RESUMO
INTRODUCTION: Ginkgo Folium tablet (GFT) is a patented traditional Chinese medicine prepared from Ginkgo biloba leaves extract (GBE). However, the current quality indicators for GFT or GBE as designated by the Chinese Pharmacopoeia are insufficient in preventing counterfeit events. OBJECTIVE: This study aimed to putatively identify compounds in GFT and to further develop a quality marker (Q-marker) system for GFT. METHODS: A novel strategy utilizing database-aided ultrahigh-performance liquid chromatography-quadrupole-orbitrap mass spectrometry was employed to analyze the lyophilized aqueous powder of GFT. Subsequently, the identified compounds underwent quantum chemical calculations, network pharmacology, and molecular simulations through in silico approaches to evaluate the Q-marker principles of traceability, specificity, and efficiency-relevance. RESULTS: The results revealed the putative identification of a total of 66 compounds, including 36 flavonoids, 7 phenolic acids and derivatives, 5 terpene lactones, 4 fatty acids and derivatives, 3 alkaloids, 1 amino acid, and 10 other compounds. Particularly, 16 compounds were unexpectedly observed, and seven compounds met the Q-marker principles. CONCLUSION: This study recommends the seven compounds, namely, (-)-gallocatechin, matrine, (-)-epicatechin, ginkgolide C, ginkgolide A, ginkgolide B, and curdione, as the anti-counterfeiting pharmacopoeia Q-markers for GFT. The reconstruction of the Q-marker system for GFT not only enhances the understanding of the compounds in GFT and other GBE-based preparations but also provides valuable recommendations for the Pharmacopoeia Commission.
Assuntos
Ginkgo biloba , Ginkgo biloba/química , Cromatografia Líquida de Alta Pressão/métodos , Comprimidos , Farmacologia em Rede , Extratos Vegetais/química , Flavonoides/análise , Flavonoides/química , Espectrometria de Massas/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Folhas de Planta/química , Alcaloides/análise , Alcaloides/química , Extrato de GinkgoRESUMO
AIMS: Alzheimer's disease (AD) is a neurodegenerative disorder with limited treatment options. This study aimed to investigate the therapeutic effects of Ginkgo biloba leaf extract (GBE) on AD and explore its potential mechanisms of action. METHODS: Key chemical components of GBE, including quercetin, luteolin, and kaempferol, were identified using network pharmacology methods. Bioinformatics analysis revealed their potential roles in AD through modulation of the PI3K/AKT/NF-κB signaling pathway. RESULTS: Mouse experiments demonstrated that GBE improved cognitive function, enhanced neuronal morphology, and reduced serum inflammatory factors. Additionally, GBE modulated the expression of relevant proteins and mRNA. CONCLUSION: GBE shows promise as a potential treatment for AD. Its beneficial effects on cognitive function, neuronal morphology, and inflammation may be attributed to its modulation of the PI3K/AKT/NF-κB signaling pathway. These findings provide experimental evidence for the application of Ginkgo biloba leaf in AD treatment and highlight its potential mechanisms of action.
Assuntos
Doença de Alzheimer , Ginkgo biloba , Extratos Vegetais , Folhas de Planta , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Camundongos , Masculino , Folhas de Planta/química , NF-kappa B/metabolismo , Cognição/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Extrato de GinkgoRESUMO
Background: Lead (Plumbum/Pb) has been identified as a potential cause of Parkinson's disease as well as possibly contributing to disease progression. Ginkgo biloba extract has been widely used to prevent and treat stroke which prevents brain cell apoptosis and neuroinflammation. This has been shown to be beneficial in cognitive recovery in stroke incidents. Aim: This study aimed to determine the effect of G. biloba on the expression of superoxide dismutase (SOD), malondialdehyde (MDA), and apoptosis-inducing factor (AIF) in the brain cells of rats (Rattus novergicus) exposed to Plumbum. Methods: The experimental animals used were 36 male white rats divided into 4 groups with different treatments of Plumbum and G. biloba at varying doses for 42 days, after which the brains were collected for examination of SOD, MDA, and AIF expressions using immunohistochemical methods and analyzed using analysis of variance and Duncan's test. Results: Plumbum administration caused a significant decrease in SOD expression and an increase in MDA and AIF expressions (p < 0.05). Ginkgo biloba administration significantly increased SOD expression and decreased MDA and AIF expressions (p < 0.05), with optimal increases in SOD, decreases in MDA, and modulation of AIF observed in the group exposed to 50 mg/kg BW Pb and 300 mg/kg BW G. biloba. Conclusion: Preventive administration of G biloba increased SOD expression, and reduced MDA and AIF expressions in Pb-exposed rats, with an optimal dose of 300 mg/kg BW, suggesting its potential as an affordable drug to prevent brain cell death-related diseases.
