/química , Rutina
2.
Molecules ; 29(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38792065

RESUMO

A previous study reported that the ethanolic extract of the edible fern, Diplazium esculentum (Retz.) Sw. (DE), obtained from a non-optimized extraction condition exhibited anti-Alzheimer's disease (AD) properties through the inhibition of a rate-limiting enzyme in amyloid peptide formation, ß-secretase-1 (BACE-1). Nevertheless, a non-optimized or suboptimal extraction may lead to several issues, such as a reduction in extraction efficiency and increased time and plant materials. In this study, extraction of the DE was optimized to obtain appropriate BACE-1 inhibition using a Box-Behnken design (BBD) and response surface methodology (RSM). Data revealed that the optimal extraction condition was 70% (v/v) aqueous ethanol, 50 min extraction time, 30 °C extraction temperature, and 1:30 g/mL solid/liquid ratio, giving BACE-1 inhibition at 56.33%. In addition, the extract also exhibited significant antioxidant activities compared to the non-optimized extraction. Metabolomic phytochemical profiles and targeted phytochemical analyses showed that kaempferol, quercetin, and their derivatives as well as rosmarinic acid were abundant in the extract. The optimized DE extract also acted synergistically with donepezil, an AD drug suppressing BACE-1 activities. Data received from Drosophila-expressing human amyloid precursor proteins (APPs) and BACE-1, representing the amyloid hypothesis, showed that the optimized DE extract penetrated the fly brains, suppressed BACE-1 activities, and improved locomotor functions. The extract quenched the expression of glutathione S transferase D1 (GSTD1), inositol-requiring enzyme (IRE-1), and molecular chaperone-binding immunoglobulin (Bip), while donepezil suppressed these genes and other genes involved in antioxidant and endoplasmic reticulum (ER) stress response, including superoxide dismutase type 1 (SOD1), activating transcription factor 6 (ATF-6), and protein kinase R-like endoplasmic reticulum kinase (PERK). To sum up, the optimized extraction condition reduced extraction time while resulting in higher phytochemicals, antioxidants, and BACE-1 inhibitors.


Assuntos
Doença de Alzheimer , Secretases da Proteína Precursora do Amiloide , Antioxidantes , Compostos Fitoquímicos , Extratos Vegetais , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Doença de Alzheimer/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Gleiquênias/química , Humanos , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Ácido Aspártico Endopeptidases/metabolismo
3.
Molecules ; 28(10)2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37241861

RESUMO

In the present study, response surface methodology (RSM) and Box-Behnken design (BBD) were employed to optimize the conditions for the extraction of C. maxima albedo from agricultural waste, to obtain notable phytochemicals. Ethanol concentration, extraction temperature, and extraction time were included as key factors contributing to the extraction. The results showed that the optimum extraction condition for C. maxima albedo was 50% (v/v) aqueous ethanol at 30 °C for 4 h, which provided total phenolic contents and total flavonoid contents at 15.79 mg of gallic equivalent/g dry weight (DW) and 4.50 mg of quercetin equivalent/g DW, respectively. Considerable amounts of hesperidin and naringenin at 161.03 and 3430.41 µg/g DW, respectively, were detected in the optimized extract using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). The extract was later subjected to a test for its enzyme-inhibitory activities against key enzymes relevant to Alzheimer's disease (AD), obesity, and diabetes as well as for its mutagenicity potential. Among enzyme inhibitory activities, the extract showed the highest inhibitory strength against ß-secretase (BACE-1), which is a drug target for AD treatment. The extract was also devoid of mutagenicity properties. Overall, this study demonstrated a simple and optimal extraction procedure for C. maxima albedo with a significant quantity of phytochemicals, health benefits, and genome safety.


