Transcript What is Alzheimer`s Disease?

The effects of some
herbal medicine on
psychoneuro disorders
by
Dr . Ghafghazi
Step 1: Get lots of sleep!
You may have heard the recommendation to get 8 hours of sleep
each night. While 8 hours is a good estimate, the actual amount
the body needs varies by individual. Some people may be able
to function very well on 6 hours, while others have a difficult
time remaining alert without 10. Listen to your body -- it
usually sends some pretty strong signals when you need more
rest. Make the quantity and quality of sleep just as important as
following a healthy diet and exercising regularly.
Can’t Seem to go to sleep

Need Help Falling Asleep? Put On Socks
the next time you have trouble
sleeping, try putting socks on your
feet.
 A researcher says people with
chronically cold feet might drift off
faster if they warm their feet with
socks or a hot water bottle.
 according to a study.

That's because the body appears to prepare for
sleep by widening the blood vessels in the
hands and feet to help radiate body heat away,
Warming the feet and then removing the socks
or water bottle would promote this dilation,.
Most people go through the process naturally
and wouldn't need socks or a water bottle to
help them sleep,
The scientists have analyzed data from 18
healthy young men who participated in sleep
studies. The results suggest that blood vessel
dilation in the hands and feet in late evening,
and resulting heat loss, are key to falling asleep.
Some Other Sleep Remedies
* Chamomile (Matricaria camomilla): Chamomile
tea, comprised of the dried flowers and leaves of
this common plant, can be sipped half an hour
before going to bed as a convenient, effective sleep
aid. It is especially helpful for mild or transient
insomnia. Its ability to relieve anxiety is attributed
to chrysin, a flavonoid component. Passionflower
(Passiflora incarnatus), which also contains
chrysin, has been observed to have a similar effect.
*
Lavender (L. angustifolia and others): The
essential oil of this popular flowering herb
has been demonstrated to depress the
central nervous system in a way
comparable to hypnotics or
tranquilizers.Most commonly used in
cosmeceuticals and aromatherapeutic
preparations, lavender oil can be applied
topically to relax the muscles or its aroma
may be inhaled for a calming effect.
Lavender tea before bedtime is also useful.
Valerian Root (Valeriana officinalis): The roots and rhizomes of
valerian are dried to produce this commonly available herb.
Studies suggest that valerian is by far the best natural solution for
insomnia for most people. Research by P.D. Leatherwood, Ph.D.,
and F. Chauffard, Ph.D., at Nestlé Research Laboratories in
Switzerland, established that 450 mg of valerian in an aqueous
extract is the optimum dose as an insomnia treatment; a higher
dose results in grogginess without increasing effectiveness.
Leatherwood and colleagues, in a double-blind crossover study of
128 subjects, also found valerian root to be effective for improving
quality of sleep in general.
Valerian has an effect on the body similar to that of
benzodiazepine (an active ingredient in Valium(TM)), but
without dulling effects or next-day lethargy.
Approved by the German Federal Ministry of Health as a
calming sleep aid and widely recommended for treating anxietyrelated sleep problems, it is entirely nontoxic. Past concerns
about toxicity centered on reports that the valepotriates
contained in the root were cytotoxic. However, P.R. Bradley,
writing in the British Herbal Compendium, explains that they
are unable to cross the blood/brain barrier. They also
disintegrate rapidly into nontoxic metabolites, so there is little
risk to the consumer, providing persons currently taking sedative
drugs or antidepressants take valerian only under the supervision
of a health care professional. Unlike prescription sedatives,
valerian does not impair the ability to drive or operate heavy
machinery; nor does it exaggerate the effects of alcohol.
‫‪‬‬
‫نوروگل قرص ونوروگل فورت وسدامین کپسول‬
γ-aminobutyric acid (GABA)
and Anxiety
Anxiety is a physiological, protective response to real or potential threats
“The Scream”
Edvard Munch; 1893
GABA-A Subunits,
Anxiety, and Response to
Benzodiazepines
Valeriana officinalis & mexicana


Valeriana (valerian) - whether
this herb acts as a peripheral
or central vasodilator or if
the activity is due to a general
calming effect on the
nervous system is not known
It is usually prescribed for
stressed patients.
Valeriana Officinalis

CHEMISTRY : Three distinct classes of
compounds have been associated with the
sedative properties of valerian : 1) mono – and
sesquiterpenes, 2)iridoid trimesters
(valepotriates) , and 3)pyridine alkaloids .

