Re: Gingko Biloba in lieu of HBOT - PETER

[Guest guest]

Hi Irene,

Bill Walsh and the Pfieffer group were doing some studies on autistic

brains (death from drowning - which I believe is the number one killer

of ASD kids - parents beware!).

To date I have not seen this research published, so if anyone knows

Bill, please give him a prod! One of the supposed findings of the study

was significant evidence that certain regions of the ASD brain were

oxygen deficient. If this is the case it would in part explain some of

the responses we see for some kids from HBOT.

I wouldn't go so far as to say gingko biloba will achieve the same as

HBOT, however given gingko will improve blood flow in the brain there is

certainly a chance it would increase oxygenation in regions that were

deficient.

We are giving 75mg of Gingko, 3 times a day.

Some interesting recent studies on gingko.........

Kiewert C, Kumar V, Hildmann O, Hartmann J, Hillert M, Klein J (2008)

*Role of glycine receptors and glycine release for the neuroprotective

activity of bilobalide.* Brain Res. 1201 (), 143-50. PMID: 18325484

Bilobalide, a constituent of Ginkgo biloba, has neuroprotective

properties. Its mechanism of action is unknown but it was recently found

to interact with neuronal transmission mediated by glutamate,

gamma-aminobutyric acid (GABA) and glycine. The goal of this study was

to test the interaction of bilobalide with glycine in assays of

neuroprotection. In rat hippocampal slices exposed to

N-methyl-D-aspartate (NMDA), release of choline indicates breakdown of

membrane phospholipids. NMDA-induced choline release was almost

completely blocked in the presence of bilobalide (10 microM). Glycine

(10-100 microM) antagonized the inhibitory action of bilobalide in this

assay. In a second assay of excitotoxicity, we measured tissue water

content as an indicator of cytotoxic edema formation in hippocampal

slices which were exposed to NMDA. In this assay, edema formation was

suppressed by bilobalide but bilobalide's action was attenuated in the

presence of glycine and of D-serine (100 microM each). To investigate

bilobalide's interaction with glycine receptors directly, we determined

36chloride flux in rat cortico-hippocampal synaptoneurosomes. Glycine

(100 microM) was inactive in this assay indicating an absence of

functional glycine-A receptors in this preparation. [3H]Glycine was used

to assess binding at the glycine binding site of the NMDA receptor but

bilobalide was found to be inactive in this assay. Finally, [3H]glycine

release was monitored in hippocampal slices exposed to oxygen-glucose

deprivation. In this model, glycine release was induced by ischemia, an

effect that was strongly reduced by bilobalide. We conclude that

bilobalide does not interact with glycine receptors in neurochemical

assays but it significantly reduces the release of glycine under

ischemic conditions. This effect likely contributes to bilobalide's

neuroprotective effects in assays of excitotoxicity and ischemia.

Abdel-Kader R, Hauptmann S, Keil U, Scherping I, Leuner K, Eckert A,

Müller WE (2007) *Stabilization of mitochondrial function by Ginkgo

biloba extract (EGb 761)*. Pharmacol Res. 56 (6), 493-502. PMID: 17977008

A large body of data emphasizes the central role of mitochondrial

dysfunction during aging and as an early event in neurodegenerative

diseases. In this study we used PC12 cells and dissociated mice brain

cells, as well as isolated mitochondria to investigate the effects of

EGb 761 on mitochondrial functions. We mimicked mitochondrial

abnormalities during aging by using external factors (nitrosative

stress, serum deprivation and complexes inhibitors) consequently

altering mitochondrial processes, such as energy metabolism. As markers

for the function of mitochondria, ATP levels and mitochondrial membrane

potential were measured. EGb 761 alleviated mitochondrial functions in

vitro at concentrations as low as 0.01 mg/ml. Treating two different age

groups of mice with EGb 761 (100mg/kg body weight for 14 days) showed

beneficial effects on complexes I, IV and V of the mitochondrial

respiratory chain and against nitrosative stress. Interestingly, these

effects were only observed in the aged mice group, proving higher

efficacy of EGb 761 during aging. The single components of EGb 761

showed in both cell models protection of the mitochondrial membrane

potential indicating that a complementary action of the components is

responsible for the versatile actions of EGb 761.