Assuntos
Citrus , Espectrometria de Massas em Tandem , Flavonoides/farmacologia , Flavonoides/química , Antioxidantes/química , Etanol , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/análise , Extratos Vegetais/química
4.
Int J Mol Sci ; 23(3)2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35163720

RESUMO

The Food and Agriculture Organization of the United Nations (FAO) estimates that more than 500 million people, especially in Asia and Africa, are suffering from malnutrition. Recently, livestock farming has increased to supply high-quality protein, with consequent impact on the global environment. Alternative food sources with high nutritive values that can substitute livestock demands are urgently required. Recently, edible crickets have been promoted by the FAO to ameliorate the food crisis. In this review, the distribution, nutritive values, health-promoting properties (antioxidant, anti-inflammatory, anti-diabetic and anti-obesity), safety, allergenicity as well as the potential hazards and risks for human consumption are summarized. Cricket farming may help to realize the United Nations sustainable development goal No. 2 Zero Hunger. The sustainability of cricket farming is also discussed in comparison with other livestock. The findings imply that edible crickets are safe for daily intake as a healthy alternative diet due to their high protein content and health-promoting properties. Appropriate use of edible crickets in the food and nutraceutical industries represents a global business potential. However, people who are allergic to shellfish should pay attention on cricket allergy. Thus, the objective of this review was to present in-depth and up-to-date information on edible crickets to advocate and enhance public perception of cricket-based food.


Assuntos
Gryllidae , Hipersensibilidade , Alérgenos , Animais , Pisos e Cobertura de Pisos , Cadeia Alimentar , Humanos , Valor Nutritivo
5.
J Toxicol Environ Health A ; 84(7): 298-312, 2021 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-33375906

RESUMO

The worldwide demand for a natural dye by the cosmetic and food industry has recently gained interest. To provide scientific data supporting the usage of Thai henna leaf as a natural colorant, the phytochemical constituents, safety, and bioactivity of aqueous extract of the henna leaf by autoclave (HAE) and hot water (HHE) were determined. HAE contained a higher amount of total phenolic and flavonoid contents than HHE. The major constituents in both extracts were ferulic acid, gallic acid, and luteolin. The extracts displayed no marked mutagenic activity both in vitro and in vivo mammalian-like biotransformation. HAE and HHE also exhibited non-cytotoxicity to human immortalized keratinocyte cells (HaCaT), peripheral blood mononuclear cells (PBMCs), and murine macrophage RAW 264.7 cell line with IC20 and IC50 > 200 µg/ml. The extracts exhibited antioxidant and anti-inflammatory activity as evidenced by significant scavenging of ABTS and DPPH radicals and decreasing NO levels in LPS-induced RAW 264.7 cells. The antioxidant and anti-inflammatory properties of the extracts might be attributed to their phenolic and flavonoid contents. In conclusion, the traditional use of henna as a natural dye appears not to exert toxic effects and seems biosecure. Regarding safety, antioxidant, and anti-inflammatory properties, the aqueous extract of Thai henna leaf might thus serve as a readily available source for utilization in commercial health industries.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Lawsonia (Planta)/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/efeitos adversos , Antioxidantes/efeitos adversos , Humanos , Queratinócitos/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Camundongos , Compostos Fitoquímicos/efeitos adversos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Folhas de Planta/química , Células RAW 264.7
6.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34576092

RESUMO

Genomic instability, one of cancer's hallmarks, is induced by genotoxins from endogenous and exogenous sources, including reactive oxygen species (ROS), diet, and environmental pollutants. A sensitive in vivo genotoxicity test is required for the identification of human hazards to reduce the potential health risk. The somatic mutation and recombination test (SMART) or wing spot test is a genotoxicity assay involving Drosophila melanogaster (fruit fly) as a classical, alternative human model. This review describes the principle of the SMART assay in conjunction with its advantages and disadvantages and discusses applications of the assay covering all segments of health-related industries, including food, dietary supplements, drug industries, pesticides, and herbicides, as well as nanoparticles. Chemopreventive strategies are outlined as a global health trend for the anti-genotoxicity of interesting herbal extract compounds determined by SMART assay. The successful application of Drosophila for high-throughput screening of mutagens is also discussed as a future perspective.


