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1.
Plant Physiol ; 195(2): 1446-1460, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38431523

RESUMO

Terpene trilactones (TTLs) are important secondary metabolites in ginkgo (Ginkgo biloba); however, their biosynthesis gene regulatory network remains unclear. Here, we isolated a G. biloba ethylene response factor 4 (GbERF4) involved in TTL synthesis. Overexpression of GbERF4 in tobacco (Nicotiana tabacum) significantly increased terpenoid content and upregulated the expression of key enzyme genes (3-hydroxy-3-methylglutaryl-CoA reductase [HMGR], 3-hydroxy-3-methylglutaryl-CoA synthase [HMGS], 1-deoxy-D-xylulose-5-phosphate reductoisomerase [DXR], 1-deoxy-D-xylulose-5-phosphate synthase [DXS], acetyl-CoA C-acetyltransferase [AACT], and geranylgeranyl diphosphate synthase [GGPPS]) in the terpenoid pathway in tobacco, suggesting that GbERF4 functions in regulating the synthesis of terpenoids. The expression pattern analysis and previous microRNA (miRNA) sequencing showed that gb-miR160 negatively regulates the biosynthesis of TTLs. Transgenic experiments showed that overexpression of gb-miR160 could significantly inhibit the accumulation of terpenoids in tobacco. Targeted inhibition and dual-luciferase reporter assays confirmed that gb-miR160 targets and negatively regulates GbERF4. Transient overexpression of GbERF4 increased TTL content in G. biloba, and further transcriptome analysis revealed that DXS, HMGS, CYPs, and transcription factor genes were upregulated. In addition, yeast 1-hybrid and dual-luciferase reporter assays showed that GbERF4 could bind to the promoters of the HMGS1, AACT1, DXS1, levopimaradiene synthase (LPS2), and GGPPS2 genes in the TTL biosynthesis pathway and activate their expression. In summary, this study investigated the molecular mechanism of the gb-miR160-GbERF4 regulatory module in regulating the biosynthesis of TTLs. It provides information for enriching the understanding of the regulatory network of TTL biosynthesis and offers important gene resources for the genetic improvement of G. biloba with high contents of TTLs.


Assuntos
Regulação da Expressão Gênica de Plantas , Ginkgo biloba , Lactonas , MicroRNAs , Nicotiana , Proteínas de Plantas , Terpenos , MicroRNAs/genética , MicroRNAs/metabolismo , Terpenos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ginkgo biloba/genética , Ginkgo biloba/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Lactonas/metabolismo , Plantas Geneticamente Modificadas , Vias Biossintéticas/genética
2.
Nature ; 575(7784): 643-646, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31618759

RESUMO

The Ginkgo biloba metabolite bilobalide is widely ingested by humans but its effect on the mammalian central nervous system is not fully understood1-4. Antagonism of γ-aminobutyric acid A receptors (GABAARs) by bilobalide has been linked to the rescue of cognitive deficits in mouse models of Down syndrome5. A lack of convulsant activity coupled with neuroprotective effects have led some to postulate an alternative, unidentified target4; however, steric congestion and the instability of bilobalide1,2,6 have prevented pull-down of biological targets other than the GABAΑRs. A concise and flexible synthesis of bilobalide would facilitate the development of probes for the identification of potential new targets, analogues with differential selectivity between insect and human GABAΑRs, and stabilized analogues with an enhanced serum half-life7. Here we exploit the unusual reactivity of bilobalide to enable a late-stage deep oxidation that symmetrizes the molecular core and enables oxidation states to be embedded in the starting materials. The same overall strategy may be applicable to G. biloba congeners, including the ginkgolides-some of which are glycine-receptor-selective antagonists8. A chemical synthesis of bilobalide should facilitate the investigation of its biological effects and its therapeutic potential.


