Protective effects of

ginseng on neurological
disorders
Wei-Yi Ong1,2*, Tahira Farooqui3, Hwee-Ling Koh4, Akhlaq
A. Farooqui3 and Eng-Ang Ling1

Introduction
Ginseng
(Order: Apiales, Family: Araliaceae, Genus: Panax)
Roots, stems, and leaves
Used as traditional medicine
>2000yrs

Panax ginseng Korea, China

Panax quiquefolium L USA,
Canada
Panax notoginseng China

Adaptogenic, Restorative
Immunimodulatory
Anti anxiety, Antidepressant
Anti-inflamatory
Anti-aging, Anticancer
Cognition enhancement
Anti-stress, Antioxidant

Introduction
Bioactive ingredients =
ginsenosides
>60 ginsenosides:
Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, Rg2 Rg3
Polysaccharides, fatty acids, oligopeptides, polyacetylenic alcohols

Purpose
Purpose
discuss
discuss the
the effects
effects of
of ginseng
ginseng on
on the
the normal
normal brain
brain
its
its protective
protective effects
effects in
in neurological
neurological disorders
disorders
(Alzheimersdisease ,major
,major depression,
(Alzheimersdisease
depression, stroke,
stroke, Parkinsons
Parkinsons disease
disease
multiplesclerosis)
multiplesclerosis)

Intestinal Metabolism and

Actions of Ginseng

The most commonly studied ginsenosides are Rb1,

Rg1, Rg3, Re, and Rd.

Intact ginsenosides absorbed only from intestines

Metabolized:
In stomach acid hydrolisis
In intestine bacterial hydrolisis

Metabolism and transformation of intact ginsenosides

is an important process.
Bioavailability
Potential health benefits

Ginsenosides structural
classes
Protopanaxadiol
(PD)

Protopanaxatriol
(PT)

Ra1,
Ra2,Ra3,Rb1,Rb2,
Rb3,Rc,Rd,Rg3, Rh2

Re,Rf,Rg1,Rg2,Rh1

Biovailability of Ginseng

Oral bioavailability very low

Bacterial metabolized ginsenosides More permeable and

bioactives

Ginsenosides enter brain rapidly concentrations decline

rapidly

Ginsenosides with higher concentrations in the brain :

Rg1, Re, Rb1 and Rc

Rg1 & Re better brain distribution directly affecting

CNS

Ginsenosides PD longer time in circulation protect

brain trough peripheral effect

Molecular Mechanisms of Effects

of Ginseng on the Brain
Glutamatergic
Neurotransmission

Monoamine
Neurotransmission

Estrogen Signaling

Nitric Oxide
Production

Keap1/Nrf2
Adaptive Cellular
Stress Pathway

Neuronal Cell
Survival

Apoptosis

Neural Stem Cells

and
Neuroregeneration

Microglia

Astrocytes

Oligodendrocytes
and myelination

Cerebral
Micovessels

Protective Effects of Ginseng on

Neurological Disorders

Neurodegenerative disease Loss of cognitive function &

motor disabilities.

Alzheimers disease
Parkinsons disease
Huntingtons disease
Amyotropic lateral sclerosis

Accompanied by:

Oxidative stress
Neuroinflammation
Increased generation of lipid mediators
Abnormal protein aggregation
Slow excitotoxicity
Loss of synapses and disintegration of neural network

Protective Effects of Ginseng on

Neurological Disorders

Neurotraumatic disease Metabolic or

mechanical insult to brain or spinal cord
Cerebral ischemia or stroke
Spinal cord injury
Traumatic brain injury

Neurochemical event:

Release of glutamate
Overstimulation of glutamate receptors
Rapid Ca influx
Activation of cytosolic phospolipase
Induction of oxidative stress and neuroinflammation

Protective Effects of Ginseng on

Neurological Disorders

Neuropsychiatric disorders
neurodevelopmental behavioral or psychological
difficulties

Depression
Schizophrenia
Bipolar dissorder
Impairment of cognitive processes

Abnormalities:
Cerebral cortex
Ventral striatum
Limbic system

Alzheimers Disease

Characterized by extracellular plaques:

Aggregated A peptides
Neurofibrillary tangles
Hyperphosporilated tau protein

Cerebral amyloid angiopathy:

