Foods and Dietary Supplements in the Prevention and Treatment of Disease in Older Adults

book.

Part I

Non-Nutritional Components in Diet and Supplements, Nutraceuticals and their Role in Health Promotion in the Mature Adult

Outline

Chapter 1 A Traditional Elder’s Anti-Aging Cornucopia of North American Plants

Chapter 2 Alzheimer’s Disease: Current Perspectives – Animal Models, Drugs Under Development, and Potential Nutritional Intervention

Chapter 3 Amla in the Prevention of Aging: Scientific Validation of the Ethnomedicinal Claims

Chapter 4 Sarcopenia – Potential Beneficial Effects of Creatine Supplementation

Chapter 5 Dietary Spices in the Prevention of Rheumatoid Arthritis: Past, Present, and Future

Chapter 6 Medicinal Benefits of Ginger in Various Gastrointestinal Ailments: Use in Geriatric Conditions

Chapter 7 Foods and Dietary Supplements in the Prevention and Treatment of Neurodegenerative Diseases in Older Adults

Chapter 1

A Traditional Elder’s Anti-Aging Cornucopia of North American Plants

Maria Pontes Ferreira¹, Jaclyn Palmer¹, Elder Betty McKenna² and Fidji Gendron²,    ¹Department of Nutrition & Food Science, Wayne State University, Detroit, MI, USA,    ²First Nations University of Canada, Regina, Saskatchewan, Canada

All major biomes are represented in the expansive North American continent. The continent has a rich and under-appreciated tradition of indigenous uses of foods and medicines derived from the native plants. This chapter features a discussion regarding the following cornucopia of plants, selected by a Native American/Aboriginal Elder: Indian breadroot (Pediomelum esculentum (Pursh) Rydb.), gumweed (Grindelia squarrosa (Pursh) Dunal), Labrador tea (Ledum spp.), and blueberry (Vaccinium spp.). These plants are selected for discussion due to their use or promise in the prevention/treatment of ailments commonly experienced with aging, and may benefit older adults when consumed. They are presented in a way to illustrate both the traditional uses of the plants (indigenous science) and the evidence in support of their bioactive properties (Western science). This approach to the presentation of these plants will allow readers a greater appreciation of Native North American Traditional Medicine.

Keywords

Indian breadroot (Pediomelum esculentum (Pursh) Rydb.); gumweed (Grindelia squarrosa (Pursh) Dunal); Labrador tea (Ledum spp.); blueberry (Vaccinium spp.); Native/Aboriginal

1.1 Introduction

Phytotherapy is a common form of medicine for many North American Aboriginal people, and a wide variety of plants are used as food and medicine to maintain health. Plants are a rich source of natural compounds whose various biological activities have provided medicinal value to traditional healers for centuries. About 80% of the world’s population still relies on traditional medicines for their primary health care [1]. Despite their cultural value, only 6% of the plants have been studied for their biological activity [2]. Although some pharmaceutical agents developed in labs are synthetic, many drugs originate from natural products such as those found in fungi, bacteria, animals, protists, and plants. Plant extracts and their derivatives have received considerable attention as therapeutic agents for preventing and treating health problems. Since the 1940s, for example, most molecules involved in cancer treatment have been of natural source, with almost half being either natural products or their transformed products [3]. The promising biological activities of these molecules warrant more research. Newman and Cragg strongly recommend continued exploration of these natural products to find much needed novel medicines [3].

It is important to appreciate and understand the knowledge possessed by traditional healers and Elders from North America, a vast continent with many biomes and many indigenous people. Many ethnomedicine research projects originate from collaboration of Western scientists with Aboriginal communities, to enhance appreciation regarding indigenous science. For example, several plant species used by traditional healers in the boreal regions of Canada have been examined for antioxidant activity and treatment of the symptoms of diabetes [4]. Findings from such studies corroborate the traditional land and plant knowledge of Aboriginal plant gatherers to effectively select plants with specific medicinal value. In the Native culture, traditional foods are seen as sacred and may have spiritual and medicinal value above provision of food energy. Traditional foods are rich in bioactive molecules that may have medicinal value. It is important to recognize that many plants utilized in Native North American culture fall on the continuum of foods and medicines.

Turner points out that a description of traditional plants in the Aboriginal culture is not complete without talking about the tools used to harvest, process, and prepare them (such as digging sticks), their names in different languages, and their connection to the land [5]. This information is conveyed by oral traditions, such as when younger generations spend time on the land with their families, especially the Elders. Unfortunately, the younger generation today spends less time with Elders. There is a need to find new ways to share traditional knowledge about plants with the Aboriginal and scientific communities, and to explore their documented biochemical properties.