Assuntos
Ciclopentanos/síntese química , Furanos/síntese química , Ginkgolídeos/síntese química , Técnicas de Química Analítica , Ginkgo biloba/química , Oxirredução
3.
Proc Natl Acad Sci U S A ; 119(49): e2211458119, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36442101

RESUMO

Natural structural materials typically feature complex hierarchical anisotropic architectures, resulting in excellent damage tolerance. Such highly anisotropic structures, however, also provide an easy path for crack propagation, often leading to catastrophic fracture as evidenced, for example, by wood splitting. Here, we describe the weakly anisotropic structure of Ginkgo biloba (ginkgo) seed shell, which has excellent crack resistance in different directions. Ginkgo seed shell is composed of tightly packed polygonal sclereids with cell walls in which the cellulose microfibrils are oriented in a helicoidal pattern. We found that the sclereids contain distinct pits, special fine tubes like a "screw fastener," that interlock the helicoidal cell walls together. As a result, ginkgo seed shell demonstrates crack resistance in all directions, exhibiting specific fracture toughness that can rival other highly anisotropic natural materials, such as wood, bone, insect cuticle, and nacre. In situ characterization reveals ginkgo's unique toughening mechanism: pit-guided crack propagation. This mechanism forces the crack to depart from the weak compound middle lamella and enter into the sclereid, where the helicoidal cell wall significantly inhibits crack growth by the cleavage and breakage of the fibril-based cell walls. Ginkgo's toughening mechanism could provide guidelines for a new bioinspired strategy for the design of high-performance bulk materials.


Assuntos
Fraturas Ósseas , Ginkgo biloba , Sementes , Parede Celular , Madeira
4.
J Exp Bot ; 75(11): 3351-3367, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38459807

RESUMO

In gymnosperms such as Ginkgo biloba, the arrival of pollen plays a key role in ovule development, before fertilization occurs. Accordingly, G. biloba female plants geographically isolated from male plants abort all their ovules after the pollination drop emission, which is the event that allows the ovule to capture pollen grains. To decipher the mechanism induced by pollination required to avoid ovule senescence and then abortion, we compared the transcriptomes of pollinated and unpollinated ovules at three time points after the end of the emission of pollination drop. Transcriptomic and in situ expression analyses revealed that several key genes involved in programmed cell death such as senescence and apoptosis, DNA replication, and cell cycle regulation were differentially expressed in unpollinated ovules compared to pollinated ovules. We provide evidence that the pollen captured by the pollination drop affects auxin local accumulation and might cause deregulation of key genes required for the ovule's programmed cell death, activating both the cell cycle regulation and DNA replication genes.


Assuntos
Ginkgo biloba , Óvulo Vegetal , Pólen , Polinização , Óvulo Vegetal/crescimento & desenvolvimento , Óvulo Vegetal/fisiologia , Óvulo Vegetal/genética , Pólen/genética , Pólen/crescimento & desenvolvimento , Pólen/fisiologia , Ginkgo biloba/genética , Ginkgo biloba/fisiologia , Ginkgo biloba/crescimento & desenvolvimento , Transcriptoma , Regulação da Expressão Gênica de Plantas
5.
J Neural Transm (Vienna) ; 131(3): 203-212, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38347175

RESUMO

Cognitive impairment, depression and (mental) fatigue represent the most frequent neuropsychiatric symptoms of the post-COVID syndrome. Neuroinflammation, oxidative stress and mitochondrial dysfunction have been identified as common pathophysiological mechanisms underlying these symptoms. Attempts to treat post-COVID-associated cognitive impairment and fatigue with different drugs available for other diseases have not yet been successful. One probable explanation could be that these drugs work by one specific mechanism of action only and not in a broad multi-target way. Therefore, they will not address the broad pathophysiological spectrum possibly responsible for cognitive impairment, depression and fatigue in post-COVID syndrome. Notably, nearly all drugs currently under investigation for fatigue in post-COVID syndrome are rather addressing one single target instead of the several pathomechanisms underlying this condition. Contrary to this approach, herbal drugs often consist of many different ingredients with different pharmacological properties and pharmacological targets. Therefore, these drugs might be a promising approach for the treatment of the broad symptomatic presentation and the pathophysiological mechanisms of cognitive impairment and fatigue following a SARS-CoV-2 infection. Of these herbal drugs, extracts of Ginkgo biloba and Rhodiola rosea probably are the best investigated candidates. Their broad pharmacological spectrum in vitro and in vivo includes anti-oxidative, anti-inflammatory, antidepressant as well as properties reducing cognitive impairment and fatigue. In several studies, both drugs showed positive effects on physical and mental fatigue and impaired cognition. Moreover, depressive symptoms were also reduced in some studies. However, even if these results are promising, the data are still preliminary and require additional proof by further studies.


