Ginkgo Leaf Extract Research Articles

Effect of Ginkgo biloba on brain volume after carotid artery occlusion in rats: a stereological and histopathological study.

This study investigated the effect of Ginkgo biloba (GB) on brain volume in cerebral ischemia induced by stopping carotid artery blood flow. Twenty-four adult male rats were divided into 4 groups of 6 rats each. No procedure was performed on the control group. Ischemia was applied to the rats in the ischemia and ischemia + GB groups by clamping the arteria carotis communis for 30 min. The rats in the ischemia + GB group were given 100 mg/kg drops (Tebokan Fort Drop, Abdi Ibrahim Ilaç Sanayi A.$., Turkey) containing dry GB leaf extract orally, every day for 14 days from the day of ischemia. In the sham group, surgical stress alone was applied by performing a skin incision. On the 14th day, brain tissues were extracted and evaluated stereologically and histopathologically. The only statistically significant difference was observed between the sham and control groups. This result may be interpreted as surgical stress, established by cutaneous incision, having an adverse effect on brain volume. Additionally, the absence of any difference in terms of brain volume following 30 min of ischemia between the ischemia and control groups suggests that a probable postischemic rise in brain volume disappears within 14 days.

Rapid Determination of Ginkgolic Acids in Ginkgo biloba Leaf Using Online Column Switching High-Performance Liquid Chromatography-Diode Array Detection and Confirmation by Liquid Chromatography-tandem Mass Spectrometry

In this study, an improved method for the quantitative analysis of ginkgolic acids (GAs) in Ginkgo biloba leaf extract was developed. The samples were extracted with a mixture of chloroform and 50 % ethanol, after which the chloroform extract was dried and reconstituted in methanol. GAs with 13:0, 15:1, and 17:1 in the extract were successfully separated within 40 min and determined with high throughput performance using an online column-switching HPLC method using an SP column C8 SG80 (4.6 × 150 mm, 5 µm) and a Cadenza 5CD C18 column (4.6 × 150 mm, 3 µm). The developed HPLC method was validated for Ginkgo biloba leaf extract. The validation parameters were specificity, linearity, precision, accuracy, and limits of detection and quantitation (LODs and LOQs, respectively). It was found that all of the calibration curves showed good linearity (r 2 > 0.9993) within the tested ranges. The LODs and LOQs were all lower than 0.04 µg/mL. The established method was found to be simple, rapid, and high throughput for the quantitative analysis of GAs in ten commercial Ginkgo biloba leaf extract and dietary supplements. The samples were also analyzed in LC-electrospray ionization (ESI) tandem mass spectrometry (MS/MS) - multiple-ion reaction monitoring (MRM) mode to confirm the identification results that were obtained by the column switching HPLC-DAD method. The developed method is considered to be suitable for the routine quality control and safety assurance of Ginkgo biloba leaf extract.

Phytochemicals and antioxidants in leaf extracts of Ginkgo biloba with reference to location, seasonal variation and solvent system

AimsTo determine the influence of location, seasonal variation and solvent system in production of phytochemicals and antioxidants from ginkgo leaves. MethodsTotal phenolic and flavonoid contents and antioxidant activity in ginkgo leaf extracts were estimated spectrophotometrically. Factorial analysis was performed to correlate the influence of location, season and solvent on production of phytochemicals and antioxidants. ResultsTotal phenolic and flavonoid contents as well as the antioxidants were estimated maximum in autumn. Among solvents, acetone/water extracts gave best results for phenolic and flavonoid contents while methanolic extracts were best for antioxidants. Phenolic content, the predominant indicator of phytochemicals, showed significant correlation with antioxidant activity. ConclusionFactorial analysis among location, season and solvent with respect to the phytochemicals and antioxidants, was found to be statistically significant. Presence of phytochemicals along with the protective feature in the form of antioxidants is indicative of the importance of this species in pharmacological industry.

Direct determination of underivatized amino acids from Ginkgo biloba leaves by using hydrophilic interaction ultra high performance liquid chromatography coupled with triple quadrupole mass spectrometry

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 amino acids. To determine the content of free amino acids, a reliable method has been established by using hydrophilic interaction ultra-HPLC coupled with ESI-MS. 20 free amino acids were simultaneously determined without derivatization in 12 min. The proposed method was fully validated in terms of linearity, sensitivity, repeatability, as well as recovery. Furthermore, the principal component analysis was applied to different G. biloba leaves collected in November (after fruit harvest season), which revealed that the samples from different production areas exhibited regional disparity in different clusters in accordance with their various hydrophilic interaction chromatograms coupled with mass profiles. 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 amino acids.

