Ginkgo Leaf Extract Research Articles

Effects of L-carnitine and Ginkgo bilobaon cerebral cortex in experimentally-induced epileptic seizures disease in rat

Pentylenetetrazole (PTZ) kindling is an acknowledged model for epilepsy and refers to a phenomenon in which repeated injection of this drug causes a gradual seizure. The current study aimed to determine the possible protective and ameliorative effects of L-carnitine and Ginkgo Biloba leaf extracts (GLE) against PTZinduced epileptic seizures disease in rats. A total of 80 male albino rats were equally divided into eight groups; 1st group was the control; 2nd and 3rd wereGLE and L-carnitine groups, respectively; while the 4th group was pentylenetetrazolerat group and the 5th and 6th groups were pre GLE and L-carnitine groups respectively; the 7th and 8th groups were post GLE and L-carnitine, respectively. PTZ leads to an increase in malondialdehyde (MDA), glutamate (Glu) and to a decrease in catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, glutathione reductase(GSH), gamma amino butyric acid (GABA) and acetylcholine esterase (AChE) in the cerebral cortex of rats when compared to control group. Pre- and post treatment with GLE and L-carnitine were improved the biochemicalalterations in the cerebral cortex that treated with PTZ.

Simultaneous Determination of Flavonols and Terpene Lactones in Beagle Dog Plasma by Ultra-Performance Liquid Chromatography-Tandem - Mass Spectrometry: 2. Application to Pharmacokinetic Studies on Ginkgo Leaf Extract

Purpose: To evaluate the pharmacokinetics of the major compounds in Ginkgo leaf dosage formulations (namely, Yikangning tablets, Ginaton tablets, Aoshi dropping pills and Yinxinke dispersible tablets), commonly used in traditional Chinese medicine.Methods: A randomized 4*4 crossover study with eight beagle dogs was carried out. Plasma samples were collected following oral administration of four different preparations and the effective ingredients, namely, kaempferol, quercetin, isorhamnetin, ginkgolides A, ginkgolides B, ginkgolides C and bilobalide were detected by a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-TMS). Then the pharmacokinetics of these target compounds, of different preparations were studied.Results: The adjusted pharmacokinetic data showed that the area under the concentration-time curve from time-zero to the last measurable concentration (AUC0-t) of kaempferol, quercetin, isorhamnetin, bilobalide, ginkgolides A, ginkgolides B, and ginkgolides C in plasma ranged from 124.37 ± 90.46 to 2261.87 ± 812.35, after administration of Yikangning; 142.28 ± 62.37 to 2529.46 ± 320.48 μg/L•h following administration of Ginaton; 158.52 ± 55.48 to 1987.40 ± 766.21 μg/L•h after Aoshi administration; 160.49 ± 104.66 to 2016.92 ± 1150.92 μg/L•h following Yinxinke administration. The results also indicate that the flavonoids (especially quercetin) in dispersible tablets and dropping pills hexhibited higher AUC than those in conventional tablets. There were no differences between Aoshi (dropping pills) and Yinxinke (dispersible tablets) in terms of the bioavailability of the flavonoids, but the dropping pill flavonoids showed lower tmax.Conclusion: The results indicate that UPLC-TMS can used to simultaneously evaluate the plasma pharmacokinetics of Ginko compounds in beagle dogsKeywords: Ginkgo biloba, Beagle dog plasma, Kaempferol, Quercetin, Isorhamnetin, Ginkgolides A, Ginkgolides B, Ginkgolides C, Bilobalide, Pharmacokinetics; Bioavailability

Ginkgo biloba leaf extract induces DNA damage by inhibiting topoisomerase II activity in human hepatic cells.