Assuntos
COVID-19 , Disfunção Cognitiva , Rhodiola , Humanos , Ginkgo biloba , COVID-19/complicações , SARS-CoV-2 , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia
6.
J Sep Sci ; 47(13): e2400234, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39005007

RESUMO

In this study, we employed a combination approach for the preparative separation of constituents from Ginkgo biloba L. leaves. It involved multi-stage solvent extractions utilizing two-phase multi-solvent systems and countercurrent chromatography (CCC) separations using three different solvent systems. The n-heptane/ethyl acetate/water (1:1:2, v/v) and n-heptane/ethyl acetate/methanol/water (HepEMWat, 7:3:7:3, v/v) solvent systems were screened out as extraction systems. The polarities of the upper and lower phases in the multi-solvent systems were adjustable, enabling the effectively segmented separation of complex constituents in G. biloba L. The segmented products were subsequently directly utilized as samples and separated using CCC with the solvent systems acetate/n-butanol/water (4:1:5, v/v), HepEMWat (5:5:5:5, v/v), and HepEMWat (9:1:9:1, v/v), respectively. As a result, a total of 11 compounds were successfully isolated and identified from a 2 g methanol extract of G. biloba L through two-stage extraction and three CCC separation processes; among them, nine compounds exhibited high-performance liquid chromatography purity exceeding 85%.


Assuntos
Distribuição Contracorrente , Ginkgo biloba , Extratos Vegetais , Folhas de Planta , Solventes , Ginkgo biloba/química , Solventes/química , Folhas de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Água/química , Metanol/química , Acetatos/química , Extrato de Ginkgo
7.
J Sep Sci ; 47(14): e2400342, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39031453

RESUMO

In this study, a ligand fishing method for the screening of α-glucosidase inhibitors from Ginkgo biloba leaf was established for the first time using α-glucosidase immobilized on the magnetic metal-organic framework. The immobilized α-glucosidase exhibited enhanced resistance to temperature and pH, as well as good thermal stability and reusability. Two ligands, namely quercitrin and quercetin, were screened from Ginkgo biloba leaf and identified by ultra-high performance liquid chromatography-tandem mass spectrometry. The half-maximal inhibitory concentration values for quercitrin and quercetin were determined to be 105.69 ± 0.39 and 83.49 ± 0.79 µM, respectively. Molecular docking further confirmed the strong inhibitory effect of these two ligands. The proposed approach in this study demonstrates exceptional efficiency in the screening of α-glucosidase inhibitors from complex natural medicinal plants, thus exhibiting significant potential for the discovery of antidiabetic compounds.


Assuntos
Enzimas Imobilizadas , Ginkgo biloba , Inibidores de Glicosídeo Hidrolases , Estruturas Metalorgânicas , Folhas de Planta , alfa-Glucosidases , Ginkgo biloba/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Estruturas Metalorgânicas/química , Folhas de Planta/química , alfa-Glucosidases/metabolismo , alfa-Glucosidases/química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/antagonistas & inibidores , Enzimas Imobilizadas/metabolismo , Simulação de Acoplamento Molecular , Avaliação Pré-Clínica de Medicamentos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Quercetina/química , Quercetina/análise , Quercetina/farmacologia , Quercetina/análogos & derivados , Cromatografia Líquida de Alta Pressão
8.
Planta Med ; 90(4): 286-297, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38286405

RESUMO

Extracellular senile plaques and intraneuronal neurofibrillary tangles are two devastating brain proteinopathies that are indicative of Alzheimer's disease, the most prevalent type of dementia. Currently, no effective medications are available to stop or reverse Alzheimer's disease. Ginkgo biloba extract, commonly referred to as EGb 761, is a natural product made from the leaves of the G. biloba tree. It has long been demonstrated to have therapeutic benefits in Alzheimer's disease. The current study assessed the beneficial effects of EGb 761 against Alzheimer's disease in comparison with memantine, a standard treatment for Alzheimer's disease. The scopolamine-heavy metals mixture rat Alzheimer's disease model is a newly created model to study the effects of EGb 761 oral therapy on cognitive performance and other Alzheimer's disease-like changes over a 28-day experimental period. This new Alzheimer's disease model provides better criteria for Alzheimer's disease hallmarks than the conventional scopolamine model. The EGb 761 reversed memory and learning deficits induced by the scopolamine-heavy metals mixture. These outcomes were linked to a more pronounced inhibitory effect on acetylcholinesterase, caspase-3, hippocampal amyloid-beta protein (Aß1 - 42), phosphorylated tau protein counts, and proinflammatory cytokines (tumor necrosis factor-α and interleukin-1ß) compared to the memantine-treated group. Furthermore, EGb 761 treatment considerably reduced lipid peroxidation (malondialdehyde) and improved reduced glutathione levels compared to memantine. Our results suggest EGb 761's potential in treating central nervous system disorders. It's a promising candidate for future Alzheimer's disease therapeutic exploration. This study also highlights the need for future research to focus on the positive benefits of herbal medicines.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Extrato de Ginkgo , Metais Pesados , Animais , Ratos , Doença de Alzheimer/tratamento farmacológico , Memantina/farmacologia , Memantina/uso terapêutico , Ginkgo biloba , Acetilcolinesterase/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Metais Pesados/uso terapêutico , Derivados da Escopolamina/uso terapêutico
9.
Ecotoxicol Environ Saf ; 274: 116183, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38471343

