Therapeutic Aspects of Catechin and Its Derivatives

ABMJ 2019, 2(1): 21-29 DOI: 10.2478/abmj-2019-0003

Acta Biologica Marisiensis

THERAPEUTIC ASPECTS OF CATECHIN AND ITS DERIVATIVES – AN UPDATE

Sanda COȘARCĂ1, Corneliu TANASE1*, Daniela Lucia MUNTEAN1

1University of Medicine, Pharmacy, Science and Technology of Târgu-Mureș, Faculty of Pharmacy, 38 Gheorghe Marinescu Street.

*Correspondence: Corneliu TANASE [email protected]

Received: 1 May 2019; Accepted: 20 June 2019; Published: 30 Iune 2019

Abstract: Catechin and its derivatives are polyphenolic benzopyran compounds. The condensation of catechin units leads to the formation of condensed tannins. It is found in appreciable amount in green tea leaves, cocoa, red wines, beer, chocolate, etc. It possesses important antioxidant, antibacterial, antifungal, antidiabetic, anti-inflammatory, antiproliferative and antitumor properties. The present review outlines recent updates and perspectives of the effects of catechins and the pharmacodynamic mechanisms involved.

Keywords: catechin, antitumor, antioxidant, antibacterial, hypolipidemic.

1. Introduction

Catechins are flavanols which belong to catechins have an important role in protection polyphenolic compounds. Condensed or non- against degenerative diseases (Ide et al., 2018). hydrolyzable tannins are formed by the Other studies have demonstrated an inverse condensation of catechin (epicatechin and a reaction between catechin intake and the risk of catechin epimer) (Fig. 1). Catechin, together cardiovascular diseases (Ikeda et al., 2018). It with epicatechin and epigallocatechin gallate, has been reported that catechins appear to are the main flavonoids which are found in the produce greater antibacterial activity against composition of green tea (Li et al., 2018). Gram-positive bacteria than Gram-negative Many research results have highlighted that ones (Ajiboye et al., 2016; Gomes et al., 2018).

Fig. 1. Chemical structure of catechin and its derivatives

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The present paper is a critical review of the several antioxidant, antihypertensive, anti- recent literature on therapeutic aspects and inflammatory, antithrombogenic, hypo- pharmacodynamic mechanisms of catechin and lipidemic, etc. effects (Rothwell et al., 2018). It its derivatives. was also shown that catechin and its derivatives, namely epigallocatechin gallate, 2. Bioavailability and biological effects would inhibit platelet aggregation. These of catechin and its derivatives effects were explained by the inhibition of The bioavailability of catechin and its cytoplasmic calcium growth (Lill et al., 2003; derivatives differs significantly depending on Watson et al., 2014). Catechins also have an the form under which it is found (Table 1). important role in maintaining homeostasis When administered in esterified form with (Matsui, 2015), their cardioprotective and gallic acid, the absorption is much slower. antidiabetic effects have been demonstrated by Methylated forms were identified as a result of several studies (Thielecke et Boschmann, 2009; metabolization in the case of epigallocatechin. Hashemipour et al. 2017). In another study, the plasma concentration of 4’-O-methyl-epigallocatechin was determined, 3. Antiallergic properties whose value was 5 times higher in plasma and New studies have been conducted on the 3 times higher in urine than the concentration anti-inflammatory and anti-allergic effects of of epigallocatechin (Rothwell et al., 2018). catechin (Hussein et al., 2015). The Epigallocatechin gallate is the only flavonol pharmacological effects of catechin in mice form which is present in plasma in a significant with allergic rhinitis were determined by percentage (48-55%). performing haematoxylin and eosin staining The other catechins are detected as the and Giemsa staining of the nasal tissues glucoronidated or sulphated form. The main essential in observing the allergic symptoms. epicatechin metabolites are: epicatechin-3’-O- The results showed that catechin, at 75, 150 or glucuronide, 4’-O-methylepicatechin-3’-O- 300 mg/kg bodyweight, reduced the allergic glucuronide, 4’-O-methyl-epicatechin-5- or 7- symptoms in mice with allergic rhinitis, such as O-glucuronide, 4’-O-methylepicatechine and sneezing and nasal rubbing. Catechin could epicatechin aglycone (Liao et al., 2018; reduce interleukin-5, interleukin-13 and Casanova et al., 2019). Metabolization leads to ovalbumin E serum concentrations and restore metabolites that can extend the beneficial effect T helper type 2 / T helper type 1 cell balance. of catechins, having a longer half-life (5 hours Catechin has efficiently decreased the for epigallocatechin-3-gallate). In this case, inflammation in allergic rhinitis. The renal excretion of catechins is very rapid mechanism of action would be that catechin (Manach et al., 2005; Ikeda et al., 2018). inhibited the expression of TSLP (lymphatic Catechin influences molecular mechanisms stromal lymphopoietin) in epithelial cells by involved in angiogenesis, extracellular matrix influencing the NF-κB / TSLP pathway (Pan et degradation, regulation of cell motility, and al., 2018). multiple resistance to cancers and associated disorders. 4. Cardiovascular effects Based on epidemiological and Recent evidence demonstrates that experimental studies, a correlation between catechins can be key mediators in green tea consumption rich in catechins and cardiovascular health through mechanisms cardiovascular health has been highlighted by underlying blood pressure reduction, 22