Pharmacologic action : Valerian has
demonstrated a number of pharmacological
effects including : Normalizing of the central
nervous system (it acts as a sedative in states of
agitation and a stimulant in cases of extreme
fatigue ) .

Valerenic acid given intraperitoneally had CNS
depressant effects in mice , including
potentiating barbiturate sleeping time and
decreasing spontaneous motor activity and
rotorod performance . The valepotriates
isovaltrate and valtrate , along with valerenone ,
were found to have antispasmodic effects in
isolated guinea pig ileum , as well as other
smooth muscle preparations .

Aqueous and hydroalcoholic extracts of valerian
induced release of [3H] GABA from synaptosomal
preparations, which was interpreted as an effect on the
GABA transporter . The in vitro effect was correlated
with the content of GABA itself in the extract . Thus
GABA may by responsible for some of the peripheral
effects of valerian , while glutamine , another free
amino acid in the extract , can cross the blood – brain
barrier and be metabolized to GABA in situ , thereby
producing central sedation .

Elderly patients with nervous disorders
responded positively to a commercial valerian
preparation in a placebo – controlled study , as
measured by both subjective and objective
parameters . Sleep latency was decreased in a
group of 8 poor sleepers give and aqueous
extract of valerian in a double – blind , placebo
– controlled study .

A sleep laboratory study found minor sedative
effects in healthy volunteers . An uncontrolled
multicenter study of > 11,000 patients suffering
from sleep – related disorders found subjective
improvements in 94% of those treated. Another
multicenter trial of the same preparation in a
younger study population found progressive
symptomatic improvement over 10 days of
treatment .

Valerian was found to increase slow – wave
sleep in a pilot study of poor sleepers . In
contrast to previous studies that demonstrated a
prompt decrease in symptoms , one study found
that 2 to 4 weeks was required to see
improvement in 121 patients with serious
insomnia .

Clinical studies have generally found valerian to
have fewer side effects than positive control
drugs such as diazepam , producing little
hangover effect when used as a sleep aid . An
intentional overdose has been reported in which
20 times the recommended dose was ingested ;
the patient experienced mild symptoms that
resolved within 24 hours .

A recent pharmacological study indicated that
both valepotriates and valerenic acid are capable
of binding to GABA receptors in a similar
fashion to benzodiazepines .However, valerian
does not appear to act in a similar fashion,in that
side – effects such as impaired mental function
morning hangover, and dependency have not
been reported with valerian .

In addition , valerian compounds which do not
bind to GABA receptors have also been shown
to produce sedative effects . Several recent
clinical studies have substantiated valerian`s
ability to improve sleep quality and reduces
night – time awakenings in sufferes of insomnia
.

This study , performed under strict laboratory
conditions , demonstrated that valerian is as
effective in reducing sleep latency as small doses
of barbiturates or benzodiazepines. However
while these latter compounds also increase
morning sleepiness, valerian usually reduces
morning sleepiness.

In another study of insomniacs, subjects
received either a valerian preparation and / or
placebo .Compared with the placebo , valerian
showed a significant effect, with 44% reporting
perfect sleep and 89% reporting improved sleep.

Clinical trials : There is abundant evidence that
valerian is effective as a sleep aid and as a mild
antianxiety agent , although the effect appears to
be weaker in healthy subjects than in poor
sleepers . An aqueous extract of the root (400
mg extract) improved sleep quality in a number
of subjective parameters in 128 healthy
volunteers using a crossover design .

And finally , in another double – blind study of
insomniacs , 20 subjects received a combination
of valerian root (160 mg ) and Melissa officinalis
( 80 mg ) , a benzodiazepine ( triazolam 0.125 ),
or placebo .

In the insomniac group , the valerian
preparation showed an effect comparable to that
of the benzodiazepine, as well as an increase in
deep sleep stage 3 and 4. The valerian
preparation did not , however , cause day time
sedation and there was no evidence of
diminished concentration based on the
concentration performance test or impairment
of physical performance.


Valerenic acid has been found to inhibit GABA
transaminase , the principle enzyme that
catabolizes GABA .
GABA –T inhibition increases the inhibitory
effect of GABA in the CNS , and can therefore
contribute to valerian's sedative properties .