Assuntos
Apoptose , Encéfalo , Ginkgo biloba , Extratos Vegetais , Superóxido Dismutase , Animais , Ginkgo biloba/química , Masculino , Ratos , Apoptose/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Superóxido Dismutase/metabolismo , Malondialdeído/metabolismo , Fator de Indução de Apoptose/metabolismo , Extrato de GinkgoRESUMO
OBJECTIVE: This study aimed to analyze the therapeutic effect of Ginkgo biloba extract (EGb 761) on sudden sensorineural hearing loss (SSNHL) and its influence on hemorheology. METHODS: The clinical data of patients diagnosed with SSNHL and admitted to the Wendeng Hospital of Traditional Chinese Orthopedics and Traumatology of Shandong Province from May 2020 to May 2023 were retrospectively analyzed. Based on different clinical treatment protocols, patients were divided into a control group (treated with routine treatment) and an administration group (treated with routine treatment + EGb 761). Both groups underwent drug treatment for 10 days. Subsequently, the hearing threshold, hemorheological parameters (blood high shear viscosity, blood low shear viscosity, plasma viscosity, and platelet aggregation rate) and inflammatory factors and serum levels (C-reactive protein, interleukin-6, tumor necrosis factor-α and soluble vascular cell adhesion molecule-1) of these groups were compared. RESULTS: This study comprised 120 patients, with 66 cases in the control group and 54 cases in the administration group. Following treatment, the total effective rate of the administration group was significantly higher than that of the control group (90.74% vs. 72.73%) (P-value < 0.05). The hearing threshold, hemorheological parameters, inflammatory factors, and serum levels were significantly lower in the administration group than in the control group (P-value < 0.05). CONCLUSIONS: Compared with routine treatment, joint EGb 761 in the SSNHL treatment may improve the hearing threshold and hemorheological indexes of patients, inhibit the inflammatory response, and promote the recovery of hearing function. Moreover, no serious adverse reactions are observed, indicating adequate safety.
Assuntos
Ginkgo biloba , Perda Auditiva Neurossensorial , Perda Auditiva Súbita , Hemorreologia , Extratos Vegetais , Humanos , Extratos Vegetais/uso terapêutico , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Perda Auditiva Súbita/tratamento farmacológico , Perda Auditiva Súbita/sangue , Perda Auditiva Neurossensorial/tratamento farmacológico , Perda Auditiva Neurossensorial/sangue , Hemorreologia/efeitos dos fármacos , Adulto , Resultado do Tratamento , Idoso , Fitoterapia/métodos , Extrato de GinkgoRESUMO
BACKGROUND: To analyze and compare the pharmacological treatments for Alzheimer disease (AD), we will conduct a systematic review and network meta-analysis focusing on their efficacy and safety over a duration exceeding 1 year. METHODS: We searched the databases of PubMed, Scopus, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and CNKI until July 30, 2023, for randomized controlled trials (RCTs) evaluating pharmacological treatments for AD. RESULTS: Seventeen RCTs, comprising 7214 participants, investigated the efficacy of the following drugs: Donepezil, Rivastigmine, Galantamine, Memantine, Ginkgo biloba extract (EGb), Atorvastatin-calcium and Vitamin B in the treatment of AD. The network meta-analysis resulted indicated that placebo demonstrated greater effectiveness compared to Atorvastatin-calcium 80 mg (mean different [MD]â =â -6.93, confidence interval [CI] -11.57, -2.29) and Rivastigmine 12 mg (MDâ =â -3.33, CI -6.56, -0.09). EGb120 mg exhibited a greater improvement in cognition compared to Atorvastatin-calcium 80 mg (MDâ =â 7.77, CI 2.07, 13.46) and Rivastigmine 12 mgâ +â EGb120 mg (MDâ =â 9.92, CI 1.32, 17.22). EGb 120 mg emerged as the most efficient intervention for cognition, while placebo demonstrated the least harm over a period exceeding 1 year. CONCLUSIONS: In this network meta-analysis of studies of patients with AD and a follow-up period of at least 1 year, EGb 120 mg demonstrated cognitive benefits, while placebo posed the least harm for AD. More RCTs are required to address the uncertainty surrounding the efficacy of medication.