Assuntos
Drosophila melanogaster/fisiologia , Substâncias Perigosas/análise , Modelos Biológicos , Testes de Mutagenicidade , Asas de Animais/fisiologia , Animais , Poluentes Ambientais/análise , Humanos
7.
Molecules ; 26(4)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670795

RESUMO

Adenia viridiflora Craib. is an indigenous edible plant that became an endangered species due to limited consumption of the local population with unknown reproduction and growth conditions. The plant is used as a traditional herb; however, its health applications lack scientific-based evidence. A. viridiflora Craib. plant parts (old leaves and young shoots) from four areas as Kamphaeng Phet (KP), Muang Nakhon Ratchasima (MN), Pakchong Nakhon Ratchasima (PN), and Uthai Thani (UT) origins were investigated for phenolic compositions and in vitro health properties through the inhibition of key enzymes relevant to obesity (lipase), diabetes (α-glucosidase and dipeptidyl peptidase-IV), Alzheimer's disease (cholinesterases and ß-secretase), and hypertension (angiotensin-converting enzyme). Phenolics including p-coumaric acid, sinapic acid, naringenin, and apigenin were detected in old leaves and young shoots in all plant origins. Old leaves exhibited higher total phenolic contents (TPCs) and total flavonoid contents (TFCs), leading to higher enzyme inhibitory activities than young shoots. Besides, PN and MN with higher TPCs and TFCs tended to exhibit greater enzyme inhibitory activities than others. These results will be useful to promote this plant as a healthy food with valuable medicinal capacities to support its consumption and agricultural stimulation, leading to sustainable conservation of this endangered species.


Assuntos
Doença , Passifloraceae/química , Fitoterapia , Extratos Vegetais/química , Água/química , Animais , Antioxidantes/análise , Candida/enzimologia , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Flavonoides/análise , Cavalos , Humanos , Hipertensão/tratamento farmacológico , Fenóis/análise , Folhas de Planta/química , Brotos de Planta/química , Coelhos , Saccharomyces cerevisiae/enzimologia , Solventes
8.
Int J Mol Sci ; 21(5)2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32138327

RESUMO

Neuronal insulin resistance is a significant feature of Alzheimer's disease (AD). Accumulated evidence has revealed the possible neuroprotective mechanisms of antidiabetic drugs in AD. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog and an antidiabetic agent, has a benefit in improving a peripheral insulin resistance. However, the neuronal effect of liraglutide on the model of neuronal insulin resistance with Alzheimer's formation has not been thoroughly investigated. The present study discovered that liraglutide alleviated neuronal insulin resistance and reduced beta-amyloid formation and tau hyperphosphorylation in a human neuroblostoma cell line, SH-SY5Y. Liraglutide could effectively reverse deleterious effects of insulin overstimulation. In particular, the drug reversed the phosphorylation status of insulin receptors and its major downstream signaling molecules including insulin receptor substrate 1 (IRS-1), protein kinase B (AKT), and glycogen synthase kinase 3 beta (GSK-3ß). Moreover, liraglutide reduced the activity of beta secretase 1 (BACE-1) enzyme, which then decreased the formation of beta-amyloid in insulin-resistant cells. This indicated that liraglutide can reverse the defect of phosphorylation status of insulin signal transduction but also inhibit the formation of pathogenic Alzheimer's proteins like Aß in neuronal cells. We herein provided the possibility that the liraglutide-based therapy may be able to reduce such deleterious effects caused by insulin resistance. In view of the beneficial effects of liraglutide administration, these findings suggest that the use of liraglutide may be a promising therapy for AD with insulin-resistant condition.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Insulina/metabolismo , Liraglutida/uso terapêutico , Proteínas tau/metabolismo , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Western Blotting , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Imunoprecipitação , Proteínas Substratos do Receptor de Insulina/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
9.
Molecules ; 25(8)2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32316271