Side effects : Valerian is generally regarded as
safe and is approved for food use by the united
states food and drug administration . A major
concern for any sedative or anti – anxiety
medication is its potential to effect a person`s
ability to drive or operate potentially dangerous
machinery .

A randomized , placebo – controlled , double –
blind study evaluated the impact of a valerian /
lemon balm prepartion on psychomotor and
mental performance tests . No impact was
found on reaction time , concentration or
attentiveness.

Pregnancy and lactation : The safety of
valerian during pregnancy and lactation has not
been established and should therefore , be
avoided .
Valerian (Valeriana officinalis)


Dosage:
capsules (usually distributed as 150 mg
capsules, standardized to 0.8%
valeronic acid or 1-1.5% valtrate)
 anxiety-100-200
mg dose up to TID
 sleep-200-400 mg dose at HS

tincture of valerian=1-3 ml in 1-2 oz
water taken QD-TID or at HS, 30 min
before desired sleep


SCIENTIFIC NAME(S) : Melissa officinalis
L. Family Lamiaceae (Mints)
CHEMISTRY : Lemon balm leaves contain
0.2% to 0.3% of a lemon – scented essential oil
similar to lemon grass . Major mono – and
sesquiterpenes include geranial , neral , bcaryophyllene , b- caryophyllene oxide , linalool,
citronellal , nerol , and geraniol . R(+) – methyl
citronellate is characteristic of Melissa oil and
distinguishes it from lemon grass oil .

This extract also was active in an acetic acid
writhing analgesia assay but not in the hot plate
test . The volatile oil of the plant had much
weaker activity or was inactive in the same
assays .

PHARMACOLOGY : Lemon balm's
traditional medicinal use was as a sedative and
antispasmodic .This activity was formerly
attributed to the volatile oil . However, the
lyophilized hydroalcoholic extract , which does
not contain the volatile oil components , has
sedative in several mouse models when given
intraperitoneally .
Update on Alzheimer’s
Disease
i
What is Alzheimer’s Disease?


(a.k.a. “old timers” disease)
Alzheimer’s disease is the most common form
of dementia that affects the elderly. It generally
worsens slowly, and is marked by certain forms
of brain degeneration.
What it is dementia?
Dementia can be medically defined as the
global loss of cognitive function in clear
consciousness.
For our purposes, however, dementia can be
thought of as the gradual loss of one’s ability to
think.
What are clues that a person has
Alzheimer’s Disease?

A person who slow losses (over years)…
The ability to handle money
 The ability to care for themselves
 The ability to perform previously learned tasks
 The ability to remember the names of people and
objects
…probably has Alzheimer’s Disease

How can one be sure that a person has
Alzheimer’s disease?

A definite diagnosis of Alzheimer’s Disease can
only be made through looking at a person’s
brain after death.
How common is Alzheimer’s
Disease?

Some believe that the number of patients with
Alzheimer’s Disease doubles every 5 years after
the age of 60.
1% of 60 year-olds affected
 40% of 85 year-olds affected

What Causes Alzheimer’s
Disease?
No one knows!
What Causes Alzheimer’s
Disease?

A number of in-born and environmental factors
appear to be important
Age
 Education
 Certain genes