Assuntos
Doença de Alzheimer , Ginkgo biloba , Metanálise em Rede , Doença de Alzheimer/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Atorvastatina/uso terapêutico , Rivastigmina/uso terapêutico , Extratos Vegetais/uso terapêutico , Donepezila/uso terapêutico , Memantina/uso terapêutico , Galantamina/uso terapêutico , Resultado do Tratamento , Extrato de GinkgoRESUMO
The investigation's aim was to explore the medical usefulness and mechanism of GBE in the management of elderly ischemic cerebrovascular disease (ICVD).120 cases of elderly patients with ICVD admitted to our hospital from August 2022 to August 2023 were chosen as participants for this research and the sufferer were allocated to the conventional (60 cases) and GBE group (60 cases) using the method of randomized number. NIHSS score, Barthel index, hemodynamic indexes, serum inflammatory factor levels, platelet-activating factor (PAF) and clinical efficacy were recorded before (T0) and after treatment(T1),and recorded the adverse reactions of the two groups during the treatment. At T1, NIHSS score, WBLSV, PV, HCT, TNF-α, IL-6 and PAF in the two groups, which were all notably reduced compared to T0 and the Barthel index demonstrated a significant increase compared to its T0 value (P<0.05). At T1, GBE group exhibited notably reductions in NIHSS score, WBLSV, PV, HCT, TNF-α, IL-6 and PAF compared to conventional group, whereas Barthel index and the total effective rate were considerably elevated (P<0.05). Incidence of adverse reactions were similar in both groups (P>0.05). GBE has good therapeutic benefits in managing elderly ICVD, effectively facilitate the recuperation of patients' neurological function, has obvious anti-inflammatory effect, improves patients' cerebral circulation and hemorheology indexes and makes the patients' daily life ability significantly improved, which has a good clinical application value.
Assuntos
Ginkgo biloba , Extratos Vegetais , Humanos , Ginkgo biloba/química , Idoso , Masculino , Feminino , Extratos Vegetais/uso terapêutico , Extratos Vegetais/efeitos adversos , Resultado do Tratamento , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/sangue , Fator de Ativação de Plaquetas/metabolismo , Idoso de 80 Anos ou mais , Fator de Necrose Tumoral alfa/sangue , Hemodinâmica/efeitos dos fármacos , Interleucina-6/sangue , Extrato de GinkgoRESUMO
Ginkgo biloba extracts (GBE) have been shown to effectively improve cognitive function in patients with Alzheimer's disease (AD). One potential therapeutic strategy for AD is to prevent loss of adult hippocampal neurons. While recent studies have reported that GBE protects against oxidative stress in neurons, the underlying mechanisms remain unclear. In this study, an AD-like rat model was established via bidirectional injection of amyloid beta 25-35 (Aß25-35; 20 µg) in the hippocampal CA1 region. Learning and memory abilities of experimental rats were AD assessed in response to oral administration of 7.5 g/L or 15 g/L Ginkgo biloba extract 50 (GBE50) solution and the peroxidation phenomenon of hippocampal mitochondria determined via analysis of mitochondrial H2O2 and several related enzymes. Levels of the oxidative stress-related signaling factor cytochrome C (Cyto C), apoptosis-related proteins (Bax, Bcl-2 and caspase-3) and caspase-activated DNase (CAD) were further detected via western blot. 8-Hydroxydeoxyguanosine (8-OHdG), the major product of DNA oxidative stress, was evaluated to analyze DNA status. Our results showed elevated H2O2 levels and monoamine oxidase (MAO) activity, and conversely, a decrease in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus of AD rats. Administration of GBE50 regulated the activities of these three enzymes and induced a decrease in H2O2. GBE50 exerted regulatory effects on abnormally expressed apoptotic proteins in the AD rat hippocampus, enhancing the expression of Bcl-2, inhibiting release of Cyto C from mitochondria, and suppressing the level of caspase-3 (excluding cleaved caspase-3). Furthermore, GBE50 inhibited DNA damage by lowering the generation of 8-OHdG rather than influencing expression of CAD. The collective findings support a protective role of GBE50 in hippocampal neurons of AD-like animals against mitochondrial oxidative stress.
Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Ginkgo biloba , Hipocampo , Mitocôndrias , Neurônios , Estresse Oxidativo , Extratos Vegetais , Animais , Ginkgo biloba/química , Estresse Oxidativo/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Extratos Vegetais/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Ratos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Peptídeos beta-Amiloides/metabolismo , Peróxido de Hidrogênio/metabolismo , Ratos Sprague-Dawley , Apoptose/efeitos dos fármacos , Extrato de Ginkgo , Fragmentos de PeptídeosRESUMO
Based on high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS~E) and molecular docking technique, bitter compounds of Ginkgo biloba extract(GBE) were characterized, and their relationship with bitter efficacy was investigated. Firstly, UPLC-Q-TOF-MS~E was used for qualitative analysis of GBE components, and 60 chemical components were identified. These chemical components were molecular-docked with bitter receptors, and 26 bitter substances were selected, mainly flavonoids. Secondly, sensory and electronic tongue bitterness evaluation techniques were used to verify that total flavones of GBE were the main bitter substances, which was consistent with the molecular docking results. Finally, network pharmacology was used to predict and analyze bitter substances. The relationship between the target of bitter substance and bitter effect was explored. The key targets of bitter substances are CYP2B6, ALOX15, and PTGS2, etc., and bitter substances may exert a bitter efficacy by ac-ting on related disease targets, indicating that bitter substances of GBE are the material basis of the bitter effect. In summary, the study indicated that the molecular docking technique had a guiding effect on the screening of bitter substances in traditianal Chinese medicine(TCM), and bitter substances of GBE had a bitter efficacy. It provides ideas and references for the study of the "taste-efficacy relationship" of TCM in the future.
Assuntos
Ginkgo biloba , Simulação de Acoplamento Molecular , Extratos Vegetais , Espectrometria de Massas em Tandem , Paladar , Ginkgo biloba/química , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Humanos , Espectrometria de Massas em Tandem/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Extrato de GinkgoRESUMO
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 GinkgoRESUMO
This study aims to explore the value of nimodipine combined with Ginkgo biloba extract in improving cognitive function and daily living abilities in patients with Parkinson's disease. Clinical data from 551 patients with Parkinson's disease admitted to the Neurology Department of the Affiliated Hospital of Beihua University from January 2022 to December 2022 were retrospectively collected. Cognitive function and daily living abilities were assessed in patients before treatment, and a reevaluation was conducted after 12 weeks of medication. Patients treated solely with nimodipine were categorized into the monotherapy group, while patients treated with nimodipine combined with Ginkgo biloba extract were included in the combination group. After 1:1 propensity score matching, a total of 83 pairs of patients were matched, and differences in relevant indicators between the 2 groups were compared. The total effective rate of treatment in the combination group was 90.36%, which was higher than the control group at 72.29% (Pâ <â .05). However, after treatment, the observation group showed higher Mini-Mental State Examination and activities of daily living scores compared to the control group (Pâ <â .05). The combined treatment of nimodipine and Ginkgo biloba extract in patients with Parkinson's disease has a significant effect and can effectively improve cognitive function and enhance daily living abilities.