ABMJ 2019, 2(1): 21-29 vasodilation, and atherosclerosis (Mangels et al., 2012) processes. Generation of ROS in al, 2017). neuronal cells activates inflammatory The prevalence of coronary heart disease mediators like TNF-α, COX-2, NF-κβ as well in Asian people is demonstrated to be very low as proapoptotic mediators such as Bcl-2 and due to their increased tea consumption (Shahid caspase-9 (Suryavanshi et al, 2017; Kimura- et al., 2016; Li et al., 2018). Also, recent Ohba et al., 2016). Catechin directly or studies have demonstrated that, due to their indirectly decreases neuronal damage by antioxidant effect, they have the ability to reducing oxidative stress, scavenging ROS and reduce cytotoxicity produced by amiodarone improving antioxidant enzymes (Shai et al (commonly used antiarrhythmic drug) in 2015; Xiang et al., 2016). human lung fibroblast cells (Cooper et al., 2005; Santos et al., 2017). 6. Lipid-lowering effects Studies in rats have shown that catechin in 5. Antioxidant and anti-tumor effect green tea can reduce the risk of cardiovascular Clinical trials conducted so far have shown disease (CD). The effect has been attributed to the beneficial effects of catechin due to its the antioxidant and anti-inflammatory antioxidant action. The ability of catechins to properties of catechin. Also it is suggested that cross the blood-brain barrier has led to catechin reduces the risk of cardiovascular increased interest related to their antioxidant disease by lowering cholesterol and triglyceride properties beneficial for the prevention and levels (Cooper et al., 2005). In vitro and in vivo treatment of neurodegenerative diseases. studies show that catechins in green tea inhibit Catechin and other catechins in green tea intestinal absorption of dietary lipids, by block carcinogenesis and help modulate signal interfering with lipid digestion and their transduction pathways related to proliferation, solubilization (the critical steps involved in the transformation, inflammation and metastasis of intestinal absorption of dietary fats, cholesterol cells. It also has a chemopreventive potential and other lipids). Based on the information (Grzesik et al, 2018; Yang et al., 2018; available so far, it is clear that green tea and its Baranowska et al., 2018) and catechin catechins effectively reduce the intestinal nanohybrids significantly improve the anti- absorption of lipids (Ikeda et al., 1992). The tumour effect by inducing apoptosis of WM266 mechanism of action of catechin is based on the human melanoma versus free catechin (Di Leo fact that it inhibits the absorption of lipids. This et al., 2017). Also, the loading of catechin with effect appears to be associated with its ability PLGA (poly (1-lactide-co-glycolide)) fibers to form complexes with lipids and lipolytic had a high effect of reducing the reactive enzymes, thereby interfering with oxygen species, so processing of catechin in emulsification, hydrolysis, micellar controlled release forms could allow future solubilization processes and subsequent localized applications of great importance in absorption of lipids. These mechanisms are not the fields of tissue engineering and wound fully clarified and further studies are needed to healing (Ghitescu et al., 2018). define mechanisms underlying lipid absorption Oxidative stress plays a central role in the inhibition (Shishikura et al.; 2006; Koo et al., degeneration of neurons by activating 2007). intracellular signaling cascades, which have a role in autoimmune apoptosis and extracellular modulation (Suryavanshi et al, 2017, Bhatt et

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7. Antibacterial and antiviral effect Polyphenols are among the most abundant been reported to be associated with a number of compounds in the plant kingdom. They have organoleptic properties of drinks and foods.

