NEUROPROTECTIVE ESSENTIAL OILS 1

Running head: NEUROPROTECTIVE ESSENTIAL OILS

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Neuroprotective Essential Oils for Cognitive Enhancement and Alzheimer’s Support Dorene Petersen, B.A., ND (NZ), Dip.Acu, RH (AHG) President, American College of Healthcare Sciences Presented August 2017 at the Alliance of International Aromatherapists Conference (AIA) USA

Author Note A version of this paper was originally presented at the Asian Aroma Conference (AIC), April 2016, Delhi, India. Correspondence concerning this paper should be addressed to Dorene Petersen, American College of Healthcare Sciences, 5005 SW Macadam Ave., Portland, OR 97239. Contact: [email protected]

American College of Healthcare Sciences © 2017 www.achs.edu

NEUROPROTECTIVE ESSENTIAL OILS

2 Abstract

This presentation will explore the clinical use of aromatherapy essential oils for cognitive enhancement and aging populations. The stimulating properties of rosemary Rosmarinus officinalis (L.) essential oil have been used for years to help improve memory, clarity and focus. But current research shows some less well-known essential oils are potentially neuroprotective and effective for cognitive enhancement and both short-term and working memory loss prevention. We will explore developing research on essential oils—specifically, black pepper Piper nigrum L., coriander Coriandrum sativum L., clove Syzygium aromaticum L. Merr. et L. M. Perry (formerly Eugenia caryophyllata Thunb.), Spanish sage Salvia lavandulifolia Vahl, Greek sage Salvia fruticosa Mill., lavender Lavandula angustifolia Mill., and rosemary R. officinalis—with a focus on the potential for neuroprotection and support for the loss of cognitive and functional abilities that can occur with aging.



3 Introduction

By 2030, 13% of the world’s total population will be older than 65, which will total about 1 billion people (or one in eight) of the world’s population. According to a report published by the World Health Organization (WHO), 47.5 million people have dementia worldwide (more than the population of Spain), and there are 7.7 million new cases every year.1 As the world population continues to age, WHO estimates that in just 13 years by 2030, 75.6 million people will be living with dementia, and that number is projected to increase to 135.5 million by 2050.2 The World Alzheimer Report estimates this will increase to 131.5 million by 2050 (a slightly more optimistic estimate than the WHO’s 135.5 million projection).3 Considering this current worldwide epidemic, this paper will present an overview of research into essential oils that show potential for neuroprotective support, cognitive enhancement and the prevention and support of Alzheimer’s disease. Alzheimer’s disease (AD) is a very complex condition. This paper focuses on just one of the causes, the imbalance of acetylcholine and the potential of essential oils to counteracting the results that occur with the increase of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which can occur with normal aging. Increasing AChE results in a decrease or inhibition of acetylcholine (ACh), a neurotransmitter that is essential for the brain and nervous system to process and transmit

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World Health Organization. (March 2015). Dementia. Retrieved from: http://www.who.int/mediacentre/factsheets/fs362/en/ 2 World Health Organization. (April 2016). Dementia Fact Sheet. Retrieved from http://www.who.int/mediacentre/factsheets/fs362/en/ 3 Prince, M., Wimo, A., Guerchet, M., Ali., G-C., Wu, Y., & Prina, M. (2015). World Alzheimer Report 2015: The Global Impact of Dementia. Retrieved from: http://www.alz.co.uk/research/WorldAlzheimerReport2015.pdf American College of Healthcare Sciences © 2017 www.achs.edu


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information from one area to another. The concentration of ACh is considered to be one the most important factors involved in optimal cognitive function. Specifically, this paper reviews essential oils that exhibit inhibitory activity against the enzymes AChE and BChE.4 We also look at the antioxidant action of essential oils, which can affect brain health by suppressing neuronal oxidative damage caused by elevated levels of beta-amyloid and potentially reduce the formation of protein plaques, another major cause of AD. Of course, ACh deficit is only one of the many factors contributing to this devastating brain disorder.5

Overview of Current Statistics on Memory Loss and Degenerative Brain Diseases Dementia is a general term that is applied to a group of cognitive disorders (AD, vascular dementia, and Lewy body dementia). They are all characterized by memory impairment and a marked difficulty in the domains of language, motor activity, object recognition, and emotional disturbance. It is an illness of older adults that becomes progressively worse and increasingly widespread with the aging of the population. Dementia, and specifically AD, are already among the costliest diseases for society. The cost of caring for AD patients in the United States (U.S.) is estimated to be $259 billion in 2017, and by 2050 it is estimated to be $1.1 trillion.6,7 AD was also

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Greig, N.H., Utsuki, T., Wang, Y., et al. (2004). P1-414 selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers amyloid-beta peptide in rodents: A new treatment strategy for Alzheimer’s disease. Neurobiology of Aging, 25:S216. doi:10.1016/s0197-4580(04)80726-7. 5 Clinical Application: Acetylcholine and Alzheimer’s Disease. (n.d.). Retrieved from: https://web.williams.edu/imput/synapse/pages/IA5.html 6 alzheimers.net. (n.d.). 2015 Alzheimer’s Statistics. Retrieved from: http://www.alzheimers.net/resources/alzheimers-statistics/ 7 Retrieved from http://www.alz.org/facts/ American College of Healthcare Sciences © 2017 www.achs.edu


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determined to be the sixth leading cause of death in the U.S. and the fifth leading cause among people age 65 and older.8,9

Research Review of Neuroprotective Essential Oils for Cognitive Enhancement and Alzheimer’s Support A research review of studies conducted in the previous 12 years revealed numerous essential oils that are antioxidants and can inhibit the enzymes AChE and BChE. Some studies focused on the synergy of complete essential oils or a combination of oils that provide the specific active constituents that show potential. Table 1 Essential Oil Research References: The citations for the research papers referenced in the column Research Paper Reference can be found in the Research Paper Reference Addendum at the end of this paper. Finding: Inhibits AChE

Finding: Inhibits BChE

Research Paper Reference10

Yes

No

1

Yes

Not reported

2

Yes

Yes

3

Yes

Yes

4

Yes

Not reported

2

Yes

Not reported

5

Yes

Yes

1

Coriandrum sativum L.

Potential

Not reported

6

Croton zehntneri Pax. ex Hoff.

Yes

Not reported

7

Curcuma longa L.

Yes

Not reported

2

Eucalyptus globulus Labill.

Yes

Not reported

5

Foeniculum vulgare Mill.

Yes

Yes

3

Essential Oil Alpinia galanga L. Anethum graveolens L. Artemisia macrocephala Jacq. Boesenbergia rotunda (L.) Mansf. Cinnamomum camphora L. Citrus aurantifolia Tanaka.

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Thies, W. & Bleiler, L. (2011). Alzheimer’s disease facts and figures. Alzheimer's & Dementia, 7(2):208244. Retrieved from: http://dx.doi.org/10.1016/j.jalz.2011.02.004 9 Retrieved from http://www.alz.org/facts/ 10

Please see the Research Paper Reference Addendum at the end of this paper. American College of Healthcare Sciences © 2017 www.achs.edu


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Finding: Inhibits AChE



Yes

Not reported

8

Yes

Yes

3

Yes

Not reported

5

Melissa officinalis L.

