**6.2 Neurodegenerative diseases**

Maher explains neurodegeneration as "any pathological condition which primarily affects neurons," and terms neurodegenerative diseases as an outsized and heterogeneous group of neurological disorders that significantly affect distinct subsets of neurons in specific anatomical locations. Of a wider variety of known neurodegenerative disorders, four are of serious attention, thus Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis.

Researchers believe in an increased likelihood of neurodegenerative conditions due to suspected elevated quantities of ROS in the brain [39, 45], this lowers antioxidant activity in the human brain vis-à-vis other body organs. Accelerated senescence and neurodegeneration are caused by mitochondrial oxidative insults and impaired electron transfer, which often weaken and affect the central nervous system.

Also noted is that oxidative products clog neurons during the aging process. This event calls for the consumption of antioxidant compounds, precisely, catechins that are suspects in the delay and/or stoppage of neurodegenerative processes, and declining brain function [39].

Furthermore, scientific evidence has it that polyphenols can lower the morbidity due to PD and AD by reducing oxidative stress and regulating signaling pathways and metal chelation. Hence, scholars believe that theanine inhibits the glutamate receptors and regulates the extracellular concentration of glutamine, presenting the muchdesired neuroprotective effects.

Another possible way that the neuroprotective mode of action by which caffeine and theaflavins contribute is the ability to use their antioxidant properties in antagonizing the adenosine receptor A2AR, respectively. Besides, the element of aroma is a crucial factor affecting tea's sensory quality, with over 600 volatilities identified from the aroma of tea.

*Considering the Antioxidant Properties of Tea to Improve Human Health DOI: http://dx.doi.org/10.5772/intechopen.107148*

**Figure 7.** *EGCG inhibition of ROS role in Neuronal damage [45].*

Moreover, the legitimately generated tea volatilities from chemical reactions could lessen brain signal dissemination, soothe stress, and experience tranquilizing effects, but the mechanisms have not been well elucidated by experts [3]. From more findings, EGCG suppresses TNF-α, interleukin-1β, interleukin-6, and iNOS, in Aβ energized EOC 13.31, invigorates the extracellular antioxidants certain to nuclear factor 2, as well as the oxygenase1 (HO-1). Ultimately, EGCG also subdues nuclear factor-kB (NF-κB), and prompts the actuation of ROS by the Aβ remedy, as shown in **Figure 7**.

Another central nervous system progressive disorder that has no cure known as paralysis agitans derives its genesis from the destruction of brain cells that produce dopamine. Its impact can be minimized with green tea use as a foremost recommendation by several researchers. The reason for green tea predisposition is the fact that it protects neurons, hence prevents PD, cushions dopamine neurons, provides a shielding effect from ROS, intercepts apoptosis in the brain and CNS, and thus prevents PD [12].

Findings by Vishnoi et al. [12] from an *in vitro* study substantiated the ability of tea to restrain the human acetylcholinesterase with an IC value of 0.03 mg/ml and restrained β-secretase at a test concentration of 0.03 mg/ml by 38%. The study further hypothesized that tea infusion constituted biologically functional truths, conceivably acting in an interactive manner. Physicians could prefer this idea to retard the progression of disease with the presumption that these principles reach the brain.

Scientists think the appliance of EGCG decreases the production of beta-amyloid, a protein that shapes the plaque that obstructs the brains of Alzheimer's casualties and aggravates disease symptoms. Impeding the actions of the enzyme acetylcholinesterase and β-amyloidosis should be the first aspiration for the therapy for Alzheimer's disease [12].

Additional evidence from various studies conducted in Asia and Europe, involving over 290 participants concluded that the outset of PD and AD could amazingly be procrastinated by up to 7.7 years when subjects take between two and three cups of tea on a daily basis [8]. Additional studies have shown the significant roles of tea polyphenols in the treatment of neurodegenerative diseases by protecting the systema nervosum through improvement of learning and memory as in (AD), improvement of nerve redox disparity, and mitochondrial affliction by balancing biological time as in (PD), and lowering of neural vandalism after the cerebral ischemia at an EGCG recommended dose of fifty mg/kg.

Moreover, analysts have reported that consuming an average of 400 mg/kg of green tea polyphenols could lead to an increase in the perceptual-cognitive capacity of patients recovering from chronic cerebral hypoperfusion by scavenging oxygen free radicals, limitation of the creation of lipid peroxides, and mitigating the effect of oxidized DNA, thereby enforcing a neuroprotective function [9].