RESUMO

Arsenic is an environmentally ubiquitous toxic metalloid. Chronic exposure to arsenic may lead to arsenicosis, while no specific therapeutic strategies are available for the arsenism patients. And Ginkgo biloba extract (GBE) exhibited protective effect in our previous study. However, the mechanisms by which GBE protects the arsenism patients remain poorly understood. A liquid chromatography-mass spectrometry (LC-MS) based untargeted metabolomics analysis was used to study metabolic response in arsenism patients upon GBE intervention. In total, 39 coal-burning type of arsenism patients and 50 healthy residents were enrolled from Guizhou province of China. The intervention group (n = 39) were arsenism patients orally administered with GBE (three times per day) for continuous 90 days. Plasma samples from 50 healthy controls (HC) and 39 arsenism patients before and after GBE intervention were collected and analyzed by established LC-MS method. Statistical analysis was performed by MetaboAnalyst 5.0 to identify differential metabolites. Multivariate analysis revealed a separation in arsenism patients between before (BG) and after GBE intervention (AG) group. It was observed that 35 differential metabolites were identified between BG and AG group, and 30 of them were completely or partially reversed by GBE intervention, with 14 differential metabolites significantly up-regulated and 16 differential metabolites considerably down-regulated. These metabolites were involved in promoting immune response and anti-inflammatory functions, and alleviating oxidative stress. Taken together, these findings indicate that the GBE intervention could probably exert its protective effects by reversing disordered metabolites modulating these functions in arsenism patients, and provide insights into further exploration of mechanistic studies.


Assuntos
Arsênio , Extrato de Ginkgo , Ginkgo biloba , Humanos , Ginkgo biloba/química , Ginkgo biloba/metabolismo , Cromatografia Líquida , Espectrometria de Massa com Cromatografia Líquida , Arsênio/toxicidade , Espectrometria de Massas em Tandem/métodos , Extratos Vegetais/farmacologia , Extratos Vegetais/análise
10.
Phytother Res ; 38(8): 4272-4285, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38972848

RESUMO

Mild cognitive impairment poses an increasing challenge to middle-aged and elderly populations. Traditional Chinese medicinal herbs like Cistanche tubulosa and Ginkgo biloba (CG) have been proposed as potential agents to improve cognitive and memory functions. A randomized controlled trial involving 100 Chinese middle-aged and elderly participants was conducted to investigate the potential synergistic effects of CG on cognitive function in individuals at risk of neurodegenerative diseases. Over 90 days, both CG group and placebo group received two tablets daily, with each pair of CG tablets containing 72 mg echinacoside and 27 mg flavonol glycosides. Cognitive functions were assessed using multiple scales and blood biomarkers were determined at baseline, Day 45, and Day 90. The CG group exhibited significant improvements in the scores of Mini-Mental State Examination (26.5 at baseline vs. 27.1 at Day 90, p < 0.001), Montreal Cognitive Assessment (23.4 at baseline vs. 25.3 at Day 90, p < 0.001), and World Health Organization Quality of Life (81.6 at baseline vs. 84.2 at Day 90, p < 0.001), all surpassing scores in placebo group. Notably, both the Cognitrax matrix test and the Wechsler Memory Scale-Revised demonstrated enhanced memory functions, including long-term and delayed memory, after CG intervention. Moreover, cognitive-related blood biomarkers, including total tau, pT181, pS199, pT231, pS396, and thyroid-stimulating hormone, significantly decreased, whereas triiodothyronine and free triiodothyronine significantly increased. No treatment-related adverse events were reported, and routine blood and urine tests remained stable. These findings indicated that CG supplementation could potentially serve as an effective supplementary solution for enhancing cognitive and memory functions.