Ginkgo biloba leaf extract has been shown to increase the incidence in liver tumors in mice in a 2-year bioassay conducted by the National Toxicology Program. In this study, the DNA damaging effects of Ginkgo biloba leaf extract and many of its constituents were evaluated in human hepatic HepG2 cells and the underlying mechanism was determined. A molecular docking study revealed that quercetin, a flavonoid constituent of Ginkgo biloba, showed a higher potential to interact with topoisomerase II (Topo II) than did the other Ginkgo biloba constituents; this in silico prediction was confirmed by using a biochemical assay to study Topo II enzyme inhibition. Moreover, as measured by the Comet assay and the induction of γ-H2A.X, quercetin, followed by keampferol and isorhamnetin, appeared to be the most potent DNA damage inducer in HepG2 cells. In Topo II knockdown cells, DNA damage triggered by Ginkgo biloba leaf extract or quercetin was dramatically decreased, indicating that DNA damage is directly associated with Topo II. DNA damage was also observed when cells were treated with commercially available Ginkgo biloba extract product. Our findings suggest that Ginkgo biloba leaf extract- and quercetin-induced in vitro genotoxicity may be the result of Topo II inhibition.

Ethanolic Ginkgo biloba leaf extract prevents renal fibrosis through Akt/mTOR signaling in diabetic nephropathy

BackgroundRecently, extract of Ginkgo biloba leaves (GbE) have become widely known phytomedicines and have shown various pharmacological activities, including improvement of blood circulation, protection of oxidative cell damage, prevention of Alzheimer's disease, treatment of cardiovascular disease and diabetes complications. This study was designed to investigate the effects of an ethanolic GbE on renal fibrosis in diabetic nephropathy (DN) and to clarify the possible mechanism by which GbE prevents renal fibrosis. Study designWe investigated the protective effects of GbE on renal fibrosis in STZ-induced diabetic rats. Rats were randomized into six groups termed normal control, diabetes mellitus, low dose of GbE (50 mg/kg/d), intermediate dose of GbE (100 mg/kg/d), high dose of GbE (200 mg/kg/d) and rapamycin (1 mg/kg/d). MethodsAfter 12 weeks, the rats were sacrificed and then fasting blood glucose (FBG), creatinine (Cr), blood urea nitrogen (BUN), urine protein, relative kidney weight, glycogen and collagen accumulation, and collagen IV and laminin expression were measured by different methods. The amounts of E-cadherin, α-SMA and snail, as well as the phosphorylation of Akt, mTOR and p70S6K in the renal cortex of rats, were examined by western blotting. ResultsCompared with diabetic rats, the levels of Cr, BUN, urine protein, relative kidney weight, accumulation of glycogen and collagen, and expression of collagen IV and laminin in the renal cortex were all decreased in GbE treated rats. In addition, GbE reduced the expression of E-cadherin, α-SMA, snail and the phosphorylation of Akt, mTOR and p70S6K in diabetic renal cortex. ConclusionGbE can prevent renal fibrosis in rats with diabetic nephropathy, which is most likely to be associated with its abilities to inhibit the Akt/mTOR signaling pathway.

Identification of Ginkgo biloba supplements adulteration using high performance thin layer chromatography and ultra high performance liquid chromatography-diode array detector-quadrupole time of flight-mass spectrometry.

Ginkgo biloba is one of the most widely sold herbal supplements and medicines in the world. Its popularity stems from having a positive effect on memory and the circulatory system in clinical studies. As ginkgo popularity increased, non-proprietary extracts were introduced claiming to have a similar phytochemical profile as the clinically tested extracts. The standardized commercial extracts of G. biloba leaf used in ginkgo supplements contain not less than 6% sesquiterpene lactones and 24% flavonol glycosides. While sesquiterpene lactones are unique constituents of ginkgo leaf, the flavonol glycosides are found in many other botanical extracts. Being a high value botanical, low quality ginkgo extracts may be subjected to adulteration with flavonoids to meet the requirement of 24% flavonol glycosides. Chemical analysis by ultra high performance liquid chromatography-mass spectrometry revealed that adulteration of ginkgo leaf extracts in many of these products is common, the naturally flavonol glycoside-rich extract being spiked with pure flavonoids or extracts made from another flavonoid-rich material, such as the fruit/flower of Japanese sophora (Styphnolobium japonicum), which also contains the isoflavone genistein. Recently, genistein has been proposed as an analytical marker for the detection of adulteration of ginkgo extracts with S. japonicum. This study confirms that botanically authenticated G. biloba leaf and extracts made therefrom do not contain genistein, and the presence of which even in trace amounts is suggestive of adulteration. In addition to the mass spectrometric approach, a high performance thin layer chromatography method was developed as a fast and economic method for chemical fingerprint analysis of ginkgo samples.

