Biloba Extract Research Articles

From traditional medicine to nanomedicine: potential of Ginkgo biloba extracts in treating inflammatory skin diseases.

The use of plant extracts as a potential cure for various conditions has moved from traditional medicine to evidence-based medicine. Skin diseases have been addressed since time immemorial using plant extracts through observational and traditional knowledge and passed on through generations. With the advent of modern techniques, the molecular mechanisms of action of plant extracts/isolates are being deciphered with more precision, and more nanomedicine-based therapies are being studied to improve their therapeutic efficacy and stability. The leaves and seeds of Ginkgo biloba (G. biloba), an ancient medicinal tree species, have been used in Chinese herbal medicine for thousands of years. G. biloba extracts have been widely studied as a neuroprotective and anti-ischaemic drug for ischaemia-reperfusion injuries in the heart, lungs, brain, kidneys, and other organs. However, the use of G. biloba can be accompanied with side effects and drug interactions. Although, there is now a growing interest for its use in skincare, the mechanisms of action of the extract are not fully understood and vital aspects of G. biloba, such as its neuroprotective and angiogenic properties contributing to the treatment of inflammatory skin diseases and skin ageing, are yet to be investigated. This review critically discusses the mechanisms of action of different constituents of G. biloba extracts linked to their potential interference in the molecular mechanisms underlying the pathogenesis of inflammatory skin diseases. In addition to its ability to act on oxidative stress, G. biloba can regulate angiogenesis through its compounds such as ginkgetin or ginkgolide K, which either inhibit aberrant angiogenesis in eczema/psoriasis or increase microcirculation during skin ageing. G. biloba may also contribute to the control of pruritus in atopic dermatitis via a neuroprotective and anti-inflammatory mechanism by suppressing JAK2/STAT3 signalling pathways. This review also highlights nanomedicine strategies to decrease the side effects and enhance the efficacy of the extracts. Similar strategies have been successfully used for anticancer molecules in targeted chemotherapy and iron delivery in anaemia treatment.

Piracetam and Ginkgo biloba in the treatment of residual cognitive symptoms after the discontinuation of benzodiazepines in long-term users; case series and review of the literature

IntroductionLong-term benzodiazepine use is common although not routinely recommended. While their dependence potential is notorious, cognitive problems due to their chronic use have only recently been intensively studied. Residual cognitive symptoms may linger months after successful benzodiazepine discontinuation and significantly limit optimal functional outcome in abstinent individuals.ObjectivesWe present a series of cases, a 41-year-old man and a 33-year-old woman who successfully completed a ten-week benzodiazepine-dependence rehabilitation program at our hospital, including successful tapering and post-withdrawal integrative therapy. At subsequent monthly outpatient check-ups, abstinence was confirmed (including toxicology testing) and there was no residual anxiety or mood symptomatology. Still, patients complained of their suboptimal functioning due to residual cognitive problems, especially trouble concentrating and short-memory deficits, which were objectively confirmed via psychometric tests.MethodsDuring continuous outpatient treatment (monthly controls), patients were clinically and neurocognitively evaluated. They were reluctant to try conventional psychopharmacology agents but were open to supplement therapy. After thorough literature review, a trial of piracetam and Ginko biloba extract was suggested. Piracetam, a positive allosteric modulator of AMPA-receptors, has been used in the treatment of vascular neurocognitive changes in the elderly. Bilobalides from G. biloba, act as atypical antagonists of GABA-A receptors and were found to exert neuroprotective effects in animal models, without epileptogenic or anxiogenic risks.ResultsPatients were recommended piracetam (2.4 g a day) in divided doses and a once-daily dose of G. biloba extract (240 mg a day), in a standardized form containing 3.2% of bilobalides. No side effects were noticed. At subsequent monthly checkups, patients reported fewer cognitive problems and better everyday functioning. Neurocognitive testing confirmed subjective findings, with positive changes in all areas, but especially so in verbal memory, which may be due to this specific pharmacological combination. At the end of the observation period of sixth months, piracetam was gradually discontinued while patients were given free choice whether to continue with G. biloba supplementation.ConclusionsAccording to our findings, piracetam and G. biloba extract may prove beneficial in the treatment of residual cognitive symptoms after benzodiazepine discontinuation, in long-term benzodiazepine users. Other treatments, focusing not only on modulation of glutamate and GABA, but also on other pathways should be evaluated. Further clinical studies are warranted.Disclosure of InterestNone Declared