Assuntos
Cistanche , Cognição , Disfunção Cognitiva , Ginkgo biloba , Extratos Vegetais , Humanos , Ginkgo biloba/química , Cistanche/química , Método Duplo-Cego , Masculino , Pessoa de Meia-Idade , Feminino , Extratos Vegetais/farmacologia , Idoso , Cognição/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Qualidade de Vida , Glicosídeos/farmacologia , Biomarcadores/sangue , Extrato de Ginkgo
11.
Int J Toxicol ; 43(1_suppl): 64S-81S, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37930133

RESUMO

The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 10 Ginkgo biloba-derived ingredients, which are most frequently reported to function in cosmetics as skin conditioning agents or antioxidants. The Panel reviewed the available data to determine the safety of these ingredients. Because final product formulations may contain multiple botanicals, each containing the same constituents of concern, formulators are advised to be aware of these constituents and to avoid reaching levels that may be hazardous to consumers. The Panel was concerned about the presence of ginkgolic acid in cosmetics. Industry should use good manufacturing practices to limit impurities. The Panel concluded that 5 Ginkgo biloba leaf-derived ingredients are safe in the present practices of use and concentration described in this safety assessment when formulated to be non-sensitizing; data are insufficient to determine the safety of the remaining 5 ingredients under the intended conditions of use in cosmetic formulations.


Assuntos
Cosméticos , Ginkgo biloba , Ginkgo biloba/toxicidade , Qualidade de Produtos para o Consumidor , Extratos Vegetais/toxicidade , Cosméticos/toxicidade , Antioxidantes
12.
Phytochem Anal ; 35(6): 1428-1442, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38725319

RESUMO

INTRODUCTION: Previously reported preparation methods of Ginkgo biloba leaf extract (EGBL) have mainly focused on the enrichment of flavonoid glycosides (FG) and terpene trilactones (TT), which led to the underutilization of G. biloba leaves (GBL). OBJECTIVES: To make full use of GBL, in this study, a comprehensive optimization strategy for preparing EGBL by macroporous resin column chromatography was proposed and applied to enrich FG, TT, and shikimic acid (SA) from GBL. METHODOLOGY: Initially, the static adsorption and desorption were executed to select suitable resin. Then, the influences of solution pH were investigated by the static and dynamic adsorption. Subsequently, eight process parameters were systematically investigated via a definitive screening design (DSD). After verification experiments, scale-up enrichment was carried out, investigating the feasibility of the developed strategy for application on an industrial scale. RESULTS: It was found that XDA1 was the most appropriate adsorbent for the preparation of EGBL at solution pH 2.0. Furthermore, based on the constraints of the desired quality attributes, the optimized ranges of operating parameters were successfully acquired, and the verification experiments demonstrated the accuracy and reliability of using DSD to investigate the chromatography process for the preparation of EGBL. Finally, magnified experiments were successfully performed, obtaining the EGBL containing 26.54% FG, 8.96% TT, and 10.70% SA, which reached the SA level of EGB761, an international standard EGBL. CONCLUSION: The present study not only provided an efficient and convenient approach for the preparation of EGBL enriched in SA but also accelerated efforts to high-value utilization of GBL.


Assuntos
Ginkgo biloba , Extratos Vegetais , Folhas de Planta , Ácido Chiquímico , Ginkgo biloba/química , Folhas de Planta/química , Extratos Vegetais/química , Ácido Chiquímico/química , Adsorção , Cromatografia Líquida de Alta Pressão/métodos , Porosidade , Flavonoides/análise , Concentração de Íons de Hidrogênio , Extrato de Ginkgo
13.
Phytochem Anal ; 35(2): 254-270, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37758241

