Epigallocatechin-3-gallate therapeutic potential in human diseases: molecular mechanisms and clinical studies

Abstract

Green tea has garnered increasing attention across age groups due to its numerous health benefits, largely attributed to Epigallocatechin 3-gallate (EGCG), its key polyphenol. EGCG exhibits a wide spectrum of biological activities, including antioxidant, anti-inflammatory, antibacterial, anticancer, and neuroprotective properties, as well as benefits for cardiovascular and oral health. This review provides a comprehensive overview of recent findings on the therapeutic potential of EGCG in various human diseases. Neuroprotective effects of EGCG include safeguarding neurons from damage and enhancing cognitive function, primarily through its antioxidant capacity to reduce reactive oxygen species (ROS) generated during physiological stress. Additionally, EGCG modulates key signaling pathways such as JAK/STAT, Delta-Notch, and TNF, all of which play critical roles in neuronal survival, growth, and function. Furthermore, EGCG is involved in regulating apoptosis and cell cycle progression, making it a promising candidate for the treatment of metabolic diseases, including cancer and diabetes. Despite its promising therapeutic potential, further clinical trials are essential to validate the efficacy and safety of EGCG and to optimize its delivery to target tissues. While many reviews have addressed the anticancer properties of EGCG, this review focuses on the molecular mechanisms and signaling pathways by which EGCG used in specific human diseases, particularly cancer, neurodegenerative and metabolic diseases. It serves as a valuable resource for researchers, clinicians, and healthcare professionals, revealing the potential of EGCG in managing neurodegenerative disorders, cancer, and metabolic diseases and highlighting its broader therapeutic values.

Keywords: Cancer therapy; Epigallocatechin gallate; Natural products; Neuroinflammation; Neurological disorders; Targeted therapy.

Fig. 1

Mechanistic Overview of Modulation of Cellular Signaling Pathways by EGCG. This figure illustrates the multifaceted mechanism of EGCG and its interactions with key signaling and molecular pathways. EGCG is shown to regulate various target genes and proteins, including JAK/STAT, NF-κB, AKT, and Notch pathways, highlighting its critical roles in cellular processes such as apoptosis, proliferation, and survival. The diagram emphasizes the biological functions of EGCG, including its anti-cancer, anti-inflammatory, and antioxidant activities. By inhibiting oxidative stress, reducing inflammation, and promoting apoptosis in cancer cells, EGCG showcases its therapeutic potential in combating diseases like cancer, cardiovascular , and neurodegenerative diseases

Fig. 2

Antimicrobial Action of EGCG through Biofilm Disruption. Showing the antimicrobial mechanism of EGCG, focusing on its ability to disrupt biofilm formation. EGCG targets the σϵ regulatory pathway, which plays a crucial role in bacterial membrane adhesion. By interfering with the production of curli subunits and cyclic di-GMP (c-di-GMP), both essential for biofilm stability and bacterial adherence, EGCG effectively impairs biofilm formation. This disruption weakens bacterial colonization and enhances susceptibility to antimicrobial treatments, highlighting the potential of EGCG as a powerful agent in combating bacterial infections and biofilm-associated resistance

Fig. 3

EGCG-Mediated Pathways Targeting Oxidative Stress. Showing the diverse molecular pathways through which EGCG mitigates oxidative stress. EGCG inhibits the phosphorylation of STAT3, thereby disrupting the JAK/STAT signaling pathway, which is crucial for cell proliferation and survival. Additionally, EGCG targets key proteins in the Delta-Notch pathway, including Notch, HEY, and HES1, further influencing cellular differentiation and survival mechanisms

Fig. 4

Impact of EGCG on tumor-mediated signaling cascades through apoptosis. EGCG blocks signaling cascade activation and promotes apoptosis. Outline the promising gene targets engaged in anti- and pro-apoptotic activities of low and high EGCG concentration. This effect could be attained via the increased regulation of p53 expression. EGCG enhances the ratio of Bax/Bcl-2 and activates apoptosis

Fig. 5

Role of EGCG in inhibition of cancer growth. EGCG acts as an anti-cancer agent either by responding through the RTK pathway or by binding to its 67 -ligand-receptor (67-LR). RTK method mediates via RAS pathway regulating nuclear and cytosolic genes. RTK also alter PI3K-AKT pathway thereby inhibiting angiogenesis. EGCG regulates the process of apoptosis via FLA and TNFα

Fig. 6

The potential neuroprotective effects of EGCG in PD. The mechanisms of EGCG exert neuroprotective advantages. EGCG can prevent protein misfolding, neuronal apoptosis, oxidative stress, and neuroinflammatory responses

Fig. 7

The promising effects of EGCG in AD pathogenesis. EGCG participates in a neuroprotective function and is prospectively utilized as a therapeutic drug for managing AD

Fig. 8

The Role of EGCG in Diabetes Management. Showing the pivotal role of EGCG in diabetes, particularly through its interaction with the KEAP1-Nrf2 signaling pathway. EGCG forms a hybrid complex with glutathione (GSH), which binds to KEAP1, resulting in the dissociation of KEAP1 from Nrf2. This dissociation allows Nrf2 to translocate into the nucleus, where it initiates the transcription of crucial antioxidant proteins, including heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). These antioxidant proteins play an important role in reducing oxidative stress and inflammation, key contributors to diabetic complications