Yes

Yes

1

Mentha × piperita L.

Yes

Yes

3

Mentha spicata L.

Yes

Yes

3

Nelumbo nucifera Gaertn.

Yes

Not reported

9

No

Yes

1

Yes

Not reported

10

Origanum majorana L.

Yes

Not reported

5

Origanum minutiflorum L.

Yes

Yes

3

Origanum vulgare L.

Yes

Yes

3

Piper nigrum L.

Yes

Yes

11

Polygonum hydropiper L.

Yes

Not reported

4

Rosmarinus officinalis L.

Yes

Yes

5

Salvia fruticosa Mill.

Yes

Yes

12

Salvia lavandulifolia L.

Yes

Yes

13

Salvia officinalis L.

Yes

Yes

13

Satureja thymbra L.

Yes

Yes

3

Syzygium aromaticum Perry et L.M. Perry.

Yes

Yes

14

Essential Oil Hedychium gardnerianum Sheppard ex Ker-Gawler Lavandula angustifolia Mill. Melaleuca cajuputi Powell.

Ocimum gratissimum L.

Table 2 Chemical Constituent Research References: The citations for the research papers referenced in the column Research Paper Reference can be found in the Research Paper Reference Addendum at the end of this paper. Finding: Inhibits AChE



1,8 cineole

Yes

Yes

2, 5, 7, 12, 13

alpha-pinene

Yes

No

3, 13

beta-caryophyllene

Yes

Yes

2, 11

beta-pinene

Yes

Not reported

7

borneol

Yes

Not reported

9

Chemical Constituent

11

Please see the Research Paper Reference Addendum at the end of this paper. American College of Healthcare Sciences © 2017 www.achs.edu


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Finding: Inhibits AChE



camphor

Yes

Yes

7, 12, 13

carvacrol

Yes

No

3

carvone

No

Yes

3

citronellal

No

Yes

3

delta-3-carene

Yes

Not reported

11

dihydrocarvone

No

Yes

3

(E)-anethole

Yes

Not reported

7

eugenol

Yes

Not reported

7, 14

iso-menthone

No

Yes

3

isoeugenol

Yes

Not reported

7

menthofuran

Yes

No

3

menthol

No

Yes

3

piperitone

No

Yes

3

thujone

Yes

Yes

12

Chemical Constituent

Combinations of essential oil constituents provided more effective activity in comparison to single constituents. For example, trans-caryophyllene in combination with 1,8 cineole and camphene, or 1,8 cineole with linalool, had higher AChE inhibitory activity than the single compounds, beta-caryophyllene, 1,8 cineole, camphene, or linalool. Their anticholinesterase activity increased to more than twice the amount. However, the whole oils showed even higher AChE inhibitory activity, which indicates there were other unidentified constituents and synergy between constituents within the oils that provided the most effective anticholinesterase activity.

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The author chose to focus on the following essential oils: Black pepper, coriander, clove, Spanish sage, Greek sage, lavender, and rosemary. Black Pepper Piper nigrum L. The author identified four related research articles about black pepper essential oil published in peer-reviewed journals between 2012 and 2017. One of these studies identified the oil’s potential to inhibit AChE and BChE, while three other studies identified potential antioxidant activity. Three studies were in vitro studies and one was an animal study involving rats. The studies demonstrated that the essential oil, the ethanol



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extract, and the aqueous extract of black pepper all act as AChE and BChE inhibitors.12 The effect is due to the delta-3-carene and beta-caryophyllene present in the essential oil and the piperine, which is present only in the extracts. The study not only demonstrated that black pepper essential oil can inhibit AChE and BChE, with delta-3-carene being the most potent component followed by caryophyllene, but it also exhibited powerful antiinflammatory activity as assessed using human cells.13 In addition, the same in vitro study in 2015 revealed the complete black pepper essential oil itself was more potent than each of its major constituents alone despite the isolation and efficacy of delta-3-carene and beta-caryophyllene. Thus, it can be concluded that the activity of black pepper essential oil is not only a result of the major components tested but also other minor components. This demonstrates a synergy within the complete essential oil. Thus, we can say that black pepper essential oil acts as a strong AChE and BChE inhibitor, which research shows is most important for the prevention of AD. The essential oil also exhibits anti-inflammatory activity, which is useful for the management of some inflammatory symptoms. Unfortunately, black pepper oil exhibits weak radical scavenging activity and is therefore a poor antioxidant. If black pepper essential oil was also an effective antioxidant, it would provide the added benefit of protection from oxidation damage. However, lack of this property does

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Lomarat, P., Shripha, K., Phanthong, P., Kitphati, W., Thirapanmethee, K., & Bunyapraphatsara, N. (2015). In Vitro Biological Activities of Black Pepper Essential Oil and Its Major Components Relevant to the Prevention of Alzheimer’s Disease. The Thai Journal of Pharmaceutical Sciences, 39(3):94-101. 13 Ibid. American College of Healthcare Sciences © 2017 www.achs.edu


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not reduce its inhibiting power.14 Despite the absence of antioxidant activity it should be considered for the prevention of AD. However, another research group has not recorded AChE-inhibiting activity for black pepper essential oil.15 This may be due to variations in not only the composition of the essential oil but the ratio of constituents within the oil, which may affect the inhibitory activity of the oil. Unfortunately, the author of the second study did not report the composition of the essential oil studied thus making it difficult to compare results. There is a belief among aromatherapists that black pepper can be characterized by distinct chemotypes. However, black pepper is an essential oil that is not truly represented by clear chemotypes, making it challenging for clinical aromatherapists to choose the most effective constituent profile. To clarify this misconception, the author spoke with an essential oil expert who shared that most of the pepper essential oil in commerce is produced in Southern India in the Kerala, Tamil Nadu, and Karnataka areas and arrives at the pepper collection stations under the village names. These names have evolved into local cultivars. There are more than 50 known cultivars in India along with a number of hybridized cultivars such as the Paniyur types which were developed for their fruit size. This situation in India exists in all pepper growing countries. Each of the cultivars, which is unique to the village, possesses a specific oil composition. This results in oils that are rich in alpha- or beta-pinene, sabinene, delta-3carene, alpha-phellandrene, limonene, beta-caryophyllene, and caryophyllene oxide, or any combination of these compounds. However, when the pepper is mixed at the 14

Lomarat, P., Shripha, K., Phanthong, P., Kitphati, W., Thirapanmethee, K., & Bunyapraphatsara, N. (2015). In Vitro Biological Activities of Black Pepper Essential Oil and Its Major Components Relevant to the Prevention of Alzheimer’s Disease. The Thai Journal of Pharmaceutical Sciences, 39(3):94-101. 15 Kitphati, W., et al. (2012). Anticholinesterase of essential oils and their constituents from Thai medicinal plants on purified and cellular enzymes. JAASP, 1(1):58-67. American College of Healthcare Sciences © 2017 www.achs.edu