RESUMO

INTRODUCTION: Ginkgo biloba extract (GBE) is an effective substance from traditional Chinese medicine (TCM) G. biloba for treating ischaemic stroke (IS). However, its active ingredients and mechanism of action remain unclear. OBJECTIVES: This study aimed to reveal the potential active component group and possible anti-IS mechanism of GBE. MATERIALS AND METHODS: The network pharmacology method was used to reveal the possible anti-IS mechanism of these active ingredients in GBE. An ultra-high-performance liquid chromatography triple quadrupole electrospray tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous detection of the active ingredients of GBE. RESULTS: The active components of GBE anti-IS were screened by literature integration. Network pharmacology results showed that the anti-IS effect of GBE is achieved through key active components such as protocatechuic acid, bilobalide, ginkgolide A, and so on. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the possible anti-IS mechanism of GBE is regulating the PI3K-Akt signalling pathway and other signal pathways closely related to inflammatory response and apoptosis regulation combined with AKT1, MAPK, TNF, ALB, CASP3, and other protein targets. Nineteen main constituents in seven batches of GBE were successfully analysed using the established UPLC-MS/MS method, and the results showed that the content of protocatechuic acid, gallic acid, ginkgolide A, and so forth was relatively high, which was consistent with network pharmacology results, indicating that these ingredients may be the key active anti-IS ingredients of GBE. CONCLUSION: This study revealed the key active components and the anti-IS mechanism of GBE. It also provided a simple and sensitive method for the quality control of related preparations.


Assuntos
Isquemia Encefálica , Extrato de Ginkgo , Ginkgolídeos , Hidroxibenzoatos , Lactonas , Acidente Vascular Cerebral , Espectrometria de Massas em Tandem/métodos , Ginkgo biloba/química , Cromatografia Líquida , Espectrometria de Massa com Cromatografia Líquida , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Extratos Vegetais/farmacologia , Extratos Vegetais/química
14.
Int J Mol Sci ; 25(15)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39125680

RESUMO

Inflammatory processes in the brain can exert important neuroprotective functions. However, in neurological and psychiatric disorders, it is often detrimental due to chronic microglial over-activation and the dysregulation of cytokines and chemokines. Growing evidence indicates the emerging yet prominent pathophysiological role of neuroinflammation in the development and progression of these disorders. Despite recent advances, there is still a pressing need for effective therapies, and targeting neuroinflammation is a promising approach. Therefore, in this study, we investigated the anti-neuroinflammatory potential of a marketed and quantified proprietary herbal extract of Ginkgo biloba leaves called EGb 761 (10-500 µg/mL) in BV2 microglial cells stimulated by LPS (10 ng/mL). Our results demonstrate significant inhibition of LPS-induced expression and release of cytokines tumor necrosis factor-α (TNF-α) and Interleukin 6 (IL-6) and chemokines C-X-C motif chemokine ligand 2 (CXCL2), CXCL10, c-c motif chemokine ligand 2 (CCL2) and CCL3 in BV2 microglial cells. The observed effects are possibly mediated by the mitogen-activated protein kinases (MAPK), p38 MAPK and ERK1/2, as well as the protein kinase C (PKC) and the nuclear factor (NF)-κB signaling cascades. The findings of this in vitro study highlight the anti-inflammatory properties of EGb 761 and its therapeutic potential, making it an emerging candidate for the treatment of neuroinflammatory diseases and warranting further research in pre-clinical and clinical settings.


Assuntos
Anti-Inflamatórios , Ginkgo biloba , Lipopolissacarídeos , Microglia , Extratos Vegetais , Ginkgo biloba/química , Microglia/efeitos dos fármacos , Microglia/metabolismo , Extratos Vegetais/farmacologia , Animais , Camundongos , Anti-Inflamatórios/farmacologia , Linhagem Celular , Citocinas/metabolismo , NF-kappa B/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extrato de Ginkgo
15.
Int J Mol Sci ; 25(3)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38339192

RESUMO

Natural products derived from medicinal plants offer convenience and therapeutic potential and have inspired the development of antimicrobial agents. Thus, it is worth exploring the combination of nanotechnology and natural products. In this study, silver nanoparticles (AgNPs) were synthesized from the leaf extract of Ginkgo biloba (Gb), having abundant flavonoid compounds. The reaction conditions and the colloidal stability were assessed using ultraviolet-visible spectroscopy. X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy (FTIR) were used to characterize the AgNPs. AgNPs exhibited a spherical morphology, uniform dispersion, and diameter ranging from ~8 to 9 nm. The FTIR data indicated that phytoconstituents, such as polyphenols, flavonoids, and terpenoids, could potentially serve as reducing and capping agents. The antibacterial activity of the synthesized AgNPs was assessed using broth dilution and agar well diffusion assays. The results demonstrate antibacterial effects against both Gram-positive and Gram-negative strains at low AgNP concentrations. The cytotoxicity of AgNPs was examined in vitro using the CCK-8 method, which showed that low concentrations of AgNPs are noncytotoxic to normal cells and promote cell growth. In conclusion, an environmentally friendly approach for synthesizing AgNPs from Gb leaves yielded antibacterial AgNPs with minimal toxicity, holding promise for future applications in the field of biomedicine.


