The effects of The effects of some herbal some herbal medicine on medicine on psychoneuro psychoneuro

disordersdisordersbyby

Dr . GhafghaziDr . Ghafghazi

Step 1: Get lots of sleepStep 1: Get lots of sleep!!

You may have heard the recommendation to get 8 You may have heard the recommendation to get 8 hours of sleep each night. While 8 hours is a hours of sleep each night. While 8 hours is a good estimate, the actual amount the body good estimate, the actual amount the body needs varies by individual. Some people may be needs varies by individual. Some people may be able to function very well on 6 hours, while able to function very well on 6 hours, while others have a difficult time remaining alert others have a difficult time remaining alert without 10. Listen to your body -- it usually without 10. Listen to your body -- it usually sends some pretty strong signals when you need sends some pretty strong signals when you need more rest. Make the quantity and quality of more rest. Make the quantity and quality of sleep just as important as following a healthy sleep just as important as following a healthy diet and exercising regularly. diet and exercising regularly.

CanCan’’t Seem to go to sleept Seem to go to sleep Need Help Falling Asleep? Put Need Help Falling Asleep? Put

On SocksOn Socks the next time you have the next time you have

trouble sleeping, try putting trouble sleeping, try putting socks on your feet. socks on your feet.

A researcher says people A researcher says people with chronically cold feet with chronically cold feet might drift off faster if they might drift off faster if they warm their feet with socks warm their feet with socks or a hot water bottle. or a hot water bottle.

according to a study. according to a study.

That's because the body appears to That's because the body appears to prepare for sleep by widening the prepare for sleep by widening the blood vessels in the hands and feet blood vessels in the hands and feet to help radiate body heat away, to help radiate body heat away, Warming the feet and then Warming the feet and then removing the socks or water bottle removing the socks or water bottle would promote this dilation,. Most would promote this dilation,. Most people go through the process people go through the process naturally and wouldn't need socks naturally and wouldn't need socks or a water bottle to help them or a water bottle to help them sleep, sleep, The scientists have analyzed data The scientists have analyzed data from 18 healthy young men who from 18 healthy young men who participated in sleep studies. The participated in sleep studies. The results suggest that blood vessel results suggest that blood vessel dilation in the hands and feet in dilation in the hands and feet in late evening, and resulting heat late evening, and resulting heat loss, are key to falling asleep.loss, are key to falling asleep.

* Chamomile (Matricaria camomilla): * Chamomile (Matricaria camomilla): Chamomile tea, comprised of the dried Chamomile tea, comprised of the dried flowers and leaves of this common flowers and leaves of this common plant, can be sipped half an hour before plant, can be sipped half an hour before going to bed as a convenient, effective going to bed as a convenient, effective sleep aid. It is especially helpful for sleep aid. It is especially helpful for mild or transient insomnia. Its ability to mild or transient insomnia. Its ability to relieve anxiety is attributed to chrysin, relieve anxiety is attributed to chrysin, a flavonoid component. Passionflower a flavonoid component. Passionflower (Passiflora incarnatus), which also (Passiflora incarnatus), which also contains chrysin, has been observed to contains chrysin, has been observed to have a similar effect.have a similar effect.

**

Some Other Some Other Sleep RemediesSleep Remedies

Lavender (L. angustifolia and Lavender (L. angustifolia and others): The essential oil of this others): The essential oil of this popular flowering herb has been popular flowering herb has been demonstrated to depress the demonstrated to depress the central nervous system in a way central nervous system in a way comparable to hypnotics or comparable to hypnotics or tranquilizers.Most commonly tranquilizers.Most commonly used in cosmeceuticals and used in cosmeceuticals and aromatherapeutic preparations, aromatherapeutic preparations, lavender oil can be applied lavender oil can be applied topically to relax the muscles or topically to relax the muscles or its aroma may be inhaled for a its aroma may be inhaled for a calming effect. Lavender tea calming effect. Lavender tea before bedtime is also useful. before bedtime is also useful.

Valerian Root (Valeriana officinalis): The roots Valerian Root (Valeriana officinalis): The roots and rhizomes of valerian are dried to produce and rhizomes of valerian are dried to produce this commonly available herb. Studies suggest this commonly available herb. Studies suggest that valerian is by far the best natural solution that valerian is by far the best natural solution for insomnia for most people. Research by P.D. for insomnia for most people. Research by P.D. Leatherwood, Ph.D., and F. Chauffard, Ph.D., at Leatherwood, Ph.D., and F. Chauffard, Ph.D., at NestlNestléé Research Laboratories in Switzerland, Research Laboratories in Switzerland, established that 450 mg of valerian in an established that 450 mg of valerian in an aqueous extract is the optimum dose as an aqueous extract is the optimum dose as an insomnia treatment; a higher dose results in insomnia treatment; a higher dose results in grogginess without increasing effectiveness. grogginess without increasing effectiveness. Leatherwood and colleagues, in a double-blind Leatherwood and colleagues, in a double-blind crossover study of 128 subjects, also found crossover study of 128 subjects, also found valerian root to be effective for improving quality valerian root to be effective for improving quality of sleep in general. of sleep in general. Valerian has an effect on the body similar to that Valerian has an effect on the body similar to that of benzodiazepine (an active ingredient in of benzodiazepine (an active ingredient in Valium(TM)), but without dulling effects or next-Valium(TM)), but without dulling effects or next-day lethargy.day lethargy.

Approved by the German Federal Ministry of Approved by the German Federal Ministry of Health as a calming sleep aid and widely Health as a calming sleep aid and widely recommended for treating anxiety-related sleep recommended for treating anxiety-related sleep problems, it is entirely nontoxic. Past concerns problems, it is entirely nontoxic. Past concerns about toxicity centered on reports that the about toxicity centered on reports that the valepotriates contained in the root were valepotriates contained in the root were cytotoxic. However, P.R. Bradley, writing in the cytotoxic. However, P.R. Bradley, writing in the British Herbal Compendium, explains that they British Herbal Compendium, explains that they are unable to cross the blood/brain barrier. They are unable to cross the blood/brain barrier. They also disintegrate rapidly into nontoxic also disintegrate rapidly into nontoxic metabolites, so there is little risk to the metabolites, so there is little risk to the consumer, providing persons currently taking consumer, providing persons currently taking sedative drugs or antidepressants take valerian sedative drugs or antidepressants take valerian only under the supervision of a health care only under the supervision of a health care professional. Unlike prescription sedatives, professional. Unlike prescription sedatives, valerian does not impair the ability to drive or valerian does not impair the ability to drive or operate heavy machinery; nor does it exaggerate operate heavy machinery; nor does it exaggerate the effects of alcohol.the effects of alcohol.