Late Onset Alzheimer’s Disease
90% of all Alzheimer patients
above age 70 yrs
slow progressive disease
Protective factors:
anti-inflammatory drugs
antioxidant agents
oestrogen
high educational level
Risk Factors:
cardiovascular disease
obesity
diabetes
chronic inflammation
Increased risk with:
APO-E4 genotype 
to 40~70% of cases
TNF-alpha polymorphism
Trisomy 21
Risk Factors:
Aging, menopause
low education level
head trauma,
cerebral ischaemia
Minati L, et al. 2008. Current Concepts in Alzheimer's Disease: A Multidisciplinary Review..
J Alzheimers Dis Other Demen.
Alzheimer’s Disease
3 Major processes
Emerit, J., M. Edeas, et al. (2004). "Neurodegenerative diseases and oxidative stress."
Biomedicine & Pharmacotherapy 58(1): 39-46.
Inflammation
Present at cellular level
~brain microglia activation
~ not systemic inflammation Increased cytokine
production
Increased lipid
mediators:
Leukotrienes
TNF-alpha
IL-1
Reduced DHA
impairs
Neuronal signalling
Exacerbated by
* cerebral iron & copper
* Vascular endothelial
disease
* APO E4 gene
* Insulin Resistance
Tan, Z. S., A. S. Beiser, et al. (2007). "Inflammatory markers and the risk of Alzheimer disease:
The Framingham Study." Neurology 68(22): 1902-1908.
Lukiw, W. J. (2009). "Docosahexaenoic acid and Amyloid-beta Peptide Signaling in Alzheimer's
Disease." World Rev Nutr Diet 99: 55-70.
Oxidant Stress
derives from
Environmental oxidant
exposure
Smoking
Air pollution
Heavy metals ~ Hg, Mn
Low antioxidant status
Ascorbate
Bioflavonoids
proanthocyanidins
Heavy metal overload
iron, copper
mercury
EFA imbalance
omega-3-FA insufficiency
Inflammation
APO e4 gene
TNF-alpha polymorphism
Chronic inflammatory
disease
Insulin Resistance
Cardiovascular Disease
Diabetes
Yan, S. D., X. Chen, et al. (1996). "RAGE and amyloid-[beta] peptide neurotoxicity in Alzheimer's disease."
Nature 382(6593): 685-691.
Emerit, J., M. Edeas, et al. (2004). "Neurodegenerative diseases and oxidative stress."
Biomedicine & Pharmacotherapy 58(1): 39-46.
Omega-3-EFA deficiency
inadequate intake of
Fish & fish oils
Mineral Depletion
Zinc•
Magnesium•
Chromium•
Chronic
Inflammation
Obesity and
Overweight
DIET
High Carbohydrate intake
High saturated fat intake
Lack of
EXERCISE
Carbohydrate-responsive
Gene Polymorphisms
PPARS
SREBP
ChREBP
Sabayan, B., F. Foroughinia, et al. (2008). "Role of Insulin Metabolism Disturbances in the Development of Alzheimer
Disease: Mini Review." American Journal of Alzheimer's Disease and Other Dementias 23(2): 192-199.
Neurodegenerative Disease
Reduced mitochondrial
and axonal transport
Progressive cell atrophy &
apoptosis
Increased tissue oxidative
damage
Common
characteristics
Increased Tau protein
phosphorylation
Accumulation of abnormal
protein fragments
Increased inflammatory
cytokine production
Decreased neurotransmitter
production
Progressive cell atrophy &
apoptosis
Increased inflammatory
lipid mediators
Skovronsky et al. 2006. "NEURODEGENERATIVE DISEASES … Ann Rev Path Mech Dis. 1(1)
Can Alzheimer’s Disease be
Prevented?


No medications are available to prevent
Alzheimer’s disease
Living “right” may help
Stay active mentally and physically
 Monitor and control high blood pressure
 Avoid excessive alcohol use

What Treatments Exist for
Alzheimer’s Disease

The only FDA approved medications for
Alzheimer’s Disease are ones that increase a
certain chemical in the brain (acetylcholine)
Aricept
 Cognex
 Exelon
 Reminyl

Alzheimer’s Disease
TREATMENT
Primary Antioxidant Therapy
Vitamin C ~ mixed mineral ascorbates
Mixed tocopherols & Tocotrienols
Mixed bioflavonoids
Phytonutrient Therapy
Blueberries
Green tea
Resveratrol
Curcumin
Pomegranate
DIGESTIVE SUPPORT
Gastric acid and Digestive enzymes
DIET
Low-allergy & Low Glycemic Load
High protein & vegetable intake
Consider
Paleolithic or ketogenic diet
Essential Fatty Acid Supplements
DHA-rich omega-3-FAs
alpha-Linolenic acid
Additional Treatments for
Alzheimer’s Disease



Vitamin E may slow the progression of the
disease
Non-steroidal anti-inflammatory agents may
help prevent the disorder
Mild sedatives (Haldol) are helpful in reducing
agitation and behavior disturbances
What Research is on the
Horizon?