Zhu L, Wu XM, Yang L, Du F, Qian ZM (2007) *Up-regulation of HIF-1alpha

expression induced by ginkgolides in hypoxic neurons.* Brain Res. 1166

(), 1-8. PMID: 17662966

Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular and

systemic oxygen homeostasis. Recently, we demonstrated that ginkgolides,

the main constituents of the non-flavone fraction of the standardized

Ginkgo biloba (Ginkgoaceae) extract EGb 761, have a significant

protective role against chemical and physical hypoxia-induced injury in

neurons and PC12 cells. Based on the findings and the function of HIF-1

as a master regulator of oxygen homeostasis, we speculate that the

protective role of ginkgolides might be mediated by HIF-1. In this

study, we therefore investigated the effects of ginkgolides on the

expression of HIF-1alpha, the cell viability and the lactate

dehydrogenase (LDH) release in the hypoxic cortical neuron. We

demonstrated that ginkgolides significantly increase the expression of

HIF-1alpha and the cell viability as well as decrease the release of LDH

in the hypoxic neuron. The findings suggested that the neuroprotective

role of ginkgolides against hypoxia-induced injury might be associated

with its role to up-regulate the expression of HIF-1alpha in the hypoxic

neurons.

DG, Cappai R, Barnham KJ (2007) *The redox chemistry of the

Alzheimer's disease amyloid beta peptide.* Biochim Biophys Acta. 1768

(8), 1976-90. PMID: 17433250

There is a growing body of evidence to support a role for oxidative

stress in Alzheimer's disease (AD), with increased levels of lipid

peroxidation, DNA and protein oxidation products (HNE, 8-HO-guanidine

and protein carbonyls respectively) in AD brains. The brain is a highly

oxidative organ consuming 20% of the body's oxygen despite accounting

for only 2% of the total body weight. With normal ageing the brain

accumulates metals ions such iron (Fe), zinc (Zn) and copper (Cu).

Consequently the brain is abundant in antioxidants to control and

prevent the detrimental formation of reactive oxygen species (ROS)

generated via Fenton chemistry involving redox active metal ion

reduction and activation of molecular oxygen. In AD there is an over

accumulation of the Amyloid beta peptide (Abeta), this is the result of

either an elevated generation from amyloid precursor protein (APP) or

inefficient clearance of Abeta from the brain. Abeta can efficiently

generate reactive oxygen species in the presence of the transition

metals copper and iron in vitro. Under oxidative conditions Abeta will

form stable dityrosine cross-linked dimers which are generated from free

radical attack on the tyrosine residue at position 10. There are

elevated levels of urea and SDS resistant stable linked Abeta oligomers

as well as dityrosine cross-linked peptides and proteins in AD brain.

Since soluble Abeta levels correlate best with the degree of

degeneration [C.A. McLean, R.A. Cherny, F.W. Fraser, S.J. Fuller, M.J.

, K. Beyreuther, A.I. Bush, C.L. Masters, Soluble pool of Abeta

amyloid as a determinant of severity of neurodegeneration in Alzheimer's

disease, Ann. Neurol. 46 (1999) 860-866] we suggest that the toxic Abeta

species corresponds to a soluble dityrosine cross-linked oligomer.

Current therapeutic strategies using metal chelators such as clioquinol

and desferrioxamine have had some success in altering the progression of

AD symptoms. Similarly, natural antioxidants curcumin and ginkgo extract

have modest but positive effects in slowing AD development. Therefore,

drugs that target the oxidative pathways in AD could have genuine

therapeutic efficacy.

Sener G, Sehirli O, Tozan A, Veliog(lu-Ovunç A, Gedik N, Omurtag GZ

(2007) *Ginkgo biloba extract protects against mercury(II)-induced

oxidative tissue damage in rats.* Food Chem Toxicol. 45 (4), 543-50.