وسدامین فورت ونوروگل قرص وسدامین نوروگل فورت ونوروگل قرص نوروگلکپسول کپسول

γ-aminobutyric acid (GABA) and Anxiety

“The Scream” Edvard Munch; 1893

Anxiety is a physiological, protective response to real or potential threats

GABA-A Subunits, GABA-A Subunits, Anxiety, and Anxiety, and Response to Response to

BenzodiazepinesBenzodiazepines

Valeriana officinalis & Valeriana officinalis & mexicanamexicana

ValerianaValeriana (valerian) - (valerian) - whether this herb acts whether this herb acts as a peripheral or as a peripheral or central vasodilator or central vasodilator or if the activity is due to if the activity is due to a general calming a general calming effect on the nervous effect on the nervous system is not knownsystem is not known

It is usually It is usually prescribed for prescribed for stressed patients.stressed patients.

Valeriana OfficinalisValeriana Officinalis

CHEMISTRY : CHEMISTRY : Three distinct Three distinct classes of compounds have been classes of compounds have been associated with the sedative associated with the sedative properties of valerian : 1) mono properties of valerian : 1) mono –– and sesquiterpenes, 2)iridoid and sesquiterpenes, 2)iridoid trimesters (valepotriates) , and trimesters (valepotriates) , and 3)pyridine alkaloids .3)pyridine alkaloids .

Pharmacologic action : Pharmacologic action : Valerian Valerian has demonstrated a number of has demonstrated a number of pharmacological effects including : pharmacological effects including : Normalizing of the central nervous Normalizing of the central nervous system (it acts as a sedative in states system (it acts as a sedative in states of agitation and a stimulant in cases of agitation and a stimulant in cases of extreme fatigue ) . of extreme fatigue ) .

Valerenic acid given intraperitoneally had Valerenic acid given intraperitoneally had CNS depressant effects in mice , CNS depressant effects in mice , including potentiating barbiturate including potentiating barbiturate sleeping time and decreasing spontaneous sleeping time and decreasing spontaneous motor activity and rotorod performance . motor activity and rotorod performance . The valepotriates isovaltrate and The valepotriates isovaltrate and valtrate , along with valerenone , were valtrate , along with valerenone , were found to have antispasmodic effects in found to have antispasmodic effects in isolated guinea pig ileum , as well as isolated guinea pig ileum , as well as other smooth muscle preparations .other smooth muscle preparations .

Aqueous and hydroalcoholic extracts of Aqueous and hydroalcoholic extracts of valerian induced release of [3H] GABA from valerian induced release of [3H] GABA from synaptosomal preparations, which was synaptosomal preparations, which was interpreted as an effect on the GABA interpreted as an effect on the GABA transporter . The in vitro effect was correlated transporter . The in vitro effect was correlated with the content of GABA itself in the extract . with the content of GABA itself in the extract . Thus GABA may by responsible for some of the Thus GABA may by responsible for some of the peripheral effects of valerian , while peripheral effects of valerian , while glutamine , another free amino acid in the glutamine , another free amino acid in the extract , can cross the blood extract , can cross the blood –– brain barrier and brain barrier and be metabolized to GABA in situ , thereby be metabolized to GABA in situ , thereby producing central sedation .producing central sedation .

Elderly patients with nervous disorders Elderly patients with nervous disorders responded positively to a commercial responded positively to a commercial valerian preparation in a placebo valerian preparation in a placebo –– controlled study , as measured by both controlled study , as measured by both subjective and objective parameters . subjective and objective parameters . Sleep latency was decreased in a group Sleep latency was decreased in a group of 8 poor sleepers give and aqueous of 8 poor sleepers give and aqueous extract of valerian in a double extract of valerian in a double –– blind , blind , placebo placebo –– controlled study . controlled study .

A sleep laboratory study found minor A sleep laboratory study found minor sedative effects in healthy volunteers . An sedative effects in healthy volunteers . An uncontrolled multicenter study of > uncontrolled multicenter study of > 11,000 patients suffering from sleep 11,000 patients suffering from sleep –– related disorders found subjective related disorders found subjective improvements in 94% of those treated. improvements in 94% of those treated. Another multicenter trial of the same Another multicenter trial of the same preparation in a younger study population preparation in a younger study population found progressive symptomatic found progressive symptomatic improvement over 10 days of treatment .improvement over 10 days of treatment .

Valerian was found to increase slow Valerian was found to increase slow –– wave sleep in a pilot study of poor wave sleep in a pilot study of poor sleepers . In contrast to previous sleepers . In contrast to previous studies that demonstrated a prompt studies that demonstrated a prompt decrease in symptoms , one study decrease in symptoms , one study found that 2 to 4 weeks was found that 2 to 4 weeks was required to see improvement in 121 required to see improvement in 121 patients with serious insomnia . patients with serious insomnia .

Clinical studies have generally found Clinical studies have generally found valerian to have fewer side effects than valerian to have fewer side effects than positive control drugs such as positive control drugs such as diazepam , producing little hangover diazepam , producing little hangover effect when used as a sleep aid . An effect when used as a sleep aid . An intentional overdose has been reported intentional overdose has been reported in which 20 times the recommended in which 20 times the recommended dose was ingested ; the patient dose was ingested ; the patient experienced mild symptoms that experienced mild symptoms that resolved within 24 hours . resolved within 24 hours .

A recent pharmacological study A recent pharmacological study indicated that both valepotriates and indicated that both valepotriates and valerenic acid are capable of binding to valerenic acid are capable of binding to GABA receptors in a similar fashion to GABA receptors in a similar fashion to benzodiazepines .However, valerian benzodiazepines .However, valerian does not appear to act in a similar does not appear to act in a similar fashion,in that side fashion,in that side –– effects such as effects such as impaired mental function morning impaired mental function morning hangover, and dependency have not hangover, and dependency have not been reported with valerian .been reported with valerian .

In addition , valerian compounds In addition , valerian compounds which do not bind to GABA receptors which do not bind to GABA receptors have also been shown to produce have also been shown to produce sedative effects . Several recent sedative effects . Several recent clinical studies have substantiated clinical studies have substantiated valerian`s ability to improve sleep valerian`s ability to improve sleep quality and reduces night quality and reduces night –– time time awakenings in sufferes of insomnia .awakenings in sufferes of insomnia .