Systemic and cerebral exposure to and pharmacokinetics of flavonols and terpene lactones after dosing standardized Ginkgo biloba leaf extracts to rats via different routes of administration

Flavonols and terpene lactones are putatively responsible for the properties of Ginkgo biloba leaf extracts that relate to prevention and treatment of cardiovascular disease and cerebral insufficiency. Here, we characterized rat systemic and cerebral exposure to these ginkgo compounds after dosing, as well as the compounds' pharmacokinetics. Rats received single or multiple doses of ShuXueNing injection (prepared from GBE50 for intravenous administration) or GBE50 (a standardized extract of G. biloba leaves for oral administration). Brain delivery of the ginkgo compounds was assessed with microdialysis. Various rat samples were analysed using liquid chromatography/mass spectrometry. Slow terminal elimination features of the flavonols counterbalanced the influence of poor oral bioavailability on their systemic exposure levels, which also resulted in significant accumulation of the compounds in plasma during the subchronic treatment with ShuXueNing injection and GBE50. Unlike the flavonols, the terpene lactones had poor enterohepatic circulation due to their rapid renal excretion and unknown metabolism. The flavonol glycosides occurred as major forms in plasma after dosing with ShuXueNing injection, while the flavonol aglycone conjugates were predominant in plasma after dosing with GBE50. Cerebral exposure was negligible for the flavonols and low for the terpene lactones. Unlike the significant systemic exposure levels, the levels of cerebral exposure to the flavonols and terpene lactones are low. The elimination kinetic differences between the two classes of ginkgo compounds influence their relative systemic exposure levels. The information gained is relevant to linking ginkgo administration to the medicinal effects.

A novel substance with allelopathic activity in Ginkgo biloba

Ginkgo (Ginkgo biloba) is one of the oldest living tree species and has been widely used in traditional medicine. Leaf extracts of ginkgo, such as the standardized extract EGb761, have become one of the best-selling herbal products. However, no bioactive compound directed at plants has been reported in this species. Therefore, we investigated possible allelopathic activity and searched for allelopathically active substances in ginkgo leaves. An aqueous methanol leaf extract inhibited the growth of roots and shoots of garden cress (Lepidium sativum), lettuce (Lactuca sativa), timothy (Phleum pratense) and ryegrass (Lolium multiflorum) seedlings. The extract was purified by several chromatographic runs and an allelopathically active substance was isolated and identified by spectral analysis to be the novel compound 2-hydroxy-6-(10-hydroxypentadec-11-enyl)benzoic acid. The compound inhibited root and shoot growth of garden cress and timothy at concentrations greater than 3μM. The activity of the compound was 10- to 52-fold that of nonanoic acid. These results suggest that 2-hydroxy-6-(10-hydroxypentadec-11-enyl)benzoic acid may contribute to the allelopathic effect caused by ginkgo leaf extract. The compound may also have potential as a template for the development of new plant control substances.

Effects of Extracts of Ginkgo, Onion, and Celery on the Contractility of Isolated Rat Atria

The acute negative inotropic and chronotropic effects of the commercial extract of ginkgo leaf (Gingium®) and ethanolic extracts of onion bulbs and celery root on spontaneous and noradrenalin-stimulated contractions of the Wistar rat atria were investigated. All analyzed extracts exerted negative inotropic effects on the isolated rat atria. Among the tested extracts, the extract of ginkgo showed the strongest negative inotropic effects on rat atria, either in spontaneous or noradrenalin-induced contractions, being more potent than the onion and celery extracts, respectively.

Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo biloba extract for two years differ from spontaneous liver tumors in cancer gene mutations and genomic pathways.

