6. (−)-Bilobalide from Ginkgo biloba leaves ≥93% (HPLC) (−)-Epicatechin ≥98% (HPLC), from green tea (−)-Epicatechin purum, ≥95.0% (HPLC) (−)-Epigallocatechin ≥95%
(HPLC), from green tea (−)-Epigallocatechin analytical standard (−)-Gallocatechin ≥98% (HPLC) (−)-Riboflavin ≥98% (−)-Riboflavin BioReagent, suitable for cell culture,
insect cell culture tested, ≥99% (+)-Catechin hydrate ≥98% (HPLC), powder (+)-γ-Tocopherol ≥96% (HPLC) 1-Docosanol 98% 1-Docosanol purum, ≥97.0% (GC) 1-
Heptacosanol ≥98% 1-Hexacosanol ≥97% (capillary GC) 1-Hexacosanol synthetic, ≥97.0% (GC) 1-Octacosanol ≥99% (GC) 2-Isopropylphenol 98% 3,4-Dihydroxybenzoic
acid purum, ≥97.0% (T) 4-Hydroxybenzoic acid ≥99% D-(−)-Fructose ≥99% D-(−)-Fructose SAJ special grade, ≥98.0% D-(+)-Xylose ≥99% D-(+)-Xylose SAJ special grade,
98.0-101.0% D-(−)-Quinic acid 98% D-(−)-Quinic acid purum, ≥98.0% (T) D-(+)-Galactose ≥99% D-(+)-Galactose BioUltra, ≥99.5% (sum of enantiomers, HPLC) D-(+)-
Galactose anhydrous, cell culture tested, insect cell culture tested, powder D-(+)-Glucose ≥99.5% (GC) D-(+)-Glucose BioUltra, anhydrous, ≥99.5% (sum of enantiomers,
HPLC) D-(+)-Mannose BioUltra, ≥99.5% (sum of enantiomers, HPLC) D-(+)-Mannose from wood, ≥99% D-(+)-Raffinose pentahydrate ≥98.0% D-(+)-Raffinose pentahydrate
for microbiology, ≥99.0% D-(+)-Raffinose pentahydrate powder, BioReagent, suitable for cell culture D-Pantothenic acid hemicalcium salt cell culture tested, insect cell
culture tested, plant cell culture tested D-Pinitol 95% L-(−)-Malic acid 95-100% (enzymatic) L-(−)-Malic acid 97%, optical purity ee: 99% (GLC) L-(−)-Malic acid SAJ special
grade, ≥99.0% L-(−)-Malic acid puriss., ≥99.5% (T) L-(+)-Arabinose ≥99% L-(+)-Arabinose 98% L-(+)-Lactic acid ~98% L-Alanine ≥98% (TLC) L-Alanine ≥99.0% (NT) L-
Alanine SAJ special grade, ≥99.0% L-Arginine SAJ special grade, ≥98.0% L-Arginine meets EP, USP testing specifications, BioXtra, cell culture tested, 98.5-101.0%, from non-
animal source L-Arginine reagent grade, ≥98% (TLC), powder L-Ascorbic acid ≥99.0% L-Ascorbic acid 99% L-Ascorbic acid JIS special grade, ≥99.0% L-Ascorbic acid
puriss. p.a., ≥99.0% (RT) L-Ascorbic acid reagent grade, crystalline, ~325 mesh L-Asparagine monohydrate ≥99% (TLC) L-Aspartic acid ≥98% L-Aspartic acid ≥99.0%
(T) L-Aspartic acid SAJ special grade, ≥99.0% L-Aspartic acid reagent grade, ≥98% (TLC) L-Cysteine 97% L-Cysteine SAJ special grade, ≥98.5% L-Cysteine hydrochloride
BioReagent, cell culture tested, anhydrous, from non-animal source, ≥98.0% L-Cysteine hydrochloride monohydrate JIS special grade, ≥99.0% L-Cysteine hydrochloride
monohydrate from non-animal source, cell culture tested, meets EP, USP testing specifications L-Cystine ≥99.0% (T) L-Cystine SAJ special grade, ≥99.0% L-Cystine
crystalline L-Glutamic acid JIS special grade, ≥99.0% L-Glutamic acid ReagentPlus®, ≥99% (TLC) L-Histidine BioUltra, ≥99.5% (NT) L-Histidine ReagentPlus®, ≥99% (TLC) L-
Histidine SAJ special grade, ≥98.5% L-Histidine cell culture tested, meets EP, USP testing specifications, from non-animal source L-Homoserine L-Homoserine ≥98.0%