This study , performed under strict This study , performed under strict laboratory conditions , demonstrated laboratory conditions , demonstrated that valerian is as effective in that valerian is as effective in reducing sleep latency as small reducing sleep latency as small doses of barbiturates or doses of barbiturates or benzodiazepines. However while benzodiazepines. However while these latter compounds also increase these latter compounds also increase morning sleepiness, valerian usually morning sleepiness, valerian usually reduces morning sleepiness.reduces morning sleepiness.

In another study of insomniacs, In another study of insomniacs, subjects received either a valerian subjects received either a valerian preparation and / or preparation and / or placebo .Compared with the placebo placebo .Compared with the placebo , valerian showed a significant , valerian showed a significant effect, with 44% reporting perfect effect, with 44% reporting perfect sleep and 89% reporting improved sleep and 89% reporting improved sleep.sleep.

Clinical trials :Clinical trials : There is abundant There is abundant evidence that valerian is effective as a evidence that valerian is effective as a sleep aid and as a mild antianxiety agent sleep aid and as a mild antianxiety agent , although the effect appears to be , although the effect appears to be weaker in healthy subjects than in poor weaker in healthy subjects than in poor sleepers . An aqueous extract of the root sleepers . An aqueous extract of the root (400 mg extract) improved sleep quality (400 mg extract) improved sleep quality in a number of subjective parameters in in a number of subjective parameters in 128 healthy volunteers using a 128 healthy volunteers using a crossover design . crossover design .

And finally , in another double And finally , in another double –– blind study of insomniacs , 20 blind study of insomniacs , 20 subjects received a combination of subjects received a combination of valerian root (160 mg ) and Melissa valerian root (160 mg ) and Melissa officinalis ( 80 mg ) , a officinalis ( 80 mg ) , a benzodiazepine ( triazolam 0.125 ), benzodiazepine ( triazolam 0.125 ), or placebo .or placebo .

In the insomniac group , the valerian In the insomniac group , the valerian preparation showed an effect preparation showed an effect comparable to that of the comparable to that of the benzodiazepine, as well as an increase in benzodiazepine, as well as an increase in deep sleep stage 3 and 4. The valerian deep sleep stage 3 and 4. The valerian preparation did not , however , cause day preparation did not , however , cause day time sedation and there was no evidence time sedation and there was no evidence of diminished concentration based on of diminished concentration based on the concentration performance test or the concentration performance test or impairment of physical performance.impairment of physical performance.

Valerenic acid has been found to Valerenic acid has been found to inhibit GABA transaminase , the inhibit GABA transaminase , the principle enzyme that catabolizes principle enzyme that catabolizes GABA . GABA .

GABA GABA ––T inhibition increases the T inhibition increases the inhibitory effect of GABA in the inhibitory effect of GABA in the CNS , and can therefore contribute CNS , and can therefore contribute to valerian's sedative properties .to valerian's sedative properties .

Side effects :Side effects : Valerian is generally Valerian is generally regarded as safe and is approved for regarded as safe and is approved for food use by the united states food food use by the united states food and drug administration . A major and drug administration . A major concern for any sedative or anti concern for any sedative or anti –– anxiety medication is its potential to anxiety medication is its potential to effect a person`s ability to drive or effect a person`s ability to drive or operate potentially dangerous operate potentially dangerous machinery .machinery .

A randomized , placebo A randomized , placebo –– controlled , controlled , double double –– blind study evaluated the blind study evaluated the impact of a valerian / lemon balm impact of a valerian / lemon balm prepartion on psychomotor and prepartion on psychomotor and mental performance tests . No mental performance tests . No impact was found on reaction time , impact was found on reaction time , concentration or attentiveness.concentration or attentiveness.

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

Valerian Valerian (Valeriana officinalis)(Valeriana officinalis)

Dosage:Dosage: capsules (usually distributed as 150 mg capsules (usually distributed as 150 mg

capsules, standardized to 0.8% valeronic capsules, standardized to 0.8% valeronic acid or 1-1.5% valtrate)acid or 1-1.5% valtrate)

anxiety-100-200 mg dose up to TIDanxiety-100-200 mg dose up to TID sleep-200-400 mg dose at HSsleep-200-400 mg dose at HS

tincture of valerian=1-3 ml in 1-2 oz water tincture of valerian=1-3 ml in 1-2 oz water taken QD-TID or at HS, 30 min before taken QD-TID or at HS, 30 min before desired sleepdesired sleep

SCIENTIFIC NAME(S) :SCIENTIFIC NAME(S) : Melissa Melissa officinalis L. Family Lamiaceae (Mints) officinalis L. Family Lamiaceae (Mints)

CHEMISTRY : CHEMISTRY : Lemon balm leaves Lemon balm leaves contain 0.2% to 0.3% of a lemon contain 0.2% to 0.3% of a lemon –– scented essential oil similar to lemon scented essential oil similar to lemon grass . Major mono grass . Major mono –– and and sesquiterpenes include geranial , neral sesquiterpenes include geranial , neral , b- caryophyllene , b- caryophyllene , b- caryophyllene , b- caryophyllene oxide , linalool, citronellal , nerol , and oxide , linalool, citronellal , nerol , and geraniol . R(+) geraniol . R(+) –– methyl citronellate is methyl citronellate is characteristic of Melissa oil and characteristic of Melissa oil and distinguishes it from lemon grass oil . distinguishes it from lemon grass oil .

This extract also was active in an This extract also was active in an acetic acid writhing analgesia assay acetic acid writhing analgesia assay but not in the hot plate test . The but not in the hot plate test . The volatile oil of the plant had much volatile oil of the plant had much weaker activity or was inactive in weaker activity or was inactive in the same assays . the same assays .

PHARMACOLOGY : PHARMACOLOGY : Lemon balm's Lemon balm's traditional medicinal use was as a traditional medicinal use was as a sedative and antispasmodic .This sedative and antispasmodic .This activity was formerly attributed to activity was formerly attributed to the volatile oil . However, the the volatile oil . However, the lyophilized hydroalcoholic extract , lyophilized hydroalcoholic extract , which does not contain the volatile which does not contain the volatile oil components , has sedative in oil components , has sedative in several mouse models when given several mouse models when given intraperitoneally . intraperitoneally .

Update on Update on AlzheimerAlzheimer’’s s

DiseaseDisease

ii

What is AlzheimerWhat is Alzheimer’’s s DiseaseDisease??