In this chapter, we collaborate with a female Elder (Betty McKenna) to explore how specific plants can be used for the health of older adults. Elder Betty is an Anishinabe First Nation woman who has been teaching and practicing traditional knowledge for the past 45 years. We are interested in knowing more about selected plants she uses with older adults, and the cultural teachings centered on these plants. Plants presented in this chapter are Indian breadroot (Pediomelum esculentum (Pursh) Rydb.), gumweed (Grindelia squarrosa (Pursh) Dunal), Labrador tea (Ledum spp.), and blueberry (Vaccinium spp.). For each plant, both traditional knowledge and Western-based scientific knowledge are examined through meetings with Elder Betty, and review of the peer-reviewed published literature.

1.2 Indian Breadroot (Pediomelum esculentum (Pursh) Rydb. formerly Psoralea esculenta Pursh)

(Anishinabe name for Indian breadroot: pahkwe sikun ocheh pic)

Elder Betty:

We harvest both Indian breadroot (P. esculentum) and silverleaf root (P. argophyllum). The whole plant is picked and cut at the base of the stem. The root is chopped and used as flour in meals. The top part of the plant with the leaves, stems, and flowers are laid out on a cloth in my kitchen to dry. Once dried, I chop them with a knife or I use a coffee bean grinder to chop them finer. I harvest enough plants to keep me for the full year. I make a tea with the top part. The tea has a hearty taste. The tea is good for women going through menopause. At menopause, the hair, the nails and the skin get drier and lose their elasticity. The tea helps slow down this effect. It also serves to smooth the skin. The tea prevents bone fractures. My grandmother used to say that it is like glue for your bones. When I grew up, I did not drink milk after I was breastfed so we ate bone marrow as our source of calcium. The bone marrow is not good enough for women going through menopause so we drink the tea which would hold the bones stronger. The tea also helps to reset sleep patterns and reduces night terrors and panic attacks in menopause. Women go through stages in their life and one of them is when we go from life-giver to grandmother. The tea helps with a smooth transition from Mother Earth to Grandmother Moon. Women in their menopause could not afford to have their sleep disturbed because they have to be spiritually well to receive the message from the ancestors and Grandmother Moon. This is why it is important to have a natural dream–wake cycle that is not disturbed and the tea helps with that. It also helps balance the spiritual and mental health, especially in winter when a lot of older people might fall in depression. I drank this tea three times a week.

Pediomelum esculentum is a low, bushy herb of the Fabaceae (Leguminosae; pea or bean) family, with a strong fleshy taproot, often greatly enlarged as a bulbous tuber-like structure. Its stem is covered with bristly hairs, and its hairy leaves are palmately compound with five gray-green pubescent leaflets. The flowers are formed in a spike of bluish-purple flowers with five petals and five sepals in typical legume arrangement. After flowering the flowers rapidly wither and become brittle, causing them to detach and blow away in the wind. It is then much more difficult to locate the underground taproot. For this reason, the root is usually harvested from May to July across the prairies [6]. In Saskatchewan, roots are dug up between the middle of June and the middle of July. If left too long the root increases in size and the interior becomes woody, with lignified and inedible tissue [7,8]. It is native to central Canada and the USA [9], and is found in prairie grassland. The Lewis and Clark expedition of 1804–1806 collected specimens that were identified botanically, but it was Frederick Pursh who first published its description in 1814 [10].

Indian breadroot was known as pomme blanche (white potato) by the French Canadian voyagers, and as prairie potato by the early American settlers. Pediomelum esculentum has long been a reliable and plentiful staple of the Plains Aboriginals’ diet during spring and early summer [6]. In fact, it might have been the most important wild plant food regularly harvested by Aboriginal nomadic buffalo hunters in the northern plains during the fur trade era. It was used as a key ingredient in dishes that were prepared during gatherings, and not only as a mean of subsistence [10]. Gatherers used a digging stick with a sharpened end to extract the underground roots [6]; it has also been reported that women and children were the main gatherers, and used fire-hardened digging sticks [10]. Preparation traditionally involved cutting the roots into thin slices, or braiding them whole to let them dry. The dry roots were ground into flour to thicken soups [6]. The dry roots and flour were easily preserved, and thus could be used during the wintertime [6].

Pediomelum esculentum is a valuable food source, and its nutritional value has been examined. The tuber has 16.3% crude fiber, up to 70% starch, and between 4.22% and 6.7% protein content, which is higher than in a potato (2%). It is a good source of calcium, magnesium, iron, zinc, and potassium [7,10–12]. Large and separate deposits of starch and proteins are found in the xylem parenchyma of the root [13]. Its high starch content makes it an ideal source of energy. It has between 0.38 (fresh weight) and 17.1 (dry weight) milligrams of vitamin C per 100 grams, which is slightly lower than in citrus fruits (25–30 (dry weight) mg/100 g) [10,11].

