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The effects of some herbal medicine on psychoneuro disorders

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Title: The effects of some herbal medicine on psychoneuro disorders


1
The effects of some herbal medicine on
psychoneuro disorders
  • by
  • Dr . Ghafghazi

2
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.

3
Cant 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.

4
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.
5
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.

6
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.
7
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.
8
Approved by the German Federal Ministry of Health
as a calming sleep aid and widely recommended for
treating anxiety-related 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.
9
  • ?????? ??? ??????? ???? ??????? ?????

10
?-aminobutyric acid (GABA) and Anxiety
Anxiety is a physiological, protective response
to real or potential threats
The Scream Edvard Munch 1893
11
GABA-A Subunits, Anxiety, and Response to
Benzodiazepines
12
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.

13
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 .

14
  • 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 ) .

15
  • 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 .

16
  • 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 .

17
  • 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 .

18
  • A sleep laboratory study found minor sedative
    effects in healthy volunteers . An uncontrolled
    multicenter study of gt 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
    .

19
  • 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 .

20
  • 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 .

21
  • 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 .

22
  • 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 valerians
    ability to improve sleep quality and reduces
    night time awakenings in sufferes of insomnia .

23
  • 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.

24
  • 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.

25
  • 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 .

26
  • 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 .

27
  • 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.

28
  • 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 .

29
  • 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 persons
    ability to drive or operate potentially dangerous
    machinery .

30
  • 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.

31
  • Pregnancy and lactation The safety of valerian
    during pregnancy and lactation has not been
    established and should therefore , be avoided .

32
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 valerian1-3 ml in 1-2 oz water taken
    QD-TID or at HS, 30 min before desired sleep

33
  • 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 , b- caryophyllene , b-
    caryophyllene oxide , linalool, citronellal ,
    nerol , and geraniol . R() methyl citronellate
    is characteristic of Melissa oil and
    distinguishes it from lemon grass oil .

34
  • 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 .

35
  • 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 .

36
Update on Alzheimers Disease
  • i

37
What is Alzheimers Disease?
  • (a.k.a. old timers disease)
  • Alzheimers 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.

38
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 ones ability
    to think.

39
What are clues that a person has Alzheimers
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 Alzheimers Disease

40
How can one be sure that a person has Alzheimers
disease?
  • A definite diagnosis of Alzheimers Disease can
    only be made through looking at a persons brain
    after death.

41
How common is Alzheimers Disease?
  • Some believe that the number of patients with
    Alzheimers Disease doubles every 5 years after
    the age of 60.
  • 1 of 60 year-olds affected
  • 40 of 85 year-olds affected

42
What Causes Alzheimers Disease?
  • No one knows!

43
What Causes Alzheimers Disease?
  • A number of in-born and environmental factors
    appear to be important
  • Age
  • Education
  • Certain genes

44
Increased risk with APO-E4 genotype ? to 4070
of cases TNF-alpha polymorphism Trisomy 21
Late Onset Alzheimers Disease 90 of all
Alzheimer patientsabove age 70 yrsslow
progressive disease
Risk Factors Aging, menopause low education
level head trauma, cerebral ischaemia
Risk Factors cardiovascular disease obesity diab
etes chronic inflammation
Protective factors anti-inflammatory
drugs antioxidant agents oestrogen high
educational level
Minati L, et al. 2008. Current Concepts in
Alzheimer's Disease A Multidisciplinary Review..
J Alzheimers Dis Other Demen.
45
Alzheimers Disease 3 Major processes
Oxidantstress
InsulinResistance
Inflammation
Emerit, J., M. Edeas, et al. (2004).
"Neurodegenerative diseases and oxidative
stress." Biomedicine Pharmacotherapy 58(1)
39-46.
46
Inflammation
Present at cellular level brain microglia
activation not systemic inflammation
Increased cytokine production TNF-alphaIL-1
Exacerbated by cerebral iron copper
Vascular endothelial disease APO E4 gene
Insulin Resistance
Increased lipidmediators Leukotrienes
Reduced DHAimpairs Neuronal signalling
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.
47
Oxidant Stressderives from
EFA imbalanceomega-3-FA insufficiency
InflammationAPO e4 gene TNF-alpha
polymorphism Chronic inflammatory disease
Low antioxidant status Ascorbate Bioflavonoids pro
anthocyanidins
Environmental oxidant exposure Smoking Air
pollution Heavy metals Hg, Mn
Insulin Resistance Cardiovascular Disease Diabetes
Heavy metal overloadiron, coppermercury
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.
48
InsulinResistance
Omega-3-EFA deficiencyinadequate intake of Fish
fish oils
Obesity andOverweight
  • Mineral Depletion
  • Zinc
  • Magnesium
  • Chromium