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collection stations and eventually makes it to the oleoresin manufacturers, any chemotypic origin is lost. Combine this with the fact that pepper oil produced from pepper originating from Vietnam, Indonesia, and Sri Lanka (additional pepper growing countries) also possesses a range in composition because of the vegetative clonal cultivation of pepper. Consequently, the mixture from which the oil is produced can vary greatly in composition. The situation is further complicated by the fact that black pepper oil is produced by the oleoresin manufacturers who initially steam distill the pepper prior to solvent extraction. This is done because their prime focus is to make commercially viable solvent extracts rich in piperine and chavicine (the pungent constituents of pepper). They then blend the oil with the extract to custom produce the oleoresin requirement of their customers. The excess oil is blended and sold as pepper oil.16 Therefore, while black pepper essential oil shows promise for the management of AD, a black pepper essential oil that contains sufficient levels of beta-caryophyllene and delta-3-carene should be selected for further studies. A 2015 in vitro study demonstrated that not only the essential oil but the aqueous and ethanol extracts of black pepper also act as AChE and BChE inhibitors.17 This effect is likely to be caused by the alkaloid piperine present in the extracts though not present in the essential oil.18 In addition, an animal study involving rats supported the hypothesis that the ethanol extract can be used for the management of AD. In this study, two groups

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Author conversation with Brian Lawrence via email June 15, 2017 Kumar, S., & Dixit, S. (2015). Screening of Traditional Indian Spices for Inhibitory Activity of Acetylcholinesterase and Butyrlcholinesterase Enzymes. International Journal of Pharma and Bio Sciences, 3(1):59-65. 18 Okello, E., Coleman, A., & Seal, C. (2015). In-Vitro Anti-Cholinesterase Activities by Piperine, An Alkaloid from The Spice Family Piperaceae. Int J Pharm Sci Res., 6(9):3726-32. 17



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of rats received black pepper extract (20mg/kg/day and 200mg/kg/day) for two months. Next, aluminum chloride was supplemented to animals to induce AD. Rats that were pretreated with the extract demonstrated much better results in the water maze test. In addition, the level of cholinesterase in the brain was lower in the groups that received black pepper ethanol extract, indicating prevention of neurodegeneration, which caused an increase of the cholinesterase level.19 This shows that a holistic approach using aromatherapy black pepper essential oil and the ethanol extract, which contains piperine, may be effective for preventing and supporting cognitive function and AD. Human subject clinical research trials are now required to advance this preliminary work to evaluate if black pepper offers a viable integrative treatment for AD, which would subsequently advance to the clinical testing phase and potential product development. Coriander Coriandrum sativum L. There are a number of studies involving coriander leaf and coriander leaf essential oil (also known as cilantro oil) that demonstrated its potential use for the management of AD. Decanal, (E)-2-decenal, (E)-decenol, and other (E)-2-enals of C11-C14 are the major constituents of coriander leaf essential oil.20 Coriander’s antioxidant properties have been established by multiple studies,21 and it has also been shown to have an exceptional ability to inhibit lipid peroxidation.22

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Subedee, L. (2015). Preventive Role of Indian Black Pepper in Animal Models of Alzheimer’s Disease. JCDR, 9(4). Retrieved from: http://dx.doi.org/10.7860/jcdr/2015/8953.5767 20 Rathore, S., Sharma, L., Agarwal, D., Singh, B., & Saxena, S. (2015). Assessment of variability in leaf essential oil of three coriander (Coriandrum sativum L.) genotypes. International J. Seed Spices, 5(2):8666. 21 Wangensteen, H., Samuelsen, A., & Malterud, K. (2004). Antioxidant activity in extracts from coriander. Food Chemistry, 88(2):293-297. Retrieved from: http://dx.doi.org/10.1016/j.foodchem.2004.01.047; American College of Healthcare Sciences © 2017 www.achs.edu


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Further, C. sativum essential oil shows promise in the management of

neurodegenerative diseases, such as AD, because its many effects: reducing oxidative stress, improving memory, reducing anxiety and depression, and lowering cholesterol. Coriander leaf essential oil may also act as a cholinesterase inhibitor. However, additional research involving the essential oil of coriander leaf and seed oils is necessary to verify this. A 2014 in vivo animal study involving rats was conducted to determine if coriander could be used for the management of AD. Exposure to coriander leaf ethanol extract significantly improved performance of the rats in a maze and in a forcedswimming test. The authors concluded this suggested anxiolytic and antidepressant-like effects. In addition, exposure to the coriander volatile oil increased catalase activity23 and increased glutathione24 level in the hippocampus, suggesting that it can suppress oxidative stress associated with AD. It was concluded that coriander essential oil shows potential to counteract anxiety, depression, and oxidative stress in AD conditions.25 Further, another animal study with coriander seed oil that was predominantly linalool, geraniol, and alpha-pinene demonstrated repeated inhalation of coriander seed oil may provide neuroprotection by alleviating oxidative damage inflicted by an excess of

Darughe, F., Barzegar, M., & Sahari, M. (2012). Antioxidant and antifungal activity of Coriander (Coriandrum sativum L.) essential oil in cake. International Food Research Journal, 19(3):1253-1260. 22 Duarte, A., Luis, A., Oleastro, M., & Domingues, F. (2015). Antioxidant properties of coriander essential oil and linalool and their potential to control Campylobacter spp. Food Control, 61:115-122. Retrieved from: http://www.sciencedirect.com/science/article/pii/S0956713515302127 23 Catalase is an enzyme that degrades hydrogen peroxide, and is a so-called primary antioxidant. 24 Glutathione is an antioxidant that works together with catalase neutralizing free radicals protecting neurons. 25 Cioanca, O., Hritcu, L., Mihasan, M., Trifan, A., & Hancianu, M. (2014). Inhalation of coriander volatile oil increased anxiolytic–antidepressant-like behaviors and decreased oxidative status in beta-amyloid (1– 42) rat model of Alzheimer’s disease. Physiology & Behavior, 131: 68-74. Retrieved from: http://dx.doi.org/10.1016/j.physbeh.2014.04.021 American College of Healthcare Sciences © 2017 www.achs.edu


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beta-amyloid in the brain. Beta-amyloid is a sticky protein-like substance that accumulates and causes plaque tangles. The study also demonstrated that working memory, not just short-term memory, was improved by inhaling coriander seed oil.26 Further, recent animal studies on coriander demonstrated that supplementation with the aqueous extract27 or hydroalcoholic extract28 and addition of the fresh leaves to the daily diet29 produces anxiolytic effects and can also reverse memory impairment. As demonstrated in this research, coriander shows significant promise to potentially slow down the onset of AD and to manage progression and support symptoms in more advanced stages of the illness. A holistic, aromatherapy protocol would emphasize fresh coriander leaves in the daily diet, as well as the inhalation of coriander leaf and seed essential oil through diffusion or topical applications (such as foot or hand baths) and oral administration of an aqueous extract30 (a simple cup of tea or a hydroalcoholic extract).