In addition to its nutritive value, P. esculentum contains bioactive compounds with medicinal value. The isoflavones genistein and daidzein are found in P. esculentum. Genistein is found in various parts of the plant, with the leaves and stems having the highest concentration (3–11 mg/g dry weight), followed by the flowers and the rind of the root (0.6–1.2 mg/g dry weight), with the bulb having the lowest concentration (0.2–0.7 mg/g dry weight) [14]. The concentration of genistein, however, varies during the growing season, and is at its lowest later in the season [14]. Daizden concentrations in the rind are higher than genistein [14]. Genistein and daidzein are common bioactive components in the leaves of the Pediomelum genus, and are also found in the seeds [15]. Commercial soy bean (Glycine max (L.) Merr.) products are the main source of genistein and daidzein, with concentrations of 0.74 mg and 0.47 mg/g soy, respectively [16]. Psoralea corylifolia Linn. is a legume species widely used in Asian traditional medicine, and is related to P. esculentum. Its genistein and daidzein concentrations are 2.15 mg/g and 0.099 mg/g of leaves, respectively [15]. It is clear from these statistics that P. esculentum may be a promising avenue for supply of beneficial isoflavones from native North America.

Isoflavones have high antioxidant capacity. Free-radical damage and oxidative stress are correlated with chronic diseases and disorders [17]. Free radicals are atoms or molecules that contain an unpaired electron in an outer shell, making them highly reactive. A free radical is capable of destroying a biomolecule, such as an enzyme, or a cell. Oxidative stress in humans is associated with the build-up of highly reactive free radical species that damage biomolecules, and/or the decrease of defense mechanisms to protect against biological damage by free radicals. Once a cell is badly damaged the DNA can be altered, resulting in diseases such as cancer [17]. Isoflavones such as genistein and daidzein have demonstrated antioxidant capacity [16].

Genistein is part of the diet of people who regularly consume soy products. It is linked to a decreased risk of mortality from several types of cancer [18], and is especially associated with decreased numbers of breast and prostate cancers [1]. Genistein is involved in several steps during cancer progression: it inhibits cancer meta-stasis because of its roles in the cell cycle and apoptosis, it alters cell adhesion, and it decreases the rate of cell migration and cell invasion [18]. Genistein and daidzein decrease the production of angiogenic growth factors [19]. Angiogenesis is the development of blood vessels that supply oxygen and nutrients, allowing for the formation of new tumors. Genistein also upregulates the expression of the non-steroidal anti-inflammatory drug activated gene 1 (NAG-1) [20]. One of the roles of the NAG-1 protein is to promote the programmed death of cells, known as apoptosis.

Genistein and daidzein are called phytoestrogens because they are structurally similar to the mammalian hormone estrogen and are able to bind to the estrogen receptor. During aging, especially in menopause, there is a decrease in the production and concentration of estrogens. Low sex-steroid concentrations have a negative impact upon bone health. Reduced bone mineralization can lead to fractures such as hip fractures in older people, especially women. Soy-derived genistein and daidzein are beneficial supplements as they may reduce bone loss by binding to the estrogen receptors when the concentration of estrogen is low, such as in postmenopausal women [21]. Hot flashes and vaginitis, common symptoms associated with menopause, are reduced when women take these phytoestrogens [1,18]. We speculate that Indian breadroot, as a whole food or a natural health product, is a source of bioactive isoflavones and other molecules from native North America that is worthy of further study.

1.3 Gumweed (Grindelia squarrosa (Pursh) Dunal)

(Anishinabe name for gumweed: Pusakwan wapa gwanese)

Elder Betty:

Before I harvest gumweed, I say my prayer specific to that plant. We can put the yellow sticky flower on the cut; it is like a band-aid. There is no need for stitches as the stickiness will hold the skin together. We can pick the flowers, let them dry and store them in a glass jar for later use. The plant helps with headache and sore eyes. We never boil gumweed because it would ruin the pot by sticking to it. Instead, we crush it in a cloth and put it around the head of the people we are treating. The cloth has a strong smell. Once the flowers are ground, we can put it on cuts. It is an antibiotic so the infection will not set in. Older people usually keep ground gumweed in their home for cuts. It is very upsetting when we see someone bleeding, but older people would know exactly what to do in case of bleeding. They would not try a lot of different plants, they would know right away which one to use. They would use the tried and true method first by applying the stored ground gumweed to the cut.

Gumweed has several branched stems with a deep taproot. It is a member of the Aster family or Asteraceae, and has both yellow ray and yellow disc florets. Its numerous branches end with a yellow flower head. The plant gets one of its names, curlycup gumweed, from the overlapping rows of stiff backward-curling resinous bracts subtending the flower. The plant is sticky (or gummy) to the touch because the surfaces of the leaves, stems, and involucres of the flower heads are pitted with resin glands. Grindelia produces a high yield of resin, ranging from 5% to 20% of the plant’s dry weight depending on the species [22,23]. The generous resin may be an ecological adaptation to the arid and semi-arid environments in which these plants grow [22]. Grindelia squarrosa is native to Western Canada and most of the United States, with the exception of the lower eastern areas [9], and is commonly found on arid prairies. The related Grindelia species G. camporum Greene and G. camporum Greene var. camporum, formerly known as G. robusta[9], have also been examined for their medicinal properties. In the following section, these plants are identified according to how they were identified in the referenced paper(s).

