Gingko Biloba Extract Research Articles

The effects of gingko biloba extract (EGb 761) on experimental acute pancreatitis

Background and objective Acute pancreatitis is an important and fatal disease with high mortality and morbidity. Although the pathogenesis of acute pancreatitis is poorly understood, there are many studies that suggest the role for oxygen free radicals (OFRs) in the development of pancreatitis and its complications and show beneficial effects of scavenger treatment. In the present study, we aimed to investigate whether Egb761, the standardized extract of gingko biloba, restrains the generation of OFRs and ameliorates the histopathologic findings of acute pancreatitis. Materials and methods Sixty male Sprague Dawley rats were randomly assigned to one of the following experimental groups. In early and late pancreatitis and treatment groups, acute pancreatitis was induced by retrograde infusion of 3% sodium taurocholate. In treatment groups, 100 mg/kg Egb 761 was given intraperitoneally (IP) 24 h and immediately before induction of pancreatitis. Sham-operated rats received isotonic saline instead of sodium taurocholate. After observation times of 3.5 and 12 h, the pancreas was removed for light microscopy and determination of malondialdehyde (MDA) levels as a marker for OFRs–induced lipid peroxidation. Serum samples also were obtained for amylase and lipase levels. Results There was no significant difference in control and sham-operated groups in terms of histopathologic findings and serum enzyme levels. The tissue concentrations of MDA and serum enzyme levels were significantly elevated in early and late treatment groups as compared with the control group. The treatment with Egb 761 caused significant decrease in serum amylase and lipase levels and histopathologic scores as compared with early and late pancreatitis groups. Conclusions Prophylactic application of Egb761 exerts highly beneficial influence on the course of acute pancreatitis, and this seems to be related to the oxygen radical scavenger effect of Egb761.

Oral Ingestion of Ginkgo biloba Extract Reduces Thiobarbituric Acid Reacting (TBAR) Substances in Washed Platelets of Healthy Subjects

Thiobarbituric acid reacting (TBAR) substances were measured in washed platelets before and after ingesting 120 mg of standardized Gingko biloba extract daily for 3 months, in both normocholesterolemic (total cholesterol, 160 +/- 27 mg/dl; age 40 +/- 13 years; n = 18) and hypercholesterolemic subjects (total cholesterol, 229 +/- 35; age, 45 +/- 8 years, n = 12). Gingko biloba extract significantly reduced cellular content of TBAR substances; 42 +/- 21 vs. 28 +/- 16 pmol/10(7 platelets (p < 0.0025) and 50 +/- 17 vs. 29 +/- 13 pmol/10(7) platelets (P < 0.004), for the normo- and hypercholemic subjects, respectively. In conclusion, Gingko biloba extract is a potent antioxidant for both groups, reducing TBAR substances possibly by inhibiting platelet COX-1 isoform activity.

Effects of mexiletine, ginkgo biloba extract (EGb 761), and their combination on experimental head injury.

Lipid peroxidation (LP) and brain edema are important factors that produce tissue damage in head injury. The purpose of this study was to investigate the effect of mexiletine, gingko biloba extract (EGb 761), and their combination on LP and edema after moderate head trauma. Forty rats were randomly and blindly divided into four groups of ten animals each: control group (bolus injection of physiological saline), mexiletine group (50 mg/kg per injection), EGb 761 group (30 mg/kg per injection), and mexiletine plus EGb 761 group (50 mg/kg and 30 mg/kg per injection, respectively). The injections were given intraperitoneally at 1 h, 9 h, and 17 h after trauma. Twenty-four hours after injury, the rats were killed, and malondialdehyde (MDA) levels and brain water content were determined. Rats treated with mexiletine, EGb 761, and mexiletine plus EGb 761 had significantly lower MDA levels than the control group (P<0.01). The lowest MDA levels were measured in the mexiletine plus EGb 761 group. However, there was no significant difference in brain water content between treated groups and the control group (P>0.05). These findings show the usefulness of mexiletine and its combination with EGb 761 as a cerebroprotective agent in this model of experimental head injury.

