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Ginkgolides and Neuroprotective Effects

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Natural Products

Abstract

Ginkgo biloba is commonly known as maidenhair tree, available as a popular herbal supplementary in Asian, European, and American countries. Extensive in vitro, in vivo, and clinical studies demonstrated and confirmed the neuroprotective effects of a commercial standard ginkgo extract formulation known as EGb-761. Terpene trilactone comprises 5–7 % in EGb-761, collectively called as ginkgolides (G-A, G-B, G-C, G-J, G-K, G-L and G-M) and bilobides. Its clinical application gained popularity in herbal medicine due to treatment of early-stage Alzheimer’s disease, cerebrovascular disorders, PAF antagonism, and vestibular disorders. In addition, ginkgolides showed potent antioxidant activities via scavenging of reactive oxygen and nitrogen species. The physiological dosage of ginkgo extracts ranges between 120 and 240 mg/day in humans, and it is readily available as an over the counter product/supplementary product. According to the recent clinical findings, EGb-761 did not confirm its effect on long-term cognitive functioning, while it showed effectiveness and enhancement in shor-term cognitive and related activities. Ginkgo is generally well tolerated, but in a high dose, it can cause gastric upset, skin allergy, and increase the risk of bleeding in patients with risk factors (anticoagulant or antiplatelet treatment, surgery, etc.). Neuropharmacology, clinical issues of safety and usage are addressed in this book chapter.

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Abbreviations

5-HT:

5-Hydroxytryptamine

8-OHdG:

Hydroxyl-deoxyguanosine

ACh:

Acetylcholine

AD:

Alzheimer’s disease

ADDLs:

Amyloid beta-derived diffusible soluble ligands

APP:

Amyloid precursor protein

ATP:

Adenosine triphosphate

Aβ:

Amyloid beta

BALF:

Bronchoalveolar lavage fluid

BBB:

Blood–brain barrier

BN-52021:

Ginkgolide B

cAMP:

Cyclic adenosine monophosphate

D2 :

Dopaminergic receptor 2

DA:

Dopamine

DMSO:

Dimethylsulfoxide

DNA:

Deoxyribonucleic acid

DSC-MRI:

Dynamic susceptibility contrast-enhanced magnetic resonance imaging

EGb:

Ginkgo biloba extract

EGb-761:

Standard ginkgo extract

FFA:

Free fatty acid

G. biloba :

Ginkgo biloba

G-A:

Ginkgolide A

GABAA :

Gamma-amino butyric acid

G-B:

Ginkgolide B

G-C:

Ginkgolide C

G-J:

Ginkgolide J

G-K:

Ginkgolide K

G-L:

Ginkgolide L

G-M:

Ginkgolide M

GSH:

Glutathione

H2O2 :

Hydrogen peroxide

HO-1:

Heme oxygenase-1

i.p.:

Intraperitoneally

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

JNK:

c-jun N-terminal kinase

KYNA:

Kynurenic acid

LI-1370:

Standard Gingko extract

MAO:

Monoamine oxidase

MDA:

Malondialdeide

MGluR:

Metabotropic glutamate receptor

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

mRNA:

Messenger ribose nucleic acid

MS:

Multiple sclerosis

NCE:

Noncontact erection

NE:

Norepinephrine

NF-kappa B:

Nuclear factor kappa B

NFT:

Neurofibrillary tangles

NIDDM:

Non-insulin dependent diabetes mellitus

NMDA:

N-methyl d-aspartate receptor

NO:

Nitric oxide

P8A:

Standard Gingko extract

PAF:

Platelet activating factor

PBR:

Peripheral-type benzodiazepine receptor

PD:

Parkinson’s disease

PKA:

Protein kinase-A

PVN:

Paraventricular nucleus

RAGE:

Receptors for advanced glycation end products

RNA:

Ribose nucleic acid

RONS:

Reactive oxygen and nitrogen species

ROS:

Reactive oxygen species

USP:

United States Pharmacopeia

VF:

Ventricular fibrillation

VSMCs:

Vascular smooth muscle cells

VT:

Ventricular tachycardia

WHO:

World Health Organization

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Acknowledgements

I wish to thank CSU library for databases and Prof. Patrick Ball for valuable suggestion. I cannot finish without my family inspiration, including my parents, Saba and Ariba.

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  1. School of Biomedical Sciences and E.H. Graham Centre for Agricultural Innovation, Charles Sturt University, Wagga Wagga, New South Wales, 2678, Australia

    Syed Haris Omar (Faculty of Science)

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  1. Botany Department, M.L. Sukhadia University, Durga Nursery Road, Udaipur, 313001, Rajasthan, India

    Kishan Gopal Ramawat

  2. Institute of Vine and Wine Sciences, Biological-Active Plant Substances Study, University of Bordeaux, 210 Chemin de Leysotte CS 50008, Villenave d'Ornon, 33882, France

    Jean-Michel Mérillon

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Omar, S.H. (2013). Ginkgolides and Neuroprotective Effects. In: Ramawat, K., Mérillon, JM. (eds) Natural Products. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-22144-6_146

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