The genus name Grindelia originates from the name of the German botanist David Grindel (1766–1836) [23]. It has been used by the indigenous North American people to treat bronchial problems such as asthma, as well as skin afflictions of all kinds [23,24]. For example, Native Americans would make an infusion from the leaves and roots of the G. squarrosa plant and use that as a wash for measles [25]. In southern Alberta, indigenous people brew the flower heads into a tisane to treat migraine headaches and venereal disease [26].

Several compounds have been isolated and identified in G. squarrosa, including diterpene acids such as grindelic acid, 17-hydroxygrindelic acid, 7-8-epoxygrindelic acid, and 17-acetoxygrindelic acid [22]; phenolic acids [27]; flavonoids; and triterpenoid saponins [23]. Flowers contain higher amounts of phenolic acids than leaves [27,28]. Hexane extracts from G. squarrosa show increases during the summer, and this increase is correlated with greater resin production and higher content of diterpene acids, possibly to deter insects from feeding on the flower heads [29].

Phenolic acids are associated with the anti-inflammatory, antibacterial, spasmolytic, and antioxidant effects of G. squarrosa[27]. Inflammation is implicated in many chronic diseases that occur in older adults. It acts in the pathogenesis of diseases such as metabolic disorders, arthritis, cardiovascular disease, and cancer [30]. Grindelia robusta’s plant methanol extracts significantly reduce the production of nitric oxide and the pro-inflammatory cytokines IL-1β and IL-12, and the expression of the pro-inflammatory proteins iNOS and cyclooxygenase-2 (COX-2) in vitro[30]. Nitric oxide, cytokines, and COX-2 are all implicated in the inflammation process. For example, the enzyme COX-2 is necessary for the production of prostaglandins, which contribute to inflammation and tissue damage. This enzyme is a drug target for cancer prevention and inflammation reduction because it is a required mediator for pro-inflammatory prostaglandin production [30]. Bacterial lipopolysaccharide-induced macrophage cells were treated with methanol whole plant extracts of G. robusta. The results show a reduction in the expression of the enzyme COX-2, therefore suppressing pro-inflammatory prostaglandin production [30]. It is reported that G. robusta extracts inhibit the secretion of these pro-inflammatory mediators by inactivating the molecule that regulates their transcription in the nucleus: nuclear factor-kappa B (NF-κB) [24,30]. NF-κB is a molecule present in the cytoplasm that moves to the nucleus in response to various stimuli (e.g., free radicals, bacterial lipopolysaccharides, tumor promoters, and ultraviolet radiation). Once in the nucleus, it controls the transcription of DNA and regulates the expression of nearly all genes involved in inflammation [20]. Plant extracts with the capacity to regulate transcriptional factor NF-κB activity may be a promising avenue to explore in halting the inflammatory cascade implicated in so many chronic diseases.

As mentioned, there is an increase in the production of nitric oxide during inflammation [30]. Nitric oxide is a free radical, which can cause nucleic acid and cellular damage, contributing to the pathogenesis observed in several diseases. For nitric oxide production to occur, nitric oxide synthase must be expressed. Verma and colleagues showed in vitro that G. robusta methanol extract is associated with a significant reduction in the amount of nitric oxide synthase, thus inhibiting the production of nitric oxide [30].

Grindelic acid demonstrates in vitro antitumor activity against human breast, cervix, lung, and colon solid-tumor cell lines [2]. While this compound is naturally abundant in the Grindelia genus, it is also possible to synthesize compounds derived from this diterpene. These synthetic derivatives are also effective in vitro as antitumor derivatives, sometimes being even more effective than the original grindelic acid found in plants [2]. With cancer treatment it is imperative to find a drug that destroys the cancerous cells but is not toxic to the healthy cells, thereby causing further damage to the body. Although the studies were performed using a cell-based assay further study is encouraged, because even at a high concentration the alcohol based-extract from G. robusta plants is not found to be cytotoxic [24,30]. As previously discussed, NF-κB complex activation leads cancer cells to multiply rapidly. The G. robusta methanol extracts are able to suppress the activation of NF-κB in LPS-induced macrophages [30]. Further testing in animal models is needed to determine if Grindelia species extracts are antitumorigenic.

Essential oils give the flavor and aroma of many herbs and spices, as well as scents used in perfumes. Depending on the plant species, the functions of essential oils range from attracting pollinators to discouraging herbivores. These volatile oils are produced in specialized cells or glands. Essential oils are important compounds when examining the medicinal properties of plants. Essential oil yield is much greater in G. squarrosa flowers (0.10% of the dry weight, g/g) compared with their stems (0.01%, g/g) and their leaves (0.05%, g/g) [31]. The monoterpenes limonene and α-pinene are the major components identified in essential oils in G. squarrosa[31,32]. The essential oil of a related plant, G. robusta, demonstrates relevant antioxidant activity in vitro using the DPPH and 5-lipoxygenase assay [28]. Although monoterpenes are usually assumed to contribute to the anti-inflammatory, antimicrobial, and expectorant activities associated with Grindelia plants, some research reports that other compounds may also play a role. For example, quercetin-3-methylether, an abundant flavonol found in G. robusta, is very active at inhibiting human neutrophil elastase activity in vitro[33]. Elastases are also linked to a variety of inflammatory diseases.