Could antioxidant supplementation reduce antiretroviral therapy-induced chronic stable hyperlactatemia?

Objective. – To determine if asymptomatic stable chronic hyperlactatemia in human immunodeficiency virus (HIV)-infected patients under highly active antiretroviral therapy (HAART, including nucleoside analog reverse transcriptase inhibitors (NRTI)) could be improved by antioxidant supplementation. Design. – To match two groups of patients taking NRTI for at least 24 months: 15 without and 15 with antioxidant supplementation (vitamin E, β-carotene, N-acetylcysteine, selenium, Gingko biloba extracts and nutritional supplements). For both the groups, the supplementation by antioxidants or its lack was carefully assessed. Venous lactatemia, blood oxidative stress markers (plasma lipid peroxidation, enzymatic and non-enzymatic antioxidants), CDC revisited classification, CD4 count and viral load, NRTI (with or without stavudine) and other antiretroviral drugs used, lipoatrophy, central fat accumulation were assessed. Results. – Patients were not statistically different with respect to the CDC classification, CD4 count, viral load and characteristics of antiretroviral therapy. Blood oxidative stress markers, i.e. vitamin E, vitamin A and β-carotene tended to be higher in the supplemented group. The difference observed in venous lactate concentration between the two groups was significant (1.37 ± 0.10 vs. 1.82 ± 0.19 mmol/l in the supplemented and non-supplemented groups, respectively P = 0.04). Conclusion. – Antioxidant supplementation improves the asymptomatic stable chronic hyperlactatemia observed in HIV-infected patients taking HAART including NRTI for a long time. Controlled studies are needed to demonstrate the efficacy of this supplementation on mitochondrial toxicity observed during HAART and the possible usefulness of its combination with mitochondrial cofactors like carnitine, riboflavine, coenzyme Q, α-lipoic acid.

Response to “Molecular and cellular assessment of Gingko biloba extract as a possible ophthalmic drug”, by G. Thiagarajan, S. Chandani, S. Harinarayana Rao, A.M. Samuni, K. Chandrasekaran and D. Balasubramanian [Experimental Eye Research 75 (2002) pp. 421–430

Response to “Molecular and cellular assessment of Gingko biloba extract as a possible ophthalmic drug”, by G. Thiagarajan, S. Chandani, S. Harinarayana Rao, A.M. Samuni, K. Chandrasekaran and D. Balasubramanian [Experimental Eye Research 75 (2002) pp. 421–430

Reply to ‘Response to “Molecular and cellular assessment of gingko biloba extract as a possible ophthalmic drug”, by G. Thiagarajan, S. Chandani, S. Harinarayana Rao, A.M. Samuni, K. Chandrasekaran and D. Balasubramanian [Experimental Eye Research 75 (2002) pp. 421–430]’ by R.R. Socci

Reply to ‘Response to “Molecular and cellular assessment of gingko biloba extract as a possible ophthalmic drug”, by G. Thiagarajan, S. Chandani, S. Harinarayana Rao, A.M. Samuni, K. Chandrasekaran and D. Balasubramanian [Experimental Eye Research 75 (2002) pp. 421–430]’ by R.R. Socci

Mood-enhancing antidepressant St. John's wort inhibits the activation of human immunodeficiency virus gene expression by ultraviolet light.

