ALZHEIMER’S DISEASE

transcript

ALZHEIMER’S DISEASE-

AND ITS HERBAL TREATMENT

Presented by--- K.Swathi priya ( regd no.609209506005 ) Under the esteemed guidance of prof. Ganga rao Bottu. M.Pharm.,Ph.D.(INDIA),Ph.D(U.K.),Postdoc(Australia)

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The Impact of ADOnce considered a rare disorder, Alzheimer’s disease is now seen as a major public health problem that is seriously affecting millions of older people and their families.

What is Alzheimer’s disease (AD)?

Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills.

Although the risk of developing AD increases with age – in most people with AD, symptoms first appear after age 60 – AD is not a part of normal aging. It is caused by a fatal disease that affects the brain.

• AD is the most common cause of dementia among people age 65 and older.

• Scientists estimate that around 4.5 million people now have AD.

• For every 5-year age group beyond 65, the percentage of people with AD doubles.

• By 2050, 13.2 million older people are expected to have AD if the current numbers hold and no preventive treatments become available.

Inside the Human Brain

To understand Alzheimer’s disease, it’s important to know a bit about the brain…

The Brain’s Vital Statistics

• Adult weight: about 3 pounds

• Adult size: a medium cauliflower

• Number of neurons: 100,000,000,000 (100 billion)

• Number of synapses (the gap between neurons): 100,000,000,000,000 (100 trillion)

The Three Main Players

1. Cerebral Hemispheres – where sensory information received from the outside world is processed; this part of the brain controls voluntary movement and regulates conscious thought and mental activity:

• accounts for 85% of brain’s weight

• consists of two hemispheres connected by the corpus callosum

• is covered by an outer layer called the cerebral cortex

2. Cerebellum – in charge of balance and coordination:

• takes up about 10% of brain

• consists of two hemispheres

• receives information from eyes, ears, and muscles and joints about body’s movements and position

3. Brain Stem – connects the spinal cord with the brain

• relays and receives messages to and from muscles, skin, and other organs

• controls automatic functions such as heart rate, blood pressure, and breathing

Other Crucial Parts

• Hippocampus: where short-term memories are converted to long-term memories

• Thalamus: receives sensory and limbic information and sends to cerebral cortex

• Hypothalamus: monitors certain activities and controls body’s internal clock

• Limbic system: controls emotions and instinctive behavior (includes the hippocampus and parts of the cortex)

Inside the Human BrainThe Brain in Action

Hearing Words Speaking Words Seeing Words Thinking about Words

Different mental activities take place in different parts of the brain. Positron emission tomography (PET) scans can measure this activity..

Neurons

• The brain has billions of neurons, each with an axon and many dendrites.

• To stay healthy, neurons must communicate with each other, carry out metabolism, and repair themselves.

• AD disrupts all three of these essential jobs.

Plaques and Tangles: The Hallmarks of AD

The brains of people with AD have an abundance of two abnormal structures:

• beta-amyloid plaques, which are dense deposits of protein and cellular material that accumulate outside and around nerve cells

• neurofibrillary tangles, which are twisted fibers that build up inside the nerve cell

Beta-amyloid Plaques

Amyloid precursor protein (APP) is the precursor to amyloid plaque.

1. APP sticks through the neuron membrane.

2. Enzymes cut the APP into fragments of protein, including beta-amyloid.

3. Beta-amyloid fragments come together in clumps to form plaques.

In AD, many of these clumps form, disrupting the work of neurons. This affects the hippocampus and other areas of the cerebral cortex.

Neurofibrillary Tangles

Neurons have an internal support structure partly made up of microtubules. A protein called tau helps stabilize microtubules. In AD, tau changes, causing microtubules to collapse, and tau proteins clump together to form neurofibrillary tangles.

No one knows what causes AD to begin, but we do know a lot about what happens in the brain once AD takes hold.

Preclinical AD

Mild to Moderate AD

Severe AD

The two main types of AD are early-onset and late-onset:

• Early-onset AD is rare, usually affecting people aged 30 to 60 and usually running in families. Researchers have identified mutations in three genes that cause early-onset AD.