The Grindelia genus is used successfully as a source of antimicrobial substances. Methanol extracts from Grindelia camporum display significant antifungal activity against several pathogenic and toxinogenic fungal species in vivo[34]. Grindelia squarrosa methanolic extracts show fungal and antibacterial effects [25].

1.4 Labrador Tea (Ledum spp.)

(Anishinabe name for Labrador tea: mashkiigobag)

Elder Betty:

This is our most important tea and we drink it every day to keep us healthy. We can drink other teas but this one has all the nutrients and it also has other benefits. When I was a kid, my mom would give it to us before a canoe trip. It has a sedative effect and it would calm us down so that we would not jump in the canoe. It helps with constipation, which is common in older people. It also helps older people so that they don’t get confused. When I was young, older people had to remember where things were. For example, they had to know where the birch trees were for medicines, where the strawberry patch was, where not to go like muskeg holes that were deep and kids could sink in them, and where to hunt. We were hunters and gatherers and older people knew where everything was. They had to remember the landmarks. We could not always take people to these locations and so we had to tell them where it was: You go to the second bend on the river, and so on. This tea helps with keeping a keen memory. Today, the more store-bought food we eat the more we lose our culture! Drinking tea helps us keep our connection to Mother Earth.

Another group with interesting medicinal properties includes plants from the Ericaceae (heather) family. Commonly known in North America as Labrador tea, it is classified as Ledum or Rhododendron species [9]. Labrador tea is a small shrub, anywhere between 30 and 150 cm high, with flattened and matted twigs, hairy leaves, and white flowers on top. This shrub grows best in peaty soils, bogs, and wet pine forests, throughout Canada [35,36]. The plant is very strong and is able to survive fire by rapidly resprouting from the roots. It is powerful not only in survival but also in fragrance – for example, the fragrance of R. tomentosum is said to be so intense that it can cause a headache [36].

Labrador tea is commonly called muskeg tea in Saskatchewan. This tisane is used in traditional medicine for numerous ailments including, but not limited to, skin problems, cold and flu symptoms, inflammatory diseases, asthma, tuberculosis, stomach ache, diarrhea, rheumatism, arthritis, chest pain, swollen limbs, burns, and liver and kidney diseases [36,37].

There are many uses for Labrador tea, but one of the more common methods is to make a steeped beverage by utilizing the leaves [35]. Drinking excessive amounts of Labrador tea is not recommended, as it is very strong and can lead to serious side effects, including intestinal disturbances, drowsiness, and a strong diuretic effect [36]. Rhododendron tomentosum has a high content of toxic volatile compounds in the essential oil, so it is considered a poisonous plant [36]. Therefore, the internal use of methanol and water extracts from this plant is not advised, as there is a danger in consuming the toxic compounds. One of the more toxic compounds involved is the sesquiterpenoid ledol, which has an effect upon the nervous system. The compound can cause psychomotor stimulation, leading to seizures, paralysis, and even death [36]. However, essential oil from this plant has been used in Russia as a cough medicine, with the only side effect recorded being an allergic reaction [36]. It is possible that there is something else in the plant extract that diminishes the effect of the toxic compound’s severe side effects upon the central nervous system when it is consumed as a weak infusion. Serious reactions only seem to occur when there is chronic exposure to ledol, causing an overdose [36].

The role of reactive oxygen species in damaging cellular molecules and contributing to subsequent pathogenesis was outlined above. Dietary antioxidants from foods and phytomedicines may prevent the oxidation of molecules, and thus inhibit the dangerous effects of free radicals in the body. In vivo and ex vivo tests have determined that the methanol extracts of the leaves and twigs from L. groenlandicum Retzius show a strong antioxidant potential [35]. It is possible that this is due to phenolic compounds, as there is a strong correlation between antioxidant properties and total phenolic capacity when assessed using the ORAC assay [35]. This antioxidant activity found in the Labrador tea plants is noteworthy. The time of year in which the plant is harvested may have an effect upon the antioxidant activity. There is a negative correlation between antioxidants and daylight hours, impacting its ability to inhibit free radicals in a tumor necrosis factor-α (TNF-α) assay [36]. The antioxidant activity in vitro of Northern Labrador tea, R. tomentosum ssp. subarcticum, reaches a peak when the leaves turn red in September [38].

Labrador tea is a promising plant medicine to treat symptoms of diabetes, a common metabolic disease [39]. A person suffering from untreated diabetes fluctuates between very high and very low levels of glycemia. Cells are vulnerable to these extremes, and hyper- and hypoglycemia may initiate apoptosis and abolish peripheral nerve regeneration. Ethanol extracts of R. tomentosum leaves increase cell viability in vitro[39]. The cytoprotective activity of R. tomentosum leaves offers an interesting avenue for the treatment of symptoms of diabetes.

