Resumen de la metabolómica basal y en la respuesta al consumo de maca

Nina Patel Introduction

The scientific name for tea is Camellia sinensis, and it belongs to the Theaceae family ("Tropicos," 2012). It is one of the oldest drinks in the world, and only water surpasses it in consumption (Chow & Hakim, 2011). Other common names of tea used by different cultures include thee, cha, chai, shai, and O cha (Saberi, 2010). Archaeological evidence suggests that the origins of tea date back to China over 5,000 years ago, and from there it diffused into India, Japan, Thailand, Korea, and Sri Lanka (Meltzer, Monk, & Tewari, 2009). Tea was native to the ancient kingdoms of Shu, which was located in the “four rivers” and the neighboring kingdom of Ba in China. The Chinese book Chajin by Daoist Lu Yü, is the first book written that discusses tea, and it dates back to 780 CE (Steeped in

history : the art of tea / Beatrice Hohenegger, editor ; with essays by Terese Tse Bartholomew ... [et al.], 2009). The

medicinal use of tea was also discussed in the ancient Chinese pharmacopoeia “Ben Cao Gang Mo” (Lin, Tsai, Tsay, & Lin, 2003).

There are three main types of tea originating from the same plant: green, oolong, and black (Ferrara, Montesano, & Senatore, 2001) . Green tea is consumed mostly in China, Japan, India, some North African and Middle Eastern countries whereas black tea is consumed mostly in Asian and Western countries (Cooper, Morre, & Morre, 2005). Green tea is prepared from fresh leaves and buds that are heated by pan frying or steaming to inactivate the enzymes and stabilize the monomeric catechins, and then these leaves are dried (Ferrara et al., 2001); (Hara, 2011). To produce oolong tea, fresh leaves

are wilted in the sun, bruised a bit, and then finally fermented. However, if the wilted leaves are fermented, black tea is produced instead (Ferrara et al., 2001).

Tea is composed of three main constituents: caffeine, catechins, and theanine (Saberi, 2010). Tea also contains other compounds, such as volatile oils, vitamins, and minerals. The active compounds in tea are the polyphenols, mainly epigallocatechin, gallic acid, and bioflavonoids. These catechins may help to fight various types of cancers, such as skin, esophageal, stomach and colon cancer. Tea can also be used as a topical agent to help control bleeding that has resulted from cuts and scrapes. C. sinensis can also be used to relieve insect bites and help control blood sugar and insulin levels (Ferrara et al., 2001). Overall, tea has many medicinal uses.

Apart from its medicinal uses, it is also a historically, economically, and culturally significant plant. For example, one of the reasons that the colonization of India occurred was to control the tea trade (Steeped in history : the art of tea /

Beatrice Hohenegger, editor ; with essays by Terese Tse Bartholomew ... [et al.], 2009). C. sinensis is an important

botanical plant that still continues to have relevance 5,000 years after it was first discovered.

Botanical Description

Camellia sinensis is grown in thirty countries (Cooper et al.,

2005). It is grown 1,000-7,000 feet above sea level, in temperatures between 50-85ºF, and in areas with annual

Figure 1. Camellia sinensis. Source (Hamilton, 2010)

rainfall between 80 to 90 inches (Saberi, 2010). It is grown best in humid climates (Cooper et al., 2005). The ideal geographical area for tea to be grown ranges from Java in the south to Japan in the east and the north and India to the west. This area also includes Formosa, China, Sumatra and outer neighboring countries. It is grown best on terraced hillsides and open fields (Shalleck, 1972). It can be grown as a tree or a shrub (Mahmood, Akhtar, & Khan, 2010). It is an evergreen, perennial plant (Mondal, Bhattacharya, Laxmikumaran, & Singh Ahuja, 2004).

For tea growth, warm weather with an even distribution of rainfall throughout growing season is needed. The leaves will grow more if the weather is wetter and the rainy season is longer. The colder the weather, the slower the growth of the tea bushes, which will result in fine tea with small supple, leaves. However, frost will blacken the leaves thereby marring the tea (Shalleck, 1972).

Tea can reach a height of 10-15 meters when grown in the wild, and 0.6-1.5 meters when cultivated. The leaves are green, short stalked, coriaceous, alternate, lanceolate, serrate margin, glabrous or pubescent beneath, and vary in length from 5-30 cm and are 4 cm in width. Mature tea leaves are bright green, smooth, and leathery whereas the young tea leaves are pubescent. The flowers are white fragrant and range from 2.5-4 cm in diameter. The flowers either occur by themselves, or they can occur in clusters of two or four. They have stamens with yellow anthers, and they make brownish red capsules. The fruit is a flattened, smooth, round trigonous three celled capsule, and there are seeds the size of a small nut in each fruit (Mahmood et al., 2010). The seeds ripen on the plant, and then they germinate in damp sand pits. When the seed shell opens, the seeds are planted in either nurseries or in fields. Proper shading is crucial for tea bushes. The tea plants are prevented from developing into trees by pruning and hand-picking (Shalleck, 1972). A picture of the plant can be seen in Figure 1. Tea is a self-sterile and cross-pollinating crop (Abrol & Abrol, 2012).

