Search Results (14)

Dementia, including Alzheimer’s disease (AD), represents one of the most pressing public health challenges of the 21st century, affecting more than 55 million individuals worldwide, with projections reaching 139 million by 2050. Current pharmacological treatments offer limited efficacy and significant side effects, driving intense interest in plant-derived natural products as both preventive and therapeutic agents. This review synthesizes preclinical and clinical evidence for key phytochemical classes, including polyphenols, phenolic acids, flavonoids, terpenoids, and alkaloids, in the context of dementia and age-related cognitive decline. Molecular mechanisms are examined in detail, including effects on antioxidant defense and redox homeostasis, suppression of neuroinflammation, and enhancement of synaptic plasticity and neurotransmission. Despite promising preclinical and epidemiological evidence, most clinical trials remain limited in scale and duration and provide mixed results on the efficacy of using phytochemicals for cognitive health. Among the compounds with the most consistent clinical support are the ginkgo diterpene extract EGb 761, saffron carotenoids, curcumin, and rosmarinic acid. A dedicated section addresses the emerging evidence for aromatherapy as a non-pharmacological intervention for behavioral and cognitive symptoms of dementia. Future directions include strategies to improve bioavailability of phytochemicals, the utilization of aromatherapy together with oral supplements, and the need for larger randomized controlled trials using well-characterized and reproducibly manufactured formulations and purified active compounds. Priority areas for future investigation include resolving pharmacokinetic barriers to central nervous system (CNS) delivery, standardizing herbal product composition, and conducting adequately designed clinical trials in well-defined patient populations. Full article

Background/Objectives: An exploratory study was conducted to investigate the effect of Ginkgo biloba extract EGb 761^® in the management of chronic tinnitus, and whether comorbidities have an impact on the treatment outcome. Methods: The exploratory, uncontrolled, open-label study enrolled 170 patients (Full Analysis Set) with chronic tinnitus who took 120 mg EGb 761^® twice daily for 24 weeks. Outcomes were assessed using the Tinnitus Questionnaire, Tinnitus Handicap Inventory, and 11-Point Box Scales for loudness and annoyance. Comorbidities were recorded with audiometry, the Hospital Anxiety and Depression Scale, and the Perceived Stress Questionnaire. The effectiveness was further examined in responder analyses (at least 30% score reduction in 3 out of 4 outcomes) and in subgroups defined by baseline anxiety, hearing impairment, stress and depression. Results: At week 24, significant improvements were observed in all tinnitus-related outcomes compared to baseline (all p < 0.0001). In subgroup analyses, patients with high baseline anxiety or stress as well as those with normacusis improved more, whereas baseline depression had no influence. The overall response rate was 18.8%. Conclusions: The results of this exploratory study indicate that EGb 761^® improved complaints in patients with chronic tinnitus. The therapy appears to be particularly beneficial for patients with normal hearing and/or concomitant anxiety and/or stress. Trial registration: The study was registered at ISRCTN (ISRCTN83863387, registration date 14 October 2016). Full article

Background/Objectives: Tinnitus often occurs alongside the emotional symptoms of anxiety and depression. The Ginkgo biloba extract EGb 761^® was shown to be effective in reducing neuropsychiatric symptoms in elderly patients with both dementia and tinnitus, exerting direct effects on tinnitus severity and indirect effects mediated by improvement of anxiety, depression, and cognition. Whether the extent of the effects is influenced by the patient’s sex has not yet been investigated. We performed a conditional process analysis to evaluate this question. Methods: We analyzed the moderating role of sex on the direct and indirect effects of EGb 761^® on tinnitus severity using a first- and second-stage conditional process model. Results: Indirect effects of EGb 761^® on tinnitus severity mediated by improved cognition, anxiety, and depression did not differ between women and men (p > 0.05; all 95% bootstrap confidence intervals overlapped with zero). Moreover, direct treatment effects of EGb 761^® on tinnitus severity were statistically significant for both sexes (women, p < 0.0001; men, p = 0.0279). Conclusions: Beneficial effects of Ginkgo biloba extract EGb 761^® in dementia patients with tinnitus are likely to be unaffected by the patient’s sex. Further research into the influence of patient characteristics on the outcome of tinnitus drug treatment is encouraged. Full article