Benefit of Ginkgo biloba for Dementia

Dementia is a chronic progressive brain illness syndrome defined by the loss of numerous cognitive processes, including memory, aphasia, apraxia, agnosia, and executive function. Consciousness is usually unaffected. Psychological and behaviour issues are sometimes present. Dementia is caused by a number of diseases and accidents that affect the brain, either directly or indirectly, such as Alzheimer's disease or stroke. Vascular dementia is a loss of thinking capacity caused by disorders that impede blood flow to certain parts of the brain, depriving brain cells of oxygen and nutrients. After Alzheimer's disease, vascular dementia is the second most frequent kind of dementia. This case study looks at a 76-year-old woman who has vascular dementia. The goal of pharmacological management with risperidone in low dose, as well as psychotherapy, in patients is to preserve and maximize function, reduce behaviour problems, relieve caregiver stress, and delay advancement to the next level. Ginkgo Biloba is one of the plants classified as phytopharmacology or medicines derived from of the plant is Ginkgo biloba Plant G. biloba (Gb) is included in the family Ginkgoaceae. In the G. biloba extract has antioxidant, antiviral, anti-inflammatory, and anti-carcinogenic properties. And also have it was stated that G. biloba extract had a good effect on the function of the CNS (central nervous system).

Ginkgolic Acids Confer Potential Anticancer Effects by Targeting Pro- Inflammatory and Oncogenic Signaling Molecules.

Medicinal plants and herbal preparations in the form of traditional medicines have been used in healthcare worldwide. The extracts of Ginkgo biloba L. seeds and leaves contain a complex mixture of numerous components, such as flavonol glycosides, terpene lactones, and a group of alkylphenols (anacardic or ginkgolic acids, cardanols and cardols) that have been a part of traditional Chinese medicine. These extracts are also sold as dietary supplements worldwide. G. biloba extract (EGb 761 and LI 1370) represent the standard form of G. biloba extract. Six different 6-alkylsalicylic acids (syn. ginkgolic acids) with alkyl substituents (C13:0, C15:0, C15:1, C17:0, C17:1, and C17:2) have been identified. The aim of this review is to unravel scientific evidence on anti-inflammatory and anticancer activities of ginkgolic acids to understand its therapeutic potential against inflammatory and oncologic diseases. A structured literature search was independently performed by the authors on PubMed, ScienceDirect, Scopus, and Web of Science. Accordingly, this review article critically analyses available scientific evidence on anti-inflammatory and anticancer activities of ginkgolic acids. Moreover, the review only included articles written in the English language. Several forms of ginkgolic acids, especially C13:0, C15:0 and C17:1, isolated from the leaves of G. biloba exhibited cytotoxic activity against a variety of human cancers by suppressing various pro-inflammatory signaling cascades and oncogenic transcription factors through multiple modes of action in various in vitro and in vivo preclinical models. Ginkgolic acids have also been reported to be potent post-translational small ubiquitin-related modifiers (SUMO)ylation inhibitors. In this review, we present updated information on the anti-inflammatory and anticancer properties of ginkgolic acids both in vitro and in vivo. Although ginkgolic acids show significant therapeutic potential in inflammatory and oncologic diseases, more investigations regarding the safety and efficacy of these natural agents are warranted before the clinical transition.

Interactions between Ginkgo biloba L. and Scutellaria baicalensis Georgi in multicomponent mixtures towards cholinesterase inhibition and ROS scavenging