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Cioanca, O., Hritcu, L., Mihasan, M., & Hancianu, M. (2013). Cognitive-enhancing and antioxidant activities of inhaled coriander volatile oil in amyloid β(1–42) rat model of Alzheimer’s disease. Physiology & Behavior, 120, 193-202. doi:10.1016/j.physbeh.2013.08.00 27 Koppula, S. & Choi, C. (2012). Anti-Stress and Anti-Amnesic Effects of Coriandrum sativum Linn (Umbelliferae) Extract – an Experimental Study in Rats. Tropical Journal of Pharmaceutical Research, 11(1). Retrieved from: http://dx.doi.org/10.4314/tjpr.v11i1.5 28 Mahendra, P. & Bisht, S. (2011). Anti-anxiety activity of Coriandrum sativum assessed using different experimental anxiety models. Indian Journal of Pharmacology, 43(5):574. Retrieved from: http://dx.doi.org/10.4103/0253-7613.84975; Elahdadi-Salmani, M., Khorshidi, M., & Ozbaki, J. (2015). Reversal Effect of Coriandrum sativum Leaves Extract on Learning and Memory Deficits Induced by Epilepsy in Male Rat. Zahedan Journal of Research in Medical Sciences, 17(3). Retrieved from: http://dx.doi.org/10.17795/zjrms1279 29 Mani, V., Parle, M., Ramasamy, K., & Abdul Majeed, A. (2010). Reversal of memory deficits by Coriandrum sativum leaves in mice. Journal of The Science of Food and Agriculture, 91(1):186-192. Retrieved from: http://dx.doi.org/10.1002/jsfa.4171 30 Koppula, S. & Choi, C. (2012). Anti-Stress and Anti-Amnesic Effects of Coriandrum sativum Linn (Umbelliferae) Extract – an Experimental Study in Rats. Tropical Journal of Pharmaceutical Research, 11(1). Retrieved from: http://dx.doi.org/10.4314/tjpr.v11i1.5 American College of Healthcare Sciences © 2017 www.achs.edu


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Human subject clinical research trials are now required to advance this preliminary work to evaluate if coriander offers a viable integrative treatment for AD, which would subsequently advance to the clinical testing phase and product development.

Clove Syzygium aromaticum L. Merr. et L.M. Perry There were three studies involving clove bud essential oil, which has eugenol and eugenyl acetate as its main constituents. It has a significant antioxidant activity comparable to a widely used natural antioxidant, alpha-tocopherol (vitamin E).31 When tested against oils from spices commonly used in Mediterranean countries,32 clove essential oil had the highest amount of total phenols; it also showed the highest percentage of inhibition of the alpha-diphenyl-beta-picrylhydrazyl (DPPH) radical and the highest ferric reducing ability of plasma value (the standard used to assess “antioxidant power”).33 A 2014 in vitro study demonstrated that the methanol extract of clove essential oil and eugenol inhibit AChE and BChE. Interestingly, eugenol alone possessed better inhibition of the enzymes than the extract and oil.34 An animal study conducted in 2010 demonstrated that clove bud oil can reverse both short-term and long-term memory deficits and this effect can, to some extent, be 31

Lee, K. & Shibamoto, T. (2001). Antioxidant property of aroma extract isolated from clove buds [Syzygium aromaticum (L.) Merr. et Perry]. Food Chemistry, 74(4):443-448. Retrieved from: http://dx.doi.org/10.1016/s0308-8146(01)00161-3; Nassar, M., et al. (2007). Chemical constituents of clove (Syzygium aromaticum, Fam. Myrtaceae) and their antioxidant activity. Rev. Latinoamer. Quím, 35(3):4757. 32 Oregano Origanum vulgare (L.), thyme Thymus vulgaris (L.), rosemary Rosmarinus officinalis (L.), and sage Salvia officinalis (L.) 33 Viuda-Martos, M., Ruiz Navajas, Y., Sanchez Zapata, E., Fernandez-Lapez, J., & Parez-Alvarez, J. (2010). Antioxidant activity of essential oils of five spice plants widely used in a Mediterranean diet. Flavour and Fragrance Journal, 25(1):13-19. Retrieved from: http://dx.doi.org/10.1002/ffj.1951 34 Mukherjee, P., Dalai, M., Bhadra, S., Chaudhary, S., & Bandyopadhyay, A. (2014). Anti-cholinesterase activity of the standardized extract of Syzygium aromaticum L. Pharmacognosy Magazine, 10(38):276. Retrieved from: http://dx.doi.org/10.4103/0973-1296.133275 American College of Healthcare Sciences © 2017 www.achs.edu


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attributed to decreased oxidative stress.35 Scopolamine, a known agent causing memory impairment, was given to a group of mice to induce a memory deficit. Clove bud oil was given as a supplement to the treatment group. Supplementation with clove oil for three weeks significantly reversed memory impairment induced by scopolamine. Brain samples of mice from the group treated with clove bud oil showed a significant decrease in malondialdehyde36 levels, suggesting reduced oxidative stress. Malondialdehyde (MDA) is one of the most frequently used indicators of lipid peroxidation.

Spanish Sage Salvia lavandulifolia Vahl There were four studies involving Spanish sage. In vitro studies demonstrated that the 96% ethanolic extract and the steam-distilled oil of both sage Salvia officinalis (L.) and Spanish sage inhibited AChE at quite low concentrations.37 Spanish sage oil was selected for further investigation rather than sage essential oil since the latter contains a relatively high percentage (35-50%) of neurotoxic beta-thujone, which is present in only very small amounts in Spanish sage. When individual constituents were studied in Spanish sage, results revealed a constituent profile of alpha-pinene (13%), which demonstrated the most significant anticholinesterase activity, followed by camphor (15%) and 1,8 cineole (27%). In addition, it was suggested that there is a high degree of synergy in the combined action of the terpenes. 35

Halder, S., Mehta, A., Kar, R., Mustafa, M., Mediratta, P., & Sharma, K. (2010). Clove Oil Reverses Learning and Memory Deficits in Scopolamine-Treated Mice. Planta Med, 77(08):830-834. Retrieved from: http://dx.doi.org/10.1055/s-0030-1250605 36 Nielsen, F., Mikkelsen, B.B., Nielsen, J.B., Andersen, H.R., & Grandjean, P. (1997). Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem., 43(7):1209-14. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/9216458 37 Perry, N., Court, G., Bidet, N., Court, J., & Perry, E. (1996). European Herbs with Cholinergic Activities: Potential in Dementia Therapy. Int. J. Geriat. Psychiatry, 11(12):1063-1069. American College of Healthcare Sciences © 2017 www.achs.edu