RESUMO

Alzheimer's disease (AD) is the most common form of dementia, characterized by chronic neuron loss and cognitive problems. Aggregated amyloid beta (Aß) peptides, a product of cleaved amyloid precursor protein (APP) by beta-secretase 1 (BACE-1), have been indicated for the progressive pathogenesis of AD. Currently, screening for anti-AD compounds in foodstuffs is increasing, with promising results. Hence, the purpose of this study was to investigate the extraction conditions, phytochemical contents, and anti-AD properties, targeting Aß peptides of Morus cf. nigra 'Chiang Mai' (MNCM) both in vitro and in vivo. Data showed that the aqueous extract of MNCM contained high amounts of cyanidin, keracyanin, and kuromanin as anthocyanidin and anthocyanins. The extract also strongly inhibited cholinesterases and BACE-1 in vitro. Moreover, MNCM extract prevented Aß-induced neurotoxicity and promoted neurite outgrowth in neuronal cells. Interestingly, MNCM extract reduced Aß1-42 peptides and improved locomotory coordination of Drosophila co-expressing human APP and BACE-1, specifically in the brain. These findings suggest that MNCM may be useful as an AD preventive agent by targeting Aß formation.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/toxicidade , Antocianinas/administração & dosagem , Antioxidantes/administração & dosagem , Morus/química , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Antocianinas/isolamento & purificação , Antocianinas/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Colinesterases/metabolismo , Modelos Animais de Doenças , Drosophila , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Células PC12 , Compostos Fitoquímicos/química , Ratos
10.
Molecules ; 25(16)2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32824050

RESUMO

Sacred lotus (Nelumbo nucifera) has long been used as a food source and ingredient for traditional herbal remedies. Plant parts contain neuroprotective agents that interact with specific targets to inhibit Alzheimer's disease (AD). Organic solvents including methanol, ethyl acetate, hexane, and n-butanol, are widely employed for extraction of sacred lotus but impact food safety. Seed embryo, flower stalk, stamen, old leaf, petal, and leaf stalk of sacred lotus were extracted using hot water (aqueous extraction). The extractions were analyzed for their bioactive constituents, antioxidant and anti-AD properties as key enzyme inhibitory activities toward acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and ß-secretase 1 (BACE-1). Results showed that the sacred lotus stamen exhibited significant amounts of phenolics, including phenolic acids and flavonoids, that contributed to high antioxidant activity via both single electron transfer (SET) and hydrogen atom transfer (HAT) mechanisms, with anti-AChE, anti-BChE, and anti-BACE-1 activities. To enhance utilization of other sacred lotus parts, a combination of stamen, old leaf and petal as the three sacred lotus plant components with the highest phenolic contents, antioxidant activities, and enzyme inhibitory properties was analyzed. Antagonist interaction was observed, possibly from flavonoids-flavonoids interaction. Further in-depth elucidation of this issue is required. Findings demonstrated that an aqueous extract of the stamen has potential for application as a functional food to mitigate the onset of Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , Nelumbo/química , Fenóis/análise , Extratos Vegetais/farmacologia , Folhas de Planta/química , Acetilcolinesterase , Doença de Alzheimer/enzimologia , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Butirilcolinesterase/química , Proteínas Ligadas por GPI/antagonistas & inibidores , Humanos
11.
Molecules ; 25(11)2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32503261

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. To fight the disease, natural products, including mulberry, with antioxidant activities and inhibitory activities against key enzymes (acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-secretase 1 (BACE-1)) are of interest. However, even in the same cultivars, mulberry trees grown in different populated locations might possess disparate amounts of phytochemical profiles, leading to dissimilar health properties, which cause problems when comparing different cultivars of mulberry. Therefore, this study aimed to comparatively investigate the phytochemicals, antioxidant activities, and inhibitory activities against AChE, BChE, and BACE-1, of twenty-seven Morus spp. cultivated in the same planting area in Thailand. The results suggested that Morus fruit samples were rich in phenolics, especially cyanidin, kuromanin, and keracyanin. Besides, the aqueous Morus fruit extracts exhibited antioxidant activities, both in single electron transfer (SET) and hydrogen atom transfer (HAT) mechanisms, while strong inhibitory activities against AD key enzymes were observed. Interestingly, among the twenty-seven Morus spp., Morus sp. code SKSM 810191 with high phytochemicals, antioxidant activities and in vitro anti-AD properties is a promising cultivar for further developed as a potential mulberry resource with health benefits against AD.