Background: Plants have long been recognized for their potential to influence neurological health, with both neuroprotective and neurotoxic properties. This review explores the dual nature of plant-derived compounds and their impact on the human brain. Discussion: Numerous studies have highlighted the neuroprotective effects of various phytoconstituents, such as those found in Ginkgo biloba, Centella asiatica, Panax ginseng, Withania somnifera, and Curcuma longa. The neuroprotective compounds have demonstrated antioxidant, anti-inflammatory, and cognitive-enhancing properties, making them promising candidates for combating neurodegenerative diseases and improving brain function. Polyphenolic compounds, triterpenic acids, and specific phytocompounds like the ones from EGb 761 extract have shown interactions with key enzymes and receptors in the brain, leading to neuroprotective outcomes. However, this review also acknowledges the neurotoxic potential of certain plants, such as the Veratrum species, which contains steroidal alkaloids that can cause DNA damage and disrupt neurological function, or Atropa belladonna, which interfere with the normal functioning of the cholinergic system in the body, leading to a range of symptoms associated with anticholinergic toxicity. Conslusions: This review also emphasizes the need for further research to elucidate the complex mechanisms underlying the neuroprotective and neurotoxic effects of plant-derived compounds, as well as to identify novel phytoconstituents with therapeutic potential. Understanding the complex relationship between plants and the human brain is crucial for harnessing the benefits of neuroprotective compounds while mitigating the risks associated with neurotoxic substances. This review provides a comprehensive overview of the knowledge on the neurological properties of plants and highlights the importance of continued research in this field for the development of novel therapeutic strategies targeting brain health and neurological disorders. Full article

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. Full article

Alzheimer’s disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords—GB in AD and dementia—yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761^® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies. Full article

The main bioactive constituents in the standardized Ginkgo biloba leaf extract (EGb 761) are the terpene lactones and flavonoid glycosides. EGb 761’s antioxidant and anti-inflammatory properties have previously been demonstrated. Indomethacin-induced gastric ulcers have a multifactorial etiology and represent a major restriction to its therapeutic utility. The underlying ulcerogenic process involves oxidative and inflammatory biomolecular insults. This study was performed to explore the curative and preventative benefits of EGb 761 in experimentally-induced ulcers. To develop gastric ulcers in mice, indomethacin (40 mg/kg) was administered orally. EGb 761 (200 mg/kg) was given by gavage for 7 days before (preventative) and after (therapeutic) indomethacin administration. The histological alterations and macroscopic mucosal lesions were assessed. In gastric tissue homogenates, malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), and inflammatory cytokines were measured. The expressions of cyclooxygenase-2 (COX-2), cytokines, and proliferating cell nuclear antigen (PCNA) in the stomach mucosa were also investigated. The ulcer index, histological alterations, gastric oxidants, and inflammatory biomarkers were all significantly increased by indomethacin. In stomach specimens, it increased COX-2 and PCNA expression. EGb 761 treatments, both prophylactic and therapeutic, resulted in significant reductions in ulcer lesions, nitrosative and oxidative damage, and inflammatory markers, along with the lowering of COX-2 and PCNA expressions. Furthermore, in the fight against stomach ulcers, EGb 761 treatment was found to be more efficient than prevention. Full article