A deposition on arterioles & capillaries wall in brain

Panax notoginseng flavonol glycosides:

inhibited aggregation of A
Modulated cell death
Reduced memory impairment

Alzheimers Disease

Effect on A Formation
Neuroprotective effects by reducing A levels
Gintonin:
Supress neuroblastoma by decrease A142 release,
and attenuated A140 induced toxicity.
Attenuated amyloid plaque deposition
Attenuated short- and long-term memory impairment

Chronic suplementation of ginsenosides:

Modulated age-related memory impairment
Preserve cognitive function
Protection of spatial learning abilities and memory

Alzheimers Disease

Effect on tau Phosporilation:

Effect by reducing tau hyperphosporilation and
neurofibrillary tangle formation
Rd(10mg/kg 7 days) activities of protein phosphatase
2A (PP2A) okadaic acid-induced neurotoxicity & tau
hyperphosphorylation.
Rb1 mantain PP2A level in cortex and hippocampus.
Rg1(20mg/kg) Supress A formation & phosporilated
tau reversed memory impairment

Alzheimers Disease

Effect on Reactive Oxygen and Nitrogen Species:

Increased Superoxide dismutase (SOD) & glutathione
peroxidase (GSH-Px) activity improve learning &
memory
Rg1 modulated reactive nitrogen species in endothelial
cells

Effect on Cholinergic and neurotropic Signaling:

Loss of ACh is found in AD brain
Rg5 Acetylcholine ssterase(AChE) & Choline
acetyltransferase (ChAT)
modulated cognitive dysfunction and neuroinflammation

Alzheimers Disease

Clinical Studies on Use of Ginseng in AD:

High-dose Korean Red Ginseng (9g/day)
Significant improvement on Alzhemers Disease
Assessment Scale (ADAS) & Clinical Dementia Rating
(CDR) after 12 weeks.
In long term (24th, 48th, 96th weeks) MMSE score
remained without significant decline
Long- term beneficial effects of Korean Red Ginseng
in patients with AD.

Major Depression

Precilinical Studies:
Ginseng saponins attenuated depression in rats via:
Effects on Glutamanergic Neurotransmission
Effects on Esterogen Signalling
Effect on Neural Stem Cells and Neuroregeneration

Clinical Studies:
Post menopausal women treated with ginseng shows
significant difference favor of ginseng when
compared with placebo.
Korean red ginseng 3g/day decrease depressive
symptom by Depression Residual Symptom Scale

Stroke

Neuroprotective effect via inhibition of ion channels or

modulation of vasospasm.

Interaction + anticoagulant Risk of bleeding

Ginsenosides Rd (10-50mg/kg):
Significantly decreased infarct volume after middle cerebral artery
occusion (MCAO).
Neuroprotection transient MCAO/ permanent MCAO

Ginsenosides Rb1 on Hemorrgahic stroke reduce:

Neurological deficits
Brain edema
BBB disruption

Parkinsons Disease

Ginsenosides Rb1, Rg1, Rd, Re

Neuroprotective for Parkinsons Disesase

Inhibition of oxidatives stress & neuroinflammation

Decrease toxin-induced apoptosis
Decrease nigral iron levels
Regulation of N-methyl-D-aspartate receptor
channel activity

Panax notoginseng provided neuroprotection

against loss of dopaminergic neurons and
behavioral impairment

Multiple Sclerosis

Ginsenosides Rd:
Intraperitoneally administered ginsenoside Rd at
40 mg/kg/day:
reduced the permeability of the BBB
regulated the secretion of interferon-gamma and IL4, and decreased the severity
Decreased the severity of multiple sclerosis

Conclusions and Future

Directions

Many ginsenosides have been isolated and

characterized

Molecular mechanism :
scavenging free radicals
inhibition of inflammation
prevention of excitotoxicity

Animal and cell culture studies have indicated

that ginsenosides have different activities in both
physiological and pathologic conditions.

Conclusions and Future

Directions

Ginsenosides produce neuroprotective

effects by reducing free radical production
and enhancing brain function.

Studies involving each ginsenoside should:

include mechanisms of action

Specificity
structure and function relationship
detailed pharmacokinetics and toxicity studies
therapeutic studies in animal models