study of butterfly pea root to increase acetylcholine

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STUDY OF BUTTERFLY PEA ROOT TO INCREASE ACETYLCHOLINE LEVELS IN ALZHEIMER’S DISEASE

By

Samantha Tiara Widjaja 11606004

BACHELOR’S DEGREE in

BIOMEDICAL ENGINEERING LIFE SCIENCES & TECHNOLOGY

SWISS GERMAN UNIVERSITY The Prominence Tower

Jalan Jalur Sutera Barat No. 15, Alam Sutera Tangerang, Banten 15143 - Indonesia

July 2020

Revision after Thesis Defense on 16 July 2020

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Samantha Tiara Widjaja STATEMENT BY THE AUTHOR

I hereby declare that this submission is my own work and to the best of my knowledge, it contains no material previously published or written by another person, nor material which to a substantial extent has been accepted for the award of any other degree or diploma at any educational institution, except where due acknowledgement is made in the thesis.

Samantha Tiara Widjaja

_____________________________________________

Student Date

Approved by:

Dr.rer.nat. Maruli Pandjaitan

_____________________________________________

Thesis Advisor Date

Dr. Ir. Abdullah Muzi Marpaung, M.P.

_____________________________________________

Thesis Co-Advisor Date

Dr. Dipl. -Ing. Samuel Priyantoro Kusumocahyo _____________________________________________

Dean Date

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Samantha Tiara Widjaja ABSTRACT

STUDY OF BUTTERFLY PEA ROOT TO INCREASE ACETYLCHOLINE LEVEL IN ALZHEIMER’S DISEASE

By

Dr.rer.nat. Maruli Pandjaitan, Advisor Dr. Ir. Abdullah Muzi Marpaung, M.P., Co-Advisor

SWISS GERMAN UNIVERSITY

Butterfly pea is an antioxidant-rich plant. It functions to inhibit oxidation, which is a reaction that produces free radicals. Those free radicals will lead to a chain reaction that will damage organism cells. The extraction of butterfly pea root has active compounds that are believed to have the ability to increase acetylcholine levels in the human brain. Acetylcholine is a neurotransmitter that plays a role of memory and learning. The most prominent active compounds that have been found in the extraction of butterfly pea root are alkaloids, phenols, and triterpenoids. These compounds have been reported to have the ability to inhibit the activity of acetylcholinesterase enzyme. In addition, butterfly pea root extract has been reported to also have a cholinergic effect that enhances the production level of acetylcholine neurotransmitter. Thus, butterfly pea root extract might have a medicinal effect to treat Alzheimer’s disease. Animal studies of butterfly pea root extraction using rats showed the aqueous extract of 200 mg/kg is the optimum prescription to treat the symptoms by increasing acetylcholine levels and inhibiting acetylcholinesterase enzyme activity, with the lethal concentration of 3.2g/kg.

Keywords: Alzheimer’s disease, Butterfly pea root, Clitoria ternatea L., Extraction, Acetylcholine.

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Samantha Tiara Widjaja DEDICATION

I dedicate this work for human cognitive health.

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Samantha Tiara Widjaja ACKNOWLEDGEMENTS

I wish to express my sincere gratitude to my advisor Dr.rer.nat. Maruli Pandjaitan for the continuous support, patience, motivation, and tremendous knowledge. His teaching style, guidance, and enthusiasm for the topic have always carried positive and delightful memories. He was always open whenever I ran into a problem or questions regarding my research.

I would also like to thank my co-advisor Dr. Ir. Abdullah Muzi Marpaung, M.P. for his insightful comments, structural and critical thinking that have widen my research perspectives. He provided me with the necessary information and resources regarding my research. Without his participation and input, this work could not have been neatly completed.

I would also like to acknowledge all lecturers of the Faculty of Life Sciences &

Technology at Swiss German University, especially lecturers from the Department of Biomedical Engineering for their valuable courses for the past years that have prepared me for writing a decent research paper.

Getting through my thesis work required more than just academic support. Therefore, I am very grateful to have Joshua Kristiadi & his family by my side for the tolerance and the continuous encouragement, for the time spent, and for many memorable evenings in and out throughout this venture.