Ultraviolet (UV) radiation is a potent activator of the human immunodeficiency virus (HIV) gene expression in a HeLa cell clone with stably integrated copies of the HIVcat reporter construct. Recently, we have shown that activation of p38 MAP kinase and NF-kappaB is necessary but not sufficient for triggering efficient HIV gene expression in response to UV. Here we demonstrate that St. John's wort is a potent inhibitor of the UV-induced activation of HIV gene expression in HeLa cells. Stably transfected HIVcat/HeLa cells were preincubated with different amounts (25-100 microl) of St. John's wort or gingko biloba extracts for 30 min, then irradiated with UV (30 J/m2). In contrast to ginkgo biloba, St. John's wort inhibited the UV-induced HIV gene expression in a dose-dependent manner. Furthermore, preincubation with St. John's wort (10, 20, and 30 microl) for 30 min before UV (30 J/m2) irradiation, PMA- and UV-induced NF-kappaB activation was completely blocked, whereas ginkgo biloba did not affect the PMA- and UV-induced NF-kappaB activation in HeLa cells. UV activation of p38 MAP kinase was not inhibited by St. John's wort or by ginkgo biloba. However, we found that p38 MAP kinase and JNK1 and -2 were activated by St. John's wort, but p44/42 MAP kinase was not activated by St. John's wort in HeLa cells. Hypericin an active ingredient in St. John's wort also inhibited the UV activation of HIV gene expression in HeLa cells. These results firmly confirm that St. John's wort is a potent inhibitor of the UV-induced activation of HIV gene expression in HeLa cells.

Selective extraction of functional components derived from herb in plasma by using a molecularly imprinted polymer based on 2,2-bis(hydroxymethyl)butanol trimethacrylate

To make molecularly imprinted polymer (MIP) solid-phase extraction (SPE) capable of direct clean-up of aqueous biological samples, an anti-quercetin MIP with evident hydrophobic matrix was synthesized using acrylamide (AA) as the functional monomer and 2,2-bis(hydroxymethyl)butanol trimethacrylate (TRIM) as the crosslinker. The affinity and selectivity were evaluated by liquid chromatography, and the binding sites and the dissolution constants were measured by frontal chromatography. Compared with the AA–co-ethyleneglycol dimethacrylate (EDMA) MIP, the anti-quercetin AA–co-TRIM MIP exhibited stronger binding and possessed improved column efficacy. A linear plot of the peak area versus sample size (in the range of 0.4–2.2 μg) was obtained, which made it promising for the MIP columns to be directly used for analysis. Before MIP-SPE of the sample of plasma, several washing solvents were tested and it was shown that the careful choice of the right washing solvent is the key step to successful sample extraction. The anti-quercetin AA–co-TRIM polymer selectively extracted quercetin, the effective component in the plasma of rats fed the hydrolyzed extract of Gingko biloba L. The recovery (67%) for MIP-SPE was calculated using spiked plasma. The results of the present work showed that the properties of MIP could be improved by modifying the polymerization and that MIP-SPE could be used for direct clean-up of biological samples for the analysis of functional components in vivo originating from an extract of medicinal herbs.

Overview of phytopharmaceuticals for therapy of dementia. Quality and activity of Gingko biloba extract

Aus dem Bereich der Phytopharmaka stehen ausschlieslich standardisierte Ginkgo-Extrakte (Bezeichnung EGb 761®, LI 1370) zur symptomatischen Behandlung der Demenz (Alzheimer-Krankheit, vaskularen Demenz sowie Mischformen aus beiden) zur Verfugung. Die Extrakte werden in einem hochtechnisierten, vielstufigen Extraktionsverfahren hergestellt, wobei pharmakologisch relevante Inhaltsstoffe (Ginkgoflavonglycoside, Terpenlactone) angereichert und unerwunschte Stoffgruppen bzw. Stoffe, die keinen Beitrag zur Wirksamkeit leisten oder die Vertraglichkeit mindern (z.B. Ginkgolsauren), abgereichert werden. Ginkgo-Spezialextrakte besitzen ein multifaktorielles Wirkprofil, das u. a. Radikalfangereigenschaften, neuroprotektive Effekte und Effekte auf altersbedingte Defizite der Neurotransmission umfasst, und das die rationale Basis fur die klinische Anwendung bei dementiellen Erkrankungen bildet. Die Wirksamkeit von Ginkgo-Spezialextrakten bei der Demenz wurde in placebokontrollierten Doppelblindstudien nachgewiesen. Besonders hervorzuheben sind zwei mit dem Ginkgo-Spezialextrakt EGb 761® durchgefuhrte grosangelegte Studien an uber 500 Patienten mit leichter bis mittelgradiger Demenz bei Alzheimer-Krankheit und vaskularer Demenz, die den aktuellen Anforderungen zum Wirksamkeitsnachweis von Antidementiva entsprechen.