Differences in antioxidant properties of ginkgo leaves collected from male and female trees.

Total phenolic content and antioxidant capacity (FRAP method) of Ginkgo biloba L. leaves collected from male and female trees were determined and compared. Different water and aqueous ethanolic (water/ethanol 80/20, V/V) extracts were prepared by varying the time of infusing, boiling and steeping in order to determine the effect of the extraction method on the above parameters. Antioxidant activity and phenolic content of ginkgo leaf extracts correlated well with significant correlation coefficients. Slopes of linear regression lines were not statistically different for either sex.

Malignant Melanoma of the Temporal Bone Initially Presenting with Dizziness

A 48-year-old male presented to the otolaryngology outpatient clinic with a 3-month history of dizziness. Physical examination showed horizontal nystagmus toward the left on left lateral gaze and an intact tympanic membrane. No other neurological abnormalities were observed in the neurology department consultation. Thus, vestibular neuritis was suspected, and conservative treatment (dimenhydrinate, flunarizine, and ginkgo biloba leaf extract) was thus carried out. On follow-up after 1months, the dizziness symptom was maintained. Caloric tests were underwent and demonstrated right-sided unilateral weakness of 70%. On the ENT outpatient department after 2 months, the symptoms had relapsed and right pulsatile tinnitus and diplopia were noted. Puretone audiometry showed mild, mixed-type hearing loss in the right ear. Computed tomography (CT) of the temporal bone showed a soft tissue density from the right mastoid to the petrous apex with bony erosion. The lesion extended to the middle ear cavity at the cochlear promontory (Fig. 1). Magnetic resonance imaging (MRI) revealed an approximately 4.5 cm, irregularly contoured mass centered at the right petrous apex. The mass showed iso-to-low signal intensity on T2-weighted images and heterogeneous high-signal Malignant Melanoma of the Temporal Bone Initially Presenting with Dizziness

<i>Stachys sieboldii</i> (Labiatae, Chorogi) Protects against Learning and Memory Dysfunction Associated with Ischemic Brain Injury

Stachys sieboldii (Labiatae; Chinese artichoke, a tuber), "chorogi" in Japanese, has been extensively used in folk medicine, and has a number of pharmacological properties, including antioxidative activity. However, few studies have examined the neuroprotective effects of S. sieboldii tuber extract (chorogi extract), and it remains unknown whether the extract can alleviate learning and memory dysfunction associated with vascular dementia or Alzheimer's disease. Therefore, in this study, we investigated the neuroprotective effects of chorogi extract, and examined its protection against learning and memory dysfunction using Ginkgo biloba leaf extract (ginkgo extract) as a positive control. Mice were subjected to bilateral carotid artery occlusion (BCAO) for 30 min. Oral administration of chorogi extract or ginkgo extract significantly reduced post-ischemic glucose intolerance on day 1 and neuronal damage including memory impairment on day 3 after BCAO, compared with the vehicle-treated group. Neither herbal medicine affected locomotor activity. Furthermore, neither significantly alleviated scopolamine-induced learning and memory impairment. In primary neurons, neuronal survival rate was significantly reduced by hydrogen peroxide treatment. This hydrogen peroxide-induced neurotoxicity was significantly suppressed by chorogi extract and ginkgo extract. Taken together, our findings suggest that chorogi extract as well as ginkgo extract can protect against learning and memory dysfunction associated with ischemic brain injury through an antioxidative mechanism.