Assuntos
Atividades Cotidianas , Cognição , Quimioterapia Combinada , Ginkgo biloba , Nimodipina , Doença de Parkinson , Extratos Vegetais , Humanos , Nimodipina/uso terapêutico , Nimodipina/administração & dosagem , Masculino , Extratos Vegetais/uso terapêutico , Feminino , Estudos Retrospectivos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/psicologia , Idoso , Cognição/efeitos dos fármacos , Pessoa de Meia-Idade , Resultado do Tratamento , Extrato de GinkgoRESUMO
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 GinkgoRESUMO
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 GinkgoRESUMO
In posterior spine surgery, retractors exert pressure on paraspinal muscles, elevating intramuscular pressure and compromising blood flow, potentially causing muscle injury during ischemia-reperfusion. Ginkgo biloba extract (EGb 761), known for its antioxidant and free radical scavenging properties and its role in treating cerebrovascular diseases, is investigated for its protective effects against muscle ischemia-reperfusion injury in vitro and in vivo. Animals were randomly divided into the control group, receiving normal saline, and experimental groups, receiving varying doses of EGb761 (25/50/100/200 mg/kg). A 2-h hind limb tourniquet-induced ischemia was followed by reperfusion. Blood samples collected pre-ischemia and 24 h post-reperfusion, along with muscle tissue samples after 24 h, demonstrated that EGb761 at 1000 µg/mL effectively inhibited IL-6 and TNF-α secretion in RAW 264.7 cells without cytotoxicity. EGb761 significantly reduced nitric oxide (NO) and malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity, and increased glutathione (GSH) levels compared to the control after 24 h. Muscle tissue sections revealed more severe damage in the control group, indicating EGb761's potential in mitigating inflammatory responses and oxidative stress during ischemia-reperfusion injury, effectively protecting against muscle damage.
Assuntos
Anti-Inflamatórios , Antioxidantes , Ginkgo biloba , Membro Posterior , Músculo Esquelético , Extratos Vegetais , Traumatismo por Reperfusão , Animais , Ginkgo biloba/química , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Extratos Vegetais/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/irrigação sanguínea , Camundongos , Membro Posterior/irrigação sanguínea , Masculino , Ratos , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Interleucina-6/metabolismo , Ratos Sprague-Dawley , Extrato de GinkgoRESUMO
Neurological disorders (NDs) are diseases that seriously affect the health of individuals worldwide, potentially leading to a significant reduction in the quality of life for patients and their families. Herbal medicines have been widely used in the treatment of NDs due to their multi-target and multi-pathway features. Ginkgo biloba leaves (GBLs), one of the most popular herbal medicines in the world, have been demonstrated to present therapeutic effects on NDs. However, the pharmacological mechanisms of GBLs in the treatment of neurological disorders have not been systematically summarized. This study aimed to summarize the molecular mechanism of GBLs in treating NDs from the cell models, animal models, and clinical trials of studies. Four databases, i.e., PubMed, Google Scholar, CNKI, and Web of Science were searched using the following keywords: "Ginkgo biloba", "Ginkgo biloba extract", "Ginkgo biloba leaves", "Ginkgo biloba leaves extract", "Neurological disorders", "Neurological diseases", and "Neurodegenerative diseases". All items meeting the inclusion criteria on the treatment of NDs with GBLs were extracted and summarized. Additionally, PRISMA 2020 was performed to independently evaluate the screening methods. Out of 1385 records in the database, 52 were screened in relation to the function of GBLs in the treatment of NDs; of these 52 records, 39 were preclinical trials and 13 were clinical studies. Analysis of pharmacological studies revealed that GBLs can improve memory, cognition, behavior, and psychopathology of NDs and that the most frequently associated GBLs are depression, followed by Alzheimer's disease, stroke, Huntington's disease, and Parkinson's disease. Additionally, the clinical studies of depression, AD, and stroke are the most common, and most of the remaining ND data are available from in vitro or in vivo animal studies. Moreover, the possible mechanisms of GBLs in treating NDs are mainly through free radical scavenging, anti-oxidant activity, anti-inflammatory response, mitochondrial protection, neurotransmitter regulation, and antagonism of PAF. This is the first paper to systematically and comprehensively investigate the pharmacological effects and neuroprotective mechanisms of GBLs in the treatment of NDs thus far. All findings contribute to a better understanding of the efficacy and complexity of GBLs in treating NDs, which is of great significance for the further clinical application of this herbal medicine.