Ginkgo biloba leaf extract (GBE) has been used for centuries in traditional Chinese medicine and today is used as an herbal supplement touted for improving neural function and for its antioxidant and anticancer effects. Herbal supplements have the potential for consumption over extended periods of time, with a general lack of sufficient data on long-term carcinogenicity risk. Exposure of B6C3F1 mice to GBE in the 2-year National Toxicology Program carcinogenicity bioassay resulted in a dose-dependent increase in hepatocellular tumors, including hepatocellular carcinoma (HCC). We show that the mechanism of hepatocarcinogenesis in GBE exposed animals is complex, involving alterations in H-ras and Ctnnb1 mutation spectra, WNT pathway dysregulation, and significantly altered gene expression associated with oncogenesis, HCC development, and chronic xenobiotic and oxidative stress compared to spontaneous HCC. This study provides a molecular context for the genetic changes associated with hepatocarcinogenesis in GBE exposed mice and illustrates the marked differences between these tumors and those arising spontaneously in the B6C3F1 mouse. The molecular changes observed in HCC from GBE-treated animals may be of relevance to those seen in human HCC and other types of cancer, and provide important data on potential mechanisms of GBE hepatocarcinogenesis.

Ginkgo biloba leaf extract improves the cognitive abilities of rats with D-galactose induced dementia

Standardized Ginkgo biloba leaf extract has been used in clinical trials for its beneficial effects on brain functions, particularly in dementia. Substantial experimental evidences indicated that Ginkgo biloba leaf extract (EGB) protected neuronal cells from a variety of insults. We investigated the effect of EGB on cognitive ability and protein kinase B (PKB) activity in hippocampal neuronal cells of dementia model rats. Rats received an intraperitoneal injection of D-galactose to induce dementia. Forty-eight Spraque-Dawley rats were randomly divided into six groups, including the control group, D-galactose group (Gal), low-dose EGB group (EGB-L), mid-dose EGB group (EGB-M), high-dose EGB group (EGB-H) and treatment group. The EGB-L, EGB-M and EGB-H groups were administered with EGB and D-galactose simultaneously. Y-maze, cresyl violet staining, TUNEL assays and immunohistochemistry staining were performed to detect learning and memory abilities, morphological changes in the hippocampus, neuronal apoptosis and the expressing level of phospho-PKB, respectively. Rats in the Gal group showed decreased abilities of learning and memory, and hippocampal pyramidal cell layer was damaged, while EGB administration improved learning and memory abilities. The Gal group exhibited many stained, condensed nuclei and micronuclei, either isolated or within the cytoplasm of cells (39.5±1.4). Apoptotic cells decreased in the groups of EGB-L (35.9±0.9), EGB-M (16.8±1.0) and EGB-H (10.1±0.8), and there were statistical significances compared with the Gal group. Immunoreactivity of phospho-PKB was localized diffusely throughout the cytosol of cells in all groups, while the immunoreactivity of the Gal group was weak. EGB significantly attenuated learning and memory impairment in a dose-dependent manner, while it could decrease the nmber of TUNEL-positive cells, and increase the activity of PKB. Our results demonstrated that EGB attenuated memory impairment and cell apoptosis in galactose-induced dementia model rats by activating PKB.

Anti-influenza virus activity of Ginkgo biloba leaf extracts

We examined the influence of Ginkgo biloba leaf extract (EGb) on the infectivity of influenza viruses in Madin-Darby canine kidney (MDCK) cells. Plaque assays demonstrated that multiplication of influenza viruses after adsorption to host cells was not affected in the agarose overlay containing EGb. However, when the viruses were treated with EGb before exposure to cells, their infectivity was markedly reduced. In contrast, the inhibitory effect was not observed when MDCK cells were treated with EGb before infection with influenza viruses. Hemagglutination inhibition assays revealed that EGb interferes with the interaction between influenza viruses and erythrocytes. The inhibitory effect of EGb was observed against influenza A (H1N1 and H3N2) and influenza B viruses. These results suggest that EGb contains an anti-influenza virus substance(s) that directly affects influenza virus particles and disrupts the function of hemagglutinin in adsorption to host cells. In addition to the finding of the anti-influenza virus activity of EGb, our results demonstrated interesting and important insights into the screening system for anti-influenza virus activity. In general, the plaque assay using drug-containing agarose overlays is one of the most reliable methods for detection of antiviral activity. However, our results showed that EGb had no effects either on the number of plaques or on their sizes in the plaque assay. These findings suggest the existence of inhibitory activities against the influenza virus that were overlooked in past studies.