Scientists are currently studying the ability of a
vaccine to prevent or reverse the damage done
by the disorder ( in animals )

In eight years brain function can be reduced by
almost 1/3
Alzheimers versus normal brain
Normal versus degenerating
neuron
Anatomical findings
Alzheimer’s





1. plaques: clusters of abnormal cells
2. tangles of neurofilaments inside neurons
3. deterioration of dendrites
4. loss of neurons
5. hippocampus is 47% reduced in size (in
normals it shrinks 27%).
Signatures of Alzheimers



Deposits of protein fragments called beta
amyloid – fill up spaces between brain cells
Tangles of protein called tau inside the cells
(thought to be causal)
Anatomical findings
(continued)




6. Amydgala 26% decrease in volume
7.cell density reduced by 75% (increase in
ventricular size)
8.Those who died show marked loss of cells in
the nucleus basilis (releases ACh and projects to
hippocampus and cortex.
9. cortex has plaques and tangles.
Causes of Alzheimers



Two hallmarks of Alzheimers disease are
accumulation in the brain of beta amyloid and
reduction of the concentration of ACh.
A gene implicated in heart disease also appears
to be involved in most “Alzheimer cases= apo
E.
E-2 version protects people from getting
Alzheimers. E-4 is the worst


The same forces that trigger this beta amyloid
deposits might harm arteries and cause heart
attacks.
Culprits=oxygen damage (cellular equivalent of
rust) and harmful effects of chronic
inflammation
Preventative measures



ginkgo biloba: possibly due to anti-inflammatory
or circulatory properties
Anti-inflammatory drugs: limit the production of
amyloid
Vitamen E
Statin drugs- (for high cholesterol), reduce
Alzheimer’s risk.
 Folate-lowers the amino acid homocysteine
(that increases Alzheimer’s and heart
disease risk).
 Mental exercise- active- do better. Use it
or lose it.



Take: (HRT), anti-inflamatory painkillers, and
statins
= people are 30-50% less likely to get
Alzheimer’s.
Ginkgo biloba
History and Background

Ancient use in China and Japan
as a tonic.






Poor Circulation
Inner ear disorders
Absent-mindedness, Dementia,
Depression, and Hypertension in
the elderly
Impotence in men
Chinese used leaves and nuts
Use dates back over 5000 years
About the plant…





Commonly known as maidenhair tree
Known for its green, fan-shaped leaves that turn
yellow in autumn
Unique seeds (not used in extracts)
Extracts prepared from dried, green, whole
leaves
Tree can reach up to 80 feet tall and 60 feet
wide in urban areas
A Living Fossil



The world’s oldest tree
In existence for over 250 million years
Darwin referred to it as “a living fossil”
Present Usage

Uses in Medicine
 Age-associated memory
impairment (AAMI),
dementia and
Alzheimer's.
 Peripheral arterial
occlusive disease
Active Substances
 Flavonoids
 Terpene
Lactones
 ginkolides
 allergic
inflammation
 anaphylactic shock
 asthma
Structures

Phenolic Substituents

Terpene Substituents
Physiologic Mode of Action

Attributed to a
combination of the
flavonoid glycosides and
the diterpene lactones
(ginkgolides).
How’s it Work?
 Powerful
antioxidant
 premature
 Controls
 relax
aging and dementia
hardening of arteries
blood vessels
Physiologic Mode of Action Cont’d



Acts by releasing vasodilators,
specifically nitric oxide and PGI2,
which allows increased blood flow
throughout the circulatory system and
therefore increase oxygen and nutrient
delivery to the tissues.
Allows increased microcirculation in
the capillaries (i.e. better exchange on
the cellular level)
Decreases blood viscosity
Molecular Mode of Action




Treatment with ginkgo increases the production of NO
(nitric oxide) through NOS (nitric oxide synthase).
NO increases the activity of KCa channels and invokes
the influx of Ca2+ into endothelial cells.
This mode was double checked against a known Ca2+
channel blocker (TEA) and inhibited the effects of
ginkgo.
Ginkgo does not affect ATP K+ channels.
Ginkgo and Memory

Effects on AAMI and cerebral insufficiency

All but 1 of the 8 studies found a reduction in the
symptoms of these diseases.

May take 4-6 weeks to see improvement.

UCLA study
Peripheral Arterial Disease



Intermittent Claudication (IC)
One study showed that patients on
ginkgo extract therapy had increased
pain-free walking distance.
Another study showed that there was a
reduction in pain at rest with patients
on ginkgo therapy.
Other Positive Effects of Ginkgo




Improvements in cerebral
metabolism (increases the
efficiency of the oxygen that’s
present)
Increase in the release of
neurotransmitters
Antioxidant activity
Prevention of free radical
damage
Ginkgo Extracts
 Inhibit
platelet activating factor
 Over-stimulate immune system
Fountain of Youth?
Enhances memory
 Treatment of vertigo
 Counteracts
 lack of energy
 mental fatigue
 aging