### **6.3 Cardiovascular disease**

Cardiovascular disease (CVD) is an aggregation of ailments entailing numerous aspects. Amongst those factors are inflammation, cumulative damage done by free radicals, thrombolytic aggregation, and metabolic processes [12]. Other previous studies have highlighted that habitual consumers of green tea were less likely to suffer from diseases of the heart and cardiovascular accidents. Research published by Harvard University further confirms a link between taking tea and wellness; drinking at least one cup of tea daily reduced heart attacks by up to 44%.

Green tea also dramatically raises the antioxidant capacity of the blood, which in effect shields the LDL cholesterol particles from being oxidized, limiting one part of the heart disease pathways. Research findings further entrench that women dying from cardiovascular disease and stroke were lower than 31% for those who consumed five or more cups of tea every day [12].

Oxidative stress has been incriminated as a victim in the progression of various cardiovascular infirmities, including high blood pressure, endothelial dysfunction and hardening of arteries, ischemic heart diseases, cardiomyopathy, cardiac hypertrophy, and congestive heart failure [39].

A summary of findings from over 150 human interventions and animal studies involving more than 35,000 subjects between 1992 and 2017 from across the world by Li et al. Ref. [4] has postulated that tea relaxes muscles facilitating smooth contraction, enhancing endothelial nitric oxide synthase activity, reducing vascular inflammation, inhibiting renin activity, and anti-vascular oxidative stress, thus confirmed that both tea and tea metabolites have anti-hypertensive effects in *ex vivo* tissue and *in vitro* cell culture studies, although some controversial reports existed [39].

Correspondingly, wrap-up evidence from a plethora of studies by Serafini et al. [14] deduced that taking a capsule containing theaflavin-enriched GTE (375 mg) daily with two cups of GT, containing about 250 mg of total catechins could provide tea flavan-3-ols enough to control CVDs by up to 10 mg/dL [0.25 mmol/L] of LDL.

### **6.4 Diabetes**

Diabetes is a serious global, long-term condition with a major impact on the lives and well-being of individuals, families, and societies worldwide [46, 47]. Diabetes is an amalgam of metabolic conditions that cause high blood sugar and could be a result of autoimmune and hereditary defects. High blood glucose is either because of impaired insulin production, low cellular sensitivity to insulin, or a combination of the two factors [48].

Diabetes is one of the top 10 causes of death among grownups, causing an estimated four million deaths globally in 2017. During the same year, 2017, global health expenditure on diabetes soared to a high USD 727 billion [49] Diabetes is into three categories; T1D, T2D, and GDM [48].

It may not be feasible to prevent T1D but is treatable by health professionals with insulin supplementation, whereas T2D can both be averted, and/or reversed by altering diet and management of lifestyle factors [46]. T2D is a heterogeneous disorder, characterized by the resistance of glucose and lipid metabolism in peripheral tissues to the biological activity of insulin, and inadequate secretion of insulin by pancreatic β cells [12], the loss of functional β-cell mass plays a central role in the deterioration of blood glucose control [50], inherited and/or acquired deficiencies in insulin secretion and/or by decreased responsiveness of the organs to secrete insulin also called

## *Considering the Antioxidant Properties of Tea to Improve Human Health DOI: http://dx.doi.org/10.5772/intechopen.107148*

insulin resistance culminates into increased blood glucose, this in turn can damage many of the body's systems, including blood vessels and nerves [51].

Diabetes has high morbidity and mortality, attributed to its complications, such as diabetic nephropathy, diabetic cardiovascular complications, diabetic neuropathy, diabetic retinopathy, and diabetic hepatopathy [52]. An aggregate of findings by Imran et al. [53] from several experiments using rats to determine the effects of theaflavins and thearugibin drink on blood glucose levels indicated a reduction in cholesterol, LDL, and triglyceride levels of experimental rats in all studies with a significant increase in HDL. In this context, theaflavins-based drink imparted maximum reduction in cholesterol, the highest glucose decline, and maximum insulin increase in all studies as compared to other nutraceutical drinks.

Functional drinks can be useful for combating lifestyle-related maladies with special reference to hypercholesterolemia and hyperglycemia. What's more, Li et al. [4] reported consequential therapeutic qualities of tea on hypertensive diabetic patients where diabetics who took green tea infusions after meals, three times daily for a period of four weeks, had their blood pressure reduced significantly. In a short time of 15 days, both the SBP and DBP had reduced significantly by 4.6 mmHg and 3.6 mmHg, respectively.

A similar case-control study meant to determine the effects of green tea extracts involved diabetic Japanese adults and a control group who were healthy and revealed a noticeable drop in sugar levels with the continued use of the tea extract.