PMID: 17267089

Mercury(II) is a highly toxic metal which induces oxidative stress in

the body. In this study we aimed to investigate the possible protective

effect of Ginkgo biloba (EGb), an antioxidant agent, against

experimental mercury toxicity in rat model. Following a single dose of

5mg/kg mercuric chloride (HgCl(2); Hg group) either saline or EGb

(150mg/kg) was administered for 5days. After decapitation of the rats

trunk blood was obtained and the tissue samples from the brain, lung,

liver, and kidney were taken for the determination of malondialdehyde

(MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and

collagen contents. Formation of reactive oxygen species in the tissue

samples was monitored by chemiluminescence (CL) technique. BUN,

creatinin, ALT, and AST levels and tumor necrosis factor-alpha

(TNF-alpha) and lactate dehydrogenase (LDH) activity were assayed in

serum samples. The results revealed that HgCl(2) induced oxidative

damage caused significant decrease in GSH level, significant increase in

MDA level, MPO activity and collagen content of the tissues. Treatment

of rats with EGb significantly increased the GSH level and decreased the

MDA level, MPO activity, and collagen contents. Similarly, serum ALT,

AST and BUN levels, as well as LDH and TNF-alpha, were elevated in the

Hg group as compared to control group. On the other hand, EGb treatment

reversed all these biochemical indices. Our results implicate that

mercury-induced oxidative damage in brain, lung, liver, and kidney

tissues protected by G. biloba extract, with its antioxidant effects.

Deng YK, Wei F, Zhang DG (2006) *[brain protective effects of ginkgo

biloba leaf extract (ginaton) in patients undergoing hypothermic

cardiopulmonary bypass]* Zhongguo Zhong Xi Yi Jie He Za Zhi. 26 (9),

795-8. PMID: 17058828

OBJECTIVE: To investigate the brain protective effects of Ginkgo biloba

leaf extract (ton) in patients who underwent hypothermic

cardiopulmonary bypass (CPB). METHODS: Sixty patients with rheumatic

heart disease of ASA grade II-III, who were scheduled for mitral valve

replacement with intravenous anaesthesia, were randomly assigned to two

groups, the ton group (30 patients) treated with ton 1 mg/kg by

intravenous dripping before open heart for CPB, and the control group

(30 patients) with normal saline instead. Blood was synchronously

collected from arteriae radialis and vena jugularis interna at 5 time

points, namely, before CPB (T1), nasopharyngeal temperature (lowered to

30-31 degrees C) stabilized stage (T2), nasopharyngeal temperature

restoration (36 degrees C) stage (T3), 30 min after CPB (T4) and 3 after

CPB (Ts) for determining blood gas, lactate acid concentration, activity

of superoxide dismutase (SOD) and malonaldehyde (MDA) content. And the

oxygen content in artery (CaO2) and jugular vein (CjvO2), the difference

of oxygen contents in arterial and jugular vein (Ca-jvO2), the cerebral

oxygen extraction ratio (ERO2) as well as the arteriojugular lactate

difference (ADVL) were calculated. RESULTS: After the beginning of CPB,

as compared with those in the control group, in the ton group, the

reduction of Ca-jvO2 and ERO2 was significantly higher (P & lt; 0.05 or P

& lt; 0.01) and the increase of lactate acid, ADVL and MDA were

significantly lower, and with a remarkably higher SOD activity (P & lt;

0.01). CONCLUSION: ton could improve cerebral oxygen supply, promote

SOD activity to inhibit production of free radicals in patients

undergoing CPB, and thus shows an evident protective effect in the brain.

Brunetti L, Orlando G, Menghini L, Ferrante C, Chiavaroli A, Vacca M

(2006) *Ginkgo biloba leaf extract reverses amyloid beta-peptide-induced

isoprostane production in rat brain in vitro.* Planta Med. 72 (14),

1296-9. PMID: 17022004

Isoprostanes are prostaglandin (PG) isomers generated from oxygen

radical peroxidation of arachidonic acid, which are reliable markers of

membrane oxidative damage. Aging is characterized by an imbalance

between the generation of reactive oxygen species and antioxidant

detoxification pathways. Ginkgo biloba leaf extract is reputed as a

neuroprotective antioxidant agent. We have tested the effects of a

Ginkgo biloba extract {containing 24.1 % flavonoids and 181 % terpene

lactones [bilobalide (0.542 %), ginkgolide A (0.570 %), ginkgolide B

(0.293 %), ginkgolide C (0.263 %), and ginkgolide J (0.138 %)]} on the

production of 8-iso-PGF2alpha from rat brain synaptosomes obtained from

young (3 months old) or aged (12 and 24 months old) rats, both in the

basal state and after oxidative stress induced by either hydrogen

peroxide or amyloid beta-peptide. Our findings show that Ginkgo biloba

extract pretreatment is able to completely reverse both basal and

hydrogen peroxide-stimulated isoprostane production (IC50 of 81.92

microM and 31.89 microM, respectively). Amyloid beta-peptide-induced

isoprostane production was also inhibited, both in young and aged rats,

to a level even lower than that in unstimulated synaptosomes. This

suggests that the oxygen radical scavenging properties of the Ginkgo

biloba extract are fully effective in young, as well as in old rats,

showing a greater inhibition of isoprostane production in the latter.