Pharmacokinetics and Bioavailability of a Ginkgo Biloba Extract

The aim of the present study was to assess the bioavailability of the main active ingredient in Ginkgo biloba extract, ginkgolid B. The study also focused on the pharmacokinetics of two different dosage regimens for orally administered Gingko biloba extract, 80 mg once daily and 40 mg twice daily for 7 days. Twelve healthy volunteers took part in the study. They were randomly assigned to one of the two treatment groups: 40 mg twice daily or 80 mg once daily, with an interval of 21 days between cycles. Statistical analysis was used to assess the main pharmacokinetic parameters. The results show that a dosage of 40 mg twice daily (every 12 hrs) is accompanied by a significantly longer half-life (t1/2) and mean residence time (MRT) than a single 80 mg dose, even though the latter causes a higher concentration peak (Cmax). The maximum concentration time (Tmax) is 2.3 hrs after administration in both treatments.

Anti-inflammatory antioxidants attenuate the expression of inducible nitric oxide synthase mediated by advanced glycation endproducts in murine microglia.

Advanced glycation endproducts (AGEs) accumulate on long-lived protein deposits including beta-amyloid plaques in Alzheimer's disease (AD). AGE-modified amyloid deposits contain oxidized and nitrated proteins as markers of a chronic neuroinflammatory condition and are surrounded by activated microglial and astroglial cells. We show in this study that AGEs increase nitric oxide production by induction of the inducible nitric oxide synthase (iNOS) on the mRNA and protein level in the murine microglial cell line N-11. Membrane permeable antioxidants including oestrogen derivatives (e.g. 17beta-oestradiol) thiol antioxidants (e.g. (R+)-alpha-lipoic acid) and Gingko biloba extract EGb 761, but not phosphodiesterase inhibitors such as propentophylline, prevent the up-regulation of AGE-induced iNOS expression and NO production. These results indicate that oxygen free radicals serve as second messengers in AGE-induced pro-inflammatory signal transduction pathways. As this pharmacological mechanism is not only relevant for Alzheimer's disease, but also for many chronic inflammatory conditions, such membrane-permeable antioxidants could be regarded not only as antioxidant, but also as potent therapeutic anti-inflammatory drugs.

Protective effect of Gingko biloba extract on doxorubicin induced cardiotoxicity in mice

Protective effect of Gingko biloba extract on doxorubicin induced cardiotoxicity in mice

Therapeutic efficacy of EGb761 (Gingko biloba extract) in a transgenic mouse model of amyotrophic lateral sclerosis.

EGb761 is a standardized extract of green Gingko biloba, which exerts protective effects against mitochondrial damage and oxidative stress. We examined whether oral administration of 0.022% or 0.045% EGb761 in the diet could impart neuroprotective effects in a transgenic mouse model (G93A) of amyotrophic lateral sclerosis (ALS). EGb761 significantly improved motor performance and survival, and protected against a loss of spinal-cord anterior motor horn neurons in male G93A mutant transgenic ALS mice, but not in littermate female mutant transgene mice. While EGb761 extended survival in littermate female G93A mice, significance was not reached. EGb761, however, significantly improved weight loss in both male and female transgenic ALS mice. These findings provide evidence for a gender-specific neuroprotective effect of EGb761 in a transgenic model of ALS and suggest that EGb761 may be a potential effective treatment in patients with ALS.