Assuntos
Nanopartículas Metálicas , Prata , Prata/farmacologia , Prata/química , Ginkgo biloba , Nanopartículas Metálicas/química , Antibacterianos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
16.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38732008

RESUMO

Neuropathy affects 7-10% of the general population and is caused by a lesion or disease of the somatosensory system. The limitations of current therapies highlight the necessity of a new innovative approach to treating neuropathic pain (NP) based on the close correlation between oxidative stress, inflammatory process, and antioxidant action. The advantageous outcomes of a novel combination composed of Hop extract, Propolis, Ginkgo Biloba, Vitamin B, and palmitoylethanolamide (PEA) used as a treatment was evaluated in this study. To assess the absorption and biodistribution of the combination, its bioavailability was first examined in a 3D intestinal barrier model that replicated intestinal absorption. Further, a 3D nerve tissue model was developed to study the biological impacts of the combination during the essential pathways involved in NP. Our findings show that the combination could cross the intestinal barrier and reach the peripheral nervous system, where it modulates the oxidative stress, inflammation levels, and myelination mechanism (increased NRG, MPZ, ERB, and p75 levels) under Schwann cells damaging. This study proves the effectiveness of Ginkgo Biloba, Propolis, Hop extract, Vitamin B, and PEA in avoiding nerve damage and suggests a potential alternative nutraceutical treatment for NP and neuropathies.


Assuntos
Amidas , Suplementos Nutricionais , Etanolaminas , Neuralgia , Ácidos Palmíticos , Plantas Medicinais , Etanolaminas/farmacologia , Ácidos Palmíticos/farmacologia , Ácidos Palmíticos/administração & dosagem , Animais , Neuralgia/tratamento farmacológico , Amidas/farmacologia , Amidas/química , Plantas Medicinais/química , Polifenóis/farmacologia , Polifenóis/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ratos , Masculino , Antioxidantes/farmacologia , Ginkgo biloba/química , Humanos
17.
Molecules ; 29(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38611884

RESUMO

Ginkgo biloba L. (ginkgo) is a widely used medicinal plant around the world. Its leaves, which have been used as a traditional Chinese medicine, are rich in various bioactive components. However, most of the research and applications of ginkgo leaves have focused on terpene trilactones and flavonol glycosides, thereby overlooking the other active components. In this study, a lipophilic extract (GL) was isolated from ginkgo leaves. This extract is abundant in lipids and lipid-like molecules. Then, its effect and potential mechanism on glucose uptake and insulin resistance in C2C12 myotubes were investigated. The results showed that GL significantly enhanced the translocation of GLUT4 to the plasma membrane, which subsequently promoted glucose uptake. Meanwhile, it increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream targets. Both knockdown of AMPK with siRNA and inhibition with AMPK inhibitor compound C reversed these effects. Additionally, GL ameliorated palmitate-induced insulin resistance by enhancing insulin-stimulated glucose uptake, increasing the phosphorylation of protein kinase B (PKB/AKT), and restoring the translocation of GLUT4 from the cytoplasm to the membrane. However, pretreatment with compound C abolished these beneficial effects of GL. In conclusion, GL enhances basal glucose uptake in C2C12 myotubes and improves insulin sensitivity in palmitate-induced insulin resistant myotubes through the AMPK pathway.