Results of the use of antioxidant and angioprotective agents in type 2 diabetes patients with diabetic retinopathy and age-related macular degeneration

to investigate changes in clinical, functional, and morphological parameters of the retina in type 2 diabetes patients with diabetic retinopathy (DR) and those with combined fundus pathology (DR plus age-related macular degeneration (AMD)) before and after a course of antioxidants and angioprotectors in the form of mono- or combination therapy. The study included 180 patients (180 eyes) with type 2 diabetes divided into 6 groups of 30 each. DR was graded according to E. Kohner and M. Porta classification, AMD--AREDS classification. Thus, group 1 consisted of patients with DRO,; group 2--DR1 without DM, group 3--DR1 with DM, group 4--DRO and "dry" AMD (AREDS 1-3), group 5--DR1 with no DM but with AMD (AREDS 1-3), and group 6--DR1 with DM and AMD (AREDS 1-3). A drug containing lutein 6 mg, zeaxanthin 0.5 mg, vitamin C 60 mg, vitamin E 7 mg, vitamin A 1.5 mg, vitamin B2 1.2 mg, rutin 25 mg, zinc 5 mg, selenium 25 mcg, and bilberry extract 60 mg was used for antioxidative therapy. Ginkgo biloba leaf extract 60 mg was chosen as the angioprotector. In all patients visual acuity, macular thickness and morphology (OCT) as well as light sensitivity (microperimetry) were assessed before and after the treatment course. Analysis of baseline measurements demonstrated a significant decrease in best corrected visual acuity (p < 0.05) in study groups 2-6 as compared with group 1. Macular thickness was increased in all groups, however, the changes were statistically significant only in groups 3 and 6 (p<0.05). Light sensitivity of the macula showed a reduction, which was statistically significant in groups 4-6 (p < 0.05). After the course of antioxidant and angioprotective therapy, these parameters improved in all groups. The greatest effect was achieved with simultaneous antioxidant and double-dose angioprotective therapy (240 mg per day): visual acuity increased significantly (p < 0.05) in all groups except group 1; macular thickness decreased in all groups, however, the changes were statistically significant (p < 0.05) only in groups 1-3 and 5; light sensitivity also improved in all groups, significantly (p < 0.05) in groups 1-3 and 4. Extended analysis of clinical, functional and morphological changes in the retina at the onset of DR in type 2 diabetes patients with concomitant "dry" AMD enables timely diagnosis, prognosis, prevention, and early treatment. Conservative treatment with antioxidant and angioprotective agents has been proved effective in type 2 diabetes patients with preclinical (DRO) and early (DR1) diabetic retinopathy and those with DR and "dry" AMD (AREDS 1-3) in terms of functional and morphological parameters of the retina. From all the regimens, a combined antioxidant and double-dose angioprotective (240 mg) therapy appeared to be the most effective and can be considered not only a preventive, but also a therapeutic measure in type 2 diabetes patients with initial stages of DR (DRO, DR1) or those with DR and DM or combined DR and AMD (AREDS 1-3).

Rethinking Ginkgo biloba L.: Medicinal uses and conservation.

Ginkgo biloba (G. biloba) is an ancient medicinal tree species that has been in existence for millennia without undergoing modifications due to its resistance to environmental stresses. Palaeobotanical history showed a wide distribution of the species across the globe but declined over geological time, becoming restricted to narrow geographical range with few surviving individuals in the modern day. The tree is slow growing, adapted to many ecological conditions and shows numerous adaptation in developmental patterns. Medicinal use of the species is attracting research interest, especially the various parts of the tree that are used in orthodox or traditional medicine to treat diseases due to the many bioactive compounds. The primary compounds receiving increasing research interest are the triterpene lactones and flavonoids; these are the target of biotechnological strategies being employed to enhance production. Many genetic and environmental factors have contributed to the endangered status of the species; conservation measures are required to protect it from extinction. In many countries, the cultivation of plantations for the supply of ginkgo leaf-based pharmaceutical formulations is in progress, and efforts to standardize ginkgo leaf extract as herbal medication for human use are being made. Microcuttings and cuttings, cryopreservation, and plant tissue culture have all aided to conserve G. biloba.