포도재배를 위한 친환경 유기농자재의 엽면시비 효과

친환경 포도재배를 위하여 농가에서 용이하게 구입 및 제조가 가능한 유기농자재의 효과를 조사한 결과 본 연구에 사용한 농자재의 pH는 4.6이하였고, 아미노산액은 상대적으로 높은 비료성분을 함유하였다. 포도수확기 토양의 pH는 시험초기 (농자재 처리 전)와 비교할 때 감소하였고, EC와 유기물함량은 증가하였으며, 유효인산은 대조구 (관행처리)를 제외하고 증가하였다. 치환성 K는 은행잎추출액 처리구와 대조구, 치환성 Ca는 무처리구와 아미노산용액 처리구에서 감소하였고, 치환성 Mg는 모든 농자재 처리구에서 감소하였다. 포도 잎의 질소 (N) 함량은 chitosan과 아미노산액 처리구, P는 chitosan, 목초액 및 아미노산액 처리구, K는 chitosan과 아미노산액 처리구, Ca은 chitosan 처리구, Mg 함량은 아미노산액 처리구에서 가장 높았다. 포도 수량은 목초액 처리구와 대조구에서 <TEX>$1,581{\sim}1,583kg\;10^{-1}$</TEX>로 가장 많았고, 당도는 무처리구를 제외하고 같은 수준을 보였다. This study was conducted to investigate foliar treatment effects of organic agricultural materials for the environmentally-friendly cultivation of grape. The organic materials applied were chitosan, wood vinegar (pyroligneous acid), amino acid solution, and ginkgo leaf extract. All the organic materials were relatively strong acidic ranging lower than pH 4.6. when comparing with other organic materials, amino acid solution contained relatively high contents of selected plant nutrients, such as N, P, K, Ca, Mg, Cu, Fe, Mn, and Zn. As comparison of selected soil properties in the grape cultivating field, soil pH values were lower at the harvest stage than at the first stage of grape growing (before treating the organic materials), and electrical conductivity (EC) and soil organic matter content were higher at the harvest stage in the all plots. The concentrations of available phosphorus increased in most of the plot soils except in control plot (conventional treatment). The concentrations of exchangeable K decreased in the plot treated with ginkgo leaf extract and the control plot. The exchangeable Mg concentrations decreased in soils of all the plots. On the other hand, the concentrations of N and K in the grape leaves were higher with the treatments of chitosan and amino acid solution, P concentrations were higher with the applications of chitosan, wood vinegar and amino acid solution, and Ca and Mg concentrations were higher with chitosan and amino acid solution treatments, respectively, than with others. The yields of grape were higher, <TEX>$1,581{\sim}1,583kg\;10a^{-1}$</TEX>, in the control and wood vinegar treatment plots than others. Sugar contents of grape were not different among all the plots.

A simple HPLC method for detecting adulteration of ginkgo extracts with flavonol aglycones

We have shown that current USP and EP/BP methods for quantifying ginkgo flavonoids cannot detect adulteration with free flavonol aglycones. We propose a simple modification of these methods, based on the measurement of aglycones preand post-hydrolysis, to allow for the accurate estimation of the amounts of both glycosides and free aglycones in ginkgo leaf extracts. The presence of genistein in products with high levels of free aglycones is consistent with adulteration with Sophora japonica L., which contains genistein, quercetin and kaempferol glycosides [5], and has previously been reported as a suspected adulterant of ginkgo extracts [4]. Pharmacopoeial tests for ginkgo extracts should be improved in order that they might effectively ensure the authenticity, efficacy and safety of this important phytomedicine.

Ginkgo Biloba extract modulates proteasomal activity and reduces polyglutamine aggregation in vitro and in vivo

The Ginkgo biloba leaf extract EGb 761 has a wide range of neuroprotective activities and has been proposed as a potential neuroprotectant for several neurodegenerative disorders. Our present study describes a novel modulatory effect of EGb 761 in the maintenance of protein homeostasis in cell culture and C. elegans models of polyglutamine protein aggregation of mutated huntingtin (mhtt). Analyzing proteasomal activity, which is reduced in mhtt expressing cells, we find that EGb 761 treatment leads to an increase of activity independently of the extent of mhtt aggregation. In addition, EGb 761 treatment is shown (i) to reduce the size of mhtt aggregates and (ii) to increase the soluble cytosolic mhtt fraction. Strengthening these observations, we find that EGb 761 alleviates motility defects in C. elegans bearing polyglutamine aggregates and reduces their aggregation tendency. These findings suggest that EGb 761 treatment can have modulatory properties on mhtt aggregation in vitro and in vivo, presumably by enhancing proteasomal activity.