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An in vitro animal study also supported the use of Spanish sage essential oil. Rats were orally administered on separate occasions (four months apart) either 20mcL or 50mcL of Spanish sage essential oil in a standard dose of sunflower oil once per day for five days, with a control group given sunflower oil alone. After the five-day period (during which the behavior, eating, and motor function of both groups of animals was observed as normal and healthy), the rats were euthanized, and three parts of the brain were assessed for AChE activity. At the lower dose (20mcL) there was a trend for decreased AChE activity in the striatum38,39 of the Spanish sage-treated rats compared to the control group without prior inhibition of BChE. The striatum is the part of the brain associated with excitatory responses. Abnormalities in this part of brain are often associated with the onset of AD. The difference was more pronounced and significant when BChE was inhibited prior to analysis, suggesting that only AChE, and not BChE, had been inhibited by Spanish sage in vivo. These results suggested that one or more constituents of Spanish sage essential oil or their metabolites, following oral administration, reach the brain (crossing the gastrointestinal and blood-brain barriers) and inhibit cholinesterase in select brain areas, consistent with evidence of inhibition of the brain enzyme in vitro.40 To date, no clinical studies using sage preparations on AD patients have been reported, but one study evaluated the effect of sage on the memory and mood of a group 38

The striatum is the part of the brain associated with excitatory responses. Abnormalities in this part of brain are often associated with the onset of AD. 39 Pievani, M., Bocchetta, M., Boccardi, M., Cavedo, E., Bonetti, M., Thompson, P., et al. (2013). Striatal morphology in early-onset and late-onset Alzheimer’s disease: a preliminary study. Neurobiology of Aging, 34(7):1728-1739. Retrieved from: http://dx.doi.org/10.1016/j.neurobiolaging.2013.01.016 40 Perry, N., Houghton, P., Jenner, P., Keith, A., & Perry, E. (2002). Salvia lavandulifolia essential oil inhibits cholinesterase in vivo. Phytomedicine, 9(1):48-51. Retrieved from: http://dx.doi.org/10.1078/09447113-00082 American College of Healthcare Sciences © 2017 www.achs.edu


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of healthy volunteers. In this placebo-controlled, double-blind, balanced, crossover design study, participants received three doses of a standardized essential oil extract of Spanish sage in sunflower oil as well as the sunflower oil alone (34 female and 10 male participants were included age 18-37 years old; the mean age was 23.2 years). Doses were administered on different days, each separated by a seven-day wash-out period using a pseudo-random treatment order. Cognitive assessment and subjective mood rating measurements took place immediately prior to treatment and 1 hour, 2.5 hours, 4 hours, and 6 hours thereafter. Several significant effects on cognition were associated with the lowest (50 mcL) dose of Spanish sage. These included a significant increase in the percentage of the number of words recalled correctly both in the “immediate” and “delayed” recall tests. The same dose was associated with reductions in self-rated “alertness” and an increase in “calmness.” These results represent the first systematic evidence that Spanish sage oil is capable of acute modulation of mood and cognition in healthy young adults.41 In addition to the results mentioned above, a few other actions for Spanish sage were reported that might make it useful for AD management42: a) Antioxidant effects were shown to be present in the ethanolic extract as well as some essential oil constituents (1,8 cineole, beta-pinene, and alpha-pinene) of

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Tildesley, N., Kennedy, D., Perry, E., Ballard, C., Savelev, S., Wesnes, K., et al. (2003). Salvia lavandulaefolia (Spanish Sage) enhances memory in healthy young volunteers. Pharmacology Biochemistry and Behavior, 75(3):669-674. Retrieved from: http://dx.doi.org/10.1016/s00913057(03)00122-9 42 Perry, N., Houghton, P., Theobald, A., Jenner, P., & Perry, E. (2000). In-vitro Inhibition of Human Erythrocyte Acetylcholinesterase by Salvia lavandulaefolia Essential Oil and Constituent Terpenes. Journal of Pharmacy and Pharmacology, 52(7):895-902. Retrieved from: http://dx.doi.org/10.1211/0022357001774598 American College of Healthcare Sciences © 2017 www.achs.edu


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Spanish sage. Unfortunately, it was not possible to test the whole oil in the system used.43 b) The chloroform-soluble portion of the ethanol extract of Spanish sage inhibited eicosanoid synthesis, which is a part of the inflammatory response; alpha-pinene was identified as the most active constituent. Based on the activity of individual constituents, it was concluded that the essential oil should exhibit antiinflammatory activity if constituents interact in the additive fashion. It is worth noting that research has shown that essential oil constituents often interact in a synergistic fashion, significantly enhancing each other. If this is true in this situation, Spanish sage essential oil can exhibit much stronger anti-inflammatory action than isolated alpha-pinene. c) Mild estrogenic activity was observed in the ethanolic extract and the essential oil of Spanish sage, specifically geraniol. This is beneficial as studies have shown that an early postmenopausal use of estrogens may delay the on-set of AD.44,45

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Perry, N., Houghton, P., Sampson, J., Theobald, A., Hart, S., & Lis-Balchin, M. et al. (2001). In-vitro activity of S. lavandulaefolia (Spanish sage) relevant to treatment of Alzheimer’s disease. Journal of Pharmacy and Pharmacology, 53(10): 1347-1356. Retrieved from: http://dx.doi.org/10.1211/0022357011777846 44 Simpkins, J., Perez, E., Xiaofei, W., ShaoHua, Y., Yi, W., & Singh, M. (2009). Review: The potential for estrogens in preventing Alzheimer’s disease and vascular dementia. Therapeutic Advances in Neurological Disorders, 2(1): 31-49. Retrieved from: http://dx.doi.org/10.1177/1756285608100427 45 Perry, N., Houghton, P., Sampson, J., Theobald, A., Hart, S., Lis-Balchin, M., et al. (2001). In-vitro activity of S. lavandulaefolia (Spanish sage) relevant to treatment of Alzheimer's disease. Journal of Pharmacy and Pharmacology, 53(10), 1347-1356. American College of Healthcare Sciences © 2017 www.achs.edu


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Greek Sage Salvia fruticosa Mill. There were two studies involving Greek sage. The essential oil content and composition of Greek sage demonstrates a noticeable variation in the amount of the four main components: 1,8 cineole (22.7-64.2% of total oil), alpha-thujone (1.0-19.2%), betathujone (0.9-25.6%), and camphor (0.8-30.3%).46 It was also reported to exhibit significant antioxidant properties (thought to be due to the presence of oxygenated terpenes and allylic alcohols, such as viridiflorol and manool).47 An in vitro study demonstrated that Greek sage essential oil (1,8 cineole (36%), camphor (19%), and thujone (8%)) inhibits AChE and BChE,48 while another in vitro study demonstrated that it can protect neurological cells in the brain from oxidative damage. The protective effect was attributed to alpha-humulene and alpha-pinene.49

Lavender Lavandula angustifolia Mill. There are six studies using lavender that demonstrate lavender essential oil can be useful as an adjunct therapy for AD. This evidence supports its efficacy in helping to