(NT) L-Isoleucine BioUltra, ≥99.5% (NT) L-Isoleucine SAJ special grade, ≥99.0% L-Isoleucine meets EP, JP, USP testing specifications, BioXtra, cell culture tested, 98.5-101.0%,
from non-animal source L-Isoleucine reagent grade, ≥98% (TLC) L-Leucine SAJ special grade, ≥99.0% L-Leucine reagent grade, ≥98% (TLC) L-Lysine ≥98% (TLC) L-Lysine
SAJ special grade, ≥98.0% L-Lysine purum, crystallized, ≥98.0% (NT) L-Methionine BioXtra, meets EP, JP, USP testing specifications, cell culture tested, 99.0-101.0%, from
non-animal source L-Methionine SAJ special grade, ≥98.5% L-Methionine reagent grade, ≥98% (TLC) L-Phenylalanine ≥99.0% (NT) L-Phenylalanine BioXtra, meets EP, JP,
USP testing specifications, suitable for cell culture, 98.5-101.0%, from non-animal source L-Phenylalanine SAJ special grade, ≥99.0% L-Phenylalanine reagent grade,
≥98% L-Proline ≥99.0% (NT) L-Proline ReagentPlus®, ≥99% (TLC) L-Proline SAJ special grade, ≥99.0% L-Proline meets EP, USP testing specifications, cell culture tested, from
non-animal source L-Serine ≥99.0% (NT) L-Serine ReagentPlus®, ≥99% (TLC) L-Threonine BioXtra, cell culture tested, meets EP, JP, USP testing specifications, from non-
animal source, 99.0-101.0% L-Threonine reagent grade, ≥98% (TLC) L-Tryptophan BioUltra, ≥99.5% (NT) L-Tryptophan meets EP, JP, USP testing specifications, BioXtra, cell
culture tested, ≥99.0%, from non-animal source L-Tryptophan reagent grade, ≥98% (TLC) L-Tyrosine BioXtra, cell culture tested, meets EP, USP testing specifications,
≥99.0%, from non-animal source L-Tyrosine SAJ special grade, ≥99.0% L-Valine SAJ special grade, ≥98.5% L-Valine meets EP, JP, USP testing specifications, cell culture
tested, 98.5-101.0%, from non-animal source L-Valine reagent grade, ≥98% (TLC) Acacetin ≥97.0% (HPLC) Acenaphthene 99% Acetic acid ≥99.7% Acetic acid
≥99.7% Acetic acid ≥99.7%, SAJ super special grade Acetic acid 99.5-100.0% Acetic acid JIS special grade, ≥99.7% Acetic acid ReagentPlus®, ≥99% Acetic acid SAJ first
grade, ≥99.0% Acetic acid purum, ≥99.0% (T) Amentoflavone ≥99.0% (HPLC) Apigenin ≥95.0% (HPLC) Apigenin 95% Apigenin ~95% (TLC), from parsley, powder Arachidic
acid ≥99% Arachidic acid puriss., synthetic, ≥99.0% (GC) Behenic acid 99% Behenic acid puriss., ≥99.0% (GC) Benzoic acid ReagentPlus®, 99% Benzoic acid SAJ first grade,
≥99.5% Benzoic acid SAJ special grade, ≥99.5% Benzoic acid purum, ≥99.0% (T) Butyric acid ≥99% Butyric acid SAJ special grade, ≥99.5% Campesterol ~65%,
crystalline Choline chloride BioReagent, suitable for cell culture, suitable for insect cell culture, ≥98%, powder Citric acid ≥99% Citric acid 99% Citric acid BioUltra,
anhydrous, ≥99.5% (T) Citric acid SAJ first grade, ≥99.5% Citric acid cell culture tested, anhydrous Dodecanoic acid ≥99% (GC/titration) Ergosterol ≥95.0% (HPLC) Formic
acid JIS special grade, ≥98.0% Formic acid SAJ first grade, 88.0-89.5% Formic acid puriss. p.a., ~98% (T) Formic acid reagent grade, ≥95% Ginkgolide A purum, analytical
standard, ≥98.0% (GC) Ginkgolide C purum, analytical standard, ≥96.0% (GC) Glycine ReagentPlus®, ≥99% (TLC) Glycine SAJ special grade, ≥99.0% Heptacosane purum,