There are four varieties of plants: the Assam (Indian) plant; the Chinese plant (Bohea); a relative of the Indian plant which is grown in Ceylon, Java, and Sumatra; and a relative of the Chinese plant which is cultivated in Formosa and Japan (Saberi, 2010). These types are mainly distinguished by their leaves (Mondal et al., 2004). Bohea is a small and stunted bush that is compactly branched containing small stiff leaves and purple leaf buds (Saberi, 2010). The relative of Bohea is similar in appearance, but it is larger and contains bigger leaves. Assam tea can reach up to a tree height of thirty feet when grown in its wild state. This Indian tea plant contains huge leaves and few flowers. The relative of Assam is similar, but it is composed of smaller, thicker, and more precisely serrated flowers (Shalleck, 1972). The Chinese plant can live

for hundreds of years whereas the Assam variety can live for about 40 years (Saberi, 2010).

Traditional Uses

Traditional Medicinal Applications

Tea has been used an ethnomedical remedy for centuries. For example, in the Chinese book Kissa Yojoki (ca 1191), tea was described as a medicine to help control bleeding, heal wounds, regulate blood sugar, help with digestion, and regulate body temperature (Meltzer et al., 2009). During the Zhou dynasty in China, tea was used as a stimulant to promote positive moods. Tea was consumed to calm and clear the mind, sharpen mental acuity, and relax smooth muscles. It was also used as a diuretic, antitoxin, mild disinfectant, and as an efficacious rinse to soothe strained, tired eyes and to alleviate skin ailments (Steeped in history : the art of tea / Beatrice

Hohenegger, editor ; with essays by Terese Tse Bartholomew ... [et al.], 2009). The remedy used to treat many of these

discussed problems was drunk as a bitter medicinal drink. This drink was prepared by infusing tea leaves in hot water. Salt was often added (Saberi, 2010). When rinsed in the mouth, tea cleansed the palate and since it contains trace minerals like fluoride, it promoted dental health and aided digestion (Steeped in history : the art of tea / Beatrice

Hohenegger, editor ; with essays by Terese Tse Bartholomew ... [et al.], 2009). In the ancient world, tea was thought to

increase blood flow, act as an immunostimulant, speed up metabolism, help with anemia, fight the effects of summer heat, and increase the number of years a person lived (Blofeld, 1985).

For the Daoists, tea was thought to promote health and increase life span. It was prescribed as a tonic and remedy by

apothecaries and Daoist healers. These healers worked with chefs of noble houses to infuse tea into healthy recipes and tasty dishes. It was a bitter herb that was used in cooking and took on many forms: fresh leaves, pulp, pastes, and gels in season, dried loose leaves or “bricks” of compresses leaves, and “wafers” and “cake” of dried paste (Steeped in history : the

art of tea / Beatrice Hohenegger, editor ; with essays by Terese Tse Bartholomew ... [et al.], 2009)

Many of these ancient uses still have relevance in modern CAM applications as well as modern day traditional medicines. Powerful infusions of tea are used often for bathing the feet and to treat fungoid infections. Tea (in the drinking form) can be used as cleanser for the face to help get rid of pimples and skin rashes. In rural China, strong tea is used as a mild disinfectant for new skin lacerations. Hair can become soft and glossy when washed with tea. It is also used for halitosis in the leaf form by placing the leaves in the mouth. In North China, individuals rinse their mouths with green tea after eating. Toothaches can be relieved by chewing tea leaves (Blofeld, 1985). Green tea is consumed between meals or after meals in Japan and Asian countries (Lee et al., 1997). In Japan, tea can be found in foods, such as kanten (tea jelly) and a green tea ice cream called matcha. It is also found in O-

chazuke, which is a rice dish (Saberi, 2010)

Oolong tea has hypocholesteromic properties that become active after a fatty meal, and this can help with hypertension and arterial disease by being an anti-clot agent. Black tea has a high content of tannins, which can help with diarrhea and headaches. Damp black tea bags can help with tired, red eyes as well and relieve itching and redness caused by insect bites (Ferrara et al., 2001). Many of the ancient day uses of tea still apply today.