Assuntos
Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , Morus/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Acetilcolinesterase , Doença de Alzheimer/prevenção & controle , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Butirilcolinesterase/química , Proteínas Ligadas por GPI/antagonistas & inibidores , Humanos
12.
Nucleic Acids Res ; 43(17): 8325-39, 2015 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-26187992

RESUMO

REV1 is a eukaryotic member of the Y-family of DNA polymerases involved in translesion DNA synthesis and genome mutagenesis. Recently, REV1 is also found to function in homologous recombination. However, it remains unclear how REV1 is recruited to the sites where homologous recombination is processed. Here, we report that loss of mammalian REV1 results in a specific defect in replication-associated gene conversion. We found that REV1 is targeted to laser-induced DNA damage stripes in a manner dependent on its ubiquitin-binding motifs, on RAD18, and on monoubiquitinated FANCD2 (FANCD2-mUb) that associates with REV1. Expression of a FANCD2-Ub chimeric protein in RAD18-depleted cells enhances REV1 assembly at laser-damaged sites, suggesting that FANCD2-mUb functions downstream of RAD18 to recruit REV1 to DNA breaks. Consistent with this suggestion we found that REV1 and FANCD2 are epistatic with respect to sensitivity to the double-strand break-inducer camptothecin. REV1 enrichment at DNA damage stripes also partially depends on BRCA1 and BRCA2, components of the FANCD2/BRCA supercomplex. Intriguingly, analogous to FANCD2-mUb and BRCA1/BRCA2, REV1 plays an unexpected role in protecting nascent replication tracts from degradation by stabilizing RAD51 filaments. Collectively these data suggest that REV1 plays multiple roles at stalled replication forks in response to replication stress.


Assuntos
Dano ao DNA , Replicação do DNA , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/fisiologia , Proteínas Nucleares/fisiologia , Nucleotidiltransferases/fisiologia , Camptotecina/toxicidade , Linhagem Celular , DNA/metabolismo , Proteínas de Ligação a DNA/fisiologia , DNA Polimerase Dirigida por DNA , Proteína do Grupo de Complementação D2 da Anemia de Fanconi/metabolismo , Conversão Gênica , Humanos , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Nucleotidiltransferases/química , Nucleotidiltransferases/metabolismo , Domínios e Motivos de Interação entre Proteínas , Estresse Fisiológico/genética , Inibidores da Topoisomerase I/toxicidade , Ubiquitina-Proteína Ligases
13.
Nucleic Acids Res ; 42(17): 11071-82, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25170086

RESUMO

Short-wave ultraviolet light induces both mildly helix-distorting cyclobutane pyrimidine dimers (CPDs) and severely distorting (6-4) pyrimidine pyrimidone photoproducts ((6-4)PPs). The only DNA polymerase (Pol) that is known to replicate efficiently across CPDs is Polη, a member of the Y family of translesion synthesis (TLS) DNA polymerases. Phenotypes of Polη deficiency are transient, suggesting redundancy with other DNA damage tolerance pathways. Here we performed a comprehensive analysis of the temporal requirements of Y-family Pols ι and κ as backups for Polη in (i) bypassing genomic CPD and (6-4)PP lesions in vivo, (ii) suppressing DNA damage signaling, (iii) maintaining cell cycle progression and (iv) promoting cell survival, by using mouse embryonic fibroblast lines with single and combined disruptions in these Pols. The contribution of Polι is restricted to TLS at a subset of the photolesions. Polκ plays a dominant role in rescuing stalled replication forks in Polη-deficient mouse embryonic fibroblasts, both at CPDs and (6-4)PPs. This dampens DNA damage signaling and cell cycle arrest, and results in increased survival. The role of relatively error-prone Pols ι and κ as backups for Polη contributes to the understanding of the mutator phenotype of xeroderma pigmentosum variant, a syndrome caused by Polη defects.