Assuntos
Ginkgo biloba , Resistência à Insulina , Proteínas Quinases Ativadas por AMP , Extratos Vegetais/farmacologia , Insulina , Fibras Musculares Esqueléticas , Glucose
18.
Int J Environ Health Res ; 34(2): 979-990, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36960596

RESUMO

This study investigated the modulatory effect of Ginkgo biloba extract on lead acetate-induced endothelial dysfunction. Animals were administered GBE (50 mg/kg and 100 mg/kg orally) after exposures to lead acetate (25 mg/kg orally) for 14 days. Aorta was harvested after euthanasia, the tissue was homogenised, and supernatants were decanted after centrifuging. Oxidative, nitrergic, inflammatory, and anti-apoptotic markers were assayed using standard biochemical procedure, ELISA, and immunohistochemistry, respectively. GBE reduced lead-induced oxidative stress by increasing SOD, GSH, and CAT as well as reducing MDA levels in endothelium. Pro-inflammatory cytokines (TNF-α and IL-6) were reduced while increasing Bcl-2 protein expression. GBE lowered endothelin-I and raised nitrite levels. Histological changes caused by lead acetate were normalised by GBE. Our findings suggest that Ginkgo biloba extract restored endothelin-I and nitric oxide functions by increasing Bcl-2 protein expression and reducing oxido-inflammatory stress in endothelium.


Assuntos
Extrato de Ginkgo , Ginkgo biloba , Chumbo , Ratos , Animais , Extratos Vegetais/farmacologia , Endotelinas , Proteínas Proto-Oncogênicas c-bcl-2 , Acetatos
19.
J Sci Food Agric ; 104(10): 5896-5906, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38477402

RESUMO

BACKGROUND: The structural changes of starch would have a more crucial impact on oil absorption and quality changes in starch-rich fruits and vegetables during frying process with enhanced heat transfer (such as infrared frying). In the present study, the influence of integrated ultrasonic and ethanol (US + ethanol) pretreatment on oil uptake in infrared fried (IF) ginkgo seeds was evaluated regarding modifications in the physicochemical properties of starch. The pretreatment was performed with ultrasonic (40 kHz, 300 W) and ethanol osmotic (95%, v/v) treatment individually or integrated for 40 min. RESULTS: The mass transfer in the pretreatment was facilitated by combined ultrasound and ethanol. The swelling power, solubility, and gelatinization degree of starch was significantly increased. Low-frequency-NMR curves and images revealed that the bound water fraction in ginkgo seeds was increased and the water distribution was homogenized. The results of Fourier transform-infrared spectrum and differential scanning calorimeter revealed that the crystalline regions of starch were reduced and the thermal enthalpy was decreased after US + ethanol pretreatment. The total, surface and structural oil content in IF ginkgo seeds with US + ethanol pretreatment was reduced by 29.10%, 34.52% and 29.73%, respectively. The US + ethanol pretreatment led to a thinner crust layer with increased porosity and smaller-sized pores in the IF ginkgo seeds as observed by stereo microscopy and scanning electron microscopy. CONCLUSION: The changes in structural and physicochemical properties of starch by combined ultrasound and ethanol affect the crust ratio and pore characteristics in fried high-starch fruits and vegetables, thereby reducing oil absorption. © 2024 Society of Chemical Industry.


Assuntos
Etanol , Ginkgo biloba , Sementes , Amido , Amido/química , Amido/metabolismo , Sementes/química , Etanol/química , Ginkgo biloba/química , Culinária , Solubilidade , Óleos de Plantas/química , Ultrassom , Temperatura Alta , Raios Infravermelhos , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Learn Mem ; 30(4): 85-95, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37072140

RESUMO

Long-term memory (LTM) formation is dependent on neurochemical changes that guarantee that a recently formed memory (short-term memory [STM]) remains in the specific neural circuitry via the consolidation process. The persistence of recognition memory has been evidenced by using behavioral tagging in young adult rats, but it has not been effective on aging. Here, we investigated the effects of treatment with a standardized extract of Ginkgo biloba (EGb) associated with novelty on the consolidation of object location memory (OLM) and its persistence after weak training of spatial object preference in young adult and aged rats. The object location task used in this study included two habituation sessions, training sessions associated or not associated with EGb treatment and contextual novelty, and short-term or long-term retention testing sessions. Altogether, our data showed that treatment with EGb associated with novelty close to the time of encoding resulted in STM that lasted for 1 h and persisted for 24 h for both young adult and aged rats. In aged rats, the cooperative mechanisms induced robust long-term OLM. Our findings support and extend our knowledge about recognition memory in aged rats and the modulating effects of EGb treatment and contextual novelty on the persistence of memory.


Assuntos
Ginkgo biloba , Extratos Vegetais , Ratos , Animais , Ratos Wistar , Extratos Vegetais/farmacologia , Reconhecimento Psicológico , Memória de Longo Prazo
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