Ginkgo’s Advantage

Increased blood flow to brain and body
Blood Circulation
 Carry
nutrients(oxygen, sugars,
enzymes)
 Removes waste
 Feeds the brain
Circulation Importance
 Constant
circulation critical
 waste
not removed
 cells age more rapidly
 sit in waste
 Improper
 wear
cell nourishment
out faster
 experience aches, pains, stiffness
Circulation Benefits
 Boosts
oxygen level to brain
 Improved short term and long term
memory
 increased reaction time
 Improved mental clarity
Elderly Usage
 Alzheimer’s
 degenerative
 Cerebral
disease that attacks brain
insufficiency
 concentration
 confusion
 lack
of energy
difficulties
EGb 761
 Extract
used to alleviate cognitive
disorders
 Antioxidant properties of flavoniods
and terpeniods
 Scavenger of radicals associated with
Alzheimer disease



Typical dose (used in many experiments) is 120
milligrams of dried extract in two or three oral doses.
Extract in German product is named EGb 761,
manufactured by Schwabe Pharmaceuticals.
The extract contains


flavonoids and biflavonoids, a large group of natural plant
products
terpenes (active ingredients in catnip and marijuana)



Dozens of clinical trials have examined the
cognitive effects of gingko in humans.
Great majority of studies have involved subjects
with mild to moderate impairment, usually an early
diagnosis of Alzheimer's.
Most experiments test learning and memory; less
often attention, motivation or anxiety.
Turmeric and Alzheimer

Diets rich in curcumin--a compound found in
the curry spice turmeric--may help explain why
rates of Alzheimer's disease are much lower
among the elderly in India
compared
with their Western peers.

Alzheimer's disease is characterized by the
buildup of amyloid protein ``plaques'' within the
brain. In studies in rats, curcumin ``not only
reduces the amyloid, but also reduces the
(brain's) response to the amyloid,'' according to
researcher Dr. Sally Frautschy of the University
of California, Los Angeles

Previous studies have noted that elderly individuals living in
Indian villages appear to have the lowest incidence of
Alzheimer's disease in the world, with just 1% of those aged 65
and older contracting the degenerative brain condition. The
reasons for this low incidence remain unclear, however.
Frautschy speculated that curcumin found in curry could provide
a clue to this puzzle since the compound has ``a long history of
dietary and herbal medicinal use'' and is also a powerful
antioxidant and anti-inflammatory agent.

, Frautschy fed middle-aged (9 months old) and aged (22 months
old) rats diets rich in curcumin. All of the rats had received brain
injections of amyloid to mimic progressive Alzheimer's disease.
``Curcumin reduced the accumulation of beta-amyloid and the
associated loss of Synapses connect nerve cells and are crucial for
memory,'' the California researcher explained. Keeping synapses
free of plaque is important because ``their loss correlates well
with memory decline in Alzheimer's.'' This type of memory
preservation may have been reflected in the fact that rats
fed
curcumin also performed much better in
memory-dependent maze tests compared with
rats on normal diets, according to Frautschy.

. Curcumin also appeared to reduce Alzheimer's-related
inflammation in neurologic tissue. in the synapses, or
gaps, between individual brain cells, Frautschy reported.
Because ``a combined anti-inflammatory and
antioxidant approach will be useful for Alzheimer's
prevention or treatment,'' Frautschy speculates that
curcumin could be especially valuable in the fight
against the disease, especially in combination with antiinflammatory drugs like ibuprofen

Researchers in India have suggested performing clinical trials on
humans to explore turmeric's efficacy as a novel antidepressant.
However, as of 2008, numerous clinical trials in humans were
underway, studying the effect of curcumin on various diseases,
including multiple myeloma, pancreatic cancer, myelodysplastic
syndromes, colon cancer, psoriasis, and Alzheimer's disease.
 In vitro and animal studies have proven that curcumin has
antitumor,[antioxidant, antiarthritic, antiamyloid, antiischemic,[and anti-inflammatory properties.[Anti-inflammatory
properties may be due to inhibition of eicosanoid biosynthesis.

Numerous studies have demonstrated curcumin,
amongst only a few other things, such as high
impact exercise, learning, bright light, and
antidepressant usage, has a positive effect on
neurogenesis in the hippocampus and
concentrations of brain-derived neurotrophic
factor (BDNF), reductions in both of which are
associated with stress, depression, and anxiety.

