Catechin

General information

Cianidanol is an antioxidant flavonoid that occurs especially in woody plants. It is one constituent of green tea. It has immunomodulatory properties, including effects on T lymphocytes and killer cells [1].

Of 40 patients with chronic active hepatitis, 22 took cianidanol 3 g/day and 18 took placebo [2]. Adverse reactions to cianidanol were fever (n = 4), hemolysis (n = 1), and urticaria (n = 1).

Serious adverse reactions were not observed when cianidanol was used to treat HBe-antigen-positive chronic hepatitis in 338 patients [3]. The only adverse reaction of note that appeared to be drug-related was transient pyrexia in 13, necessitating withdrawal of therapy in eight. Four patients also had a skin eruption.

Sources of Catechins

As green tea is the most common aromatic beverage around the globe, many epidemiological studies correlated the tea consumption and decreased risk of various metabolic disorders as well as mortality in a dose-dependent fashion. Eighty percent of all polyphenols present in green tea are contributed by catechins. Mainly, EGCG, EGC, ECG, and EC are found in green tea. EGCG is the most abundant and the most pharmacologically potent catechin found in green tea [12].

Catechin is present in many dietary products, plants, fruits (such as apples, blueberries, gooseberries, grape seeds, kiwi, strawberries), green tea, red wine, beer, cacao liquor, chocolate, cocoa, etc. Tea and red wine are some of the most popular beverages in the world. The antioxidant action of catechin is well-established by various in vitro, in vivo and physical methods. Catechin affects the molecular mechanisms involved in angiogenesis, extracellular matrix degradation, the regulation of cell death, and multidrug resistance in cancers and related disorders. A positive correlation between green tea consumption and cardiovascular health due to several actions such as antioxidative, antihypertensive, anti-inflammatory, antiproliferative, antithrombogenic, and anti-hyperlipidemic etc., is well established based upon epidemiological and experimental studies. Clinical studies have shown the beneficial effects of catechin due its antioxidant action.

Summary Points

Catechins

Catechins, phytochemicals found in especially high concentrations in teas and cocoa (Lee et al., 2003), are known to provide protection to C. elegans from oxidative and thermal stressors, particularly when used as a pretreatment (Zheng et al., 2009; González-Manzano et al., 2012). Work by Sucro-Laos et al. (2012) also showed that pretreatment with catechins increased survival when oxidative stress was induced by juglone (79% in controls vs 89%–98% in pretreated) when assayed on the first day of adulthood. This increase persisted for up to 6 days post-juglone exposure (56% in controls vs 84%–99% in pretreated), suggesting potential long-term changes in the oxidative stress response. Furthermore, catechin pretreatment protection extends to other forms of stress as well. Worms exposed to thermal stress following being pretreated with catechins had a survivability rate of 87%–99%, compared to only 83% in the control worms (Sucro-Laos et al., 2012). The protection also appeared to be chemical-specific and age-specific. This was borne out in studies showing that methylated catechins may have a greater protective effect in older worms compared to younger ones.

Along these lines, Abbas and Wink (2009) demonstrated that galloate moieties contributed to the stress-resistant properties of catechins in C. elegans. If life span, and not survival, was used as an endpoint, only the methylated catechins were effective, but marginally (6%–12%, compared to controls). These studies also demonstrate that C. elegans can be used to inform structure–function studies when moving to more complex model organisms.

Saul et al. (2009) provided evidence that catechin treatment (200 μM) resulted in a significantly enhanced life span, adding approximately 10 days to their normal life span of around 21 days. These data were followed up with oxidative stress tests using hydrogen peroxide to assess survival rate independent of longevity. As before, worms treated with catechin showed a dose-dependent protective response to the stress, with increasing survival rates of 9%, 15%, and 28% (100 μM, 200 μM, and 300 μM, respectively). When worms were co-exposed to catechins, rather than being pretreated, protection was no longer afforded. Rather, co-administration resulted in shorter body length and increased pharyngeal pumping rates compared to control worms grown in standard media (Saul et al., 2009).

It has been suggested that the disposable soma hypothesis (Saul, et al., 2009) may help explain the positive effects of catechins. This hypothesis states that energy normally devoted to increasing body length is diverted to maintenance. This leads to an increased life span, but shorter body length, which is often observed following catechin exposure. This was tested (Saul et al., 2009) using various short-lived mutants (age-1, daf-16, jnk-1, osr-1, sek-1, sir-2.1, unc-43, akt-2, daf-2, abnormal methyl viologen sensivity-1 (mev-1), and nhr-8; see Table 28.3). This study design also helped rule out the possibility that catechins were acting as direct antioxidants capable of detoxicating or inhibiting the production of reactive oxygen species (ROS).

6.3 Catechins (Catechin, Epicatechin, and Epigallocatechin-3-Gallate)

4.5.7 Catechin and derivatives

Catechin and its derivatives form a major team of active polyphenolic components from plants. There are many compounds come under the category, such as catechin, epicatechin (EC), epigallocatechin (EGC), and epigallocatechin gallate (EGCG). Catechin exerts its pharmacological effects by reducing IL-5 and IL-13 levels and suppressing the NF-κB signal pathway [96]. Besides a pretreatment of catechin significantly ameliorated the activation of NF-κB and the expressions of COX-2, TNF-α, and IL-6 in benzo(a)pyrene-induced cells [97]. The mRNA expression levels of TLR4/NFκB-dependent inflammatory genes were lowered with the treatment with catechin [98]. EGCG was proved to target the COX, LO, IKK, AP-1, and NF-κB, during the antiinflammatory action. In addition, EGCG regulates MMP-2, COX-2, IL-6, TNF-α, and chemokines [99, 100]. Interestingly, EGCG could inhibit the action of TGF-β-activated MAP kinase (TAK1) and thus abrogate the production of IL-6 and IL-8 [100]. In a comparison, EGCG was the more effective inhibitor of IL-6 and IL-8, than EGC and EC. EGC and EGCG were effective in the downregulation of IL-1β-induced MMP-2 activity. Specific inhibition of COX-2 was observed with both EGC and EGCG. Together, these polyphenolic compounds exert synergic therapeutic benefits. Product rich in these polyphenols, such as green tea, is identified to have better beneficial effects [100].