Effects of flavonoid glycosides obtained from a Ginkgo biloba extract fraction on the physical and oxidative stabilities of oil-in-water emulsions prepared from a stripped structured lipid with a low omega-6 to omega-3 ratio

In this study, we have produced a structured lipid with a low ω6/ω3 ratio by lipase-catalysed interesterification with perilla and grape seed oils (1:3, wt/wt). A Ginkgo biloba leaf extract was fractionated in a column packed with HP-20 resin, producing a flavonoid glycoside fraction (FA) and a biflavone fraction (FB). FA exhibited higher antioxidant capacity than FB, showing 58.4mmol gallic acid equivalent (GAE)/g-of-total-phenol-content, 58.8mg quercetin equivalent (QUE)/g-of-total-flavonoid-content, 4.5mmol trolox/g-of-trolox-equivalent antioxidant capacity, 0.14mg extract/mL-of-free-radical-scavenging-activity (DPPH assay, IC50), and 2.3mmol Fe2SO4·7H2O/g-of-ferric-reducing-antioxidant-power. The oil-in-water emulsion containing the stripped structured lipid as an oil phase with FA exhibited the highest stability and the lowest oil globule diameters (d43 and d32), where the aggregation was unnoticeable by Turbiscan and particle size analyses during 30days of storage. Furthermore, FA was effective in retarding the oxidation of the emulsions.

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.

Real-world analysis of concurrent diseases and medicine use among patients with insomnia

This study aims to explore and analyze the condition of concurrent diseases and medicine use of traditional Chinese medicine (TCM) and western medicine among the patients with insomnia. One thousand and sxity seven cases of data from 20 national hospitals' hospital information system (HIS) databases were collected. The frequent concurrent diseases included hypertension (26.9%), brain blood supply insufficiency (24.93%), cerebral infarction (19.49%), blood lipoprotein disturbance (15.28%), coronary heart disease (14.15%), headache (10.68%), chronic gastritis (8.81%), type 2 diabetes mellitus (7.87%), depressive disorder (7.4%) and anxiety disorder (6.65%). The 10 most frequently-used western drugs included alprazolam (35.99%), aspirin (25.4%), olanzapine (24.18%), cinepazide (23.06%), flupentixol & melitracen (18.74%), zolpidem (18.37%), oxiracetam (15.65%), estazolam (15%), aniracetam (13.4%) and piracetam (13.31%). The 10 most frequently-used TCM included Shuxuening injection (16.4%), Shuxuetong injection (15.18%), extract of ginkgo biloba leaf (14.71%), gastrodin (12.46%), Dengzanxixin injection (11.34%), Xueshuantong (8.53%), Danhong injection (6.37%), compound liquorice tablet (5.81%), Sanqi Tongshu capsule (5.72%) and sowthistle-leaf ixeridium injection (5.34%). Among all combined uses, the most frequent western drug use was alprazolam and olanzapine, while combined use of hypnotic drug and Huoxuehuayu formula is the most frequent. This study concludes that the concurrent diseases mainly include cardio-cerebrovascular diseases, metabolic disorders and anxiety-depression disorders, with increasing tendency of diseases types by ages, especially for cardio-cerebrovascular diseases. The most frequently-used hypnotic is alprazolam in the insomnia patients, and it is worth being concerned about the off-label use of olanzapine as an antipsychotic for the treatment of insomnia However, due to the fact that all cases data are from the inpatients, these findings have some limitations.

Flavonoid ingredients of Ginkgo biloba leaf extract regulate lipid metabolism through Sp1-mediated carnitine palmitoyltranferase 1A up-regulation.