• Late-onset AD is more common. It usually affects people over age 65. Researchers have identified a gene that produces a protein called apolipoprotein E (ApoE). Scientists believe this protein is involved in the formation of beta-amyloid plaques.

Signs and symptomsSigns and symptoms

Increasing and persistent forgetfulnessIncreasing and persistent forgetfulness

DifficultiesDifficulties with abstract thinking.with abstract thinking. Difficulty finding the right word.Difficulty finding the right word. Disorientation.Disorientation. Loss of judgment.Loss of judgment. Difficulty performing familiar tasks.Difficulty performing familiar tasks. Personality changes. Personality changes.

ComplicationsComplications

Pneumonia. Pneumonia. Infections. Untreated urinary tract infections can lead to more Infections. Untreated urinary tract infections can lead to more

serious, life-threatening infections. serious, life-threatening infections. Falls and their complications. Falls and their complications. 1.1. DisorientedDisoriented2.2. Falls lead to fractures. Falls lead to fractures. 3.3. Serious head injuries (bleeding of brain). Serious head injuries (bleeding of brain). 4.4. Surgery to repair injury carries risks. Surgery to repair injury carries risks.

5.5. Prolonged immobilization increases the risk of pulmonary Prolonged immobilization increases the risk of pulmonary embolism, which can be life-threatening.embolism, which can be life-threatening.

• Apart from synthetic drugs, Alzheimer's’ disease can be cured as well as prevented by natural herbal drugs. This is regarded as Complementary Alternative Medicine system. Which is been widely used due to less risk of side effects.

Herbal drugs used to treat Alzheimer's diseaseHerbal drugs used to treat Alzheimer's disease

Ginkgo bilobaGinkgo biloba Vinca minorVinca minor Rosemarinus officanalis Rosemarinus officanalis Salvia officanalis Salvia officanalis Allium sativumAllium sativum Macleaya cordataMacleaya cordata

Galanthus woronowiiGalanthus woronowii

Melissa officinalisMelissa officinalis Lycorus radiata Lycorus radiata Curcuma longaCurcuma longa Centella asiaticaCentella asiatica Coptis chinenses Coptis chinenses Securinega suffruticosa Securinega suffruticosa Withania somnifera Withania somnifera

Ginkgo biloba (maidenhair tree) Kingdom : plantaeKingdom : plantae

Division : ginkgophytaDivision : ginkgophyta

Class Class : ginkgoopsida : ginkgoopsida

OrderOrder : ginkgoales : ginkgoales

Family : ginkgoaceaeFamily : ginkgoaceae

Genus : ginkgoGenus : ginkgo

Species : G.bilobaSpecies : G.biloba

Active constituents :Active constituents :

• Flavonoids

• Triterpenoids

• Ginkgetin

• Flavones • Isoginkgetin

• 5-methoxybilobitol

• Belobetol

• Sciadopitysin

• Ginkgolides

• Bilobalide

Mechanism of action :Mechanism of action :

Other pharmacological properties:Other pharmacological properties:

• Cardioprotective effect

• Anti inflammatory

• Anti oxidant

• Anticancer effect

• Anxiety syndromes

• Effects on tinnitus, geriatrics and psychiatric disorders

Adverse effects:• Gastrointestinal problems

• Allergic reactions

• Nausea

• Headache

Herbal drug-drug interactions :

• Anti coagulant drugs leading to hemorrhage

• Anti depressants (trazadone) leading to mental disorders

• Others

Dosage :

• Doses of 120mg to 240mg daily………..

• Ginkgolic acid (alkyl phenol) toxic in nature

• Hence, the concentration of Ga should be less than 5ppm

In Market:

• It can be taken in its original form or it is available in the market in the form of capsules.

• Jarrows formulation-- Jarrows ginkgo biloba-- 120mg,60 capsules .