Mdzinarishvili A, Kiewert C, Kumar V, Hillert M, Klein J (2007)

*Bilobalide prevents ischemia-induced edema formation in vitro and in

vivo.* Neuroscience. 144 (1), 217-22. PMID: 17014966

EGb761, a standardized extract of Ginkgo biloba, has neuroprotective

properties in animal models of ischemia, an activity that is partially

attributed to its constituent, bilobalide. EGb761 has also been reported

to inhibit edema formation induced by toxins such as triethyltin. The

goal of this study was to test the activity of pure bilobalide to

prevent edema formation in models of ischemia. Oxygen-glucose

deprivation (OGD) in rat hippocampal slices served as a model of in

vitro-ischemia. OGD caused cellular edema formation as indicated by an

increase of slice water contents in 30 min. Bilobalide (1-10 microM)

reduced slice water contents in ischemic slices in a

concentration-dependent manner. As a model of in vivo-ischemia, we

performed middle cerebral artery occlusion (MCAO) in mice. Permanent

MCAO caused cell death and swelling of the ischemic hemisphere within 24

h. Pretreatment of the mice with bilobalide (10 mg/kg i.p.) reduced

infarct area by 43% (as judged by 2,3,5-triphenyl-tetrazolium chloride

(TTC) staining) and edema formation by 70% (as judged by hemispheric

enlargement). In parallel experiments, pretreatment with bilobalide also

reduced forebrain water contents in the ischemic hemisphere by 57%. As

an alternative model of brain edema formation, we used water

intoxication to increase brain water content; bilobalide, was, however,

inactive in this model. We conclude that bilobalide strongly and

specifically attenuates edema formation in models of brain ischemia in

vitro and in vivo. Bilobalide may be therapeutically effective in brain

edema which occurs secondarily to large hemispheric stroke and traumatic

brain injury in humans.

Ilhan A, Iraz M, Kamisli S, Yigitoglu R (2006)

*Pentylenetetrazol-induced kindling seizure attenuated by Ginkgo biloba

extract (EGb 761) in mice.* Prog Neuropsychopharmacol Biol Psychiatry.

30 (8), 1504-10. PMID: 16815619

Ginkgo biloba extract (EGb 761) has been used therapeutically for

centuries. It has attracted great attention as agents for improving

circulation, particularly cerebral circulation, which may lead to

improved mental function. Many researches hypothesized on the role of

the extract in the treatment of diseases involving free radicals and

oxidative damage. In the present study, anticonvulsant and antioxidant

effects of EGb 761 were investigated in pentylenetetrazol (PTZ)-kindled

mice. Valproic acid (VA), a major antiepileptic drug, was also tested

for comparison. EGb 761-treated mice displayed a significant attenuated

response to PTZ on the test day (day 26) compared with saline-treated

and VA-treated animals. Valproic acid significantly increased seizure

latency. Pretreatments with EGb 761 significantly protected against

PTZ-induced convulsive behaviors (seizure latency, seizure score). EGb

761 and VA significantly decreased PTZ-induced oxidative injury in brain

tissue. EGb 761 was found to be the most effective in preventing

PTZ-induced oxidative damage among both substances studied. The data

obtained support our speculation that neuroprotective action of EGb 761

may correlate with its ability to inhibit not only excessive reactive

oxygen species (ROS) formation but also seizure generation. Taken

together, the results of the present study show that the effect of EGb

761 on ROS production contributes to their neuroprotective action. It

might be concluded that the suppression of seizure-induced ROS

generation may be involved in the mechanism of action of antiepileptic

drugs.

iflow97 wrote:

>

> Hi . Recently, in a thread about HBOT, you wrote that you use

> gingko biloba to achieve the same affect as some parents report with

> HBOT. What type of dose/protocol do you use? When do you give it?

> And specifically how has it helped your daughter? I was curious to

> try it, as my spouse will not even consider HBOT as he feels it is too

> " kooky " and alternative, I think, and is not convinced it will help,

> even though I have a couple of friends who have used HBOT with great

> success with their kids.

>

> Irene

>

> Thanks. Irene

>

>