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Karousou, R., Vokou, D., & Kokkini, S. (1998). Variation of Salvia fruticosa Essential Oils on the Island of Crete (Greece). Botanica Acta., 111(3):250-254. Retrieved from: http://dx.doi.org/10.1111/j.14388677.1998.tb00705.x 47 Papageorgiou, V., Gardeli, C., Mallouchos, A., Papaioannou, M., & Komaitis, M. (2008). Variation of the Chemical Profile and Antioxidant Behavior of Rosmarinus officinalis L. and Salvia fruticosa Miller Grown in Greece. J. Agric. Food Chem., 56(16):7254-7264. Retrieved from: http://dx.doi.org/10.1021/jf800802t 48 Şenol, F., Orhan, I., Erdem, S., Kartal, M., Şener, B., Kan, Y., et al. (2011). Evaluation of Cholinesterase Inhibitory and Antioxidant Activities of Wild and Cultivated Samples of Sage (Salvia fruticosa) by Activity-Guided Fractionation. Journal of Medicinal Food, 14(11):1476-1483. Retrieved from: http://dx.doi.org/10.1089/jmf.2010.0158 49 Elmann, A., Mordechay, S., Rindner, M., Larkov, O., Elkabetz, M., & Ravid, U. (2009). Protective Effects of the Essential Oil of Salvia fruticosa and Its Constituents on Astrocytic Susceptibility to Hydrogen Peroxide-Induced Cell Death. J. Agric. Food Chem., 57(15):6636-6641. Retrieved from: http://dx.doi.org/10.1021/jf901162f American College of Healthcare Sciences © 2017 www.achs.edu


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manage the agitated behavior50 often found in patients with dementia.51 It was also shown to reduce stress (while the study involved infants the physiological results of stress are not age related),52 improve sleep quality (study involved mid-age women with insomnia),53 and even to improve coronary blood circulation (study involved healthy men).54,55 All if these issues are implicated in the onset of dementia. In addition, animal studies demonstrated that lavender essential oil exhibits a neuroprotective action for brain cells (likely due to the antioxidant activity)56,57 and can provide protection from brain seizures.58 It has also been reported as inhibiting both AChE and BChE with an even higher inhibition reported using lavender essential oil cultivated using organic fertilizer.59 Based

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Lin, P.W., Chan, W.C., Ng, B.F., & Lam, L.C. (2007). Efficacy of aromatherapy (Lavandula angustifolia) as an intervention for agitated behaviours in Chinese older persons with dementia: a crossover randomized trial. Int J Geriatr Psychiatry, 22(5):405-10 51 Holmes, C., Hopkins, V., Hensford, C., MacLaughlin, V., Wilkinson, D., & Rosenvinge, H. (2002). Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study. Int J Geriatr Psychiatry, 17(4):305-8. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/11994882. 52 Field, T., Field, T., Cullen, C., Largie, S., Diego, M., Schanberg, S., et al. (2008). Lavender bath oil reduces stress and crying and enhances sleep in very young infants. Early Human Development, 84(6):399401. 53 Chien, L., Cheng, S., & Liu, C. (2012). The Effect of Lavender Aromatherapy on Autonomic Nervous System in Midlife Women with Insomnia. Evidence-Based Complementary and Alternative Medicine, 2012(2012): 1-8. Retrieved from: http://dx.doi.org/10.1155/2012/740813 54 Shiina, Y., Funabashi, N., Lee, K., Toyoda, T., Sekine, T., Honjo, S., et al. (2008). Relaxation effects of lavender aromatherapy improve coronary flow velocity reserve in healthy men evaluated by transthoracic Doppler echocardiography. International Journal of Cardiology, 129(2):193-197. Retrieved from: http://dx.doi.org/10.1016/j.ijcard.2007.06.064 55 Lin, P.W., Chan, W.C., Ng, B.F., & Lam, L.C. (2007). Efficacy of aromatherapy (Lavandula angustifolia) as an intervention for agitated behaviours in Chinese older persons with dementia: a crossover randomized trial. Int J Geriatr Psychiatry, 22(5):405-10 56 Hancianu, M., Cioanca, O., Mihasan, M., & Hritcu, L. (2013). Neuroprotective effects of inhaled lavender oil on scopolamine-induced dementia via anti-oxidative activities in rats. Phytomedicine, 20(5):446-52. 57 Wang, D., Yuan, X., Liu, T., Liu, L., Hu, Y., Wang, Z., et al. (2012). Neuroprotective activity of lavender oil on transient focal cerebral ischemia in mice. Molecules, 17(8):9803-17. 58 Koutroumanidou, E., Kimbaris, A., Kortsaris, A., Bezirtzoglou, E., Polissiou, M., Charalabopoulos, K., et al. (2013). Increased Seizure Latency and Decreased Severity of Pentylenetetrazol-Induced Seizures in Mice after Essential Oil Administration. Epilepsy Res Treat, 2013(2013): 532657. 59 Orhan, I., Kartal, M., Kan, Y., & Şener, B. (2008). Activity of Essential Oils and Individual Components against Acetyl and Butyrylcholinesterase. Zeitschrift Für Naturforschung C, 63(7-8). Retrieved from: http://dx.doi.org/10.1515/znc-2008-7-813. American College of Healthcare Sciences © 2017 www.achs.edu


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on these results an effective blend would be lavender, Spanish sage, and coriander. This blend has the potential to provide AD support and manage associated symptoms such as anxiety. Further clinical studies are recommended. Rosemary Rosmarinus officinalis (L.) Six research articles published in peer-reviewed journals that focus on rosemary and brain health were reviewed. Four were animal studies involving rats and two were randomized, placebo-controlled, double-blind studies. The animal studies indicated that rosemary supplementation (in a form of hydroalcoholic extract60 and essential oil61) does improve the quality of memory62. The effect was determined to be due to the inhibition of AChE and BChE activity in the brain, as well as the reduction of oxidative stress.63 In addition, an increase in the speed of memory was observed in a small-scale, randomized, placebo-controlled, double-blind study involving 28 older adults given a daily dose of 750mg of dried rosemary leaf powder.64

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Zanella, C., Treichel, H., Cansian, R., & Roman, S. (2012). The effects of acute administration of the hydroalcoholic extract of rosemary (Rosmarinus officinalis L.) (Lamiaceae) in animal models of memory. Brazilian Journal of Pharmaceutical Sciences, 48(3):389-397. Retrieved from: http://dx.doi.org/10.1590/s1984-82502012000300005. 61 Hosseinzadeh, H., Karimi, G., & Noubakht, M. (2004). Effects of Rosmarinus officinalis L. Aerial Parts Essential Oil on Intact Memory and Scopolamine-Induced Learning Deficits in Rats Performing the Morris Water Maze Task. Journal of Medicinal Plants, 3(12):68. 62 Rasoolijazi, H., Mehdizadeh, M., Soleimani, M., Nikbakhte, F., Eslami Farsani, M., & Ababzadeh, S. (2015). The effect of rosemary extract on spatial memory, learning and antioxidant enzymes activities in the hippocampus of middle-aged rats. Med J Islam Repub Iran, 29. Retrieved from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431423/ 63 Ozarowski, M., Mikolajczak, P., Bogacz, A., Gryszczynska, A., Kujawska, M., Jodynis-Liebert, J., et al. (2013). Rosmarinus officinalis L. leaf extract improves memory impairment and affects acetylcholinesterase and butyrylcholinesterase activities in rat brain. Fitoterapia, 91:261-271. Retrieved from: http://dx.doi.org/10.1016/j.fitote.2013.09.012 64 Pengelly, A., Snow, J., Mills, S., Scholey, A., Wesnes, K., & Butler, L. (2012). Short-Term Study on the Effects of Rosemary on Cognitive Function in an Elderly Population. Journal of Medicinal Food, 15(1):1017. Retrieved from: http://dx.doi.org/10.1089/jmf.2011.0005 American College of Healthcare Sciences © 2017 www.achs.edu


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Another larger-scale, randomized, placebo-controlled, double-blind study involving 144 participants demonstrated that exposure to rosemary essential oil (via inhalation) enhanced the overall quality of memory.65

A Summary of the Primary Mechanisms Black pepper, clove, coriander, Spanish sage, Greek sage, lavender, and rosemary all inhibit the activity of AChE and BChE enzymes and consequently increase the concentration of ACh, which diminishes as we age: •

AChE (BChE) normally reduces the concentration of ACh through the hydrolysis of the ester group of this compound.