Tea Drinking

Around the world, many forms of drinking tea occur, and this is intricately tied into the cultures of many societies. In Central Asia and Tibet, the oldest form of tea drinking still remains. This ancient practice consists of boiled tea that is made with compressed tea, which is either shaved off a brick or broken off a cake. Then, it is boiled with water and usually other ingredients. Indian chai is made in a similar manner. During the Song Dynasty (960-1279), whisked tea arose in China and diffused into Japan, where it was integrated into ceremonial practices. Whisked tea is made from leaves that are grounded into a fine powder, and then whipped with bamboo sticks and hot water in separate bowls. Steeped tea, in which tea leaves are steeped in the tea pot, became a common practice during the Ming dynasty in China (1368-1644). It was steeped tea that maritime traders introduced into Europe (Steeped in

history : the art of tea / Beatrice Hohenegger, editor ; with essays by Terese Tse Bartholomew ... [et al.], 2009).

Tea drinking is intricately tied into the Japanese culture as it has influenced the fine arts, including garden design, flower arrangement, architecture, calligraphy, painting, lacquer, and ceramic arts. The tea ceremony in Japan is called chado, ‘The

Way of Tea,’ and it was originally a Buddhist ritual. This tea

ceremony still continues on today in Japan (Saberi, 2010). In Korea, nconsumption of tea is tied with the Panyaro Seon (Zen) of tea. Tea ceremonies are seen as a spiritual activity that results in inner awakening and even total enlightenment. Temples in Korea also serve tea to visitors (Saberi, 2010). In England in the 1850s, tea began to become the focus of social visits. It was served with sandwiches, biscuits, cakes, and pastries. Fancy silver or fine bone china tea-ware arose to accommodate this important social event. Afternoon tea became a unique event. It became common among the high,

middle, and lower classes in Great Britain. Although today this tradition has declined, tearooms can be found across Great Britain, and they are very popular placaces (Saberi, 2010).

The Economics and History of Tea

Camellia sinensis is a historically important plant and is closely

interlaced with the histories and economies of China, India, and Britain. China used to dominate the international tea trade till the mid-nineteenth century. China lost control because Great Britain started to compete with them, as they were eager to make their own tea. To do this, Britain turned to other regions. For example, the colonialization of India started in 1757 in part because the British wanted to make their own tea, and India presented the perfect opportunity with its huge population of peasant cultivators. As in other British islands, the indenture system was eventually established in India. This system recruited and constrained laborers to tea plantations under a penal system. Indian indentured laborers also supported the British plantation economy in other places besides India, such as Fiji and East Africa and the lives of these laborers were like those of the African slaves. This indenture system eventually caused Indian tea to surpass Chinese tea in the global market (Steeped in history : the art of tea / Beatrice

Hohenegger, editor ; with essays by Terese Tse Bartholomew ... [et al.], 2009).

The history of tea is also closely interlaced with the history of sugar because sweetened tea was a common beverage. Both tea and sugar entered the British market as rare and expensive items during the mid-seventeenth century that only the elite could afford. Two hundred years later, sweet tea replaced both beer and malt liquor as the top beverage. The United Kingdom drank 40 percent of the tea worldwide by 1900. This was due to industrialization—it helped the new

industrial workers meet their caloric needs and helped to keep them awake by acting as a stimulant—and the growth of the British Empire. In the British Caribbean colonies, over a million African slaves worked under arduous conditions to produce sugar. These workers were overworked, malnourished, and disease ridden and their death rate far exceeded their birth rate. This cheap land and labor increased the demand for tea by making it cheap and readily accessible to the lower classes in Britain (Steeped in history : the art of

tea / Beatrice Hohenegger, editor ; with essays by Terese Tse Bartholomew ... [et al.], 2009).

Tea has a rich history that was tied to the exploitation of native populations. It has changed the world, and it still is relevant today. As a highly consumed beverage, tea is still an economically significant commodity. For example, in the United Kingdom, around 165 million cups of tea are consumed daily (Saberi, 2010). Also, 2/3rd _{of the world population}

consumes tea daily as a morning drink, and about 2.2 millions tones of it are produced annually (Mondal et al., 2004).

Chemistry and Pharmacology

The constituents of tea possess biological properties that are beneficial for one’s health as they have been shown to be possess antiallergenic, antioxidant, antimutagenic, anticancer, antiartherosclerotic, and antibacterial properties (Ferrara et al., 2001). Many of these biological activities can be traced back to the three main components of tea: caffeine, catechins, and theanine. Catechins are polyphenolic flavonoids (tannins), and they are responsible for the briskness and astringent flavor of tea. Caffeine, a mild stimulant, also brings about the bitter flavor of tea. In contrast to caffeine, theanine is an amino acid that is responsible for the sweetness of tea, and it

Epicatechin Epigallocatechin

Epicatechin-3-gallate Epigallocatechin-3-gallate Figure 2. Chemical structures of the four major catechins found in Camellia sinensis. These catechins are EC (epicatechin), EGC (epigallocatechin), ECG (epicaetchin-3- gallate), and EGCG (epigallocatechin-3-gallate). Source (Kim et al., 2010)

acts to suppress the stimulant activity of caffeine (Saberi, 2010).