Noise trauma-induced loss of ribbon synapses at the inner hair cells (IHC) of the cochlea may lead to hearing loss (HL), resulting in tinnitus. We are convinced that a successful and sustainable therapy of tinnitus has to treat both symptom and cause. One of these causes may be the mentioned loss of ribbon synapses at the IHC of the cochlea. In this study, we investigated the possible preventive and curative effects of the Ginkgo biloba extract EGb 761^® on noise-induced synaptopathy, HL, and tinnitus development in Mongolian gerbils (Meriones unguiculatus). To this end, 37 male animals received EGb 761^® or placebo orally 3 weeks before (16 animals) or after (21 animals) a monaural acoustic noise trauma (2 kHz, 115 dB SPL, 75 min). Animals’ hearing thresholds were determined by auditory brainstem response (ABR) audiometry. A possible tinnitus percept was assessed by the gap prepulse inhibition acoustic startle reflex (GPIAS) response paradigm. Synaptopathy was quantified by cochlear immunofluorescence histology, counting the ribbon synapses of 15 IHCs at 11 different cochlear frequency locations per ear. We found a clear preventive effect of EGb 761^® on ribbon synapse numbers with the surprising result of a significant increase in synaptic innervation on the trauma side relative to placebo-treated animals. Consequently, animals treated with EGb 761^® before noise trauma did not develop a significant HL and were also less affected by tinnitus compared to placebo-treated animals. On the other hand, we did not see a curative effect (EGb 761^® treatment after noise trauma) of the extract on ribbon synapse numbers and, consequently, a significant HL and no difference in tinnitus development compared to the placebo-treated animals. Taken together, EGb 761^® prevented noise-induced HL and tinnitus by protecting from noise trauma-induced cochlear ribbon synapse loss; however, in our model, it did not restore lost ribbon synapses. Full article

Following reports of bleeding upon Ginkgo intake, we assessed whether Ginkgo extract EGb 761^® affects coagulation or platelet function or increases the risk of bleeding. In a double-blind, placebo-controlled trial, prothrombin time, activated partial thromboplastin time, international normalized ratio and bleeding time were measured in patients with Alzheimer’s dementia at baseline, weeks 6 and 26. A total of 513 patients were randomized to 120 mg (n = 169) or 240 mg EGb 761^® (n = 170) or placebo (n = 174). No relevant changes were found for coagulation parameters and bleeding time. Numbers of bleeding-related adverse events were similar in all groups. Concomitant intake of acetylsalicylic acid was documented for 68 patients in the placebo group and 105 in the EGb 761^® groups. Within these groups, the means at baseline and week 26 differed by less than 1 unit for prothrombin time and bleeding time and less than 0.1 unit for international normalized ratio. Data on warfarin treatment in nine patients each taking placebo or EGb 761^® did not indicate enhancement of warfarin effects by EGb 761^®. No evidence was found that EGb 761^® affects hemostasis or increases the bleeding risk. No pharmacodynamic interactions with warfarin or acetylsalicylic acid were found. Full article

Background: Comorbid occurrence of tinnitus and emotional symptoms of anxiety and depression is highly prevalent. The Ginkgo biloba extract EGb 761^® has been shown to be effective in reducing neuropsychiatric symptoms in patients with dementia and tinnitus. Methods: We performed a mediation analysis to evaluate direct effects of EGb 761^® on tinnitus severity, as well as indirect effects mediated by symptoms of depression and anxiety and by changed cognition. We pooled data from subsets of patients suffering from tinnitus that were enrolled in three double-blind, randomized, placebo-controlled clinical trials, which investigated the efficacy of EGb 761^® (240 mg/day for 22–24 weeks) in dementia with concomitant neuropsychiatric symptoms. Results: In total, 594 patients suffered from tinnitus (EGb 761^®, 289; placebo, 305). Direct effects of EGb 761^® on tinnitus severity (p < 0.001) in patients with mild to moderate dementia were found to represent about 60% of the total effect, whereas the indirect effects (p < 0.001) mediated by improvement of anxiety, depression and cognition represented about 40% of the total effect. Conclusions: EGb 761^® could be considered as a supporting treatment for tinnitus in elderly patients suffering from dementia, with added benefit in those with symptoms of depression or anxiety. Full article