Antimicrobial Potential of Leaf Extracts of Ginkgo biloba L., Growing in Uttarakhand, India

Antimicrobial potential and minimum inhibitory concentration (MIC) of leaf extracts of Ginkgo biloba has been determined through plate assays. Species of Gram +ve, Gram −ve bacteria, actinomycetes (5 each), and fungi (4) were used as test organisms. Leaf extracts were prepared in different organic solvents (methanol, ethyl acetate, and n-butanol) and distilled water. Leaf extracts exhibited antimicrobial activity against all the 3 groups of microorganisms, bacteria being most sensitive, followed by actinomycetes and fungi. While methanolic extract gave best results amongst the organic solvents used, aqueous leaf extract did not show any activity. The reference substances, ginkgolide A, ginkgolide B, and bilobalide also exhibited some antimicrobial activity. Values obtained for MIC were found to be in line with the antimicrobial activity.

Ginkgo biloba - effekt, bivirkninger og interaksjoner

Ginkgo is probably one of the most widely used medicinal herbs in Europe. In Norway products of ginkgo leaf extract have been approved by the Norwegian Medicines Agency for the following indication: traditionally used to improve blood circulation, for example, cold hands and feet. Elsewhere, ginkgo is used for cognitive impairment and dementia, acute ischaemic stroke, intermittent claudication, tinnitus and age-related macular degeneration. Evidence of the efficacy of ginkgo for these indications has previously been studied by the Cochrane Collaboration. In this update we have repeated all the searches in Medline and EMBASE exactly as described in the five Cochrane Systematic Reviews (last search date: 16.02.2011). We identified two new randomised and placebo-controlled studies on cognitive impairment and dementia (3187 patients) and one study on acute ischaemic stroke (3069 patients). The results of these studies gave no reason to change the conclusions of earlier reviews by the Cochrane Collaboration. There is no convincing evidence that ginkgo is effective for cognitive impairment or dementia, acute ischaemic stroke, intermittent claudication or tinnitus. There is still a lack of conclusive evidence for the effect on age-related macular degeneration. Ginkgo leaf extract appears to be safe to use, with no excess side effects compared with placebo. It can cause some minor side effects such as stomach upset, headache, dizziness, constipation, forceful heartbeat, and allergic skin reactions. There is some concern that ginkgo leaf extract might increase the risk of bruising and bleeding, and interactions with anticoagulants/antiplatelet drugs cannot be ruled out. As a general precaution, it is recommended withdrawing ginkgo two weeks before elective surgery.

Use of combinations of gum arabic, maltodextrin and soybean protein to microencapsulate ginkgo leaf extracts and its inhibitory effect on skeletal muscle injury

Abstract In this study, ethanol extracts of ginkgo leaf were microencapsulated with maltodextrin, gum arabic or a soluble soybean protein by spray-drying. The results indicated that, for the microcapsules, the encapsulation efficiency of 81.3% was achieved when air inlet temperature was 181 °C. The oxidation of ginkgo leaf polyphenol under the conditions was retarded by its microencapsulation with gum arabic, maltodextrin or the soybean protein. Thus, microencapsulation of ethanol extracts of ginkgo leaf significantly improved its oxidative stability. Pharmacological experiment showed that ethanol extracts of ginkgo leaf could enhance ALP activities and collagen I in mouse osteoblast MC3T3-E1 cells. Rabbits pretreated with microcapsules of ethanol extracts of ginkgo leaf significantly inhibited ischemia/reperfusion-induced oxidative injury in rabbits’ skeletal muscle.