Most importantly, I must express my very profound gratitude for my parents for the financial support, continuous encouragement, for telling me that everything is going to be okay throughout my years of study, and for providing me with all the necessary facilities for me to complete this research. This work stands as a testament to your unconditional love. Thank you.

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Samantha Tiara Widjaja TABLE OF CONTENTS

Page

STATEMENT BY THE AUTHOR ... 2

ABSTRACT ... 3

DEDICATION ... 5

ACKNOWLEDGEMENTS ... 6

CHAPTER 1 - INTRODUCTION ... 12

1.1 Background ... 12

1.2 Objectives ... 13

CHAPTER 2 - METHODOLOGY ... 14

CHAPTER 3 – ALZHEIMER’S DISEASE ... 16

3.1 Diagnosis of Alzheimer’s disease ... 17

3.2 Stages of Alzheimer’s disease ... 20

3.3 Treatment of Alzheimer’s disease ... 21

3.3.1. Herbal treatment to treat Alzheimer’s disease... 24

3.3.2. FDA-approved medicines to treat Alzheimer’s disease ... 27

3.4 Potential natural compounds to treat Alzheimer’s disease ... 31

CHAPTER 4 – THE ROLE OF BUTTERFLY PEA ROOT IN TREATING ALZHEIMER’S DISEASE... 38

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4.2 Butterfly pea root extraction & screening... 39

4.3 Animal studies using butterfly pea root extraction ... 45

CHAPTER 5 – CONCLUSION ... 48

REFERENCES ... 50

CURRICULUM VITAE ... 62

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Samantha Tiara Widjaja LIST OF FIGURES

Figures Page

Imaging of brain atrophy in Alzheimer’s disease (Bagad & Khan, 2013) ... 16

PET imaging of cognitively normal brain (CN), mild cognitive impaired brain (MCI), and Alzheimer’s disease brain (AD) using [18F]florbetapir (Leuzy, Zimmer, Gauthier, & Rosa-Neto, 2014). ... 20

Chemical structure of acetylcholine ... 22

Synthesis and rupturing process of Acetylcholine. ... 23

Amyloidogenesis mechanism (K. P. Devi & Syad, 2014). ... 25

Donepezil (Aricept) of 5Mg, 10Mg, 23Mg (WebMD, 2014). ... 27

Chemical structure of Aricept (donepezil hydrochloride) (Khairuzzaman, 2009). ... 28

Chemical structure of Razadyne (Galantamine HBr) (Ortho-McNeil Neurologics, 2007). ... 28

Galantamine (Razadyne) of 4Mg, 8Mg, 12Mg (WebMD, 2009b). ... 29

Chemical structure of Exelon (rivastigmine tartrate) capsules (Novartis, 2013). ... 29

Chemical structure of Namenda (memantine hydrochloride) (FDA, 2010) ... 30

Memantine (Namenda) of 5Mg, 10Mg (WebMD, 2009a) ... 31

Combination of donepezil and memantine (Namzaric) of 7Mg-10Mg, 21Mg-10Mg, 28Mg-10Mg (WebMD, 2015). ... 31

Butterfly pea flower (Chai-udom, n.d.) ... 39

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Samantha Tiara Widjaja LIST OF TABLES

Table Page

List of databases ... 14 Potential natural compounds in treating Alzheimer’s disease ... 32 Phytochemical screening of butterfly pea plant primary metabolites (Chauhan,

Rajvaidhya, & Dubey, 2012). ... 40 Screening results of Clitoria ternatea L. root extract powder, alcohol/ethanol extract, aqueous extract, and methanol extract. ... 42 Effectiveness of acetylcholinesterase inhibitory effects in comparison with

Neostigmine standard (Shahnas & Akhila, 2014). Acetylcholinesterase inhibitor drug that chemically known as (m-hydroxy-phenyl)trimethylammonium bromide

dimethylcarbamate (Drugs.com, 2020; RxList, 2019) ... 46 Effectiveness of acetylcholinesterase inhibitory effects in comparison with

Prostigmine standard from Swiss German University experiments. ... 47