Assuntos
Ginkgo biloba , Doenças do Sistema Nervoso , Fármacos Neuroprotetores , Extratos Vegetais , Folhas de Planta , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Animais , Doenças do Sistema Nervoso/tratamento farmacológico , Folhas de Planta/química , Fitoterapia , Extrato de GinkgoRESUMO
BACKGROUND: Choline alfoscerate (alpha-glycerylphosphorylcholine) is a phospholipid that includes choline, which increases the release of acetylcholine. The ASCOMALVA trial, a combination of donepezil and choline alfoscerate, slowed cognitive decline in Alzheimer disease. This study aims to replicate the effect by combining donepezil with other nootropics currently used in South Korea. METHODS: The 119 patients with cognitive decline who were eligible to use donepezil, with an mini-mental state examination (MMSE) score of 26 or less, were assigned to: donepezil alone (DO); donepezil and choline alfoscerate (DN); donepezil and acetyl-l-carnitine (DA); or donepezil and ginkgo biloba extract (DG). Cognitive evaluations such as MMSE, clinical dementia rating, Alzheimer disease assessment scale-cognitive subscale (ADAS-Cog), and Alzheimer disease assessment scale-noncognitive subscale were performed at the 12th and 24th weeks from the baseline time point. RESULTS: At the 12th week, the MMSE score increased 3.52% in the DN group, whereas it increased by 1.36% in the DO group. In the DAâ +â DG group, it decreased by 2.17%. At the 24th week, the MMSE score showed an increase of 1.07% in the DO group and 1.61% in the DN group, but decreased by 5.71% in the DAâ +â DG group. ADAS-Cog decreased by 0.9% in the DO group, while it improved by 13.9% in the DN group at the 12th week. At the 24th week, ADAS-Cog showed improvement in the DN group by 18.5%, whereas it improved by 9.4% in the DO group. Alzheimer disease assessment scale-noncognitive subscale also revealed better performance in the DN group than in the DO group at the 12th and 24th weeks. CONCLUSION: Choline alfoscerate exhibits additional cognitive improvement in both cognitive and noncognitive domains, supporting the findings of the ASCOMALVA trial.
Assuntos
Donepezila , Quimioterapia Combinada , Ginkgo biloba , Glicerilfosforilcolina , Indanos , Nootrópicos , Humanos , Donepezila/uso terapêutico , Donepezila/administração & dosagem , Masculino , Feminino , Idoso , Método Duplo-Cego , Glicerilfosforilcolina/uso terapêutico , Glicerilfosforilcolina/administração & dosagem , Nootrópicos/administração & dosagem , Nootrópicos/uso terapêutico , Indanos/uso terapêutico , Indanos/administração & dosagem , Doença de Alzheimer/tratamento farmacológico , Piperidinas/uso terapêutico , Piperidinas/administração & dosagem , Extratos Vegetais/uso terapêutico , Extratos Vegetais/administração & dosagem , República da Coreia , Acetilcarnitina/uso terapêutico , Acetilcarnitina/administração & dosagem , Disfunção Cognitiva/tratamento farmacológico , Testes de Estado Mental e Demência , Resultado do Tratamento , Idoso de 80 Anos ou mais , Cognição/efeitos dos fármacos , Extrato de GinkgoRESUMO
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 GinkgoRESUMO
BACKGROUND: The efficacy and safety of different oral ginkgo-based Chinese patent medicines (CPMs) regimens for hypertension patients were analyzed based on the network meta-analysis of the frequency framework. METHODS: We conducted a comprehensive search of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, and Chinese Biomedical Literature Database to gather data on randomized controlled trials (RCTs) evaluating the efficacy of 8 ginkgo biloba oral preparations for the treatment of hypertension. The trials included in the analysis were conducted from the inception of the databases up to September 2023. Methodological quality and risk of bias were assessed using the RoB 2.0 evaluation tool, and a reticulated meta-analysis was conducted using STATA MP 14 software. The RCTs included in this study were published studies and therefore did not require ethics committee review or patient consent. RESULTS: We ultimately included 46 RCTs covering 8 CPMs including ginkgo biloba tablet (GBT), GB capsule (GBC), ginkgo biloba drop (GBD), ginkgo biloba ketone ester drop, Fufangyinxing capsule, fufangyinxingtongmai oral liquid, Yinxingmihuan oral liquid, Yindanxinanotong softgel capsule (YDXNT). GBDâ +â CT demonstrated the highest effectiveness