Oxidative injury in diseases of the central nervous system: focus on alzheimer’s disease

Alzheimer’s disease is one of the most challenging brain disorders and has profound medical and social consequences. It affects approximately 15 million persons worldwide, and many more family members and care givers are touched by the disease. The initiating molecular event(s) is not known, and its pathophysiology is highly complex. However, free radical injury appears to be a fundamental process contributing to the neuronal death seen in the disorder, and this hypothesis is supported by many (although not all) studies using surrogate markers of oxidative damage. In vitro and animal studies suggest that various compounds with antioxidant ability can attenuate the oxidative stress induced by beta-amyloid. Recently, clinical trials have demonstrated potential benefits from treatment with the antioxidants, vitamin E, selegiline, extract of Gingko biloba, and idebenone. Further studies are warranted to confirm these findings and explore the optimum timing and antioxidant combination of such treatments in this therapeutically frustrating disease.

Antioxidant compounds EGB-761 and BN-520 21 attenuate heat shock protein (HSP 72 kD) response, edema and cell changes following hyperthermic brain injury. An experimental study using immunohistochemistry in the rat.

Influence of the extract of Gingko biloba (EGB-761) and one of its constituent Gingkolide B (BN-52021) on hyperthermia induced cellular damage and heat shock protein (HSP 72kD) response was examined in a rat model. Rats subjected to 4h heat stress at 38 degrees C in a biological oxygen demand (BOD) incubator (relative humidity 50-55%, wind velocity 20-25cm/sec) resulted in profound edema and cell injury in many parts of the cerebral cortex, hippocampus, cerebellum, thalamus, hypothalamus and brain stem. Immunostaining of HSP 72 kD showed marked upregulation in the damaged and distorted neurons located within the edematous area. Pretreatment with EGB-761 (50mg/kg/day, p.o.) and BN-520 21 (2mg/kg, p.o.) per day for 5 days significantly reduced HSP expression and attenuated cell damage. Our results show that EGB-761 and its component Gingkolide B (BN-52021) has the capacity to reduce edema and cell injury following hyperthermia and this effect of the compound is somehow associated with a reduction in cellular stress response as evidenced with a reduction in HSP expression.

Facilitative Effects of EGb 761 on Olfactory Recognition in Young and Aged Rats

The aim of the present study was to evaluate the effects of chronic and acute treatment by the Gingko biloba extract, EGb 761 (IPSEN, France) on olfactory short-term memory in rats, using a spontaneous recognition procedure. The effects of a daily EGb 761 treatment (30 or 60 mg/kg) over a period of 30 days (Experiment 1) were evaluated in young male rats. Those of a single injection of EGb 761 were assessed either in young male rats at 60 or 120 mg/kg (Experiment 2) or in aged female rats at 60 mg/kg (Experiment 3). Results showed that, at the highest dose (60 mg/kg), chronic EGb 761 treatment enhanced the recognition performances, allowing recognition at delays at which control animals did not show any recognition. Acute treatment enhanced recognition at both doses tested. The results of the third experiment showed that EGb 761 had an overall enhancement effect on the performances of aged rats. In summary, our results provide evidence for a short-term memory enhancement effect of EGb 761 in both young and aged rats.

Protective and rescuing abilities of IGF-I and some putative free radical scavengers against beta-amyloid-inducing toxicity in neurons.

beta-Amyloid (A beta) peptides are most likely involved in the neurodegenerative process occurring in Alzheimer's Disease (AD) and are enriched in senile plaques. The mechanisms of A beta toxicity are not clear but likely involve free radicals and apoptosis. Much interest is currently aiming at developing effective approaches to block A beta toxicity in order to slow down disease progression. In that context, we are particularly interested in studying the role of insulin-like growth factors, particularly IGF-I and purported free radical scavengers including a Gingko biloba extract (EGb761) as blocker of A beta toxicity in a simple in vitro model of hippocampal primary cultures. We observed that both IGF-I and EGb761 are unique in that they are able not only to protect but even to rescue neurons against A beta toxicity. These results are summarized here and possible mechanisms of action are discussed to explain the protective properties of these two classes of agents.