•

Essential oil constituents bind to AChE and BChE enzymes and deactivate the enzyme active site in a process called reversible inhibition.

•

Binding is reversible. After some time, the chemical bond is broken and the essential oil molecular constituents leave the enzyme, at which time the enzyme starts to perform (making it active again).

Additional Mechanisms Antioxidant Coriander, clove, lavender, and rosemary are also important due to their antioxidant properties. Spanish sage and Greek sage also exhibit antioxidant activity, but to a lesser extent.

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Moss, M., Cook, J., Wesnes, K., & Duckett, P. (2003). Aromas of Rosemary and Lavender Essential Oils Differentially Affect Cognition and Mood in Healthy Adults. Int J Neurosci., 113(1):15-38. doi:10.1080/00207450390161903 American College of Healthcare Sciences © 2017 www.achs.edu


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All of these antioxidant essential oils contain constituents that reduce reactive oxygen species by pairing with unpaired electrons that are highly reactive damaging molecules, thus protecting the neurological cells in the brain from oxidative damage. Anti-inflammatory Black pepper and Spanish sage have an anti-inflammatory action: •

Black pepper essential oil acts as a COX-2 inhibitor; COX-2 is an enzyme responsible for inflammation and pain. The exact mechanism is not known.

•

Spanish sage essential oil inhibits eicosanoid synthesis, which is a part of the inflammatory response. Eicosanoids are lipids. There are three types of eicosanoids: prostaglandins, leukotrienes, and thromboxanes. The most important, in this case, is prostaglandins. These compounds cause several aspects of the inflammatory response, such as pain and fever. Blockage of synthesis prevents formation of new prostaglandins and, respectively, helps to relieve symptoms. The exact mechanism of how this synthesis is stopped is not known. It is known, however, that inflammation in the brain promotes development of AD. Thus, these compounds can delay it by targeting inflammatory pathways.

Adjunct Modalities Coriander and lavender are also useful as an adjunct modality as they were shown to reduce anxiety and depression.

Medicinal Quality and Environmental Concerns: Our Planet, Our Brains, and Essential Oils The certified organic essential oil market is expanding at a significant rate over conventionally produced essential oils. In 2014, 100% organic essential oils had a dollar American College of Healthcare Sciences © 2017 www.achs.edu


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growth rate of +34.6%, higher than the rate of conventional essential oils, which increased at a rate of +22.5%.66 One contributing cause for this marked increase is growing consumer awareness of the dangers of pesticides. It is imperative that the essential oils grown and produced for aromatherapy uses (such as for the management of AD symptoms) are rigorously tested and shown to be free from pesticides and other adulterants. It was established in the late 1990s that organophosphorus (OP) pesticides (a type of pesticide currently used in agriculture) inhibit AChE.67 Reduction of AChE activity is a classical biomarker (indication) of exposure to OP pesticides.68 A significant decrease in AChE activity was reported for the population continually exposed to the pesticides, including pesticide manufacturing workers69 and farmers.70,71 Further, chronic exposure to OP pesticides can cause acetylcholine to build up to dangerous levels, while the protective levels of the cholinesterase enzyme decrease. Also, OPs induce oxidative stress, one of the main mechanisms of their toxicity.72 Not surprisingly, studies conducted in different parts of the world have demonstrated that 66

Source: SPINSscan Natural 2014 Naravaneni, R. & Jamil, K. (2007). Determination of AChE levels and genotoxic effects in farmers occupationally exposed to pesticides. Human & Experimental Toxicology, 26(9): 723-731. http://dx.doi.org/10.1177/0960327107083450 68 Mileson, B., Chambers, J., Chen, W., Dettbarn, W., Ehrich, M., Eldefrawi, A., et al. (1998). Common Mechanism of Toxicity: A Case Study of Organophosphorus Pesticides. Toxicol Sci., 41(1): 8-20. Retrieved from: http://dx.doi.org/10.1093/toxsci/41.1.8 69 Ranjbar, A., Pasalar, P., & Abdollahi, M. (2002). Induction of oxidative stress and acetylcholinesterase inhibition in organophosphorous pesticide manufacturing workers. Human & Experimental Toxicology, 21(4):179-182. Retrieved from: http://dx.doi.org/10.1191/0960327102ht238oa 70 Lopez, O., Hernandez, A., Rodrigo, L., Gil, F., Pena, G., & Serrano, J., et al. (2007). Changes in antioxidant enzymes in humans with long-term exposure to pesticides. Toxicology Letters, 171(3):146-153. Retrieved from http://dx.doi.org/10.1016/j.toxlet.2007.05.004 71 von Osten, J., Tinoco-Ojanguren, R., Soares, A., & Guilhermino, L. (2004). Effect of Pesticide Exposure on Acetylcholinesterase Activity in Subsistence Farmers from Campeche, Mexico. Archives of Environmental Health: An International Journal, 59(8):418-425. Retrieved from: http://dx.doi.org/10.3200/aeoh.59.8.418-425 72 Ranjbar, A., Solhi, H., Mashayekhi, F., Susanabdi, A., Rezaie, A., & Abdollahi, M. (2005). Oxidative stress in acute human poisoning with organophosphorus insecticides; a case control study. Environmental Toxicology and Pharmacology, 20(1):88-91. Retrieved from: http://dx.doi.org/10.1016/j.etap.2004.10.007 67



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chronic pesticide exposure increases the risk of developing AD.73,74 It is interesting to note that as the earth becomes more and more saturated in pesticides we are seeing a corresponding increase in AD.

