Introduction

(-)-Epigallocatechin gallate (EGCG, Figure 1) is a polyphenol present in green tea (Camellia sinensis (L.) Kuntze) leaves. The most popular ways of consuming (-)-epigallocatechin gallate are green tea-based beverages and dietary supplements containing a complex mixture of polyphenols called green tea extract (GTE) consisting of green tea catechins (GTCs) such as catechin, epicatechin, epigallocatechin, epicatechin gallate and epigallocatechin gallate (EGCG) [1].

(-)-Epigallocatechin gallate Bioavailability

The main issue discussed in the context of the use of (-)-epigallocatechin gallate in therapy is its metabolism and bioavailability. A single-dose (-)-epigallocatechin gallate pharmacokinetic evaluation was studied. Serum (-)-epigallocatechin gallate greater than 1 μM was observed with oral doses greater than one gram of EGCG (dose: 1600 mg; Cmax = 3392 ng/mL; range: 130–3392 ng/mL). In addition, it was found that after 1.3–2.2 h, the maximum concentration was reached. The safety and kinetics of (-)-epigallocatechin gallate and decaffeinated green tea extract were also evaluated by Chow et al. [47]. EGCG intake at doses of 400 and 800 mg resulted in serum concentrations of both free and total EGCG in the high nanomolar range. The chronic administration of a dose of 800 mg resulted in an increase in the bioavailability of (-)-epigallocatechin gallate with only minor gastrointestinal side effects. The content of polyphenols in one sachet of green tea is about 80–100 mg, which translates into 25–30 mg of (-)-epigallocatechin gallate. Therefore, a therapeutic dose may be provided, either as a dietary supplement with a condensed high amount of (-)-epigallocatechin gallate or as a pro-EGCG compound with enhanced bioavailability. The presence of a hydroxyl group in (-)-epigallocatechin gallate determines its low bioavailability in the human body. The alkaline environment causes the rapid oxidation of EGCG and is not conducive to protons on the phenolic groups, resulting in the production of a phenolate anion that acts on electrophilic agents such as free radicals in the body. To prevent the breakdown of EGCG in the body, various methods of delivery are designed, e.g., the encapsulation or formation of a prodrug. Pro-EGCG was shown to act as an angiogenesis inhibitor in in vitro and in vivo models of endometrial cancer. Additionally, pro-EGCG was also found to be more bioavailable and stable than traditional (-)-epigallocatechin gallate extract in breast cancer in vitro and in vivo. The antiproliferative, antiangiogenic, and antifibrotic effects of pro-EGCG were confirmed in human leiomyoma cell lines.[2]

Potential medical properties

In the in vitro and in vivo biological study, (-)-epigallocatechin gallate reveals anti-tumor activity against adrenal, bladder, breast, cervical, colorectal, esophageal, gastric, liver, lung, oral, ovarian, pancreatic, prostate, and skin cancer. Most of the in vitro studies have been conducted with doses of (-)-epigallocatechin gallate in the range of 5–200 μM (or 2–92 μg/mL). The mechanisms of the anti-tumor activity of (-)-epigallocatechin gallate described in the literature are inhibition of growth/proliferation, adhesion, migration, invasion, metastasis, and suppression of angiogenesis. Moreover, (-)-epigallocatechin gallate can induce apoptosis and sensitize the immunological system against tumors. Due to its high antioxidant potential and original molecular properties, (-)-epigallocatechin gallate has been reported to regulate gene expression and molecular signaling pathways. It inhibits phosphorylation of p38 and JNK protein kinases, as well as nuclear translocation of NF-κB, and therefore decreases the expression of proinflammatory genes and proteins in various cell types. Additionally, EGCG reduces the accumulation of malfunctioning and abnormal proteins and other waste products during cellular aging. In addition to the most popular research directions, such as anticancer, there are also other studied areas linked to (-)-epigallocatechin gallate supplementation: fertility, diabetes, endometriosis, COVID-19, antimicrobial activity, non-alcoholic fatty liver disease management, and anti-inflammatory action [1].