(a.k.a. (a.k.a. ““old timersold timers”” disease) disease) AlzheimerAlzheimer’’s disease is the most s disease is the most

common form of dementia that common form of dementia that affects the elderly. It generally affects the elderly. It generally worsens slowly, and is marked by worsens slowly, and is marked by certain forms of brain degeneration.certain forms of brain degeneration.

What it is dementiaWhat it is dementia??

DementiaDementia can be medically defined can be medically defined as the global loss of cognitive as the global loss of cognitive function in clear consciousness. function in clear consciousness.

For our purposes, however, For our purposes, however, dementiadementia can be thought of as the can be thought of as the gradual loss of onegradual loss of one’’s ability to think. s ability to think.

What are clues that a person What are clues that a person

has has AlzheimerAlzheimer’’s Diseases Disease?? A person who slow losses (over A person who slow losses (over

years)years)…… The ability to handle moneyThe ability to handle money The ability to care for themselvesThe ability to care for themselves The ability to perform previously The ability to perform previously

learned tasks learned tasks The ability to remember the names of The ability to remember the names of

people and objectspeople and objects

……probably has Alzheimerprobably has Alzheimer’’s Diseases Disease

How can one be How can one be suresure that a that a person has Alzheimerperson has Alzheimer’’s s

diseasedisease??

A A definitedefinite diagnosis of Alzheimer diagnosis of Alzheimer’’s s Disease can only be made through Disease can only be made through looking at a personlooking at a person’’s brain after s brain after death. death.

How common is How common is AlzheimerAlzheimer’’s Diseases Disease??

Some believe that the number of Some believe that the number of patients with Alzheimerpatients with Alzheimer’’s Disease s Disease doubles every 5 years after the age doubles every 5 years after the age of 60.of 60. 1% of 60 year-olds affected1% of 60 year-olds affected 40% of 85 year-olds affected40% of 85 year-olds affected

What Causes AlzheimerWhat Causes Alzheimer’’s s DiseaseDisease??

No one knowsNo one knows!!

What Causes AlzheimerWhat Causes Alzheimer’’s s DiseaseDisease??

A number of in-born and A number of in-born and environmental factors appear to be environmental factors appear to be importantimportant AgeAge EducationEducation Certain genesCertain genes

Late Onset Alzheimer’s Disease90% of all Alzheimer patientsabove age 70 yrsslow progressive disease

Risk Factors:Aging, menopauselow education levelhead trauma, cerebral ischaemia

Protective factors :

anti-inflammatory drugsantioxidant agentsoestrogenhigh educational level

Risk Factors: cardiovascular

diseaseobesitydiabeteschronic inflammation

Increased risk with:

APO-E4 genotype to 40~70% of casesTNF-alpha polymorphismTrisomy 21

Minati L, et al. 2008. Current Concepts in Alzheimer's Disease: A Multidisciplinary Review.. J Alzheimers Dis Other Demen.

Inflammation

Inflammation

Oxidantstress

Oxidantstress

Insulin

ResistanceInsulin

Resistance

Alzheimer’s Disease

3 Major processes

Emerit, J., M. Edeas, et al. (2004). "Neurodegenerative diseases and oxidative stress." Biomedicine & Pharmacotherapy 58(1): 39-46 .

InflammationInflammationPresent at cellular level~brain microglia activation ~ not systemic inflammation

Increased cytokine production

TNF-alphaIL-1

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.

Increased lipid

mediators:Leukotrienes

Reduced DHAimpairs

Neuronal signalling

Exacerbated by* cerebral iron & copper* Vascular endothelial disease* APO E4 gene* Insulin Resistance

Oxidant Stress

derives from

Oxidant Stress

derives from

Insulin ResistanceCardiovascular DiseaseDiabetes

EFA imbalanceomega-3-FA insufficiency

Heavy metal overloadiron, coppermercury

InflammationAPO e4 gene

TNF-alpha polymorphism

Chronic inflammatory disease

Low antioxidant

statusAscorbateBioflavonoidsproanthocyanidins

Environmental oxidant exposureSmokingAir pollution

Heavy metals ~ Hg, MnYan, 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.

InsulinResistance

InsulinResistance

DIETHigh

Carbohydrate intake

High saturated fat intake

Carbohydrate-responsive Gene PolymorphismsPPARSSREBPChREBP

Mineral Depletion

• Zinc• Magnesium• Chromium

Omega-3-EFA deficiency

inadequate intake of

Fish & fish oils Obesity andOverweight

Lack ofEXERCISE

ChronicInflammation

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 DiseaseNeurodegenerative Disease

Common character

istics

Reduced mitochondrial and axonal transport

Progressive cell atrophy & apoptosis

Increased tissue oxidative damage

Increased inflammatory cytokine production

Accumulation of abnormal protein fragments

Increased Tau protein phosphorylation

Decreased neurotransmitter production

Increased inflammatory lipid mediators

Progressive cell atrophy & apoptosis

Skovronsky et al. 2006. "NEURODEGENERATIVE DISEASES … Ann Rev Path Mech Dis. 1(1)

Can AlzheimerCan Alzheimer’’s Disease s Disease be Preventedbe Prevented??

No medications are available to No medications are available to prevent Alzheimerprevent Alzheimer’’s diseases disease

Living Living ““rightright”” may help may help Stay active mentally and physicallyStay active mentally and physically Monitor and control high blood Monitor and control high blood

pressurepressure Avoid excessive alcohol useAvoid excessive alcohol use

What Treatments Exist What Treatments Exist for Alzheimerfor Alzheimer’’s Diseases Disease

The only FDA approved medications The only FDA approved medications for Alzheimerfor Alzheimer’’s Disease are ones that s Disease are ones that increase a certain chemical in the increase a certain chemical in the brain (acetylcholine)brain (acetylcholine) AriceptAricept CognexCognex ExelonExelon ReminylReminyl

Alzheimer’s Disease

TREATMENT

DIGESTIVE SUPPORTGastric acid and Digestive enzymes

DIETLow-allergy & Low Glycemic LoadHigh protein & vegetable intakeConsider Paleolithic or ketogenic diet

Essential Fatty Acid SupplementsDHA-rich omega-3-FAsalpha-Linolenic acid

Primary Antioxidant TherapyVitamin C ~ mixed mineral ascorbatesMixed tocopherols & TocotrienolsMixed bioflavonoids

Phytonutrient TherapyBlueberriesGreen teaResveratrolCurcuminPomegranate

Additional Treatments Additional Treatments for Alzheimerfor Alzheimer’’s Diseases Disease

Vitamin E Vitamin E maymay slow the progression slow the progression of the diseaseof the disease

Non-steroidal anti-inflammatory Non-steroidal anti-inflammatory agents agents maymay help prevent the help prevent the disorderdisorder

Mild sedatives (Haldol) are helpful in Mild sedatives (Haldol) are helpful in reducing agitation and behavior reducing agitation and behavior disturbancesdisturbances

What Research is on the What Research is on the HorizonHorizon??