The effect of extract of ginkgo biloba leaf during the formation of HBV-related hepatocellular carcinoma

To investigate the effect of extract of ginkgo biloba leaf (EGb) during the formation of HBV-related hepatocellular carcinoma (HCC). 99 HBV transgenic mice were randomly divided into control group, high-dose group, low-dose group. High-dose group and low-dose group were intraperitoneal injected 35mg/(kg x d) and 17.5 mg/(kg x d) of the shuxuening injection. Control group without special treatment. The serological markers and immunohistochemical markers in liver tissue will be done at the first 12 months and 18 months. (1) HBV transgenic mice can be found HCC at the 18 months. The incidence of HCC was lower in high-dose group and low-dose group, there was statistically different among the three groups. (2) The semi-quantitative scoring of liver HBx expression was highest in the control group at the 12 months. The semi-quantitative scoring of liver HBx, p53 and Bcl-2 expression was highest in the control group at the 18 months. They all appeared statistically different among the three groups. (3) Spearman correlation analysis showed that HCC incidence and liver tissue HBx, p53, Bcl-2 expression was a certain degree of positive correlation, r was 0.536, 0.487 and 0.403, P < 0.05. EGb can reduced the incidence of the HCC with HBV transgenic mice. The reason may be that the EGb can reduce liver HBx, p53, Bcl-2 protein expression in the HBV transgenic mice.

Effect of Ginkgo leaf extract and dipyridamole injection combined with methylcobalamin treatment to heart rate variability of patients with diabetic cardiac autonomic neuropathy

Objective To evaluate the effect of Ginkgo leaf extract and dipyridamole injection combined with methylcobalamin treatment to heart rate variability of patients with diabetic cardiac autonomic neuropathy. Methods 66 patients of diabetic cardiac autonomic neuropathy were randomly divided into treatment group and control group, 33 cases of each group, the treatment group were treated with normal saline 250 ml plus Ginkgo leaf extract and dipyridamole injection 20 ml intravenous infusion,and normal saline 10 ml plus methylcobalarnmin 0.5 mg intravenousry once a day,with a total course of treatment for3 weeks. Control group was injected with vitamin B1 and vitamin B12, once a day. 24-hour ambulatory ECG testing was used to collect heart rate variability index of all patients before and after treatment, changes in these indicators were also observed and analyzed. Results After treatment, the heart rate variability index was significantly increased compared with before treatment, and autonomic neuropathy symptoms improved, compared with the control group, the differences was statically significant (P＜0.05). Conclusion Ginkgo leaf extract and dipyridamole injection combined with methylcobalamin treatment of diabetic cardiac autonomic neuropathy has significant effect and can improve heart rate variability. Key words: Ginkgo leaf extract and dipyridamole; Methylcobalamin; Diabetes; Cardiac autonomic neuropathy; Heart rate variability

Can Plant-Made Copper Chaperones Heal Early Alzheimer’s Disease?

AbstractCommercially available medicinal plant extracts such as Ginkgo biloba leaf extract show no consistent pattern of clinical benefit for people with dementia or cognitive impairment, and have been suggested to be toxic to cells at higher doses. However, medicinal plants may contain other more efficient bioactive molecules apart from the well-known flavonoids and terpenoids. Therapeutic recombinant proteins, plant-made copper chaperone for superoxide dismutase (CCS) derived from Ginkgo biloba leaves, may establish and maintain physiologic Cu levels through restoration and modulation of biometal metabolism in organ systems of younger Alzheimer patients (&gt; 50 years). Medications developed from plant-made copper chaperone proteins may delay progression during early disease stages or even be a basis for a possible causal treatment of preclinical stages of Alzheimer’s disease by preventing formation of A β plaques in the brain, a major putative factor involved in Alzheimer’s disease pathogenesis.

Can Plant-Made Copper Chaperones Heal Early Alzheimer’s Disease?

Commercially available medicinal plant extracts such as Ginkgo biloba leaf extract show no consistent pattern of clinical benefit for people with dementia or cognitive impairment, and have been suggested to be toxic to cells at higher doses. However, medicinal plants may contain other more efficient bioactive molecules apart from the well-known flavonoids and terpenoids. Therapeutic recombinant proteins, plant-made copper chaperone for superoxide dismutase (CCS) derived from Ginkgo biloba leaves, may establish and maintain physiologic Cu levels through restoration and modulation of biometal metabolism in organ systems of younger Alzheimer patients (> 50 years). Medications developed from plant-made copper chaperone proteins may delay progression during early disease stages or even be a basis for a possible causal treatment of preclinical stages of Alzheimer’s disease by preventing formation of A β plaques in the brain, a major putative factor involved in Alzheimer’s disease pathogenesis.