≥98.0% (GC) Hexanoic acid ≥99.5% Hexanoic acid purum, ≥98.0% (GC) Isorhamnetin ≥95.0% (HPLC) Kaempferol ≥97.0% (HPLC) Linalool oxide purum, mixture of isomers,
≥97.0% (GC) Linoleic acid ≥99% Linolenic acid ≥99% Luteolin ≥98% (TLC), powder Myristic acid Sigma Grade, ≥99% Nicotinic acid ≥98% Nicotinic acid ≥99.5%
(HPLC) Nicotinic acid SAJ special grade, ≥99.5% Nicotinic acid cell culture tested, insect cell culture tested, ~98% Nonacosane 99% Octanoic acid ≥96.0% Octanoic acid
≥98% Octanoic acid ≥99% Oleic acid ≥99% (GC) Oleic acid SAJ first grade, ≥70.0% Oleic acid suitable for cell culture, BioReagent Oxalic acid SAJ first grade,
≥97.0% Oxalic acid puriss. p.a., anhydrous, ≥99.0% (RT) Palmitic acid ≥99% Palmitic acid SAJ first grade, ≥95.0% Palmitoleic acid ≥99% (capillary GC), liquid Procyanidin
B1 analytical standard Procyanidin B2 analytical standard Propionic acid 99.5% Propionic acid SAJ first grade, ≥98.0% Propionic acid insect cell culture tested,
~99% Propionic acid puriss. p.a., ≥99.5% (GC) Propionic acid reagent grade, ~99% Pyrocatechol ≥99%, powder Pyrocatechol ReagentPlus®, ≥99% Pyruvic acid
98% Quercetin 3-β-D-glucoside ≥90% (HPLC) Rutin hydrate ≥94% (HPLC), powder Rutin trihydrate purum, ≥95.0% (HPLC) Sesamin ≥95%, crystalline Shikimic acid
≥99% Sodium pyruvate ≥99%, powder, cell culture tested, insect cell culture tested Sodium pyruvate SAJ special grade, ≥95.0% Sodium succinate dibasic hexahydrate SAJ
first grade, 98.0-102.0% Sodium succinate dibasic hexahydrate cell culture tested, insect cell culture tested Stearic acid CP Stearic acid Grade I, ≥98.5% (capillary
GC) Stearic acid SAJ first grade, ≥90.0% Stearic acid SAJ first grade, ≥90.0%, powder Stearic acid SAJ special grade, ≥95.0% Stearic acid puriss., ≥98.5% (GC) Stigmasterol
~95% Succinic acid ReagentPlus®, ≥99.0% Succinic acid SAJ first grade, ≥99.0% Succinic acid SAJ special grade, ≥99.5% Succinic acid purum p.a., ≥99.0% (T) Sucrose
≥99.5% (GC) Sucrose JIS special grade Sucrose SAJ first grade Sucrose reagent grade Tannic acid SAJ first grade Tannic acid Source: Chinese natural gall nuts (from
grass) Thiamine hydrochloride BioReagent, suitable for insect cell culture, suitable for cell culture Thiamine hydrochloride SAJ special grade, ≥98.5% Thymol
≥99.5% Thymol SAJ first grade, ≥98.0% Tricosane 99% Tricosane puriss., ≥99.0% (GC) Valeric acid ≥99% Valeric acid puriss., ≥99.0% (GC) Vanillic acid 97% Vanillic acid
purum, ≥97.0% (HPLC) Xanthophyll from marigold Zeaxanthin purum p.a., ≥95.0% (TLC) α-Ionone technical grade, 90% β-Carotene Type II, synthetic, ≥95% (HPLC),
crystalline β-Carotene purum, ≥97.0% (UV) β-Eudesmol ≥90% (HPLC) β-Ionone 96% β-Sitosterol synthetic, ≥95% γ-Aminobutyric acid ≥99% p-Coumaric acid ≥98.0%
(HPLC) p-Coumaric acid purum, ≥98.0% (HPLC) p-Cymene 99% … etc
Merck
7. EGb 761: a standardized Ginkgo b. extract
Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals, T.A. van Beek, P. Montoro / J. Chromatogr. A 1216 (2009)
2002–2032
8. Extract is made from Ginkgo leaves
EGb 761:
◦ 5% to 7 % Terpenlactones
◦ 22% to 27 % Flavonglykosides
◦ useful subst. (Ginkgolides, Terpenlactones,…)
◦ toxic ginkgolic acid (>5ppm),...