Scientists are currently studying the Scientists are currently studying the ability of a vaccine to prevent or ability of a vaccine to prevent or reverse the damage done by the reverse the damage done by the disorder ( in animals )disorder ( in animals )

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

Alzheimers versus normal Alzheimers versus normal brainbrain

Normal versus Normal versus degenerating neurondegenerating neuron

Anatomical findings Anatomical findings AlzheimerAlzheimer’’ss

1. plaques: clusters of abnormal 1. plaques: clusters of abnormal cells cells

2. tangles of neurofilaments inside 2. tangles of neurofilaments inside neuronsneurons

3. deterioration of dendrites 3. deterioration of dendrites 4. loss of neurons 4. loss of neurons 5. hippocampus is 47% reduced in 5. hippocampus is 47% reduced in

size (in normals it shrinks 27%). size (in normals it shrinks 27%).

Signatures of AlzheimersSignatures of Alzheimers

Deposits of protein fragments called Deposits of protein fragments called beta amyloid beta amyloid –– fill up spaces fill up spaces between brain cellsbetween brain cells

Tangles of protein called tau inside Tangles of protein called tau inside the cellsthe cells

(thought to be causal) (thought to be causal)

Anatomical findingsAnatomical findings(continued)(continued)

6. Amydgala 26% decrease in volume 6. Amydgala 26% decrease in volume 7.cell density reduced by 75% 7.cell density reduced by 75%

(increase in ventricular size)(increase in ventricular size) 8.Those who died show marked loss 8.Those who died show marked loss

of cells in the nucleus basilis (releases of cells in the nucleus basilis (releases ACh and projects to hippocampus and ACh and projects to hippocampus and cortex.cortex.

9. cortex has plaques and tangles.9. cortex has plaques and tangles.

Causes of AlzheimersCauses of Alzheimers

Two hallmarks of Alzheimers disease Two hallmarks of Alzheimers disease are accumulation in the brain of beta are accumulation in the brain of beta amyloid and reduction of the amyloid and reduction of the concentration of ACh. concentration of ACh.

A gene implicated in heart disease A gene implicated in heart disease also appears to be involved in most also appears to be involved in most ““Alzheimer cases= apo E.Alzheimer cases= apo E.

E-2 version protects people from E-2 version protects people from getting Alzheimers. E-4 is the worstgetting Alzheimers. E-4 is the worst

The same forces that trigger this The same forces that trigger this beta amyloid deposits might harm beta amyloid deposits might harm arteries and cause heart attacks. arteries and cause heart attacks.

Culprits=oxygen damage (cellular Culprits=oxygen damage (cellular equivalent of rust) and harmful equivalent of rust) and harmful effects of chronic inflammationeffects of chronic inflammation

Preventative measuresPreventative measures

ginkgo biloba: possibly due to anti-ginkgo biloba: possibly due to anti-inflammatory or circulatory inflammatory or circulatory propertiesproperties

Anti-inflammatory drugs: limit the Anti-inflammatory drugs: limit the production of amyloid production of amyloid

Vitamen E Vitamen E

Statin drugs- (for high cholesterol), Statin drugs- (for high cholesterol), reduce Alzheimerreduce Alzheimer’’s risk. s risk.

Folate-lowers the amino acid Folate-lowers the amino acid homocysteine (that increases homocysteine (that increases AlzheimerAlzheimer’’s and heart disease risk). s and heart disease risk).

Mental exercise- active- do better. Mental exercise- active- do better. Use it or lose it. Use it or lose it.

Take: (HRT), anti-inflamatory Take: (HRT), anti-inflamatory painkillers, and statins painkillers, and statins

= people are 30-50% less likely to = people are 30-50% less likely to get Alzheimerget Alzheimer’’s. s.

Ginkgo bilobaGinkgo biloba

History and BackgroundHistory and Background Ancient use in China and Ancient use in China and

Japan as a tonic.Japan as a tonic. Poor CirculationPoor Circulation Inner ear disordersInner ear disorders Absent-mindedness, Absent-mindedness,

Dementia, Depression, and Dementia, Depression, and Hypertension in the elderly Hypertension in the elderly

Impotence in menImpotence in men Chinese used leaves and Chinese used leaves and

nutsnuts Use dates back over Use dates back over

5000 years5000 years

About the plantAbout the plant…… Commonly known as maidenhair Commonly known as maidenhair

treetree Known for its green, fan-shaped Known for its green, fan-shaped

leaves that turn yellow in autumnleaves that turn yellow in autumn Unique seeds (not used in extracts)Unique seeds (not used in extracts) Extracts prepared from dried, green, Extracts prepared from dried, green,

whole leaveswhole leaves Tree can reach up to 80 feet tall and Tree can reach up to 80 feet tall and

60 feet wide in urban areas60 feet wide in urban areas

A Living FossilA Living Fossil The worldThe world’’s oldest trees oldest tree In existence for over 250 million yearsIn existence for over 250 million years Darwin referred to it as Darwin referred to it as ““a living fossila living fossil””

Present UsagePresent Usage

Uses in MedicineUses in Medicine Age-associated Age-associated

memory memory impairment (AAMI), impairment (AAMI), dementia and dementia and Alzheimer's.Alzheimer's.

Peripheral arterial Peripheral arterial occlusive diseaseocclusive disease

Active Active SubstancesSubstances

FlavonoidsFlavonoids Terpene LactonesTerpene Lactones

ginkolidesginkolidesallergic inflammationallergic inflammationanaphylactic shockanaphylactic shockasthmaasthma

StructuresStructures

Phenolic Phenolic SubstituentsSubstituents

Terpene Terpene SubstituentsSubstituents

Physiologic Mode of Physiologic Mode of ActionAction

Attributed to a Attributed to a combination of the combination of the flavonoid flavonoid glycosides and the glycosides and the diterpene lactones diterpene lactones (ginkgolides).(ginkgolides).

HowHow’’s it Works it Work??