Curcumin has also been demonstrated to be a
selective monoamine oxidase inhibitor (MAOI)
of type MAO-A. Fluorescent imaging in a
mouse model of Alzheimer's disease showed
that curcumin crosses the blood-brain
barrier.Several studies have demonstrated that
unlike glucuronidated curcumin, free curcumin,
which is lipophilic, readily passes the blood
brain barrier
Protein Plaques
 [Curcumin,
the active constituent in turmeric, reduces the
damaging effects of protein plaques in the brains of
Alzheimer's disease patients according to a U.S. study
published in the September 2010 "Journal of Biological
Chemistry." The study on laboratory mice revealed that
curcumin inhibited the production of amyloid-beta
protein, which comprises the plaques that disrupt brain
function in Alzheimer's. The researchers noted that this
study represents the first of its kind to pinpoint a
mechanism for the effects of curcumin on this disease
process
Anti-inflammatory and Antioxidant

Turmeric's antioxidant, anti-inflammatory and lipidsoluble properties give it particular benefits for
improving the symptoms of Alzheimer's disease
according to a study published in the January 2008
"Annals of the Indian Academy of Neurology."
Turmeric relieves oxidative stress, reduces damage
caused by free radicals, inhibits the formation of betaamyloid proteins, reduces inflammation and protects
against disruption of brain function by toxic metals that
contribute to the development of the disease. These
benefits to nerve function improved memory for
Alzheimer's patients.
Depression

Depressive symptoms associated with Alzheimer's
disease may respond to treatment with turmeric,
according to an Indian study published in the
November 2009 "Scientific World Journal." Turmeric
could have the ability to regulate the release of the
neurotransmitters serotonin and dopamine and the
spice has been shown to promote nerve growth in the
frontal lobe, which is an area of the brain responsible
for cognition, and also in the hippocampus, which is
an area of the brain associated with memory. The
researchers called for further testing, including clinical
trials, to clearly define the role of turmeric in
depression

Phytoarthrit Capsule: Boswellia Serrata,
Zingiber, Turmeric, Cat,s claw
Hypericum perforatum
(Clusiaceae)
SJW: Background

Ancient Greece: medicinal plants
Hippocrates (460- 377 B.C.)
 Therapeutic applications
 External: contusions, myalgia, first degree burns,
poisonous reptile bites.
 Internal: neuralgia,anxiety, neurosis, insomnia, depression.
Current Use/ Popularity
 Europe: Germany
 U.S., Australia


Active compounds








Hypericin (the red resin)
Hyperforin
Flavonoids
Glycosides
Tannin
Essential oils
Bioflavones
Pseudohypericin
Structures
SJW: Pharmacokinetics

Absorption



Route of administration: oral
Peak levels: 5 hrs
Daily doses vary
450- 900 mg
 900- 1800 mg


Distribution

Blood - brain barrier
 Steady state: 4 – 6 days
SJW: Pharmacokinetics


Distribution
 Placental barrier: unknown
Inactivation
 Metabolism
P450: CYP3A4
 P-glycoprotein


Elimination
Kidneys: urine
 Half –life: 25 hr

SJW: Pharmacodynamics

Cellular sites and mechanism(s) of action




Non-selective reuptake inhibitor
 5-HT, NE, DA
 GABA, glutamate
NMDA, BDZ
MAOI, COMT enzyme
Sites of Action


Cerebellum/ brain stem
Hypothalamus
SJW: Pharmacodynamics

Sites of Action
Hippocampus
 Cerebral cortex: esp. frontal cortex
 Nucleus accumbens
 Locus coeruleus

SJW: Tolerance and Dependence

Tolerance
 Metabolic
 Cellular/ pharmacodynamic
Downregulation B1- adrenoreceptors: frontal cortex
 Progressive sensitization/ upregulation postsynaptic 5HT1: hippocampus
 Upregulation 5-HT2
 Hyperforin –rich: downregulation

Mode of Action

Crude extracts of SJW have a variety of
neuropharmacologic actions
Inhibits monoamine oxidase (MAO), GABA,
norepinephrine and dopamine reuptake
 Increases free intracellular Na+, which inhibits
serotonin reuptake

Pharmacology cont.

It is likely that Hypericum
acts on many levels
simultaneously, creating an
accumulating effect by
being both a MAOinhibitor, serotonin,norepinephrine-, and
dopamine- reuptake
inhibitor, a cortisol
secretion inhibitor etc.