in reducing systolic blood pressure (surface under the cumulative ranking [SUCRA]â =â 78.7%) and improving total effective rate (SUCRAâ =â 86.7%). GBCâ +â CT exhibited the greatest efficacy in reducing diastolic blood pressure (SUCRAâ =â 92.6%). GBTâ +â CT was identified as the most effective in lowering total cholesterol (TC) (SUCRAâ =â 100%). Additionally, YDXNTâ +â CT demonstrated notable improvements in triglyceride levels (SUCRAâ =â 92.2%), Nitric oxide (NO) (SUCRAâ =â 93.9%), and ET-1 (SUCRAâ =â 67.5%). In terms of safety, 14 studies reported the occurrence of adverse reactions with a high degree of clinical heterogeneity, which was only qualitatively analyzed in this study. CONCLUSION SUBSECTIONS: We found that a combination of 8 ginkgo-based CPMsâ +â CT was effective in hypertension compared with CT. The evidence showed that GBDâ +â CT were the best in improving systolic blood pressure and total effective rate, GBCâ +â CT improved diastolic blood pressure, GBTâ +â CT were the most effective in improving TC, and YDXNTâ +â CT was the most effective in improving TG, NO, and ET-1. Adverse effects were only analyzed qualitatively, and the number of adverse effects of CPMs treatment was relatively low compared to CT. In addition, the quality of the literature included in the study was low, and further validation through RCTs with larger sample sizes, higher quality, and more rigorously designed is needed.
Assuntos
Medicamentos de Ervas Chinesas , Extrato de Ginkgo , Ginkgo biloba , Hipertensão , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Hipertensão/tratamento farmacológico , Resultado do TratamentoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba is a traditional Chinese medicine extracted from the Ginkgophyta and is commonly used in the treatment of cardiovascular diseases in China. Clinical trials have demonstrated the clinical benefits of Ginkgo biloba extract (GBE) preparations for patients with unstable angina pectoris (UAP). AIM OF THE STUDY: The efficacy of different GBE preparations in treating UAP may vary, leading to a lack of guidance for physicians when choosing GBE preparations. How to make choices among different GBE preparations is a topic worthy of investigation. In order to clarify the efficacy differences among different GBE preparations, provide a reference for their optimal use conditions, this study was conducted. MATERIALS AND METHODS: This study included literature from eight databases from inception to November 2023. It included UAP patients, with the control group receiving conventional treatment and the treatment group receiving different GBE preparations in addition to conventional treatment. Angina efficacy, electrocardiogram (ECG) improvement, and frequency of angina were chosen as outcomes. This study employed a systematic review and Bayesian network meta-analysis, and the surface under the cumulative ranking (SUCRA) curve was used for estimating the efficacy ranking. RESULTS: A total of 98 studies involving 9513 patients and 9 interventions were included. Compared with conventional treatment, GBE preparations combined with conventional treatment had better efficacy in angina symptoms and ECG improvement. According to the SUCRA ranking, Shuxuening injection was most effective in improving angina symptoms and reducing the frequency of angina. Among oral GBE preparations, Ginkgo tablets had the best performance in improving angina symptoms and ECG manifestations, and reducing the frequency of angina. There was no significant difference in the incidence of adverse events between the treatment group and the control group, and all adverse events were mild and self-limiting. Compared with oral preparations, the incidence of adverse events for injections was higher. CONCLUSIONS: GBE preparations may alleviate angina symptoms and myocardial ischemia in the treatment of UAP with favorable safety. Shuxuening injection may be the most effective among all GBE preparations in improving angina symptoms, while Ginkgo tablets may perform best among oral formulations. The optimal use of GBE injection may be for rapidly alleviating angina symptoms and myocardial ischemia in patients with UAP, and oral formulation of GBE may be more suitable for the long-term treatment of patients with milder symptoms. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361487, ID: CRD42022361487.