Assuntos
Dano ao DNA , DNA Polimerase Dirigida por DNA/fisiologia , Raios Ultravioleta/efeitos adversos , Animais , Ciclo Celular , Linhagem Celular , Quebras de DNA de Cadeia Dupla , Replicação do DNA , DNA Polimerase Dirigida por DNA/metabolismo , Fibroblastos/enzimologia , Fibroblastos/metabolismo , Genoma , Camundongos , Dímeros de Pirimidina/metabolismo , DNA Polimerase iota
14.
Heliyon ; 10(1): e23175, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38163201

RESUMO

Gynmena inodorum (GI) is a green leafy vegetable used in the Northern Thai cuisine which has antioxidant activities and may be applicable for preventing oxidative stress and aging-related disease. However, understanding the relationship between GI phytonutrients and their antioxidant properties has been unclear. The aims of this study were to identify the GI leaf phytochemicals and to study their antioxidant activities. A chromatogram of LC-ESI-MS/QTOF-MS showed that the GI leaves were potentially composed of phenolics, quinic acids, flavonoids, and triterpenoid saponins. This study was able to authenticate quercetin, kaempferol, and triterpenoid GIA1 in the samples. The GI materials with high contents of phenolics, flavonoids, quercetin, and kaempferol showed significant relation to antioxidation and protection in endothelial cell death suppressed by reactive nitrogen species. Meanwhile, triterpenoids had a low antioxidant impact. Ultimately, GI leaves with high phenolic compounds are a promising raw material to develop as an antioxidant functional food.

15.
Pharmaceuticals (Basel) ; 17(3)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38543127

RESUMO

Alzheimer's disease (AD) is the most common type of dementia and a significant concern to global public health due to the prevalence of aging populations. Donepezil is one of only a few medications approved for use as an anti-AD agent but all have adverse side effects. Reducing the dosage of AD drugs with plant extracts (phytotherapy) while maintaining efficacy is one strategy to minimize adverse side effects. We previously reported the anti-AD properties of an edible fern, Diplazium esculentum (Retz.) Sw. (DE), which inhibited key enzymes involved in AD pathogenesis including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and ß-secretase 1 (BACE-1). This study aimed to determine whether DE exhibited a synergistic effect with donepezil. The enzyme inhibitory assay showed that DE extract and its bioactive compounds, kaempferol, and quercetin, slightly impeded AChE inhibition with donepezil, while DE extract and quercetin showed synergistic or additive effects with donepezil against BChE and BACE-1, respectively. DE extract combined with donepezil also improved eye phenotypes in a Drosophila model of AD by preventing ommatidia atrophia and bristle breakages. Furthermore, the DE extract exhibited no genotoxic activities, as determined by the Ames test. Our data revealed that DE extract showed promise when combined with donepezil during AD treatment by targeting BChE and BACE-1.

16.
Foods ; 13(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38472782

RESUMO

Pectin was extracted from cocoa husks, a food-processing biowaste, using an autoclave approach. A Box-Behnken design (BBD) and response surface methodology (RSM) were used to optimize pectin extraction. Three factors including extraction time (5-40 min), temperature (105-135 °C), and solid to liquid ratios (SLRs) (10-30 w/v) were employed. Results showed that the optimal conditions for high cocoa-husk-pectin (CHP) yield of 26.22% was 105 °C for 5 min with an SLR at 20 w/v. The physicochemical characteristics of CHP were compared with commercial high-methoxyl pectin (CHMP) and commercial low-methoxyl pectin (CLMP). CHP was classified as low-methoxyl pectin, with a degree of esterification at 34.74% and methoxyl content of 5.08%. The galacturonic acid content of CHP was 32.71% which was lower than CHMP (72.69%) and CLMP (41.24%). The intrinsic viscosity and viscosity-average molecular weight was similar to CLMP but higher than CHMP. No significant differences in water-holding capacity were found among samples. CHP showed higher oil-holding capacity but lower solubility compared with commercial pectin. CHP solutions showed pseudoplastic behavior. The viscosities of CHP solutions improved at increasing concentrations and decreasing pH. The CHP solution viscosities were lower than CLMP at the same condition. The viscoelastic properties of CHP solutions increased at higher concentrations, with the optimal value at pH 3. CHP showed no genotoxicity when assayed using the Ames test. Autoclave extraction as an accessible fast method showed potential for high pectin yield recovery from cocoa husks.