Galanthus woronowii: Kingdom : plantaeKingdom : plantae

Clade : AngiospermsClade : Angiosperms

Clade Clade : Monocots : Monocots

OrderOrder : Asparagales : Asparagales

Family :amaryllidaceaeFamily :amaryllidaceae

Subfamily :amaryllidoiceaeSubfamily :amaryllidoiceae

Genus : GalanthusGenus : Galanthussnowdrop

Active constiuents:

• GALANTAMINE

• An alkaloid obtained from the bulbs and flowers of galanthus woronowii.

Structure :

Mechanism of action:

Absorption, bioavailability and distribution:

• Absorption : rapid and complete

• Max plasma conc: 0.5 – 2 hours.

• Food decreases rate of absorption

• Bioavailability: 80% to 100%.

• Distribution : large volumes, rapid and non-specific distribution of the drug.

Metabolism and Excretion :

• Metabolism -major route liver.

• Excreted - through urine.

dose :• The dose of galantamine should not exceed 16mg/day…..

Precautions :

• If they have peptic ulcers, Parkinson's, heart diseases, hypotension or if the patient is pregnant.

Adverse effects:

Herbal drug-drug interactions :

• Gastrointestinal problems

• Allergic reactions

• Nausea

• Headache etc….

• Antagonizes the action of anticholinergic drugs.

• Cimetidine increases galantamine bioavailabiliy.

• It shows interactions with digoxin, warfarin etc….

In market:

It is available in the form of capsules

Reminyl™ ER(extended release galantamine hydrobromide) Life Enhancement, GalantaMind, Memory Function Support, 90 Capsules

Curcuma longa :

Kingdom : plantaeKingdom : plantae

OrderOrder : zingiberales : zingiberales

Family : zingiberaceaeFamily : zingiberaceae

Genus : curcumaGenus : curcuma

Species : C.longaSpecies : C.longa

turmeric

Active constiuents:

• CURCUMIN

• A Polyphenol..

Keto form Enol form

Mechanism of action:• Inhibits beta-amyloid plaque formation

• Other MOA….• Lowers oxidative damage

• Cognitive defects

• Inhibits damage to neuronal synapse

• Antitumor

• Antioxidant

• Antiarthritic

• Antibacterial

• Hepatoprotective etc…

Dosage :

• Turmeric can be used in food and it is readily available in powdered form. Curcumin extracts in liquid form are also available. Turmeric powder can be consumed with herb based teas, honey or hot water..

• Usually about a half to a quarter teaspoon of powdered turmeric should be consumed two to three times a day.

• Curcumin capsules with a dosage 250-500 mg can also be taken three times a day.

It has been found that, in vitro, turmeric can have antiplatelet effects with antiplatelet or anticoagulant drugs

Interactions :

Centella asiatica:(Gotu Kola )

Kingdom : PlantaeKingdom : Plantae

Clade Clade : Eudicots : Eudicots

OrderOrder : Apiales : Apiales

Family : Mackinlayaceae Family : Mackinlayaceae

Genus : CentellaGenus : Centella

Species : C.asisticaSpecies : C.asistica

Active constiuents:

• GLYCOSIDES:

brahmoside, brahminoside, asiaticoside, indocentelloside etc…..

• Also contains mesoinosetol, a new oligosaccharide, centellose, kaempherol etc…

Mechanism of action:

• Oxidative stress also leads to AD because of harmful production of free radicals……

• Gastric ulcers

• Anti oxidant

• Cognitive property

• Anti epileptic

• Anti depressant

• Anxiolytic properties.

Dosage :• 1000mg/ 3 times a day and about 1 hour before meal.

Interactions :

• It shows interaction with CNS depressants as result increases sleeping time .