A study discovered that the methylene chloride extracts from L. palustre show 99% anticancer activity in mouse leukemia cells [40]. Unfortunately there are some downsides to this extraction as a future anticancer agent, in that it might cause necrosis of healthy cells [40]. There is a safe compound found in the Labrador tea extract called ursolic acid; this acid is found in the twigs of the plant L. groenlandicum and has many beneficial properties, including its anticancer properties [35]. In Japan, ursolic acid has been used and recommended for skin cancer treatment, [35] although it is not clear whether this was recommended in traditional medicine or modern Western medicine. Ursolic acid is also moderately effective against colon- and lung-cancer cell lines [35]. This alcohol extract of ursolic acid does not cause genetic toxicity, so it is safe at acute levels in cells [36].

Labrador tea has anti-inflammatory potential, but it seems to have its greatest effect upon cancer cells in vitro. The Labrador tea extract is so strong that it results in damage to the healthy cells, and therefore further study is warranted. There is promise in the ursolic acid found in the Labrador tea extract, however. It is not as dangerous, yet is effective in inhibiting tumor growth in vitro.

1.5 Blueberry (Vaccinium spp.)

(Anishinabe name for blueberry plant: miinan)

Elder Betty:

When picking blueberry, I put down tobacco as an offering and I say my prayer. I am from the Bear Clan so I ask the bear if I can use its food. We used to let the berries dry to store them but now we freeze them and make juice throughout the year. We drink blueberry juices for different reasons. It is a blood cleanser, it prevents gout by cleansing the blood, and it helps with eyesight and glaucoma. Older people are at a greater risk of developing eye problems and the blueberry helps with that. You can eat blueberries or drink blueberry juice, but it has more benefits if you drink it because you can drink more juice than you can eat berries.

Blueberries are the fruit of the plant genus Vaccinium, which also is a member of the Ericaceae family [9]. Many species of blueberries grow in different parts of North America, and they are all native to the continent [9]. Blueberry bushes range in size depending on the species, and have long, leaf-filled stems, with the fruit itself growing at the end of the stem. For blueberry bushes to thrive, a more acidic soil is recommended but not required [41]. This helps to explain why they grow throughout all of North America, as the boreal forests of Canada have more acidic soils. Blueberry consumption is beneficial in the prevention of cardiovascular disease, diabetes, neurodegenerative diseases, and cancer [42]. Cardiovascular disease risk can be reduced by the consumption of polyphenol flavonoids, in particular anthocyanins [43]. Blueberries have high anthocyanin concentrations, and this helps explain their health benefits [44]. Anthocyanins have a beneficial effect upon inflammation, lipid metabolism, endothelial function, and oxidative damage [43,44]. Blueberries have strong antioxidant capabilities, and this is mostly explained by the 27 different anthocyanin pigments present in the fruit itself [45].

One of the risk factors for cardiovascular disease is high cholesterol, especially low density lipoproteins (LDLs) [46]. It is believed that cholesterol is partly disposed of through biliary excretion by conversion to bile acids. By adding blueberry anthocyanins to the diet of hamsters at 0.5% and 1.0%, the fecal excretion of bile acids significantly increases by 37% and 66%, respectively [42]. There is no observed impact upon gene expression of CYP7A1 and LXRx – enzymes that are involved in bile acid synthesis. The anthocyanins do not have an impact at the gene level by upregulating these enzymes; therefore, there may be an interaction between anthocyanins and bile acids in the intestine [42]. There is also an observed increase in excretion of neutral sterols by 24–30%, which is another mechanism by which serum cholesterol is lowered [42]. These two mechanisms together are associated with dose-dependent decreases in the total cholesterol concentration in plasma [42].

A reduction in total, LDL, and high-density lipoprotein (HDL) plasma concentrations is observed in pigs that were fed blueberries as part of their diet [43]. The most effective dosage in lowering total cholesterol is 2% (weight per weight) blueberry powder [43]. In a different experiment performed by Çoban and associates, some guinea pigs were fed a control diet with or without blueberries, while others received a high cholesterol diet with or without blueberries [47]. An 8% w/w (weight per weight) of fresh blueberries was chosen for the guinea pigs [47]. Significant decreases in serum cholesterol (and specifically LDL) levels were found in the guinea pigs fed a high cholesterol diet with blueberries [47]. The HDL cholesterol and triglycerides remained unchanged for that group of guinea pigs [47]. There were also some histopathological changes observed in the high dietary cholesterol and blueberry intervention group. There was a decrease in hepatic retention of lipids and an improvement in the aortic atherosclerotic lesions [47]. This suggests that blueberries ameliorate or prevent the hardening of the arteries that high dietary cholesterol causes.