1. (-)-Epigallocatechin gallate for Parkinson's disease.

In this paper, they review the potential use of (-)-epigallocatechin gallate (EGCG) for Parkinson's disease (PD), a devastating neurodegenerative disorder. Some intracellular signalling pathways have been described to play central functions in (-)-epigallocatechin gallate-promoted neuronal protection against various extracellular insults such as the MAPK, PKC and phosphatidylinositol-3-kinase (PI-3 kinase)-Akt pathways. Stress-activatedprotein kinases (SAPK)/Jun amino-terminal kinases (JNK) are members of the MAPK family and are activated by various environmental stresses,inflammatory cytokines, and growth factors. (-)-Epigallocatechin gallate neuroprotective activity also involves the intracellular signalling mediator PKC, which increases the mitochondrial protein Bcl2, and turns to Bax inhibition. An extracellular signal-regulated kinase (ERK) is also thought to have anessential role in regulating cell survival and programmed cell death by increasing Bad. EGCG promotes cell survival by increasing the ratio of Bcl-2to pro-apoptotic Bax and phosphorylation of another pro-apoptotic Bcl-2 family member, Bad, through ERK and Akt signalling pathways. In addition, (-)-epigallocatechin gallate modulates survival via negative regulation of the activity of the transcription factor NF-κB. Green tea-derived (-)-epigallocatechin gallate is a powerful molecule with multiple therapeutic properties against different neurological conditions.[3]

2.(-)-Epigallocatechin Gallate for the Treatment of Benign and Malignant Gynecological Diseases

The polyphenols present in green tea, in addition to (-)-epigallocatechin gallate, include catechin, epicatechin, epicatechin gallate, and epigallocatechin. Due to their similar chemical structures, itis postulated that the mechanisms of their actions on cells are similar and include, amongothers, pro-apoptotic, antiproliferative, pro-oxidant, and antioxidant effects (Figure 2).Their antioxidant effects can be exerted directly though scavenging free radicals or metalchelation. Indirectly, catechins may affect pro-oxidant and antioxidant enzymes or signal transduction pathways involving TNF or NFKB. (-)-Epigallocatechin gallate has been reported tointeract with transmembrane receptors or proteins involved in disease progression, forexample, TGF-β in cell differentiation and migration pathways or fibronectin in ECM formation. Many studies have proven the pro-apoptotic and antiproliferating effects of (-)-epigallocatechin gallate, but only a few have recognized their epigenetic mechanisms. Typically, the levels ofmethylation or expression of selected genes or the activity of selected enzymes catalyzingreactions important for epigenetic mechanisms are assessed. To answer the question of theactual impact of (-)-epigallocatechin gallate, the methylation patterns of all genes should be compared to indicate what changes have occurred precisely. Due to the relatively small number of studiesexploring the epigenetic mechanisms of (-)-epigallocatechin gallate in gynecological cancers, we can rely on thepublished results regarding other types of cancer, where (-)-epigallocatechin gallate affects multiple molecular targets involved in cancer initiation, promotion, and progression.[2]

References

[1]Bakun P, Mlynarczyk DT, Koczorowski T, et al. Tea-break with epigallocatechin gallate derivatives - Powerful polyphenols of great potential for medicine. Eur J Med Chem. 2023;261:115820. doi:10.1016/j.ejmech.2023.115820

[2]W?odarczyk M, Ciebiera M, Nowicka G, ?oziński T, Ali M, Al-Hendy A. Epigallocatechin Gallate for the Treatment of Benign and Malignant Gynecological Diseases-Focus on Epigenetic Mechanisms. Nutrients. 2024;16(4):559. Published 2024 Feb 17. doi:10.3390/nu16040559

[3]Sergi CM. Epigallocatechin gallate for Parkinson's disease. Clin Exp Pharmacol Physiol. 2022;49(10):1029-1041. doi:10.1111/1440-1681.13691