• There is concern that gotu kola might cause liver damage. People who already have a liver disease such as hepatitis should avoid using gotu kola. It might make liver problems worse. . It is safe during pregnancy…

Safety and precautions :

In market:

It is available in the form of capsules, tablets

GOTU KOLA - VALLARAI - TABLETS

Centella AsiaticaIMPCOPS - ORGANIC AND WILD

100 tablets of 500 mg

Other herbal drugs:

Withania somnifera:

OrderOrder : Solanales : Solanales

Family : SolanaceaeFamily : Solanaceae

Genus : WithaniaGenus : Withania

Species : W.somniferaSpecies : W.somniferaAshwagandha

Bacopa monnieri: Kingdom : PlantaeKingdom : Plantae

OrderOrder : Lamiales : Lamiales

Family : Scrophulariaceae Family : Scrophulariaceae

Genus : BacopaGenus : Bacopa

Species : B.monnieriSpecies : B.monnieri

brahmi

Macleaya cordata: Kingdom : PlantaeKingdom : Plantae

Division : MagnoliophytaDivision : Magnoliophyta

Class Class : Magnoliopsida : Magnoliopsida

OrderOrder : Ranunculates : Ranunculates

Family : Papaveraceae Family : Papaveraceae

Genus : MacleayaGenus : Macleaya

Species : M.cordataSpecies : M.cordata

Plume poppy

Vinca minor: Kingdom : PlantaeKingdom : Plantae

OrderOrder : Gentianales : Gentianales

Family : Apocynaceae Family : Apocynaceae

Genus : VincaGenus : Vinca

Species : V.minorSpecies : V.minor

periwinkle

Allium sativum : Kingdom : PlantaeKingdom : Plantae

Clade Clade : monocots : monocots

OrderOrder : asparagales : asparagales

Family : Amarylidaceae Family : Amarylidaceae

Genus : alliumGenus : allium

Species : A.sativumSpecies : A.sativum

garlic

Coptis chinenses : Kingdom : PlantaeKingdom : Plantae

Division : MagnoliophytaDivision : Magnoliophyta

Class Class : Magnoliopsida : Magnoliopsida

OrderOrder : Ranunculales : Ranunculales

Family : Ranunculaceae Family : Ranunculaceae

Genus : CoptisGenus : Coptis

Species : C.chinensesSpecies : C.chinenses

Chinese goldthread

Rosemarinus officanalis:

Family : LamiaceaeFamily : Lamiaceae

Genus : RosamarinusGenus : Rosamarinus

Species : R.officinalisSpecies : R.officinalis

rosemary

Panax ginseng: Kingdom : PlantaeKingdom : Plantae

OrderOrder : Apiales : Apiales

Family : AraliaceaeFamily : Araliaceae

Genus : AralioideaeGenus : Aralioideae

Species : Panax L.Species : Panax L. ginseng

Lycoris radiata: Kingdom : PlantaeKingdom : Plantae

OrderOrder : Asparagales : Asparagales

Family : AmaryllidaceaeFamily : Amaryllidaceae

Genus : LycorisGenus : Lycoris

Species : L.radiataSpecies : L.radiata

Red spider lily

Melissa officinalis:

Family : LamiaceaeFamily : Lamiaceae

Genus : MelissaGenus : Melissa

Species : M.officinalisSpecies : M.officinalisLemon balm

Conclusion • Alzheimer’s disease develops when Genetic, life style and

environmental factors work together to cause the disease process to start.

• Herbal treatment for Alzheimer's disease helps in management of the disease but its not a complete cure.

• Though herbal drugs contain less or null side effects compared to synthetic drugs, in the case of Alzheimer's they play a half role.

• For complete cure of Alzheimer's disease it is necessary to know the cause, and should have changes in the lifestyle in addition with herbal treatment.

References

• http://www.raysahelian.com/alzheimer.html• http://en.wikipedia.org/wiki/Alzheimer's_disease• http://www.alz.org/alzheimers_disease_alternative_treatments.asp• http://aja.sagepub.com/content/21/2/113.short• www.researcharticles.net• http://www.tandfonline.com/doi/abs/10.1080/01459740.2011.582473• Medical anthropology by Bianca Brijnath• www.sciencedirect.com• www.pubmed.com• www.elsevier.com• anatomy and physiology by Ross and Wilson• http://www.healthiertalk.com/india n-super-spices-combat-cancer-

arthritis-and-alzheimer-s-3585• Aging in INDIA (Alzheimer's disease)- by A.B.bose

ALZHEIMER’S DISEASE

Health & Medicine