Powerful antioxidantPowerful antioxidantpremature aging and premature aging and

dementiadementia Controls hardening of Controls hardening of

arteriesarteriesrelax blood vesselsrelax blood vessels

Physiologic Mode of Action Physiologic Mode of Action ContCont’’dd

Acts by releasing vasodilators, Acts by releasing vasodilators, specifically nitric oxide and specifically nitric oxide and PGI2, which allows increased PGI2, which allows increased blood flow throughout the blood flow throughout the circulatory system and circulatory system and therefore increase oxygen and therefore increase oxygen and nutrient delivery to the nutrient delivery to the tissues.tissues.

Allows increased Allows increased microcirculation in the microcirculation in the capillaries (i.e. better capillaries (i.e. better exchange on the cellular level)exchange on the cellular level)

Decreases blood viscosityDecreases blood viscosity

Molecular Mode of Molecular Mode of ActionAction

Treatment with ginkgo increases the Treatment with ginkgo increases the production of NO (nitric oxide) through production of NO (nitric oxide) through NOS (nitric oxide synthase).NOS (nitric oxide synthase).

NO increases the activity of KNO increases the activity of KCaCa channels channels and invokes the influx of Caand invokes the influx of Ca2+2+ into into endothelial cells.endothelial cells.

This mode was double checked against a This mode was double checked against a known Caknown Ca2+2+ channel blocker (TEA) and channel blocker (TEA) and inhibited the effects of ginkgo.inhibited the effects of ginkgo.

Ginkgo does not affect ATP KGinkgo does not affect ATP K++ channels. channels.

Ginkgo and MemoryGinkgo and Memory

Effects on AAMI and cerebral insufficiencyEffects on AAMI and cerebral insufficiency

All but 1 of the 8 studies found a reduction All but 1 of the 8 studies found a reduction in the symptoms of these diseases.in the symptoms of these diseases.

May take 4-6 weeks to see improvement.May take 4-6 weeks to see improvement.

UCLA studyUCLA study

Peripheral Arterial Peripheral Arterial DiseaseDisease

Intermittent Claudication (IC) Intermittent Claudication (IC) One study showed that One study showed that

patients on ginkgo extract patients on ginkgo extract therapy had increased pain-therapy had increased pain-free walking distance.free walking distance.

Another study showed that Another study showed that there was a reduction in pain there was a reduction in pain at rest with patients on at rest with patients on ginkgo therapy. ginkgo therapy.

Other Positive Effects of Other Positive Effects of GinkgoGinkgo

Improvements in Improvements in cerebral metabolism cerebral metabolism (increases the efficiency (increases the efficiency of the oxygen thatof the oxygen that’’s s present)present)

Increase in the release Increase in the release of neurotransmittersof neurotransmitters

Antioxidant activityAntioxidant activity Prevention of free Prevention of free

radical damageradical damage

Ginkgo Ginkgo ExtractsExtracts

Inhibit platelet activating Inhibit platelet activating factorfactor

Over-stimulate immune Over-stimulate immune systemsystem

Fountain of YouthFountain of Youth??

Enhances memoryEnhances memory Treatment of vertigoTreatment of vertigo CounteractsCounteracts

lack of energylack of energymental fatigue mental fatigue agingaging

GinkgoGinkgo’’s s AdvantageAdvantage

Increased blood flow to brain and bodyIncreased blood flow to brain and body

Blood Blood CirculationCirculation

Carry nutrients(oxygen, Carry nutrients(oxygen, sugars, enzymes)sugars, enzymes)

Removes wasteRemoves waste Feeds the brainFeeds the brain

Circulation Circulation ImportanceImportance

Constant circulation criticalConstant circulation critical waste not removedwaste not removed cells age more rapidlycells age more rapidly sit in wastesit in waste

Improper cell nourishmentImproper cell nourishment wear out fasterwear out faster experience aches, pains, stiffnessexperience aches, pains, stiffness

Circulation Circulation BenefitsBenefits

Boosts oxygen level to Boosts oxygen level to brainbrain

Improved short term and Improved short term and long term memorylong term memory

increased reaction timeincreased reaction time Improved mental clarityImproved mental clarity

Elderly UsageElderly Usage AlzheimerAlzheimer’’ss

degenerative disease that degenerative disease that attacks brainattacks brain

Cerebral insufficiencyCerebral insufficiencyconcentration difficultiesconcentration difficultiesconfusionconfusion lack of energylack of energy

EGb 761EGb 761 Extract used to alleviate Extract used to alleviate

cognitive disorderscognitive disorders Antioxidant properties of Antioxidant properties of

flavoniods and terpeniodsflavoniods and terpeniods Scavenger of radicals Scavenger of radicals

associated with Alzheimer associated with Alzheimer diseasedisease

Typical dose (used in many experiments) is Typical dose (used in many experiments) is 120 milligrams of dried extract in two or 120 milligrams of dried extract in two or three oral doses. three oral doses.

Extract in German product is named EGb Extract in German product is named EGb 761, manufactured by Schwabe 761, manufactured by Schwabe Pharmaceuticals.Pharmaceuticals.

The extract contains The extract contains flavonoids and biflavonoids, a large group of flavonoids and biflavonoids, a large group of

natural plant productsnatural plant products terpenes (active ingredients in catnip and terpenes (active ingredients in catnip and

marijuana)marijuana)

Dozens of clinical trials have examined Dozens of clinical trials have examined the cognitive effects of gingko in the cognitive effects of gingko in humans.humans.

Great majority of studies have involved Great majority of studies have involved subjects with mild to moderate subjects with mild to moderate impairment, usually an early diagnosis of impairment, usually an early diagnosis of Alzheimer's.Alzheimer's.

Most experiments test learning and Most experiments test learning and memory; less often attention, motivation memory; less often attention, motivation or anxiety.or anxiety.

Turmeric and AlzheimerTurmeric and Alzheimer

Diets rich in curcumin--a compound Diets rich in curcumin--a compound found in the curry spice turmeric--found in the curry spice turmeric--may help explain why rates of may help explain why rates of Alzheimer's disease are much lower Alzheimer's disease are much lower among the elderly in India compared among the elderly in India compared with their Western peers.with their Western peers.