Standardized Extracts for
Dementia treatment:
◦ EGb 761, LI 1370
9. traditional
◦ asthma, bronchitis, fatigue, and tinnitus
recent:
◦ improve memory; treat / prevent Alzheimer’s
disease
◦ Dementia
◦ decrease intermittent claudication (lame, limping,
leg pain b/c o. narr. arteries);
sexual dysfunction
multiple sclerosis
Other health conditions
10. National Toxicology Program: NTP
◦ Looked into- and carried out own studies: “NTP
studies” ( http://ntp-server.niehs.nih.gov/ )
best researched
◦ dementia, memory impairment,
intermittent claudication, tinnitus
Egb 761 ineffective vs
◦ Dementia, Alzheimer's
◦ slowing cognitive decline
◦ lowering blood pressure
◦ reducing hypertension
NTP Flyer (June/2010)
◦ No clear benefits of Egb 761 thus far!
◦ www.niehs.nih.gov/health/assets/docs_f_o/ntp_gingko.pdf
12. Flavonoids (- glycosides)
terpenoids (ginkgolide, bilobalide)
14C markers in Ginkgolide =terpenoid
origin(polycyclic Hydroxylactone)
Fig 2. Structural formulas of ginkgolides and biolbalide
Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals, T.A. van Beek, P. Montoro / J. Chromatogr. A 1216 (2009)
2002–2032
13. Color Atlas of Biochemistry, 3rd Edition, Jan Koolman et al, Thieme 2005
14.
15. PAF: Platelet-Activating-Factor
Ginkgolide B is a strong PAF antagonist
◦ Potent & selective
possible bleeding complications in accidents?
Mostly in-vitro studies
No drug development as of 2010
May inhibit prion neurotoxicity
16. Bleeding and Intracerebral hemorrhage
Vascular wall decreases
Potentiates Anticoagulants (e.g. Aspirin)
Definitive
PAF antagonist
Color Atlas of Pharmacology, 3rd edition, Albrecht Ziegler, et al, Thieme
17. MPN short for 4- methoxypyridoxine
In Ginkgo biloba Seeds
Low amount in leaves
Toxic Convulsant
◦ Inhibits Glutamic Acid Decarboxylase
◦ GAD decarboxylates glutamate to GABA + CO2
ID: H2O extract, IPC (C18, Fluores., [fmol])
MPN a competitive inhibitor of glutamate decarboxylase GAD and other enzymes
18. In many fruits and
vegetables
Human health effects?
Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals, T.A. van Beek, P. Montoro / J. Chromatogr. A 1216 (2009)
2002–2032
20. Human antitumor effects?
Present in many plants, incl. Ginkgo leaves
Sugar carriers in protein glycosylation
linearly linked 10–30 isoprene units
Common moiety: acetate, ω-units, two trans
isoprene units and 10 to 20 cis-isoprene
units terminal cis-isoprene unit w. ester
group
Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals, T.A. van Beek, P. Montoro / J. Chromatogr. A 1216 (2009)
2002–2032
21. Cytotoxic
Toxicity
◦ in HET (Hen‘s egg test) studies
◦ in vivo studies
Ginkgo presence
◦ Leaves 0.5%-5%, sarcotesta 5-10%, nut ~0.02%
ginkgolic acids:
Health effects: antitumour, antidepressant,
antistressant, antiamnestic (inh. prolyl
endopeptidase), antifungal, antifeedant,
acaricidal, molluscicidal, insecticidal
Side effects: contact allergenic, cytotoxic,
embryotoxic , immunotoxic, mutagenic,
probably neurotoxic!