This study gives new insights to understand the type of interactions between Ginkgo biloba L. and Scutellaria baicalensis Georgi, two Chinese medicinal plants with well documented neuroprotective effects, on three targets in Alzheimer’s disease (AD): acetylcholinesterase (AChE) and butyrylcholnesterase (BuChE) inhibition and hydrogen peroxide scavenging. Individual samples, binary mixtures with different proportions of both plant species, and also a commercial multicomponent combination containing both plants together with unroasted Coffea arabica L. and quercetin-3-O-rutinoside were used to perform this in vitro evaluation. Sample phenolic profiles were also determined by HPLC-DAD, showing the presence of several flavonoid glycosides, phenolic acids and a methylxanthine. In order to investigate the possible synergism/antagonism interaction, data obtained were analyzed by CompuSyn software. The results showed that G. biloba and S. baicalensis alone display better activities than in mixtures, most of the interactions exhibiting different degrees of antagonism. A slight synergism interaction was only observed for the commercial multicomponent mixture tested against H2O2. Further analysis was carried out to understand which compounds could be responsible for the antagonistic interaction. Seventeen single pure compounds present in all extracts were tested against AChE inhibition, most of them displaying weak or no activity. Only caffeine had a remarkable activity. Five different binary and quaternary mixture compositions were design to deepen the interaction between these compounds, revealing mainly phenolic acid-flavonoid, flavonoid-flavonoid and methylxanthine-flavonoid-phenolic acid antagonistic interactions. These results clearly show that, for the targets evaluated, there is no potentiation of the neuroprotective effect by combining S. baicalensis and G. biloba extracts.

Comparison of the terpene lactones and flavonols contents in G. Biloba commercial samples and the NIST standard reference materials using LC/UV/MS

The leaf extract of Ginkgo biloba has purported value for improving mental capacities in Alzheimer's patients. The flavonols and the terpene lactones are considered to be the two major groups of active components that influence human health. Almost all the clinical studies regarding G. Biloba were using either EGb 761®, a proprietary extract of G. Biloba leaves, or an extract prepared according to the standard set by it. Consequently, most of the commercial G. Biloba products were labeled with their content accordingly. This paper studied the compositions of both flavonols and terpene lactones of seven commercially available G. Biloba products and three standard reference materials (SRM 3246 G. Biloba leaves, SRM 3247 G. Biloba extract, and SRM 3248 G. Biloba tablet) from the National Institute of Standards and Technology (NIST). In this study, a chromatographic method with UV and mass spectroscopic detection was employed for the determination of the compositions of flavonols and the terpene lactones in Ginkgo products using gradient reversed-phase HPLC. Methanol-water (1:1) extracts of terpene lactones and flavonols out of G. Biloba products and NIST SRMs were analyzed qualitatively and quantitatively. While the relative compositions of the flavonol glycosides were similar for the NIST SRMs, those for the commercial G. Biloba products varied significantly. The relative concentrations of terpene lactones were also shown significant differences among products, but not as dramatic as that of flavonols.

Ginkgo Biloba improves bone formation during fracture healing: an experimental study in rats.

ABSTRACTOBJECTIVES: Ginkgo biloba extract (EGb 761) is a plant extract obtained from the leaves of the G. biloba tree. The aim of this study was to assess the histological and radiological effects of G. biloba extract on fracture healing in an experimental fracture model using rat femurs.METHODS: Forty-eight female Sprague-Dawley rats (weight: 195-252 g; age: 20 weeks) were used in the study. The rats were randomly divided into six groups (n=8). A transverse fracture was made in the middle of the right femur of each rat and fixed with a Kirschner wire. The G. biloba groups received 60 mg/kg oral G. biloba extract once daily. No medication was given to the control groups. On days 7, 21 and 35, both sets of femurs were evaluated radiologically and histopathologically.RESULTS: Histological evaluation revealed that the G. biloba groups had significant differences at 21 and 35 days (p<0.05). The G. biloba group showed a significant difference in terms of bone formation on day 21 when compared to the control group (p<0.05).CONCLUSIONS: This study indicated that the use of G. biloba extract accelerated fracture healing. Both radiological and histological differences were detected, but the histological differences were more remarkable. Level of Evidence I, High Quality Randomized Trial.

Efficacy and safety of Ginkgo biloba standardized extract in the treatment of vascular cognitive impairment: a randomized, double-blind, placebo-controlled clinical trial.