Alzheimer's disease is characterized Alzheimer's disease is characterized by the buildup of amyloid protein by the buildup of amyloid protein ``plaques'' within the brain. In ``plaques'' within the brain. In studies in rats, curcumin ``not only studies in rats, curcumin ``not only reduces the amyloid, but also reduces the amyloid, but also reduces the (brain's) response to the reduces the (brain's) response to the amyloid,'' according to researcher amyloid,'' according to researcher Dr. Sally Frautschy of the University Dr. Sally Frautschy of the University of California, Los Angelesof California, Los Angeles

Previous studies have noted that elderly Previous studies have noted that elderly individuals living in Indian villages appear to individuals living in Indian villages appear to have the lowest incidence of Alzheimer's disease have the lowest incidence of Alzheimer's disease in the world, with just 1% of those aged 65 and in the world, with just 1% of those aged 65 and older contracting the degenerative brain older contracting the degenerative brain condition. The reasons for this low incidence condition. The reasons for this low incidence remain unclear, however. Frautschy speculated remain unclear, however. Frautschy speculated that curcumin found in curry could provide a that curcumin found in curry could provide a clue to this puzzle since the compound has ``a clue to this puzzle since the compound has ``a long history of dietary and herbal medicinal use'' long history of dietary and herbal medicinal use'' and is also a powerful antioxidant and anti-and is also a powerful antioxidant and anti-

inflammatory agentinflammatory agent..