BackgroundLipid accumulation is the primary evidence of non-alcoholic fatty liver disease (NAFLD). Ginkgo biloba extract (GBE) and its flavonoid ingredients (quercetin, kaempferol, and isorhamnetin) could lessen the lipid accumulation associated with up-regulation of the rate-limiting enzyme, carnitine palmitoyltransferase 1A (CPT1A), in the β-oxidation of long-chain fatty acids. In this study, we investigated the mechanisms by which GBE and its flavonoids induced expression of CPT1A.ResultsCPT1A inhibition with RNAi resulted in triglyceride accumulation in HepG2 cells. Through deletion and mutation analysis of CPT1A’s promoter combined with electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments, the CPT1A promoter region (−50 to −5 nt) was determined to contain two putative Sp1 binding sites, namely Sp1a and Sp1b, which might act as the GBE regulation response DNA element. Sp1 might be induced to transfer from cytoplasma to nucleus to bind the promoter region of −50 to −5 nt by GBE. The regulatory effects of GBE on CPT1A were also verified on the flavonoid ingredients quercetin, kaempferol, and isorhamnetin.ConclusionSp1 was crucial in regulating CPT1A expression with GBE and its flavonoid ingredients, and the −50 to −5 nt region of CPT1A promoter played important roles in Sp1 binding.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-014-0087-x) contains supplementary material, which is available to authorized users.

Thyroidectomy induced hepatic toxicity and possible amelioration by Ginkgo biloba leaf extract

The liver is a major target organ for thyroid hormone action and marked changes occur in liver functions in the case of hypo- or hyperthyroidism. This studied aimed at inverstigating the biochemical and histopathological changes in the liver after thyroidectomy and the ameliorating role of Ginkgo biloba leaf extract (GLE). A total of 50 male albino rats were equally divided into five groups; 1st to 3rd groups were control, sham operated and GLE groups while 4th group was thyroidectomized rat group and 5th group was treated thyrodectomized rat with GLE. Serum T3 and T4 levels after 3weeks of thyroidectomy was significantly decreased when compared with the control group, while TSH significantly increased when compared with the control group increased. Serum ALT, AST, ALP and GGT showed significant (P<0.05) increase in thyroidectomized group when compared with control, sham operated and sham operated with GLE groups. On the one hand, treatment of thyroidectomized rats with GLE improved this increase in serum ALT, AST, ALP and GGT in thyroidectomized rat group. Liver sections of thyroidectomy group showed marked positive reaction and increase number of PCNA staining of hepatocyte nuclei. On the other hand, liver in treated of thyroidectomized rat with GLE group showed a marked reduction in the number of PCNA-positive nuclei when compared with sections in thyroidectomy group. Treatment of thyroidectomized rat with GLE improves the biochemical, histopathological and immunohistochemical alternations and the intensity of PCNA immunoreactive cells demonstrating the recovery of some injury.

HILIC‐UPLC‐MS/MS combined with hierarchical clustering analysis to rapidly analyze and evaluate nucleobases and nucleosides in Ginkgo biloba leaves

Ginkgo biloba leaf extract has been widely used in dietary supplements and more recently in some foods and beverages. In addition to the well-known flavonol glycosides and terpene lactones, G. biloba leaves are also rich in nucleobases and nucleosides. To determine the content of nucleobases and nucleosides in G. biloba leaves at trace levels, a reliable method has been established by using hydrophilic interaction ultra performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (HILIC-UPLC-TQ-MS/MS) working in multiple reaction monitoring mode. Eleven nucleobases and nucleosides were simultaneously determined in seven min. The proposed method was fully validated in terms of linearity, sensitivity, and repeatability, as well as recovery. Furthermore, hierarchical clustering analysis (HCA) was performed to evaluate and classify the samples according to the contents of the eleven chemical constituents. The established approach could be helpful for evaluation of the potential values as dietary supplements and the quality control of G. biloba leaves, which might also be utilized for the investigation of other medicinal herbs containing nucleobases and nucleosides.