Upregulation of neuronal nitric oxide synthase, edema and cell injury following heat stress are reduced by pretreatment with EGB-761 in the rat

Rats exposed to 4 h heat stress (HS) at 38°C exhibited marked upregulation of neuronal nitric oxide synthase (nNOS) in the brain regions exhibiting blood–brain barrier (BBB) breakdown, brain edema and cell damage. Pretreatment with an anti-oxidant compound EGB-761 (an extract of Gingko biloba) administered 50 mg/kg, per os for 5 days, significantly attenuated nNOS expression, BBB disruption, brain edema and cell injury. These results suggest that EGB-761 is neuroprotective in heat stress and this effect of the compound is related with the inhibition of NOS expression, not reported earlier.

Protective effects of Gingko biloba extract EGb 761 on myocardium of experimentally diabetic rats: I: Ultrastructural and biochemical investigation on cardiomyocytes

Chronic diabetes in man and animal models develops cardiomyopathic alterations which cannot be absolutely avoided by insuline therapy. Since diabetic damage is partly attributed to oxidative stress antioxidative treatment could be able to reduce the alterations. Aim of this study was to investigate the cardioprotective effects of EGb 761, known as a radical scavenger, against diabetic alterations in rats. The diabetes was induced by i.p. injection of 60 mg/kg body weight streptozotocin. Duration of diabetes was 4 months, the protected group received 100 mg/kg body weight EGb 761 with the drinking water over 3 months. Electron and light microscopic morphometry of left-ventricular samples revealed typical diabetic alterations consisting in decrease of volume fraction of myofibrils, SR and t-tubules and diminishing of cardiomyocyte diameter, increase of interstitial volume, mitochondrial size and volume fraction, and of vacuoles and of lipid drops. EGb treatment could gradually prevent the loss of myofibrils and reduction of myocyte diameter but has only little influence on interstitial and mitochondria volume. The diabetic-induced increase of lipid and vacuoles and the decrease of SR and t-tubules were not influenced. Biochemical parameters of oxidative stress: malondialdehyde (MDA) was only insignificantly altered by diabetes and EGb. The superoxide dismutase (SOD) activity was increased by diabetes and more increased by EGb treatment. Creatine kinase (CK) activity was diminished by diabetes but slightly increased by EGb. The polymerase chain reaction (PCR) of i-NOS was not different between the diabetic and protected diabetic groups.

Inhibitory effect of Ginkgo biloba extract on human platelet aggregation

The effect of pure flavonoids and Gingko biloba extract (GBE) on human platelet aggregation was investigated. Most of the flavonoids and vitamin E did not affect platelet aggregation in platelet-rich plasma (PRP); however some of these flavonoids inhibited platelet aggregation in gel-filtered platelets (GFP). GBE inhibited both ADP- and collagen-induced platelet aggregation in PRP, GFP and in whole blood in a dose-dependent manner. GBE at very low concentrations inhibited whole blood aggregation induced by ADP compared with those used for PRP or GFP. Flavonoids and GBE decreased the production of TxA 2 induced by collagen and ADP in PRP. However, no correlation was observed between the inhibition of platelet aggregation and the decrease of TxA 2 synthesis. GBE and flavonoids did not affect platelet membrane fluidity. However, the incubation of PRP with GBE increased cAMP levels in platelets, which is known to inhibit platelet activation by lowering intracellular Ca2+ levels. GBE is a mixture of many compounds, including flavonoids and gingkoglides, which affect metabolism of cAMP, TxA2 and Ca2+ in platelets. It is effective in the inhibition of platelet aggregation, both in PRP and whole blood, and thus may be potentially used as an effective oral anti-platelet therapeutic agent.