ObjectivesThe aim of this randomized, double-blind, placebo-controlled trial was to determine the efficacy and safety of Ginkgo biloba extract in patients diagnosed with vascular cognitive impairment (VCI).MethodsA total of 90 patients (aged 67.1±8.0 years; 59 women) were randomly allocated (1:1:1) to receive G. biloba 120 mg, G. biloba 60 mg, or placebo during a 6-month period. Assessment was made for efficacy indicators, including neuropsychological tests scores (Sandoz Clinical Assessment Geriatric Scale, Folstein Mini-Mental State Examination, Mattis Dementia Rating Scale, and Clinical Global Impression) and transcranial Doppler ultrasound findings. Safety indicators included laboratory findings, reported adverse reactions, and clinical examination.ResultsAt the end of 6-month study period, G. biloba 120 and 60 mg showed a statistically significant positive effect in comparison with placebo only on the Clinical Global Impression score (2.6±0.8 vs 3.1±0.7 vs 2.8±0.7, respectively; P=0.038). The Clinical Global Impression score showed a significant deterioration from the baseline values in the placebo group (−0.3±0.5; P=0.021) as opposed to G. biloba groups. No significant differences were found in the transcranial Doppler ultrasound findings. Adverse reactions were significantly more common and serious in the placebo group (16 subjects) than in either of the two G. biloba extract groups (eight and nine subjects, respectively), whereas laboratory findings and clinical examinations revealed no differences between the groups receiving G. biloba extract and placebo.ConclusionAccording to our results, G. biloba seemed to slow down the cognitive deterioration in patients with VCI, but the effect was shown in only one of the four neuropsychological tests administered. However, because of this mild effect in combination with a few adverse reactions, we cannot say that it is ineffective or unsafe either. Further studies are still needed to provide unambiguous evidence on the efficacy and safety of G. biloba extract.

Ginkgo Biloba Extract Blunts the Prothrombotic Effect of Thalidomide on Human Umbilical Endothelial Cells

Patients with multiple myeloma (MM) are at increased risk of developing venous thromboembolism (VTE) compared to general individuals. With the introduction of immunomodulatory drugs (IMiDs), such as thalidomide and lenalidomide, substantially elevates the incidence of VTE. It was reported that patients with MM have significantly increased plasminogen activator inhibitor (PAI-1) level resulting in a decrease of fibrinolytic activity. To prevent VTE in MM patients receiving IMiDs, different prophylactic strategies such as low molecular weight heparin, aspirin and warfarin have been recommended. But most of those recommendations are based on limited evidence.Ginkgo biloba extract (GBE) is one of the most widely used herbal supplements, which has been used in thrombosis prevention. It prompts us to investigate the impact of thalidomide on fibrinolysis and whether GBE has affection on fibrinolysis. In this study, the human umbilical vein endothelial cells (HUVECs) were cultured alone or co-cultured with human multiple myeloma cell line (MMCs) in the medium with or without thalidomide and in the presence or absence of GBE. After 48 hours, culture supernatants were collected and protein concentration of t-PA and PAI-1 were analyzed by enzyme-linked immunosorbent assay.Results showed that MMCs and thalidomide can both altered the profibrinolytic potential of HUVECs by decreasing t-PA and increasing PAI-1 levels. When co-cultured with MMCs, thalidomide can further elevate PAI-1 levels but not further reduce t-PA. Whether HUVECs alone or co-cultured with MMCs, GBE was able to counteract these effects caused by thalidomide through increasing t-PA and decreasing PAI-1 levels.Results in this study indicate that GBE blunts the prothrombotic effect of thalidomide on HUVECs. It supports GBE clinic use for the prevention of VTE induced by IMiDs. DisclosuresNo relevant conflicts of interest to declare.

Antifeedant Activity of Ginkgo biloba Secondary Metabolites against Hyphantria cunea Larvae: Mechanisms and Applications.

Ginkgo biloba is a typical relic plant that rarely suffers from pest hazards. This study analyzed the pattern of G. biloba pest hazards in Beijing; tested the antifeedant activity of G. biloba extracts, including ginkgo flavonoids, ginkgolide, and bilobalide, against Hyphantria cunea larvae; determined the activities of glutathione transferase (GSTs), acetylcholinesterase (AChE), carboxylesterase (CarE) and mixed-functional oxidase (MFO), in larvae after feeding on these G. biloba secondary metabolites; and screened for effective botanical antifeedants in the field. In this study, no indicators of insect infestation were found for any of the examined leaves of G. biloba; all tested secondary metabolites showed significant antifeedant activity and affected the activity of the four larval detoxifying enzymes. Ginkgolide had the highest antifeedant activity and the most significant effect on the detoxifying enzymes (P<0.05). Spraying leaves with G. biloba extracts or ginkgolide both significantly repelled H. cunea larvae in the field (P<0.05), although the former is more economical and practical. This study investigated the antifeedant activity of G. biloba secondary metabolites against H. cunea larvae, and the results provide new insights into the mechanism of G. biloba pest resistance. This study also developed new applications of G. biloba secondary metabolites for effective pest control.