, Frautschy fed middle-aged (9 months old) and aged , Frautschy fed middle-aged (9 months old) and aged (22 months old) rats diets rich in curcumin. All of the (22 months old) rats diets rich in curcumin. All of the rats had received brain injections of amyloid to mimic rats had received brain injections of amyloid to mimic progressive Alzheimer's diseaseprogressive Alzheimer's disease..

````Curcumin reduced the accumulation of beta-amyloid Curcumin reduced the accumulation of beta-amyloid and the associated loss of Synapses connect nerve and the associated loss of Synapses connect nerve cells and are crucial for memory,'' the California cells and are crucial for memory,'' the California researcher explained. Keeping synapses free of plaque researcher explained. Keeping synapses free of plaque is important because ``their loss correlates well with is important because ``their loss correlates well with memory decline in Alzheimer's.'' This type of memory memory decline in Alzheimer's.'' This type of memory preservation may have been reflected preservation may have been reflected in the fact that in the fact that

rats fed curcumin also performed much rats fed curcumin also performed much better in memory-dependent maze tests better in memory-dependent maze tests compared with rats on normal diets, compared with rats on normal diets, according to Frautschy. according to Frautschy.

. . Curcumin also appeared to reduce Curcumin also appeared to reduce Alzheimer's-related inflammation in neurologic Alzheimer's-related inflammation in neurologic tissue. in the synapses, or gaps, between tissue. in the synapses, or gaps, between individual brain cells, Frautschy reported. individual brain cells, Frautschy reported. Because ``a combined anti-inflammatory and Because ``a combined anti-inflammatory and antioxidant approach will be useful for antioxidant approach will be useful for Alzheimer's prevention or treatment,'' Alzheimer's prevention or treatment,'' Frautschy speculates that curcumin could be Frautschy speculates that curcumin could be especially valuable in the fight against the especially valuable in the fight against the disease, especially in combination with anti-disease, especially in combination with anti-inflammatory drugs like ibuprofeninflammatory drugs like ibuprofen

Researchers in India have suggested performing Researchers in India have suggested performing clinical trials on humans to explore turmeric's efficacy clinical trials on humans to explore turmeric's efficacy as a novel antidepressant. However, as of 2008, as a novel antidepressant. However, as of 2008, numerous numerous clinical trialsclinical trials in humans were underway, in humans were underway, studying the effect of curcumin on various diseases, studying the effect of curcumin on various diseases, including including multiple myelomamultiple myeloma, , pancreatic cancerpancreatic cancer, , myelodysplastic syndromesmyelodysplastic syndromes, , colon cancercolon cancer, , psoriasispsoriasis, , and and Alzheimer's disease.Alzheimer's disease.

In vitroIn vitro and animal studies have proven that curcumin and animal studies have proven that curcumin has has antitumorantitumor,,[[antioxidantantioxidant, , antiarthriticantiarthritic, , antiamyloidantiamyloid, , anti-ischemic,anti-ischemic,[[and and anti-inflammatoryanti-inflammatory properties. properties.[[Anti-Anti-inflammatory properties may be due to inhibition of inflammatory properties may be due to inhibition of

eicosanoideicosanoid biosynthesis biosynthesis..

Numerous studies have demonstrated Numerous studies have demonstrated curcumin, amongst only a few other curcumin, amongst only a few other things, such as high impact exercise, things, such as high impact exercise, learning, bright light, and antidepressant learning, bright light, and antidepressant usage, has a positive effect on usage, has a positive effect on neurogenesis in the neurogenesis in the hippocampushippocampus and and concentrations of concentrations of brain-derived brain-derived neurotrophic factorneurotrophic factor (BDNF), reductions (BDNF), reductions in both of which are associated with in both of which are associated with stress, depression, and anxiety.stress, depression, and anxiety.

Curcumin has also been demonstrated to Curcumin has also been demonstrated to be a selective be a selective monoamine oxidase monoamine oxidase inhibitorinhibitor (MAOI) of type (MAOI) of type MAO-AMAO-A. . Fluorescent imaging in a mouse model of Fluorescent imaging in a mouse model of Alzheimer's disease showed that curcumin Alzheimer's disease showed that curcumin crosses the crosses the blood-brain barrier.blood-brain barrier.Several Several studies have demonstrated that unlike studies have demonstrated that unlike glucuronidated curcumin, free curcumin, glucuronidated curcumin, free curcumin, which is lipophilic, readily passes the which is lipophilic, readily passes the blood brain barrierblood brain barrier

Protein PlaquesProtein Plaques [[Curcumin, the active constituent in turmeric, Curcumin, the active constituent in turmeric,

reduces the damaging effects of protein plaques reduces the damaging effects of protein plaques in the brains of Alzheimer's disease patients in the brains of Alzheimer's disease patients according to a U.S. study published in the according to a U.S. study published in the September 2010 "Journal of Biological September 2010 "Journal of Biological Chemistry." The study on laboratory mice Chemistry." The study on laboratory mice revealed that curcumin inhibited the production revealed that curcumin inhibited the production of amyloid-beta protein, which comprises the of amyloid-beta protein, which comprises the plaques that disrupt brain function in plaques that disrupt brain function in Alzheimer's. The researchers noted that this Alzheimer's. The researchers noted that this study represents the first of its kind to pinpoint a study represents the first of its kind to pinpoint a mechanism for the effects of curcumin on this mechanism for the effects of curcumin on this disease processdisease process

Anti-inflammatory and AntioxidantAnti-inflammatory and Antioxidant Turmeric's antioxidant, anti-inflammatory and Turmeric's antioxidant, anti-inflammatory and

lipid-soluble properties give it particular benefits lipid-soluble properties give it particular benefits for improving the symptoms of Alzheimer's for improving the symptoms of Alzheimer's disease according to a study published in the disease according to a study published in the January 2008 "Annals of the Indian Academy of January 2008 "Annals of the Indian Academy of Neurology." Turmeric relieves oxidative stress, Neurology." Turmeric relieves oxidative stress, reduces damage caused by free radicals, inhibits reduces damage caused by free radicals, inhibits the formation of beta-amyloid proteins, reduces the formation of beta-amyloid proteins, reduces inflammation and protects against disruption of inflammation and protects against disruption of brain function by toxic metals that contribute to brain function by toxic metals that contribute to the development of the disease. These benefits the development of the disease. These benefits to nerve function improved memory for to nerve function improved memory for Alzheimer's patients.Alzheimer's patients.

DepressionDepression Depressive symptoms associated with Alzheimer's Depressive symptoms associated with Alzheimer's

disease may respond to treatment with turmeric, disease may respond to treatment with turmeric, according to an Indian study published in the according to an Indian study published in the November 2009 "Scientific World Journal." November 2009 "Scientific World Journal." Turmeric could have the ability to regulate the Turmeric could have the ability to regulate the release of the neurotransmitters serotonin and release of the neurotransmitters serotonin and dopamine and the spice has been shown to dopamine and the spice has been shown to promote nerve growth in the frontal lobe, which is promote nerve growth in the frontal lobe, which is an area of the brain responsible for cognition, and an area of the brain responsible for cognition, and also in the hippocampus, which is an area of the also in the hippocampus, which is an area of the brain associated with memory. The researchers brain associated with memory. The researchers called for further testing, including clinical trials, called for further testing, including clinical trials, to clearly define the role of turmeric in depressionto clearly define the role of turmeric in depression

  

Phytoarthrit Capsule: Boswellia Phytoarthrit Capsule: Boswellia Serrata, Zingiber, Turmeric, Cat,s Serrata, Zingiber, Turmeric, Cat,s clawclaw

HypericumHypericum perforatumperforatum(Clusiaceae)(Clusiaceae)

SJW: BackgroundSJW: Background Ancient Greece: medicinal plantsAncient Greece: medicinal plants

Hippocrates (460- 377 B.C.)Hippocrates (460- 377 B.C.) Therapeutic applicationsTherapeutic applications

External: contusions, myalgia, first degree External: contusions, myalgia, first degree burns, poisonous reptile bites.burns, poisonous reptile bites.

Internal: neuralgia,anxiety, neurosis, Internal: neuralgia,anxiety, neurosis, insomnia, depression.insomnia, depression.

Current Use/ PopularityCurrent Use/ Popularity Europe: GermanyEurope: Germany U.S., AustraliaU.S., Australia

Active compoundsActive compounds

Hypericin (the red resin)Hypericin (the red resin) HyperforinHyperforin FlavonoidsFlavonoids GlycosidesGlycosides TanninTannin Essential oilsEssential oils BioflavonesBioflavones PseudohypericinPseudohypericin

StructuresStructures

SJW: PharmacokineticsSJW: Pharmacokinetics

AbsorptionAbsorption Route of administration: oralRoute of administration: oral Peak levels: 5 hrsPeak levels: 5 hrs Daily doses varyDaily doses vary

450- 900 mg450- 900 mg 900- 1800 mg900- 1800 mg

DistributionDistribution Blood - brain barrierBlood - brain barrier

Steady state: 4 – 6 daysSteady state: 4 – 6 days

SJW: PharmacokineticsSJW: Pharmacokinetics DistributionDistribution

Placental barrier: unknownPlacental barrier: unknown InactivationInactivation

MetabolismMetabolism P450: CYP3A4P450: CYP3A4 P-glycoproteinP-glycoprotein

EliminationElimination Kidneys: urineKidneys: urine Half –life: 25 hrHalf –life: 25 hr

SJW: PharmacodynamicsSJW: Pharmacodynamics

Cellular sites and mechanism(s) of actionCellular sites and mechanism(s) of action Non-selective reuptake inhibitorNon-selective reuptake inhibitor

5-HT, NE, DA5-HT, NE, DA GABA, glutamateGABA, glutamate

NMDA, BDZNMDA, BDZ MAOI, COMT enzymeMAOI, COMT enzyme

Sites of ActionSites of Action Cerebellum/ brain stemCerebellum/ brain stem HypothalamusHypothalamus

SJW: PharmacodynamicsSJW: Pharmacodynamics

Sites of ActionSites of Action HippocampusHippocampus Cerebral cortex: esp. frontal cortexCerebral cortex: esp. frontal cortex Nucleus accumbensNucleus accumbens Locus coeruleusLocus coeruleus

SJW: Tolerance and SJW: Tolerance and DependenceDependence

ToleranceTolerance MetabolicMetabolic Cellular/ pharmacodynamicCellular/ pharmacodynamic

Downregulation BDownregulation B11- adrenoreceptors: - adrenoreceptors: frontal cortexfrontal cortex

Progressive sensitization/ upregulation Progressive sensitization/ upregulation postsynaptic 5-HTpostsynaptic 5-HT11: hippocampus: hippocampus

Upregulation 5-HTUpregulation 5-HT22

Hyperforin –rich: downregulationHyperforin –rich: downregulation

Mode of ActionMode of Action

Crude extracts of SJW have a variety Crude extracts of SJW have a variety of neuropharmacologic actionsof neuropharmacologic actions Inhibits monoamine oxidase (MAO), Inhibits monoamine oxidase (MAO),

GABA, norepinephrine and dopamine GABA, norepinephrine and dopamine reuptakereuptake

Increases free intracellular Na+, Increases free intracellular Na+, which inhibits serotonin reuptakewhich inhibits serotonin reuptake

Pharmacology contPharmacology cont..

It is likely that It is likely that Hypericum Hypericum acts on acts on many levels many levels simultaneously, creating simultaneously, creating an accumulating effect an accumulating effect by being both a MAO-by being both a MAO-inhibitor, inhibitor, serotonin-,norepinephriserotonin-,norepinephrine-, and dopamine- ne-, and dopamine- reuptake inhibitor, a reuptake inhibitor, a cortisol secretion cortisol secretion inhibitor etc.inhibitor etc.