17.
Nanomaterials (Basel) ; 14(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38921877

RESUMO

Chrysin is hypothesized to possess the ability to prevent different illnesses, such as diabetes, cancer, and neurodegenerative disorders. Nonetheless, chrysin has a low solubility under physiological conditions, resulting in limited bioavailability. In a previous study, we utilized an oil-in-water emulsion system (chrysin-ES or chrysin-NE) to encapsulate chrysin, thereby increasing its bioaccessibility and preserving its antioxidant and anti-Alzheimer's properties. To promote the chrysin-ES as a supplementary and functional food, it was obligatory to carry out a safety assessment. Cytotoxicity testing showed that chrysin-ES was harmless, with no killing effect on 3T3-L1 (adipocytes), RAW 264.7 (macrophages), HEK293 (kidney cells), and LX-2 (hepatic stellate cells). The acute toxicity evaluation demonstrated that the 50% lethal dose (LD50) for chrysin-ES was greater than 2000 mg/kg BW. Genotoxicity assessments found that chrysin-ES did not induce DNA mutations in vitro or in vivo. Furthermore, chrysin and chrysin-ES exhibited anti-mutagenic properties against PhIP-induced and IQ-induced mutagenesis in the Ames test, while they inhibited urethane-, ethyl methanesulfonate-, mitomycin C-, and N-nitrosomethylurea-mediated mutations in Drosophila. The present study illustrates the safety and anti-genotoxicity properties of chrysin-ES, allowing for the further development of chrysin-based food supplements and nutraceuticals.

18.
Pharmaceuticals (Basel) ; 17(3)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38543073

RESUMO

Low-grade chronic inflammation and adipocyte dysfunction are prominent risk factors of insulin resistance and type 2 diabetes mellitus (T2DM) in obesity. Thus, prevention of inflammation and adipocyte dysfunction could be one possible approach to mitigate T2DM development. Several Ficus species have been used in traditional medicine for ameliorating inflammation and T2DM. Our previous studies reported biological effects of Ficus lindsayana including antioxidant, anti-cancer, and anti-α-glucosidase activities. Further, this study therefore investigated whether F. lindsayana latex (FLLE) and root (FLRE) extracts inhibit inflammation-stimulated insulin resistance in adipocytes and inflammation in macrophages. FLLE and FLRE (200 µg/mL) had no significant cytotoxicity for macrophages, adipocytes, and blood cells (PBMCs and RBCs). FLRE had a total flavonoid content about three times higher than FLLE, while both had similar levels of total phenolic content. FLRE showed higher abilities than FLLE in suppressing inflammation in both macrophages and adipocytes and reversing the inflammation-induced insulin resistance in adipocytes. In TNF-α-induced adipocytes, FLRE significantly improved insulin-induced glucose uptake and insulin-suppressed lipolysis, while FLLE only significantly improved glucose uptake. Moreover, FLRE and FLLE remarkably reduced chemoattractant (MCP-1) but improved adipogenic (PPARγ and CEBPα) gene expression, leading to the promotion of adipogenesis and the suppression of insulin resistance. In LPS-induced macrophages, FLRE, but not FLLE, significantly inhibited LPS-induced NO production. Moreover, FLRE significantly reduced LPS-stimulated iNOS, COX-2, IL-1ß, IL-6, and TNF-α gene expression. These results may provide the potential data for the development of this plant, especially the root part, as an alternative medicine, functional ingredient, or food supplement for the prevention of inflammation and obesity-associated insulin resistance, as well as T2DM.