The fruit itself is not the only part of the blueberry bush that has been studied. Recent findings include lowering of cholesterol levels by use of the leaves of the blueberry bush. In rats, liver triglycerides are reduced upon consumption of blueberry leaves [48]. When fed 3% (weight per weight) freeze-dried blueberry leaf powder in the diet, there was a 46.8% reduction in liver triglyceride levels [48]. Serum and liver total cholesterol levels reduced in a dose-dependent manner when increasing the dietary levels of blueberry leaves [48]. The best reduction in total cholesterol levels was 21%, observed with 3% (weight per weight) blueberry leaf powder being added to the rats’ diet [48]. When the rats in this study were fed a control diet, there was a fatty infiltration of hepatocytes [48]. This infiltration was nullified when the rats were fed the blueberry leaf diet [48]. Lastly, there was a reduction in the retention of lipids in the liver when rats were fed the diet rich in blueberry leaves, as observed in previous studies with blueberry fruit [48]. The mechanisms for these reductions in cholesterol are proposed to be decreased hepatic cholesterol synthesis, as well as increased excretion of cholesterol from the body [47]. While humans do not eat blueberry leaves, further study of aqueous and alcohol extracts of the leaves is suggested. Moermann lists several uses of infused blueberry leaves, including for gynecological purposes and blood purification [49].

Determining the mechanisms by which anthocyanins have a cholesterol lowering effect has been problematic because of their instability, unclear metabolism, and low bioavailability [50]. Bioavailability is defined as the rate at which a molecule becomes available and reaches the target tissue where it exerts a biological action [50]. Studies that have looked at anthocyanin bioavailability in animals and humans indicate that the highest levels are in the gastrointestinal tract, and there are also low levels absorbed from the circulation [50]. Theoretically, using a computer-controlled gastrointestinal model of the human upper gastrointestinal tract, it was noted that if blueberries were bound to a protein-rich matrix there would be greater amounts of anthocyanins delivered to the colon for further metabolism [50]. This suggests that anthocyanins are protected during transit when bound to a high protein-rich matrix, allowing for bioavailability to colonocytes [50]. This was confirmed in another study, where blueberry juice concentrate was bound to defatted soybean flour and added to the diet of mice [45]. The defatted soybean flour concentrated the anthocyanins and other polyphenols, but did not have a high sugar concentration after dilution and centrifuging, so only the beneficial phytonutrients were available [45].

High blood pressure, or hypertension, is another risk factor for cardiovascular disease [46]. Hypertension and the development of atherosclerosis are linked to deficits in endothelial nitric oxide synthase [51]. Although nitric oxide is a free radical and can cause damage to cells, it also has some benefits for the body. Nitric oxide is a vasodilator, which means it widens the blood vessels and helps prevent hypertension [51]. Flavonoids have the ability to increase nitric oxide bioavailability, and foods rich in flavonoids show an ability to decrease blood pressure [51]. This effect of lowering blood pressure can be observed in rats fed a high fat, high cholesterol diet for 10 weeks [51]. The systolic blood pressure was elevated to 140 mmHg by Week 4 [51]. The rats fed the non-blueberry diet had systolic blood pressures that fluctuated slightly but finished at 140 mmHg, the same as the Week 4 measurement [51]. In the rats that were given the high fat and high cholesterol diet with blueberries, systolic blood pressure was reduced by 14% by Week 10 [51]. Although a positive effect was seen with the blueberry intervention in these rats, there is a non-linear dose–response relationship, in that the more flavonoids were consumed, the less potent were the effects upon the vascular system [51].

The renin–angiotensin system regulates blood pressure and water balance. The final product of the renin–angiotensin system pathway is angiotensin II [52], which is what raises blood pressure and also plays a role in fluid and electrolyte balance [52]. A diet with 3% blueberries (weight per weight) results in a reduced plasma angiotensin converting enzyme activity in a hypertensive stroke-prone rat strain, meaning angiotensin I does not convert to angiotensin II as quickly [52]. Angiotensin II is also a vasoconstrictor, so blueberries have a potential vasorelaxation effect [52].

Consumption of blueberries and their leaves has the ability to lower blood pressure and cholesterol by a variety of possible mechanisms demonstrated by in vitro and in vivo studies. If these pathogenic factors are reduced, the risk of cardiovascular disease is also reduced. The findings from animal studies regarding beneficent impacts of blueberry consumption are especially promising, but human studies are needed to confirm these results.

1.6 Conclusion

Indian breadroot (Pediomelum esculentum (Pursh) Rydb.), gumweed (Grindelia squarrosa (Pursh) Dunal), Labrador tea (Ledum spp.), and blueberry (Vaccinium spp.) comprise an anti-aging cornucopia of medicinal plants used by Native/Aboriginal Elders of North America. An overview of each plant has been provided here, from both indigenous science and Western science perspectives. These plants have been chosen to highlight their potential use by older adults as foods or ethnomedicines. More collaborative research between indigenous and Western scientists should be undertaken for greater therapeutic and economic development regarding these North American plants.