DIET High Carbohydrate intake High saturated fat
intake
Carbohydrate-responsive Gene PolymorphismsPPARS S
REBP ChREBP
ChronicInflammation
Lack ofEXERCISE
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.
49
Neurodegenerative Disease
Increased tissue oxidative damage
Reduced mitochondrial and axonal transport
Increased Tau protein phosphorylation
Common characteristics
Progressive cell atrophy apoptosis
Accumulation of abnormal protein fragments
Increased inflammatory cytokine production
Decreased neurotransmitter production
Increased inflammatory lipid mediators
Progressive cell atrophy apoptosis
Skovronsky et al. 2006. "NEURODEGENERATIVE
DISEASES Ann Rev Path Mech Dis. 1(1)
50
Can Alzheimers Disease be Prevented?
  • No medications are available to prevent
    Alzheimers disease
  • Living right may help
  • Stay active mentally and physically
  • Monitor and control high blood pressure
  • Avoid excessive alcohol use

51
What Treatments Exist for Alzheimers Disease
  • The only FDA approved medications for Alzheimers
    Disease are ones that increase a certain chemical
    in the brain (acetylcholine)
  • Aricept
  • Cognex
  • Exelon
  • Reminyl

52
Alzheimers Disease TREATMENT
DIGESTIVE SUPPORTGastric acid and Digestive
enzymes
DIETLow-allergy Low Glycemic LoadHigh protein
vegetable intake Consider Paleolithic or
ketogenic diet
Primary Antioxidant TherapyVitamin C mixed
mineral ascorbatesMixed tocopherols
TocotrienolsMixed bioflavonoids
Phytonutrient TherapyBlueberries Green
tea Resveratrol Curcumin Pomegranate
Essential Fatty Acid SupplementsDHA-rich
omega-3-FAsalpha-Linolenic acid
53
Additional Treatments for Alzheimers 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

54
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 )

55
  • In eight years brain function can be reduced by
    almost 1/3

56
Alzheimers versus normal brain
57
Normal versus degenerating neuron
58
Anatomical findings Alzheimers
  • 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).

59
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)

60
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.

61
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

62
  • The same forces that trigger this beta amyloid
    deposits might harm arteries and cause heart
    attacks.
  • Culpritsoxygen damage (cellular equivalent of
    rust) and harmful effects of chronic inflammation

63
Preventative measures
  • ginkgo biloba possibly due to anti-inflammatory
    or circulatory properties
  • Anti-inflammatory drugs limit the production of
    amyloid
  • Vitamen E

64
  • Statin drugs- (for high cholesterol), reduce
    Alzheimers risk.
  • Folate-lowers the amino acid homocysteine (that
    increases Alzheimers and heart disease risk).
  • Mental exercise- active- do better. Use it or
    lose it.

65
  • Take (HRT), anti-inflamatory painkillers, and
    statins
  • people are 30-50 less likely to get
    Alzheimers.

66
Ginkgo biloba
67
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

68
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

69
A Living Fossil
  • The worlds oldest tree
  • In existence for over 250 million years
  • Darwin referred to it as a living fossil

70
Present Usage
  • Uses in Medicine
  • Age-associated memory impairment (AAMI), dementia
    and Alzheimer's.
  • Peripheral arterial occlusive disease

71
Active Substances
  • Flavonoids
  • Terpene Lactones
  • ginkolides
  • allergic inflammation
  • anaphylactic shock
  • asthma

72
Structures
  • Phenolic Substituents
  • Terpene Substituents

73
Physiologic Mode of Action
  • Attributed to a combination of the flavonoid
    glycosides and the diterpene lactones
    (ginkgolides).