Mechanistic Evaluation of Ginkgo biloba Leaf Extract-Induced Genotoxicity in L5178Y Cells

Ginkgo biloba has been used for many thousand years as a traditional herbal remedy and its extract has been consumed for many decades as a dietary supplement. Ginkgo biloba leaf extract is a complex mixture with many constituents, including flavonol glycosides and terpene lactones. The National Toxicology Program 2-year cancer bioassay found that G. biloba leaf extract targets the liver, thyroid gland, and nose of rodents; however, the mechanism of G. biloba leaf extract-associated carcinogenicity remains unclear. In the current study, the in vitro genotoxicity of G. biloba leaf extract and its eight constituents was evaluated using the mouse lymphoma assay (MLA) and Comet assay. The underlying mechanisms of G. biloba leaf extract-associated genotoxicity were explored. Ginkgo biloba leaf extract, quercetin, and kaempferol resulted in a dose-dependent increase in the mutant frequency and DNA double-strand breaks (DSBs). Western blot analysis confirmed that G. biloba leaf extract, quercetin, and kaempferol activated the DNA damage signaling pathway with increased expression of γ-H2AX and phosphorylated Chk2 and Chk1. In addition, G. biloba leaf extract produced reactive oxygen species and decreased glutathione levels in L5178Y cells. Loss of heterozygosity analysis of mutants indicated that G. biloba leaf extract, quercetin, and kaempferol treatments resulted in extensive chromosomal damage. These results indicate that G. biloba leaf extract and its two constituents, quercetin and kaempferol, are mutagenic to the mouse L5178Y cells and induce DSBs. Quercetin and kaempferol likely are major contributors to G. biloba leaf extract-induced genotoxicity.

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.

Antioxidant properties of extracts from Ginkgo biloba leaves in meatballs

The aim was to determine the effect of Ginkgo leaf extracts on the stability of lipids and cholesterol in pork meatballs over 21days of refrigerated storage. The antioxidants used were characterized by their antioxidant activity towards lipids and cholesterol. Extracts were prepared from green and yellow leaves from Ginkgo biloba L. trees. Water, acetone and ethanol were used as extractants. The extracts showed stabilizing effects on both lipid and cholesterol oxidation processes. The lipid oxidation process of pork meatballs was mostly inhibited by the aqueous and ethanolic extracts of the yellow leaves. Their antioxidant activity was higher than that of BHT. All the extracts had a stabilizing effect on cholesterol and most of them inhibited the formation of oxidized derivatives. The acetone and ethanol extracts of green leaves and the ethanol extract of yellow leaves inhibited the formation of cholesterol oxidation products formation most effectively.

Abrogation by Ginkgo Byloba Leaf Extract on Hepatic and Renal Toxicity Induced by Methotrexate in Rats

Methotrexate (MTX) is used as a chemotherapeutic agent and its anti-oxidant activity is used to treat many cancer types. The present study aimed to examine the possible modifying effects of Ginkgo biloba leaf extract (GLE) against hepatic and renal toxicity induced by MTX in rats. A total 60 male albino rats were equally divided into six groups; the first and second groups were the control and GLE groups respectively while the 3rd group was MTX rat group; the 4th and 5th groups were Co- and post treated MTX rat with GLE respectively and the 6th group was MTX self treated rat group. Serum GPT, GOT, urea, creatinine, uric acids and MDA levels in MTX group showed a significant increase when compared with control group, in contrast, MTX-treated group also exhibited a significant decrease in liver antioxidant machinery represented by GSH, catalase, SOD and total protein. Administration of GLE combined with MTX improved the liver and kidney damages induced by MTX. Histopathological and evidence, together with observed CD68 immunoreactivity, supported the detrimental effect of MTX and the ameliorating effect of GLE on liver and kidney toxicities. GLE possessed various protective mechanisms against MTX-induced liver and kidney toxicity throughout Co- and post- treatment. We can conclude that Co-treatment with GLE has beneficial properties and can reduce the liver and kidney damages and toxicity induced by MTX.