The Antibiofilm Effect of Ginkgo biloba Extract Against Salmonella and Listeria Isolates from Poultry.

Salmonella spp. and Listeria spp. are common foodborne pathogens in poultry and have caused a large number of outbreaks worldwide. Biofilm formation is common in the food industry and is also a mechanism of antimicrobial resistance. The aim of this work was to investigate the antimicrobial effect and mechanism of Ginkgo biloba extract against the biofilm formation of Salmonella and Listeria isolates from poultry at retail markets. Bacteria detection, isolation, and enumeration were carried out on 27 chicken and 29 ducks at retail markets. The effects of temperature and G. biloba extract against biofilm formation of Salmonella and Listeria isolates were measured using the crystal violet assay and swimming and swarming motilities. The monitoring results of Salmonella and Listeria in 56 poultry carcasses at retail markets in Korea showed that the prevalence of Salmonella spp. in poultry was low (5.4%), but the prevalence of Listeria spp (78.6%) was high. L. innocua was the predominant serotype (80%) in the isolated Listeria species. Temperature, strain, and surface affected the biofilm formation of Salmonella spp. and Listeria spp. L. innocua showed the best biofilm formation ability on a 96-well plate, while Salmonella Enteritidis formed the most biofilm on a glass slide. Biofilm formation abilities of Salmonella spp. and Listeria spp. were increased with the increase of temperature. G. biloba extract at 75 μg/mL significantly inhibited biofilm formation of Salmonella spp. and Listeria spp (p < 0.05). The mechanism of the antibiofilm effect of the G. biloba extract showed that the motility reduction may be one of the mechanisms of G. biloba extract against some serotypes of Salmonella and Listeria, but not L. monocytogenes. The findings of this study provided the basis for the application of G. biloba extract as a food additive to promote the quality and safety of poultry products.

Innovation and Validation of Neuropsychopharmacological Testing Methods for the Assessment of Memory, Attention and Cognition in Human Participants

To meet the challenges of time searching for the new method for neuropsychopharmacology is still an ongoing process. In this experiment, we proposed and validated three neuropsychopharmacological testing methods, which are Matching Capacity (MC), Dissimilarity Identification (DI) and Sense Making (SM) tests for the estimation of memory, attention and cognition respectively in healthy aged human participants. The purpose of this experiment was to generate more effective testing methods for the determination of memory, attention and cognition in human. To endorse proposed methods a randomized double blind placebo controlled clinical trial was conducted among healthy aged human participants between the period of December 2015 and February 2016. The experiment was conducted at Gazipur Sadar, Gazipur-1703, Dhaka, Bangladesh and the experiment center was the Department of Pharmacy, Southeast University, Dhaka-1213, Bangladesh. In this experiment, 60 healthy male participants between the age of 42 to 50 years were selected and divided into 4 groups with 15 participants in each by simple randomization process. Ginkgo biloba standardized extract’s capsule (Giloba?) and Bacopa monnieri standardized extract’s syrup (Monera?) were used as standard. Psyllium seed husk (i.e., seed of the Plantago ovata) was incorporated in the hard gelatin capsule shell (size 0) to prepare capsule and used as a placebo control of the capsule (PCC). Excipients of oral liquid preparation of vitamin were used to prepare syrup and used as a placebo control of the syrup (PCS). The treatment procedure for group 1 was Ginkgo biloba standardized extract’s capsule (120 mg/capsule), 3 times daily for 21 days; group 2 was treated with Bacopa monnieri standardized extract’s syrup (1.21 g/5 ml), 2 teaspoonfuls, 3 times daily for 21 days. Psyllium seed husk’s capsule and excipients of oral liquid vitamin’s syrup were used as placebo control (PC) for group 3 and group 4 and administered in the similar manner of group 1 and group 2, respectively. Administration of Ginkgo biloba (GB) and Bacopa monnieri (BM) standardized extracts for successive days significantly increased the memory, attention and cognition of the participants with respect to PC groups. In the MC test, treatment with GB extract markedly (P < 0.05) increased the memory of the participants on 21st day with respect to PCC group. On the other hand administration of BM extract remarkably (P < 0.01) increased the memory of the participants on 14th day in comparison with PCS group. For DI test, administration of GB extract noticeably (P < 0.01, P < 0.05) increased the attention of the participants on 14th and 21st day as compared to that of PCC group. Conversely BM extract significantly (P < 0.05, P < 0.01) increased the attention of the participants on 7th, 14th and 21st day with regard to PCS group. In the SM test, administration of GB extract noticeably (P < 0.05) increased the cognition of the participants on 7th and 21st day in comparison with PCC group. BM extract administration considerably (P < 0.01) increased cognition of the participants on 14th and 21st day related to the PCS groups. The experiment demonstrates that MC, DI and SM tests clearly exposed the memory, attention and cognition enhancing activity of the GB and BM standardized extracts in healthful aged human participants respectively. Therefore, the proposed method can be used for the fortitude of memory, attention and cognition in human and will generate a landmark in the sphere of neuroscience.