74
Hows it Work?
  • Powerful antioxidant
  • premature aging and dementia
  • Controls hardening of arteries
  • relax blood vessels

75
Physiologic Mode of Action Contd
  • 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

76
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.

77
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

78
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.

79
Other Positive Effects of Ginkgo
  • Improvements in cerebral metabolism (increases
    the efficiency of the oxygen thats present)
  • Increase in the release of neurotransmitters
  • Antioxidant activity
  • Prevention of free radical damage

80
Ginkgo Extracts
  • Inhibit platelet activating factor
  • Over-stimulate immune system

81
Fountain of Youth?
  • Enhances memory
  • Treatment of vertigo
  • Counteracts
  • lack of energy
  • mental fatigue
  • aging

82
Ginkgos Advantage
  • Increased blood flow to brain and body

83
Blood Circulation
  • Carry nutrients(oxygen, sugars, enzymes)
  • Removes waste
  • Feeds the brain

84
Circulation Importance
  • Constant circulation critical
  • waste not removed
  • cells age more rapidly
  • sit in waste
  • Improper cell nourishment
  • wear out faster
  • experience aches, pains, stiffness

85
Circulation Benefits
  • Boosts oxygen level to brain
  • Improved short term and long term memory
  • increased reaction time
  • Improved mental clarity

86
Elderly Usage
  • Alzheimers
  • degenerative disease that attacks brain
  • Cerebral insufficiency
  • concentration difficulties
  • confusion
  • lack of energy

87
EGb 761
  • Extract used to alleviate cognitive disorders
  • Antioxidant properties of flavoniods and
    terpeniods
  • Scavenger of radicals associated with Alzheimer
    disease

88
  • 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)

89
  • 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.

90
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.

91
  • 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

92
  • 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.

93
  • , 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.

94
  • . 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 anti-inflammatory
    drugs like ibuprofen

95
  • 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, anti-ischemic,and
    anti-inflammatory properties.Anti-inflammatory
    properties may be due to inhibition of eicosanoid
    biosynthesis.

96
  • 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.

97
  • 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

98
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

99
Anti-inflammatory and Antioxidant
  • Turmeric's antioxidant, anti-inflammatory and
    lipid-soluble 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 beta-amyloid
    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.

100
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
  •  

101
  • Phytoarthrit Capsule Boswellia Serrata,
    Zingiber, Turmeric, Cat,s claw

102
Hypericum perforatum(Clusiaceae)
103
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

104
Active compounds
  • Hypericin (the red resin)
  • Hyperforin
  • Flavonoids
  • Glycosides
  • Tannin
  • Essential oils
  • Bioflavones
  • Pseudohypericin

105
Structures
106
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

107
SJW Pharmacokinetics
  • Distribution
  • Placental barrier unknown
  • Inactivation
  • Metabolism
  • P450 CYP3A4
  • P-glycoprotein
  • Elimination
  • Kidneys urine
  • Half life 25 hr

108
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

109
SJW Pharmacodynamics
  • Sites of Action
  • Hippocampus
  • Cerebral cortex esp. frontal cortex
  • Nucleus accumbens
  • Locus coeruleus

110
SJW Tolerance and Dependence
  • Tolerance
  • Metabolic
  • Cellular/ pharmacodynamic
  • Downregulation B1- adrenoreceptors frontal
    cortex
  • Progressive sensitization/ upregulation
    postsynaptic 5-HT1 hippocampus
  • Upregulation 5-HT2
  • Hyperforin rich downregulation

111
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

112
Pharmacology cont.
  • It is likely that Hypericum acts on many levels
    simultaneously, creating an accumulating effect
    by being both a MAO-inhibitor, serotonin-,norepine
    phrine-, and dopamine- reuptake inhibitor, a
    cortisol secretion inhibitor etc.
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