Assuntos
Angina Instável , Ginkgo biloba , Extratos Vegetais , Humanos , Extratos Vegetais/uso terapêutico , Extratos Vegetais/efeitos adversos , Extratos Vegetais/administração & dosagem , Angina Instável/tratamento farmacológico , Metanálise em Rede , Resultado do Tratamento , Extrato de GinkgoRESUMO
Treatment strategies for steatohepatitis are of special interest given the high prevalence of obesity and fatty liver disease worldwide. This study aimed to investigate the potential therapeutic mechanism of L-carnitine (LC) and Ginkgo biloba leaf extract (GB) supplementation in ameliorating the adverse effects of hyperlipidemia and hepatosteatosis induced by a high-cholesterol diet (HCD) in an animal model. The study involved 50 rats divided into five groups, including a control group, a group receiving only an HCD, and three groups receiving an HCD along with either LC (300 mg LC/kg bw), GB (100 mg GB/kg bw), or both. After eight weeks, various parameters related to lipid and glucose metabolism, antioxidant capacity, histopathology, immune reactivity, and liver ultrastructure were measured. LC + GB supplementation reduced serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, glucose, insulin, HOMA-IR, alanine transaminase, and aspartate transaminase levels and increased high-density lipoprotein cholesterol levels compared with those in the HCD group. Additionally, treatment with both supplements improved antioxidant ability and reduced lipid peroxidation. The histological examination confirmed that the combination therapy reduced liver steatosis and fibrosis while also improving the appearance of cell organelles in the ultrastructural hepatocytes. Finally, the immunohistochemical analysis indicated that cotreatment with LC + GB upregulated the immune expression of GLP-1 and ß-Cat in liver sections that were similar to those of the control animals. Mono-treatment with LC or GB alone substantially but not completely protected the liver tissue, while the combined use of LC and GB may be more effective in treating liver damage caused by high cholesterol than either supplement alone by regulating hepatic oxidative stress and the protein expression of GLP-1 and ß-Cat.
Assuntos
Carnitina , Suplementos Nutricionais , Dislipidemias , Ginkgo biloba , Fígado , Extratos Vegetais , Animais , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Carnitina/farmacologia , Masculino , Ratos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Dislipidemias/tratamento farmacológico , Dislipidemias/metabolismo , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/patologia , Fígado Gorduroso/metabolismo , Ratos Sprague-Dawley , Metabolismo dos Lipídeos/efeitos dos fármacos , Antioxidantes/farmacologia , Dieta Hiperlipídica/efeitos adversos , Extrato de GinkgoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba leaf and seed have been traditionally used in ancient China for the treatment of cough and asthma. However, there is limited literature available on the anti-COPD effects and mechanisms of Ginkgo biloba. AIMS OF THE STUDY: The aim of this study was to comprehensively investigate the therapeutic potential of ginkgo extracts in COPD through a combination of in vivo and in vitro functional experiments. Transcriptomic analyses were also employed to uncover novel molecular mechanisms underlying the therapeutic effects of ginkgetin in COPD. MATERIALS AND METHODS: The therapeutic efficacy of ginkgo extracts was assessed in a COPD model. The anti-inflammatory effects of ginkgetin and its underlying molecular mechanisms were examined in A549 cells treated with cigarette smoke extract (CSE). Additionally, transcriptomic analyses were conducted to identify novel molecular pathways influenced by ginkgetin. These findings were further validated using quantitative real-time polymerase chain reaction (qPCR) and Western blot techniques. RESULTS: The ethyl acetate extract of Ginkgo biloba L. seeds and ginkgetin treatment significantly reduced cytokine production in COPD mice. Following drug administration, lung function improved in different groups. The transcriptome data strongly supports the inhibitory effect of ginkgetin on CSE-induced inflammation through the downregulation of the c/EBPß signaling pathway and subsequent inhibition of CCL2 expression. CONCLUSION: Our results demonstrate that ginkgetin, one of the biflavones found in Ginkgo biloba, exhibits inhibitory effects on smoke-induced airway inflammation. This effect is achieved through the downregulation of the c/EBPß signaling pathway and the reduction of CCL2 expression.