ALZHEIMER’S DISEASE - (AD) AND ITS HERBAL TREATMENT

1. ALZHEIMER’S DISEASE- (AD) 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) www.powerpointpresentationon.blogspot.com

2. The Impact of AD Once 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.

3. 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.

4. 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.

5. 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)

6. Inside the Human Brain 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

7. Inside the Human Brain The Three Main Players • 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

8. Inside the Human Brain The Three Main Players • 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

9. Inside the Human Brain 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)

10. Inside the Human Brain The 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..

11. Inside the Human Brain 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.

12. 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

13. 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.

14. 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.

16. 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

17. Mild to Moderate AD

18. Severe AD

19. Types 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.

20. Signs and symptoms • Increasing and persistent forgetfulness • Difficultieswith abstract thinking. • Difficulty finding the right word. • Disorientation. • Loss of judgment. • Difficulty performing familiar tasks. • Personality changes.

21. Complications • Pneumonia. • Infections. Untreated urinary tract infections can lead to more serious, life-threatening infections. • Falls and their complications. • Disoriented • Falls lead to fractures. • Serious head injuries (bleeding of brain). • Surgery to repair injury carries risks. • Prolonged immobilization increases the risk of pulmonary embolism, which can be life-threatening.

22. 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.

23. Herbal drugs used to treat Alzheimer's disease • Melissa officinalis • Lycorus radiata • Curcuma longa • Centella asiatica • Coptis chinenses • Securinega suffruticosa • Withania somnifera • Ginkgo biloba • Vinca minor • Rosemarinus officanalis • Salvia officanalis • Allium sativum • Macleaya cordata • Galanthus woronowii

24. Ginkgo biloba (maidenhair tree) • Kingdom : plantae • Division : ginkgophyta • Class : ginkgoopsida • Order : ginkgoales • Family : ginkgoaceae • Genus : ginkgo • Species : G.biloba

25. Active constituents : • Triterpenoids • Flavonoids • Ginkgolides • & • Bilobalide • Ginkgetin • Flavones • Isoginkgetin • 5-methoxybilobitol • Belobetol • Sciadopitysin

26. Mechanism of action :

27. Other pharmacological properties: • Cardioprotective effect • Anti inflammatory • Anti oxidant • Anticancer effect • Anxiety syndromes • Effects on tinnitus, geriatrics and psychiatric disorders

28. Adverse effects: • Gastrointestinal problems • Allergic reactions • Nausea • Headache

29. 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

30. 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 .

31. Kingdom : plantae • Clade : Angiosperms • Clade : Monocots • Order : Asparagales • Family :amaryllidaceae • Subfamily :amaryllidoiceae • Genus : Galanthus Galanthus woronowii: snowdrop

32. Active constiuents: • GALANTAMINE • An alkaloid obtained from the bulbs and flowers of galanthus woronowii. Structure :

33. Mechanism of action:

34. 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.

35. 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.

36. Adverse effects: • Gastrointestinal problems • Allergic reactions • Nausea • Headache etc…. Herbal drug-drug interactions : • Antagonizes the action of anticholinergic drugs. • Cimetidine increases galantamine bioavailabiliy. • It shows interactions with digoxin, warfarin etc….

37. In market: It is available in the form of capsules Reminyl™ ER(extended release galantamine hydrobromide) Life Enhancement, GalantaMind, Memory Function Support, 90 Capsules

38. Kingdom : plantae • Clade : Angiosperms • Clade : Monocots • Order : zingiberales • Family : zingiberaceae • Genus : curcuma • Species : C.longa Curcuma longa : turmeric

39. Active constiuents: • CURCUMIN • A Polyphenol.. Keto form Enol form

40. Mechanism of action: • Inhibits beta-amyloid plaque formation • Other MOA…. • Lowers oxidative damage • Cognitive defects • Inhibits damage to neuronal synapse

41. Other pharmacological properties: • Antitumor • Antioxidant • Antiarthritic • Anti inflammatory • Antibacterial • Hepatoprotective etc…

42. 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 :

43. Kingdom : Plantae • Clade : Angiosperms • Clade : Eudicots • Order : Apiales • Family : Mackinlayaceae • Genus : Centella • Species : C.asistica Centella asiatica: (Gotu Kola)

44. Active constiuents: • GLYCOSIDES: • brahmoside, brahminoside, asiaticoside, indocentelloside etc….. • Also contains mesoinosetol, a new oligosaccharide, centellose, kaempherol etc…

45. Mechanism of action: • Oxidative stress also leads to AD because of harmful production of free radicals……

46. Other pharmacological properties: • Gastric ulcers • Anti inflammatory • Anti oxidant • Cognitive property • Anti epileptic • Anti depressant • Anxiolytic properties.

47. Dosage : • 1000mg/ 3 times a day and about 1 hour before meal. Interactions : • It shows interaction with CNS depressants as result increases sleeping time . Safety and precautions : • 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…

48. In market: It is available in the form of capsules, tablets GOTU KOLA - VALLARAI - TABLETSCentella AsiaticaIMPCOPS - ORGANIC AND WILD100 tablets of 500 mg

49. Kingdom : Plantae • Clade : Angiosperms • Clade : Eudicots • Order : Solanales • Family : Solanaceae • Genus : Withania • Species : W.somnifera Other herbal drugs: Withania somnifera: Ashwagandha

50. Kingdom : Plantae • Clade : Angiosperms • Clade : Eudicots • Order : Lamiales • Family : Scrophulariaceae • Genus : Bacopa • Species : B.monnieri Bacopa monnieri: brahmi