3.5.7 Catechins

Catechins are polyphenolic phytochemicals found in green tea and cocoa fruits. Other constituents found in green tea and cocoa fruits were (−)-epicatechin, (+)-gallocatechin, (+)-catechin, (+)-catechin, (−)-epigallocatechin, flavan-3-ols. Catechins are noted for their diverse biological activities such as antiobesity, antioxidative, antiinflammatory, antiatherosclerosis, antihyperglycemia, and antihypercholesterolemia. Suzuki et al. reported that catechin improves cardiac function in experimental autoimmune rats. The study showcased significant improvement in fibrosis and reduced myocardial cell infiltration. Further, it was observed through immunohistochemistry that messenger ribonucleic acid (mRNA) of tumor necrosis factor-alpha (TNF-α) were reduced and Th 2 cytokines were increased as well as nuclear factor kappa B (NF-κB) and ICAM-1 were reduced when compared with the group kept as control [40]. Similarly the study reported by Zempo et al. supported that cocoa polyphenol efficiently reduced the fibrotic area ratio and cardiac infiltration and increase in heart weight to body weight (HW/BW) (symbolizes myocardial hypertrophy) in experimental autoimmune myocarditis rats. Moreover, reduced cardiac H₂O₂concentration, cardiac myeloperoxidase (MPO), dihydroethidium staining (DHE) intensity, NF-κB P65 phosphorylation. Collagen type 1, vascular adhesion molecule (VCAM-1) and mRNA expression of IL-6, IL-1, E-selection as observed through reverse transcriptase-PCR [41]. To summarize, catechins play important role in inflammatory autoimmune myocarditis [8].

2.3.2 Catechins

Catechins are present in a wide variety of plant products such as green tea, cacao, grape, grape juices, and wine. Catechins are polyphenolic compounds, such as epigallocatechin-3-gallate (EGCG), epigallocatechin, epicatechin-3-gallate and epicatechin, gallocatechins, and gallocatechin gallate. Catechins intake can reduce inflammatory events and platelet aggregation, and avoid cardiovascular dysfunctions, such as atherosclerosis, hypertension, endothelial dysfunction, cardiac ischemic diseases, cardiomyopathy, and cardiac hypertrophy (Khan and Mukhtar, 2018). Moreover, many studies have reported that catechins can present antitumor effect and increase chemotherapy response (Saiko et al., 2015; Mayr et al., 2015).

Saiko et al. (2015) described the antitumor action of EGCG by proapoptotic action in human cells of acute promyelocytic leukemia (HL-60). The results indicated that EGCG presented anticarcinogenic effect in HL-60 cells by inhibiting DNA synthesis, cell proliferation, increasing apoptosis, and arresting cell cycle. Also, Mayr et al. (2015) reported the synergism of catechin and cisplatin against biliary tract cancer. Different types of cell lines for this type of cancer were treated with EGCG alone and in combination with cisplatin. In addition, synergism increased apoptosis and cell cycle arrest. This association caused cell cycle arrest, decreased cell viability by increased apoptosis, and improved the chemotherapy response of biliary tract cancer treatment.

In addition, another investigation performed by Bimonte et al. (2015) indicated that catechin in combination with chemotherapeutic bleomycin generated an efficient antitumor synergism by inhibiting cell pancreatic cancer growth cell line (MiaPaCa-2). The combination of catechin and bleomycin was able to decrease cell proliferation by blocking S-phase of cell cycle and plasma membrane depolarization and activating apoptosis and DNA damage.

Saeed et al. (2015) reported that pretreatment with this molecule is able to attenuate the cardiotoxicity generated by doxorubicin in rats. Furthermore, EGCG is able to protect against neurotoxicity generated by cisplatin by inhibiting apoptosis in mice (Zou et al., 2014).

In addition, the potentiating synergistic effect of EGCG associated with doxorubicin was found in hepatocellular carcinoma cells (Hep3B), due to the increase in autophagy vesicles within tumor cells and, consequently, cell death increased (Chen et al., 2014).

Also, the antitumor action of EGCG was described by Shimizu et al. (2015). The results showed that this active molecule was able to inhibit cell growth and proliferation in human hepatocarcinoma cells by inducting apoptosis and inhibiting some molecules involved in cell proliferation and survival, such as AKT and extracellular signal-regulated kinase (ERK). Zhang et al. (2015) also found the same antitumor effect in hepatocellular carcinoma (LM6) cells and demonstrated that EGCG did not affect healthy liver cells.

Moreover, the antitumor effect of EGCG was also found in osteosarcoma (MG63 and U2OS) cell lines (Jiang et al., 2014), lung cancer (A549) (Sonoda et al., 2014; Ma et al., 2014), ovarian carcinoma (OVCAR-3) (Wang et al., 2014), and colorectal (HCT116) (Moseley et al., 2013).