Table 1. The effect of catechin and its derivates Compound Effect Reference epicatechin gallate beneficial role in muscles Kim AR et al.,2017 epigallocatechin-3-gallate regeneration epigallocatechin, antioxidant Ikeda et al., 2018 epicatechin, cardioprotective epigallocatechin-3-gallate, epicatechin-3-gallate epigallocatechin gallate antibacterial Miyamoto et al., 2017 epicatechin, bactericidal effects on oral Chang et al., 2019 epigallocatechin, bacteria, Aggregatibacter epicatechin gallate, actinomycetemcomitans epigallocatechin gallate, gallocatechin gallate epicatechin antioxidant Grzesik et al., 2018 epicatechin gallate epigallocatechin epigallocatechin gallate catechin antioxidant, Addepalli V et anti-inﬂammatory, Suryavanshi SV, 2018 beneﬁcial effect in the management of diabetic autonomic neuropathy in rats catechin antibacterial Gomes et al., 2018 catechin antioxidant Caro et al., 2019 catechin hepatoprotective Akinmoladum et al., 2018 catechin cytotoxic Di Leo et al., 2017 catechin anti-microbial Chunmei et al., 2010 epigallocatechin-3-gallate antioxidant, Roychoudhur et al., 2017 epigallocatechin-3-gallate antibacterial Founier-Larente et al., 2016 catechin antioxidant, Akiboye etal., 2016 antibacterial catechin antibacterial Diaz-Gomez et al., 2013 catechin antibacterial Diaz-Gomez et al., 2014 catechin antibacterial Li et al., 2018 antioxidant catechin antibacterial Zhang et al., 2016 catechin antifungal Saito et al., 2013s epigallocatechin gallate antibacterial Nakayama et al., 2013 24

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Several authors have highlighted the Conclusions antibacterial effect of polyphenols against bacteria that can cause gastrointestinal diseases. Catechin and its derivatives represent a Several studies associate catechin with class of phenolic compounds with a very wide different antibiotics. It has been observed that therapeutic potential. At present, not all the the combination of antibiotics like catechin- mechanisms of action are fully known, but imipenem, catechin-erythromycin, catechin- studies have shown that these compounds tetracycline would have a synergistic inhibition would be worthwhile investigating. effect against Eschericia coli, which suggests Numerous studies have shown positive that polyphenols may be considered promising effects of green tea and tea-based products due alternatives for the treatment of bacterial and to their content of catechin and its derivatives. viral infections, thus the catechin can be used These compounds would also be beneficial for for the prophylaxis of influenza and A (H1N1) the improvement of degenerative, metabolic infection (Gomes et al., 2018; You et al., 2018; and cardiovascular diseases as well as the Diaz-Gomez et al., 2013). Other studies quality of life in elderly population. Studies on demonstrate that black tea consumption would cell lines highlight the effects of catechin on influence the incidence of Helicobacter pylori cancer chemopreventive activity. However, infection due to its catechin content (Boyanova catechins and their derivatives must be given et al., 2015; Naveeda et al., 2018; Diaz-Gomez full attention due to numerous effects, for the et al., 2013). development of new, more efficient and more stable drug structures. There are currently no 8. Antidiabetic effect food supplements with catechin or its Certain studies have pointed out that derivatives in pure form, but most of the green catechin would have a significant potential to tea extract supplements are based on its effects reduce blood glucose, body weight and body and its derivatives. mass index (BMI) in both elderly and obese subjects by stimulating thermogenesis Conflict of Interest (Hashemipour et al., 2017; Pastoriza et al., The authors declare that the research was 2017; Addepalli et al., 2018). Catechins control conducted in the absence of any commercial or plasma glucose levels by modulating the financial relationships that could be construed glucose transport system (Grzesik et al., 2018). as a potential conflict of interest. 9. Immunostimulatory effect Catechin also intervenes in immune function modulation through humoral and cellular mechanisms. It has been emphasized that catechin decreases cyclophosphamide- induced myelosuppression (Ganeshpurkar et al., 2018).

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