Reversal of P-glycoprotein overexpression by Ginkgo biloba extract in the brains of pentylenetetrazole-kindled and phenytoin-treated mice

The purpose of this study was to investigate the combined effects of Ginkgo biloba extract and phenytoin (PHT) sodium as a dose regimen simulating the clinical treatment of patients with epilepsy, on P-glycoprotein (P-GP) overexpression in a pentylenetetrazole-kindled mouse model of epilepsy. Epilepsy was induced by intraperitoneal administration of pentylenetetrazole (40 mg/kg) for 7 days followed by intragastric administration of PHT (40 mg/kg) for 14 days. Thirty mice that developed seizures were randomly divided into three groups and administered PHT as well as the following treatments: saline (negative control); verapamil (20 mg/kg, positive control); and G. biloba (30 mg/kg). Seizure severity was recorded 30 minutes after treatment on Day 4 of drug administration, after which the mice were euthanized, and their brains isolated. Western blots and immunohistochemistry were performed to analyze the expression of P-GP and caspase-3, respectively, in the brain tissue. High-performance liquid chromatography was used to measure the concentrations of PHT in the brains of the treated mice. After 4 consecutive days of treatment, the seizure severity in the mice in the G. biloba extract group was more significantly reduced than the seizure severity in the saline control group, and a significant difference was observed between the G. biloba extract and verapamil control groups (p < 0.05). P-GP expression in the brain more significantly decreased in the mice treated with G. biloba extract and verapamil than it did in the saline-treated control group (p < 0.05). Compared with the saline-treated control group, the mice treated with G. biloba extract and verapamil showed significantly increased brain PHT concentrations (p < 0.05). Furthermore, caspase-3 expression in the brain tissue of the G. biloba extract group was significantly lower than that in the vehicle control group (p < 0.05); this finding demonstrated the neuroprotective effects of G. biloba. Therefore, this study showed that treatment with G. biloba extract in combination with PHT prevented the upregulation of P-GP expression in mice. Moreover, G. biloba extract decreased seizure severity in pentylenetetrazole-kindled/PHT-treated mice through a mechanism that might be related to the reduction of P-GP expression in the brain.

Ginkgo biloba extracts attenuate lipopolysaccharide-induced inflammatory responses in acute lung injury by inhibiting the COX-2 and NF-κB pathways

In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide(LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS. G. biloba extract (12 and 24 mg·kg−1) and dexamethasone (2 mg·kg−1), as a positive control, were given by i.p. injection. The cells in the bronchoalveolar lavage fluid (BALF) were counted. The degree of animal lung edema was evaluated by measuring the wet/dry weight ratio. The superoxidase dismutase (SOD) and myeloperoxidase (MPO) activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-a, interleukin-1b, and interleukin-6, were assayed by enzyme-linked immunosorbent assay. Pathological changes of lung tissues were observed by H&E staining. The levels of NF-κB p65 and COX-2 expression were detected by Western blotting. Compared to the LPS group, the treatment with the G. biloba extract at 12 and 24 mg·kg−1 markedly attenuated the inflammatory cell numbers in the BALF, decreased NF-κB p65 and COX-2 expression, and improved SOD activity, and inhibited MPO activity. The histological changes of the lungs were also significantly improved. The results indicated that G. biloba extract has a protective effect on LPS-induced acute lung injury in mice. The protective mechanism of G. biloba extract may be partly attributed to the inhibition of NF-κB p65 and COX-2 activation.