In consensus with earlier studies, further evidence was generated with findings from more clinical trials communicating the effectiveness of tea intervention on diabetics and patients with related complications [54], and the important biologic activities of green tea in anti-diabetic makeup [9]. See **Figure 8**.

Contemporaneous studies have also imputed the anti-diabetic effect of green tea mainly in the following mechanisms; the potential to reduce insulin resistance by

#### **Figure 8.**

*The molecular mechanisms of EGCG against diabetes mellitus and its complications. The effects of ECG against T2D show by improving IR, against diabetic cardiovascular disease by reducing TG and [Ga2+], against diabetic nephropathy by reducing ROS, and against diabetic neuropathy by increasing Nrf2. Black lines indicate up regulation, red dotted lines indicate down regulation.*

increasing the absorption of glucose by adipocytes and their ability to bind to insulin [51, 54], the power to enhance glucose metabolism by triggering an increase in glycogen content in the liver, change of the activity of key enzymes in glucose metabolism [43, 46], ameliorating insulin secretion, and amortizing diabetic complications [9].

In another study, investigators administered 500 mg/kg of green tea polyphenols to normal rats during an experiment. By the lapse of sixty minutes, the glucose tolerance had raised notably. A significant reduction in blood sugar in alloxan diabetic rats at specified doses, and for a given period of time justified the significance role that tea plays in improving glycolysis and lipogenesis [12].

Carotenoids in green tea play both a functional role as pro-vitamin A in the visual pathway and a structural role as macular pigments further upholding the antioxidant potency of tea in the prevention and treatment of T2DM [55]. Meanwhile, transpiring corroboration portrays the capacity of phenols to aid the secretion of intestinal L-cells and could be useful in the improvement of glycolysis and homeostasis [49].

Quercetin, another strong antioxidant component in tea has the potential to reduce insulin resistance and decrease inflammation by improving the expression of glucose transporters GLUT4 [8].

Tang et al. [44] tabled findings from several clinical trials with optimism in managing T2DM, in relation to ameliorating insulin resistance and hyperglycemia in humans. The findings advance a postulation that drinking black tea could significantly reduce the glycated hemoglobin levels (HbA1c) and ameliorated the likelihood of ailment due to T2D. Moreover, the same findings confirm that T2D aggravated by diets rich in high fat could as well be contained by regularly taking green tea.

## **6.5 Infertility**

Human infertility is a global concern and already affects one in six couples worldwide [56], research approximates that between 15 and 30% of couples are struggling to conceive [33]. Male factors contribute to 20–50% of the cases, making infertility a controversial problem across the globe, some of the factors point to several anatomical discrepancies, including but not limited to obstructions in seminal tubes, neurological anomalies, aging, and urinary tract infections, these affect spermatogenesis and weakening the sperm function.

It is also worth noting that an interplay of several environmental factors exist that reduce semen quality, hence, infertility, such as tobacco use, excessive consumption of alcohol, exposure of testis to higher temperatures, dietary inadequacies, oxidative stress, and exposure to industrial chemicals, pesticides, and radiation. An understanding of cell biology correlates with the assumption that increased levels of ROS lead to a lower antioxidant response, which is not healthy for sperm production and quality [33, 56, 57] as shown in **Figure 9**.

A synopsis of evidence by Zhang et al. [40] suggests that the secondary metabolite in green tea (EGCG) portrays diverse physiologic activities, including antioxidant, antitumor, and antiviral activities, single or a conglomerate of which could be a recipe for infertility. Further to this, investigators found that fertility in human beings is supported by EGCG through the mitigation of the impacts of excessive ROS on sperm and oocyte cells, cell death, hyperactivation of enzymes on the ERK, and signal regulating proteins operating outside cells.

According to Rahman et al. [33, 45], the high presence of antioxidants in EGCG, can reduce ROS and improve gamete quality in both males and females, at low concentrations, and that supplementation with EGCG in males can considerably increase *Considering the Antioxidant Properties of Tea to Improve Human Health DOI: http://dx.doi.org/10.5772/intechopen.107148*

#### **Figure 9.**

*Sources of oxidative stress and their impact on reproduction and fertility [57].*

#### **Figure 10.**

*The action of green tea polyphenols on major fertility reducing factors [33].*

sperm concentration, motility, fertility rate, morphology, and viability, and reduce DNA damage. It is also capable of enhancing the quality of oocytes and embryos, hence, increasing the rates of fertilization and clinical pregnancy in female beings. Consistently, using green tea has an inverse relationship with the risk of ovarian cancer, which is a factor in female infertility; a further illustration is shown in **Figure 10**.