Catechins are made by the tea plant/shrub during the day and stored in cell vacuoles in the shoot of the plant. As the temperature gets higher, the rate of production of these catechins increases These catechins may be useful secondary metabolites that may serve to protect leaves from bacteria, viruses, fungi, and vermin bites. Catechin oxidation forms

Active Ingredient Content (g/kg dry leaves) Caffeine 36 Catechins Epicatechingallate 15.2 Epigallocatechin 46.0 Epigallocatechin gallate 129 Epicatechin 0.9 Major catechins 191 Flavonols Myricetin 0.8 Quercetin 1.8 Kaempherol 2.6

Table 1. Major constituents of green tea by g/kg of weight. Source (Perva-Uzunalic et al., 2006)

dimers and polymers named theaflavins and thearubigins, which retain many of the properties of catechins. Catechin oxidation is the main chemical reaction involved in the synthesis of black tea (Shalleck, 1972).

Catechins comprise 30% of the dry weight of tea leaves (Chyu et al., 2004). They can be categorized as either free catechins or galloyl catechins. The free catechins include (+)-catechin (+C), (+) galocatechin (+GC), (-) epicatechin (EC) and (--) epigallocatechin (EGC). Galloyl catechins include (-) epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG), and (-)-galoocatechin gallate (GCG) (Hara, 2011). EGCG is also the main antioxidant catechin found in tea, and is responsible for many of the attributed health effects of tea (Chyu et al., 2004). The structures of some of these major catechins are shown in Figure 2. They consist of polyphenolic aromatic rings that contain hydroxyl groups (Hara, 2011).

In a cup of tea, the following percentages of compounds are found: caffeine constitutes 2-4% tea; amino acid constitute 4% of tea; lignins constitute 6.5%; organic acids constitute 1.5%

Components Green Tea Black Tea

Catechins 30-42 3-10 Ravanols 5-10 6-8 Other flavonoids 2-4 - Theogallin 2-3 - Ascorbic acid 1-2 - Gallic acid 0.5 - Quinic acid 2 -

Other organic acids 4-5 -

Theanine 4-6 -

Other amino acids 4-6 13-15

Methyxanthines 7-9 8-11 Carbohydrates 10-15 15 Minerals 6-8 10 Volatiles 0.02 <0.1 Theaflavins - 3-6 Thearubigins - 12-18 Caffeine 3-4 3-4

Table 2. Major constituents of green and black tea by weight % of extract solids. Source (Chow & Hakim, 2011).

of tea; proteins constitute 15% of tea; chlorophyll constitutes 0.5% of tea; the polyphenols, such as EGCG and EGC constitute 25-35% of tea. A cup of green tea can contain anywhere from 300-400 mg of polyphenols or 10-30 mg of EGCG The polyphenolic compounds present in tea are essentially colorless (Meltzer et al., 2009). Table 1 shows the percent composition of the constituents of tea as present in green and black tea.

Table 2 shows the content by weight of active ingredients in dry tea leaves. Caffeine weighs 36g/kg; the major catechins weigh 191 g/kg; the flavonols weight 5.2 g/kg (Perva-Uzunalic et al., 2006).

Among the three different types of tea, there is also a difference in chemical content as the they undergo different

levels of fermentation. Green tea has the most antioxidant content due to a higher EGCG content with black tea having the least EGCG content (Cheng, 2006). Black tea has the most caffeine content, and green tea has the least (Lin et al., 2003). Biological Activity

Many of the health benefits of tea can be attributed to its EGCG content. EGCG has strong antioxidant properties, and it also accounts for more than 65% of the catechin content of tea and more than 10% of the extract dry weight of tea (Kaedei et al., 2012).

In Vivo

Atherosclerosis

Many of the potential protective effects of catechins found in

Camellia sinensis may not work once a disease or illness is well

established. For example, many of the human clinical trials that administer antioxidants may fail because the therapy begins long after atherosclerosis is already established in the patients. In contrast, the positive results seen in laboratory animals may occur because the early initiation of antioxidant therapy occurs when atherosclerosis is still developing.

This study investigated the preventive potential of tea catechins in hypercholesterolemia apolipoprotein E-null mice. Mice with either evolving or established atherosclerotic lesions were injected daily with either intraperitoneal injections of EGCG (10 mg/kg) or PBS. These lesions were produced by periadventitial cuff injury to carotid arteries. Results were taken after 21 and 42 days of treatment. It was found that this therapy decreased evolving atherosclerosis plaque sizes at 21 days by 55% and 42 days by 73% compared

with PBS treatment (P<0.05). Also, the sizes of the plaques were the same in both day 42 and day 21 treated mice that