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Chapter 2

Alzheimer’s Disease

Current Perspectives – Animal Models, Drugs Under Development, and Potential Nutritional Intervention

Jhansi Rani Vangavaragu¹, Prabhakar Vissavajjhala² and C.Damodar Reddy²,    ¹School of Pharmacy, University of Kansas, Lawrence, KS, USA,    ²Sugen Life Sciences Pvt Ltd, Tirupati, Andhra Pradesh, India

Globally, 44 million people are diagnosed with Alzheimer’s disease, characterized by severe impairment of cognitive ability, disrupting the daily lives of old people and enforcing compulsive dependency. With no drugs to cure the disease and increasing prevalence of an elderly population, Alzheimer’s has become a major public health issue and a heavy burden on many global economies. Currently, FDA approved drugs barely help patients just to maintain their daily activity. Delaying the onset of the disease is the best option, via healthy nutrition and an active lifestyle. This chapter focuses on several hypotheses of Alzheimer’s pathology, and recent research progress exploring the efficacy of disease-modifying drugs, which may be helpful in blocking or slowing the advancement of Alzheimer’s. As well as the existing status quo of testing such candidate drugs in experimental animal models and clinical trials, other potential diversified approaches of therapy, including encouraging outcomes of promising nutritional intervention studies, are highlighted.

Keywords

Alzheimer’s disease; dementia; neurodegeneration; β-amyloid; tau; neurofibrillary tangles; disease-modifying drugs; biomarkers; animal models; antioxidants

2.1 Introduction

The onset of senility involves the impact of deteriorating physical and physiological efficiency of all the systems in the body, leading to degenerative disorders. One such disorder of the brain is dementia, a Latin term originally meaning madness (de-, without+ment, the root of mens, or mind), which is characterized by a serious loss of global cognitive ability in a previously unimpaired person. Identified as one of the types of senile dementia, the disease was first described by the German psychiatrist and neuropathologist Alios Alzheimer in 1906 and later became commonly known as Alzheimer’s disease (AD). AD is a slowly progressive old-age disease of the brain characterized by the impairment of memory and, eventually, disturbances in reasoning, planning, language, and perception.

2.1.1 Dementia

While AD is one of the most common types of dementia, it is a challenge to diagnose. The term dementia encompasses many mental disabilities, disorders, or malfunctions of the brain.

 Symptoms of dementia must include decline in memory and in at least one of the following cognitive abilities:

 to speak coherently or understand spoken or written language

 to recognize or identify objects, assuming intact sensory function

 to perform motor activities, assuming intact motor abilities and sensory function and comprehension of the required task

 to think abstractly, make sound judgments, and plan and carry out complex tasks.

 The decline in cognitive abilities must be severe enough to interfere with daily life.

Different types of dementia are associated with distinct symptom patterns and brain abnormalities, and include AD, vascular dementia, dementia with Lewy bodies, frontotemporal lobar degeneration, mixed dementia, Parkinson’s disease, Creutzfeldt-Jacob disease, and normal pressure hydrocephalus. AD and other types of dementias are irreversible, with no cure, and current available treatments help only in improving quality of life for AD patients.

2.1.2 Symptoms of Alzheimer’s Disease

While AD may affect people in different ways, the most common symptom pattern begins with a gradually worsening ability to remember new information. This occurs as the neurons that begin to die and malfunction are the neurons involved in forming new memories. As neurons in other parts of the brain malfunction and die, individuals experience other difficulties. The following are common symptoms of Alzheimer’s:

 Memory loss that disrupts daily life

 Challenges in planning or solving problems

 Difficulty completing familiar tasks at home, at work or at leisure

 Confusion with time or place

 Trouble understanding visual images and spatial relationships

 New problems with words in speaking or writing

 Misplacing things and losing the ability to retrace steps

 Decreased or poor judgment

 Withdrawal from work or social activities

 Changes in mood and personality.

As the disease progresses, the individual’s cognitive and functional abilities decline. Individuals progress from mild AD to moderate and severe disease at different rates. In advanced AD, people need help with basic activities of daily living, such as using the bathroom, bathing, dressing, and dining.

2.1.3 Diagnosis of Alzheimer’s Disease

A diagnosis of AD is typically made by the physician, who obtains a medical and family history, including psychiatric history and history of cognitive and behavioral changes. The physician may also often ask a family member or other person close to the individual for further information. In addition, the physician conducts cognitive tests and physical and neurologic examinations, and may request that the individual undergoes magnetic resonance imaging (MRI) scans that reveal changes in brain.

2.1.3.1 Differences between the Original and New Criteria in Diagnosing Alzheimer’s Disease

The 1984 diagnostic criteria and guidelines by the Alzheimer’s Association (AA) and the National Institute of Neurological Disorders and Stroke [1] were based mainly on physicians’ judgment, as described above. The new criteria and guidelines proposed by the National Institute of Aging (NIA) and the AA in 2012 [2] incorporate two notable changes to help pathologists describe and categorize the brain changes associated with AD and other