Cross matching observations on toxicological and clinical data for the assessment of tolerability and safety of Ginkgo biloba leaf extract.

Ginkgo biloba is one of the most widely used herbal remedies in Europe and the US. It may be purchased in different types of formulations, but most of the clinical studies have been performed with the controlled G. biloba extract EGb761(®). Indications include Alzheimers disease, cardiovascular disease, dementia, memory loss, and cerebral ischemia. The pharmacological modes of action cover antioxidant effects, radical scavenging, inhibition of platelet activating factor, alterations in membrane fluidity (signal transduction), and inhibition of glucocorticoid synthesis. Due to the widespread and long-term use of G. biloba - about a million doses of EGb761(®) are sold per day - tolerability and safety are a crucial issue. Based on broad and long-term clinical use of G. biloba extracts, it is regarded as well tolerated in man. Cross matching, a tool we introduced, combines different fields of knowledge and types of data to a consolidated result. In this article, we combine toxicological and clinical data and utilize other sources of information to assess tolerability and safety of G. biloba. It is well known that because of biological differences between animals and man or even between animal species, animal experiments do not necessarily mimic the effects in humans. Therefore, for adequate risk assessment, the relevance of non-clinical toxicological findings should be correlated with human data. The cross matching of toxicological data and results from clinical studies is possible because many toxicological and clinical studies are available on G. biloba. We give an in depth analysis of the modes of action in animals and describe toxicological studies with regard to metabolism, pharmacokinetics, genotoxicity, as well as carcinogenicity (e.g., the Technical Report TR 578 of the US National Toxicology Program). In addition, 75 clinical trials with high methodological quality are summarized. They included a total of 7115 patients treated with G. biloba. Based on this extensive amount of information, the broad variety of investigations, and their accordance we conclude that G. biloba extract is well tolerated and safe for humans.

A standardized extract of Ginkgo biloba prevents locomotion impairment induced by cassava juice in Wistar rats.

The long-term consumption of cassava (Manihot esculenta Crantz) juice produce neurotoxic effects in the rat, characterized by an increased motor activity in the open field test and presence of uncoordinated swim (i.e., lateral swimming), in the swim test; which has been associated with damage in the hippocampus (CA1). On the other hand, flavonoids content in the Ginkgo biloba extract has been reported to produces neuroprotective effects at experimental level; therefore we hypothesized that G. biloba extract may prevents the motor alterations produced by cassava juice and reduce cellular damage in hippocampal neurons of the rat. In present study the effect of vehicle, cassava juice (linamarin, 0.30 mg/kg), G. biloba extract (dry extract, 160 mg/kg), and combination of treatment were evaluated in the open field and swim tests to identify locomotor and hippocampal alterations in adult male Wistar rats. All treatments were administered once per day, every 24 h, for 28 days, by oral rout. The effect was evaluated at 0, 7, 14, 21, and 28 days of treatment. The results show that cassava group from day 14 of treatment increase crossing and rearing in the open field test, as compared with the vehicle group; while in the swim test produces an uncoordinated swim characterized by the lateral swim. In this same group an increase in the number of damage neurons in the hippocampus (CA1) was identified. Interestingly, both behavioral and neuronal alterations produced by cassava juice administration were prevented by treatment with G. biloba extract. The results shown that G. biloba extract exert a protective effect against behavioral and neuronal damage associated with consumption of cassava juice in the rat. These effects are possibly related with flavonoid content in the G. biloba extract.

