In Vitro and In Silico Studies of the Molecular Interactions of Epigallocatechin-3-O-gallate (EGCG) with Proteins That Explain the Health Benefits of Green Tea

Abstract

Green tea has been shown to have beneficial effects on many diseases such as cancer, obesity, inflammatory diseases, and neurodegenerative disorders. The major green tea component, epigallocatechin-3-O-gallate (EGCG), has been demonstrated to contribute to these effects through its anti-oxidative and pro-oxidative properties. Furthermore, several lines of evidence have indicated that the binding affinity of EGCG to specific proteins may explain its mechanism of action. This review article aims to reveal how EGCG-protein interactions can explain the mechanism by which green tea/EGCG can exhibit health beneficial effects. We conducted a literature search, using mainly the PubMed database. The results showed that several methods such as dot assays, affinity gel chromatography, surface plasmon resonance, computational docking analyses, and X-ray crystallography have been used for this purpose. These studies have provided evidence to show how EGCG can fit or occupy the position in or near functional sites and induce a conformational change, including a quaternary conformational change in some cases. Active site blocking, steric hindrance by binding of EGCG near an active site or induced conformational change appeared to cause inhibition of enzymatic activity and other biological activities of proteins, which are related to EGCG’s biological oligomer and formation of their toxic aggregates, leading to the prevention of neurodegenerative diseases and amyloidosis. In conclusion, these studies have provided useful information on the action of green tea/catechins and would lead to future studies that will provide further evidence for rational EGCG therapy and use EGCG as a lead compound for drug design.

EGCG Mediated Targeting of Deregulated Signaling Pathways and Non-Coding RNAs in Different Cancers: Focus on JAK/STAT, Wnt/β-Catenin, TGF/SMAD, NOTCH, SHH/GLI, and TRAIL Mediated Signaling Pathways

“…Epigallocatechin-3-gallate (EGCG) is a phenolic compound present in tea and has captivated tremendous attention in the past two decades because of its premium pharmacological properties. There is a wide variety of reviews published with reference to EGCG mediated anticancer effects [1][2][3][4]. However, in this review we focused on EGCG mediated modulation of deregulation cell signaling pathways in different cancers.…”

Anti-Cancer Effects of Green Tea Epigallocatchin-3-Gallate and Coffee Chlorogenic Acid

“…These include fibronectin, vimentin, heat shock protein 90, glucose-regulated protein 78 kDa (GRP78), insulin-like growth factor-1 receptor, Src-related proto-oncogene Fyn protein, ζ chain-associated 70-kDa protein, Ras-GTPase-activating protein Src homology (SH3) domain-binding protein-1, peptidyl-prolyl cis-transisomerase, and TNF receptor-associated factor-6. Most of these interactions were confirmed by MDA [ 82 ].…”

“…EGCG inhibited activities of these enzymes, leading to anti-cancer effects like batimastat (BB-94), a synthetic MMP inhibitor that inhibits tumor growth, local invasion, and lung metastasis of orthotopic metastatic human HCC in nude mice model [ 80 , 81 ]. Later, the binding interaction between EGCG and MMP-2 and MMP-9 was confirmed by computational molecular docking analysis (MDA) [ 82 ].…”

“…In our previous review article, we discussed binding interactions between EGCG and other cancer-related proteins revealed by affinity chromatography and pull-down methods using EGCG-agarose gel [ 82 ]. These include fibronectin, vimentin, heat shock protein 90, glucose-regulated protein 78 kDa (GRP78), insulin-like growth factor-1 receptor, Src-related proto-oncogene Fyn protein, ζ chain-associated 70-kDa protein, Ras-GTPase-activating protein Src homology (SH3) domain-binding protein-1, peptidyl-prolyl cis-transisomerase, and TNF receptor-associated factor-6.…”

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“…An accomplice, EGCG, ameliorates cytokineinduced β-apartment execration in-vitro and prevents the obligation of ait hoard induced by sedative encircling go together wretched doses of streptozotocin in-vivo 12 . Most of the complications of DM have been studied widely, but sexual dysfunctions are still incompletely understood in the male with relation to plasma levels of testosterone, FSH and LH 13 .…”