Conclusion There is no doubt that the world is facing an aging population crisis. The number of people living with dementia worldwide is expected to double every 20 years.75 Aristotle, the famous Greek philosopher, said, “Memory is the scribe of the soul.” Without memory, a person’s own idea of who they are begins to fade and even innate physiological responses, such as remembering to swallow, can decline. Those suffering from dementia face discrimination and social rejection76 and are no longer fully functioning members of society. While aromatherapy essential oils will not provide all the answers, research shows they have great potential. Black pepper, coriander leaf (and potentially the oil), clove, Spanish sage, Greek sage, lavender, and rosemary all show they can inhibit the enzymes AChE and BChE; enzyme inhibition keeps the neurotransmitter acetylcholine at a higher level by decreasing its breakdown rate. This, respectively, boosts cholinergic neurotransmission in forebrain regions and can help in the management of AD 73

Singh, N., Chhillar, N., Banerjee, B., Bala, K., Basu, M., & Mustafa, M. (2012). Organochlorine pesticide levels and risk of Alzheimer’s disease in north Indian population. Human & Experimental Toxicology, 32(1):24-30. Retrieved from: http://dx.doi.org/10.1177/0960327112456315 74 Hayden, K., Norton, M., Darcey, D., Ostbye, T., Zandi, P., Breitner, J., et al. (2010). Occupational exposure to pesticides increases the risk of incident AD: The Cache County Study. Neurology, 74(19):1524-1530. Retrieved from: http://dx.doi.org/10.1212/wnl.0b013e3181dd4423 75 Alzheimer’s Society. (n.d.). Alzheimer’s Society: About us. Retrieved from: https://www.alzheimers.org.uk/site/scripts/documents.php?categoryID=200119 76 Bonder, N. (2016, January 19). People with dementia face discrimination and social rejection. Medicalxpress. Retrieved from: http://medicalxpress.com/news/2016-01-people-dementia-discriminationsocial.html



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symptoms. In addition, lavender has a potential as an adjunct therapy for AD as it was demonstrated to be effective for the management of agitated behavior in patients with dementia and in improving quality of sleep. Human subject clinical research trials are now required to advance the preliminary work done with these essential oils. Safety, recommended daily dose, duration, and potential side effects are all issues that would need assessed. If an essential oil can impact enzyme action it could potentially cause undesirable effects at a specific dose level. Once it is proven that they offer a viable and safe integrative treatment for AD and trials are subsequently advance to the clinical testing phase, there will be potential product development. In the meantime, it seems prudent to include these aromatherapy essential oils at a low dosage in any daily preventative holistic regimens in the home, senior rest home, and clinical settings. Administrative routes including diffusion, topical patches, foot and hand soaks, foot and hand massages, and nasal inhalers all offer unobtrusive and safe solutions for essential oil therapy to the elderly.



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Table References Table 1 Essential Oil Research References: The citations for the research papers referenced in the column Research Paper Reference can be found in the Research Reference Addendum at the end of this paper. ........................................................... 5 Table 2 Chemical Constituent Research References: The citations for the research papers referenced in the column Research Paper Reference can be found in the Research Reference Addendum at the end of this paper. ........................................................... 6 Research Paper Reference Addendum Following are the full citations for the research papers referenced in Tables 1 and 2 in this paper. 1. Chaiyana, W. & Okonogi, S. (2012). Inhibition of cholinesterase by essential oil from food plant. Phytomedicine, 19(8-9):836-839. Retrieved from: http://dx.doi.org/10.1016/j.phymed.2012.03.010. 2. Kitphati, W., et al. (2012). Anticholinesterase of essential oils and their constituents from Thai medicinal plants on purified and cellular enzymes. JAASP, 1(1):58-67. 3. Orhan, I., Kartal, M., Kan, Y., & Şener, B. (2008). Activity of Essential Oils and Individual Components against Acetyl and Butyrylcholinesterase. Zeitschrift Für Naturforschung C, 63(7-8). Retrieved from: http://dx.doi.org/10.1515/znc-2008-7813. 4. Ayaz, M., Junaid, M., Ullah, F., Sadiq, A., Khan, M., Ahmad, W., et al. (2015). Comparative chemical profiling, cholinesterase inhibitions and anti-radicals properties of essential oils from Polygonum hydropiper L: A Preliminary antiAlzheimer’s study. Lipids Health Dis., 14(1). Retrieved from: http://dx.doi.org/10.1186/s12944-015-0145-8. 5. Phrompittayarat, W., Hongratanaworakit, T., Sarin Tadtong, K., Sareedenchai, V., & Ingkaninan, K. (2013). Survey of Acetylcholinesterase Inhibitory Activity in Essential Oils from Aromatic Plants. The Open Conference Proceedings Journal, 4(1):84-84. Retrieved from: http://dx.doi.org/10.2174/2210289201304010084. 6. Mani, V., Parle, M., Ramasamy, K., & Abdul Majeed, A. (2010). Reversal of memory deficits by Coriandrum sativum leaves in mice. Journal of The Science Of Food And Agriculture, 91(1):186-192. Retrieved from: http://dx.doi.org/10.1002/jsfa.4171.



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7. Santos, H.S., et al. (2010). Chemical composition and cholinesterase inhibition of essential oils of three chemotypes from Croton zehntneri. Rev. latinoam. quím, 38(1):45-51. 8. Arruda, M., Viana, H., Rainha, N., Neng, N., Rosa, J., Nogueira, J., et al. (2012). Anti-acetylcholinesterase and Antioxidant Activity of Essential Oils from Hedychium gardnerianum Sheppard ex Ker-Gawl. Molecules, 17(12):3082-3092. Retrieved from: http://dx.doi.org/10.3390/molecules17033082. 9. Khan, S., Khan, H., Ali, F., Ali, N., Khan, F., & Khan, S. (2015). Antioxidant, cholinesterase inhibition activities and essential oil analysis of Nelumbo nucifera seeds. Natural Product Research, 1-4. Retrieved from: http://dx.doi.org/10.1080/14786419.2015.1055743. 10. Owokotomo, I., Ekundayo, O., Abayomi, T., & Chukwuka, A. (2015). In-vitro anti-cholinesterase activity of essential oil from four tropical medicinal plants. Toxicology Reports, 2: 850-857. Retrieved from: http://dx.doi.org/10.1016/j.toxrep.2015.05.003. 11. Lomarat, P., Shripha, K., Phanthong, P., Kitphati, W., Thirapanmethee, K., & Bunyapraphatsara, N. (2015). In Vitro Biological Activities of Black Pepper Essential Oil and Its Major Components Relevant to the Prevention of Alzheimer’s Disease. The Thai Journal of Pharmaceutical Sciences, 39(3):94101. 12. Şenol, F., Orhan, I., Erdem, S., Kartal, M., Şener, B., Kan, Y., et al. (2011). Evaluation of Cholinesterase Inhibitory and Antioxidant Activities of Wild and Cultivated Samples of Sage (Salvia fruticosa) by Activity-Guided Fractionation. Journal of Medicinal Food, 14(11):1476-1483. Retrieved from: http://dx.doi.org/10.1089/jmf.2010.0158. 13. Perry, N., Court, G., Bidet, N., Court, J., & Perry, E. (1996). European Herbs with Cholinergic Activities: Potential in Dementia Therapy. Int. J. Geriat. Psychiatry, 11(12):1063-1069. 14. Mukherjee, P., Dalai, M., Bhadra, S., Chaudhary, S., & Bandyopadhyay, A. (2014). Anti-cholinesterase activity of the standardized extract of Syzygium aromaticum L. Pharmacognosy Magazine, 10(38):276. Retrieved from: http://dx.doi.org/10.4103/0973-1296.133275.