High resolution GC/MS methods for the quantitative analysis of ginkgolic acids in Ginkgo biloba plants, extracts and dietary supplements

High resolution GC/MS methods for the quantitative analysis of ginkgolic acids in Ginkgo biloba plants, extracts and dietary supplements

Ginkgo biloba extract potentiates human vitamin D receptor‐mediated increase in CYP2B6 reporter activity by 1α,25‐dihydroxyvitamin D3 (1141.8)

Vitamin D receptor (VDR) regulates the expression of a broad array of genes, including those involved in drug biotransformation (e.g. CYP2B6). Ginkgo biloba extract induces CYP2B6, but it is not known whether it activates VDR. Therefore, we characterized the effect of G. biloba extract on human VDR (hVDR) activity. As assessed in a cell‐based dual‐luciferase reporter gene assay, G. biloba extract did not activate hVDR in cells transfected with a hVDR expression plasmid and a CYP2B6‐PBREM/XREM reporter plasmid. In contrast, 1α,25‐dihydroxyvitamin D3, which is a hVDR agonist, increased it by 16‐fold compared to the vehicle‐treated group. The combination of G. biloba extract and 1α,25‐dihydroxyvitamin D3 further increased hVDR activity by another 14‐fold (i.e. 225‐fold increase compared to the vehicle‐treated group). This potentiation effect was evident in multiple lots of G. biloba extract and with other VDR agonists (i.e. lithocholic acid and 9‐cis retinoic acid), and it increased as the concentration of the extract or 1α,25‐dihydroxyvitamin D3 increased. In contrast, the potentiation did not occur when cells were transfected with a plasmid expressing human constitutive androstane receptor, human pregnane X receptor, or mouse VDR. Overall, the findings indicate that G. biloba extract potentiates hVDR‐mediated CYP2B6 reporter activity.Grant Funding Source: Supported by the Canadian Institutes of Health Research and Michael Smith Fdn. for Health Res.

Hepatoprotective effect of Ginkgo biloba leaf extract on lantadenes-induced hepatotoxicity in guinea pigs

The hepatoprotective effect of freeze-dried methanolic leaf extract of Ginkgo biloba was evaluated against lantadenes-induced hepatic damage in guinea pigs. The reversed-phase HPLC analysis of lantadenes confirmed the presence of 72.82% of lantadene A. UPLC-ESI-MS analysis showed the presence of ginkgolide B, C, bilobalide and traces of ginkgolide A and J in G. biloba extract. The concentration of ginkgolide B in the sample was found as 0.29%. The elevated levels of serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase due to lantadenes were significantly restored towards normal values by G. biloba extract in a dose-dependent manner. The effects of lantadenes and G. biloba extract on lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase were assayed in liver homogenates to evaluate the antioxidant activity. G. biloba extract in a dose-dependent manner produced significant decrease in lantadenes-induced increased levels of LPO. The lantadene-induced decreased levels of SOD, GSH and catalase were elevated by G. biloba extract. The findings of biochemical and antioxidant enzyme levels were supported by gross and histopathological observations. Moreover, liver sections of G. biloba group also showed a marked decrease in apoptosis in comparison to lantadenes group. This study suggested that G. biloba could be used as a promising hepatoprotectant against lantadenes-induced hepatic damage. Future studies are needed to elucidate the precise mechanism of hepatoprotection for practical application.

Ginkgolic acids and Ginkgo biloba extract inhibit Escherichia coli O157:H7 and Staphylococcus aureus biofilm formation

Infection by enterohemorrhagic Escherichia coli O157:H7 (EHEC) is a worldwide problem, and there is no effective therapy. Biofilm formation is closely related to EHEC infection and is also a mechanism of antimicrobial resistance. Antibiofilm screening of 560 purified phytochemicals against EHEC showed that ginkgolic acids C15:1 and C17:1 at 5μg/ml and Ginkgo biloba extract at 100μg/ml significantly inhibited EHEC biofilm formation on the surfaces of polystyrene and glass, and on nylon membranes. Importantly, at their working concentrations, ginkgolic acids and G. biloba extract did not affect bacterial growth. Transcriptional analyses showed that ginkgolic acid C15:1 repressed curli genes and prophage genes in EHEC, and these findings were in-line with reduced fimbriae production and biofilm reductions. Interestingly, ginkgolic acids and G. biloba extract did not inhibit the biofilm formation of a commensal E. coli K-12 strain. In addition, ginkgolic acids and G. biloba extract inhibited the biofilm formation of three Staphylococcus aureus strains. The findings of this study suggest that plant secondary metabolites represent an important resource for biofilm inhibitors.