Mild cognitive impairment (MCI) and dementia are clinically prevalent in the elderly. There is a high risk of cognitive decline in patients diagnosed with MCI or dementia. This review describes the effectiveness of Ginkgo biloba leaf special extract EGb 761^® for the treatment of dementia syndromes and EGb 761^® combination therapy with other medications for symptomatic dementia. This drug has shown convincing results, improving cognitive function, neuropsychiatric symptoms and consequent reduction of caregiver stress and maintenance of autonomy in patients with age-related cognitive decline, MCI and mild to moderate dementia. Currently, there is little evidence to support the combination therapy with anti-dementia drugs and, therefore, more evidence is needed to evaluate the role of EGb 761^® in mixed therapy. Full article

Oxidative stress has been associated to neuronal cell loss in neurodegenerative diseases. Neurons are post-mitotic cells that are very sensitive to oxidative stress—especially considering their limited capacity to be replaced. Therefore, reduction of oxidative stress, and inhibiting apoptosis, will potentially prevent neurodegeneration. In this study, we investigated the neuroprotective effect of Ginkgo biloba extract (EGb 761) against H₂O₂ induced apoptosis in SK-N-BE neuroblastoma cells. We analysed the molecular signalling pathway involved in the apoptotic cell death. H₂O₂ induced an increased acetylation of p53 lysine 382, a reduction in mitochondrial membrane potential, an increased BAX/Bcl-2 ratio and consequently increased Poly (ADP-ribose) polymerase (PARP) cleavage. All these effects were blocked by EGb 761 treatment. Thus, EGb 761, acting as intracellular antioxidant, protects neuroblastoma cells against activation of p53 mediated pathway and intrinsic mitochondrial apoptosis. Our results suggest that EGb 761, protecting against oxidative-stress induced apoptotic cell death, could potentially be used as nutraceutical for the prevention and treatment of neurodegenerative diseases. Full article

Cognitive disorders can be associated with brain trauma, neurodegenerative disease or as a part of physiological aging. Aging in humans is generally associated with deterioration of cognitive performance and, in particular, learning and memory. Different therapeutic approaches are available to treat cognitive impairment during physiological aging and neurodegenerative or psychiatric disorders. Traditional herbal medicine and numerous plants, either directly as supplements or indirectly in the form of food, improve brain functions including memory and attention. More than a hundred herbal medicinal plants have been traditionally used for learning and memory improvement, but only a few have been tested in randomized clinical trials. Here, we will enumerate those medicinal plants that show positive effects on various cognitive functions in learning and memory clinical trials. Moreover, besides natural products that show promising effects in clinical trials, we briefly discuss medicinal plants that have promising experimental data or initial clinical data and might have potential to reach a clinical trial in the near future. Full article

Different animal models are used to evaluate the process of epileptogenesis. In this investigation the kindling model of epilepsy was used. The epileptic focus was induced in Chinchilla rabbits by stimulation of the hippocampus with electric stimuli. We presumed that the extracts of Ginkgo biloba affect the formation of kindling epilepsy. Bioelectric activity of the brain was registered throughout the development of kindling with and without standardized extracts from dried ginkgo leaves (EGb 761). For each animal the following has been determined: the values of the minimum current strength necessary for the origination of threshold after-discharge (AD) – discharges appearing after the cessation of stimulation; duration of the threshold AD; number of stimulations necessary for the origination of full kindling; time latency for the development of full kindling; number of spontaneous epileptogenic discharges manifested in EEG two days following the formation of full kindling during 60-minute registration. The results show that the process of epileptogenesis was influenced by EGb 761. It has been established that if the animals received EGb 761, significantly weaker minimum current strength was necessary for the development of the epileptogenic focus and the AD were longer, while the number of necessary electrostimulations for the appearance of full kindling was less and the latency was shorter. Full article