19.
Nutrients ; 15(5)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36904098

RESUMO

The existence of neuroinflammation and oxidative stress surrounding amyloid beta (Aß) plaques, a hallmark of Alzheimer's disease (AD), has been demonstrated and may result in the activation of neuronal death and inhibition of neurogenesis. Therefore, dysregulation of neuroinflammation and oxidative stress is one possible therapeutic target for AD. Kaempferia parviflora Wall. ex Baker (KP), a member of the Zingiberaceae family, possesses health-promoting benefits including anti-oxidative stress and anti-inflammation in vitro and in vivo with a high level of safety; however, the role of KP in suppressing Aß-mediated neuroinflammation and neuronal differentiation has not yet been investigated. The neuroprotective effects of KP extract against Aß42 have been examined in both monoculture and co-culture systems of mouse neuroectodermal (NE-4C) stem cells and BV-2 microglia cells. Our results showed that fractions of KP extract containing 5,7-dimethoxyflavone, 5,7,4'-trimethoxyflavone, and 3,5,7,3',4'-pentamethoxyflavone protected neural stem cells (both undifferentiated and differentiated) and microglia activation from Aß42-induced neuroinflammation and oxidative stress in both monoculture and co-culture system of microglia and neuronal stem cells. Interestingly, KP extracts also prevented Aß42-suppressed neurogenesis, possibly due to the contained methoxyflavone derivatives. Our data indicated the promising role of KP in treating AD through the suppression of neuroinflammation and oxidative stress induced by Aß peptides.


Assuntos
Doença de Alzheimer , Células-Tronco Neurais , Zingiberaceae , Camundongos , Animais , Peptídeos beta-Amiloides/farmacologia , Extratos Vegetais/farmacologia , Técnicas de Cocultura , Microglia , Doenças Neuroinflamatórias , Inflamação , Doença de Alzheimer/tratamento farmacológico
20.
Heliyon ; 9(5): e15951, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37205996

RESUMO

Missing information on plant origin control and nutritional data on herbs, spices and vegetables could lead to sample quality deficit and misusage of the plant database. In this study, twenty vegetables that were collected and managed based on the recommendations of the Department of Agriculture, Ministry of Agriculture and Cooperatives, Thailand, were investigated regarding their proximate mineral, vitamin and carotenoid contents using the standard procedures of the Association of Official Analytical Chemists (AOAC). The results showed that these plants (100 g dry weight) exhibited similar energy levels (337.11-420.48 kcal), which were mainly distributed from high carbohydrate content (21.01-88.17 g), while protein (3.14-66.07 g) and fat (0.00-10.33 g) levels were quite low. As a form of carbohydrate, dietary fiber was found to be high in Cymbopogon citratus (DC.) Stapf (Cy. citratus) and Solanum torvum Sw. (So. torvum) (57.00-59.54 g). Interestingly, Senegalia pennata subsp. insuavis (Lace) Maslin, Seigler & Ebinger (S. pennata) exhibited exceptionally high protein content, which was between 2.3 and 3.1 times higher than its carbohydrates. High mineral contents were detected in S. pennata, Ocimum africanum Lour. (O. africanum), Ocimum basilicum L. (O. basilicum), Ocimum gratissimum L. var. macrophyllum Briq. (O. gratissimum) and Coriandrum sativum L. (Co. sativum), while Mentha cordifolia Opiz ex Fresen (M. cordifolia) was observed to be a good source of vitamin C (381.36-547.47 mg). High carotenoids were mostly found in Eryngium foetidum L. (E. foetidum), O. gratissimum, Co. sativum and O. basilicum (75.23-119.96 mg). Interestingly, the location of sample collection seemed to have minimal effect on the nutritional and carotenoid compositions. The results of this study provide reliable information concerning the nutritional and carotenoid contents in plant sources with control of origin, which could be used in the future for food development with specific nutritional requirements.

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