Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol abundant in green tea, has garnered significant attention for its diverse therapeutic applications, ranging from antioxidant and anti-inflammatory effects to potential anticancer properties. Despite its immense promise, the practical utilization of EGCG in therapeutic settings as a medication has been hampered by inherent limitations of this drug, including poor bioavailability, instability, and rapid degradation. This review comprehensively explores the current challenges associated with the application of EGCG and evaluates the potential of nanoparticle-based formulations in addressing these limitations. Nanoparticles, with their unique physicochemical properties, offer a platform for the enhanced stability, bioavailability, and targeted delivery of EGCG. Various nanoparticle strategies, including polymeric nanoparticle, micelle, lipid-based nanocarrier, metal nanoparticle, and silica nanoparticle, are currently employed to enhance EGCG stability and pharmacological activity. This review concludes that the particle sizes of most of these formulated nanocarriers fall within 300 nm and their encapsulation efficiency ranges from 51% to 97%. Notably, the pharmacological activities of EGCG-loaded nanoparticles, such as antioxidative, anti-inflammatory, anticancer, and antimicrobial effects, are significantly enhanced compared to those of free EGCG. By critically analyzing the existing literature and highlighting recent advancements, this article provides valuable insights into the promising prospects of nanoparticle-mediated EGCG formulations, paving the way for the development of more effective and clinically viable therapeutic strategies.
Animals ; Humans ; Anti-Inflammatory Agents/administration & dosage* ; Antineoplastic Agents/administration & dosage* ; Antioxidants/administration & dosage* ; Biological Availability ; Catechin/analogs & derivatives* ; Micelles ; Particle Size ; Nanoparticle Drug Delivery System/chemistry*

Epigallocatechin-3-gallate (EGCG), a prominent plant-based catechin predominantly derived from Camellia sinensis and widely available on the market as a health supplement, has garnered significant attention for its potential therapeutic benefits, particularly in the context of type 2 diabetes mellitus (T2DM). This review explores the multifaceted role of EGCG in addressing the "ominous octet"-the 8 core pathophysiological defects associated with T2DM. The literature search was carried out using key terms "EGCG" OR "epigallocatechin-3-gallate" OR "epigallocatechin gallate" AND "diabetes" OR "insulin resistance" OR "hyperglycemia" in the PubMed and Scopus databases. The search was constrained to articles published between January 2018 and April 2024, focusing on the document type. Full-text articles published in English and relevant to EGCG that featured a single active ingredient, included clearly explained diabetes relief mechanism, and included ominous octet aspects were included in the final review. The outcomes of the included studies were reviewed and categorized based on 8 core pathophysiological defects, collectively referred to as the ominous octet in T2DM. This review concludes that EGCG is a potent hypoglycemic agent that has beneficial effects against the ominous octet in addition to its pharmacological activities in modulating gut microbiota dysbiosis, carbohydrate digestion and metabolism, glucose transporter-mediated intestinal glucose-uptake, endothelial dysfunction, and renal damage that are significantly associated with pathogenesis of T2DM. This extensive scientific evidence suggests that EGCG may offer a novel approach to traditional antidiabetic therapies, potentially improving glycemic control and mitigating complications associated with T2DM. The inhibitory effects of EGCG on sodium-glucose transport proteins and their role in reducing renal glucose reabsorption remain unexplored, highlighting a significant research gap. Future research should also aim to broaden the scope by investigating the "egregious eleven," which comprise a more comprehensive range of diabetic pathophysiological features. This review underscores the therapeutic promise of EGCG for managing T2DM and encourages ongoing research to fully elucidate its clinical applications. Please cite this article as: Wong CN, Lim YM, Liew KB, Chew YL, Chua AL, Lee SK. A review on mechanistic actions of epigallocatechin-3-gallate in targeting the ominous octet of type 2 diabetes mellitus. J Integr Med. 2025; 23(4): 344-356.
Diabetes Mellitus, Type 2/physiopathology* ; Humans ; Catechin/therapeutic use* ; Hypoglycemic Agents/therapeutic use* ; Animals ; Insulin Resistance

2-Methoxy-1,4-naphthoquinone (MNQ) has been shown to cause cytotoxic towards various cancer cell lines. This study is designed to investigate the regulatory effect of MNQ on the key cancer genes in mitogen-activated protein kinase, phosphoinositide 3-kinase, and nuclear factor кB signaling pathways. The expression levels of the genes were compared at different time point using polymerase chain reaction arrays and Ingenuity Pathway Analysis was performed to identify gene networks that are most significant to key cancer genes. A total of 43 differentially expressed genes were identified with 21 up-regulated and 22 down-regulated genes. Up-regulated genes were involved in apoptosis, cell cycle and act as tumor suppressor while down-regulated genes were involved in anti-apoptosis, angiogenesis, cell cycle and act as transcription factor as well as proto-oncogenes. MNQ exhibited multiple regulatory effects on the cancer key genes that targeting at cell proliferation, cell differentiation, cell transformation, apoptosis, reduce inflammatory responses, inhibits angiogenesis and metastasis.

Objective: To explore the anti-cancer activity of maslinic acid against colorectal cancer (CRC) cell lines and its possible mechanism. Methods: The inhibitory effect of maslinic acid was screened against five CRC cell lines (HT-29, HCT 116, SW480, SW48, and LS 174T) via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle analyses were carried out using annexin V-FITC/propidium iodide staining and propidium iodide staining, respectively and subjected to fluorescence-activated cell sorting analysis. Protein expression studies of inhibitor of κB kinase-β (IKK-β), checkpoint kinase 1 (Chk1) and cyclin D1 were conducted using the JESS system. Results: Maslinic acid exhibited growth inhibitory effect in a doseand time-dependent manner in HT-29 and HCT 116 cell lines. A more prominent apoptosis induced by maslinic acid was observed in HCT 116 cell line. However, in HT-29 cell line, maslinic acid induced cell cycle arrest by inhibiting the G1-S transition, which was accompanied by the downregulation of cyclin D1. The expression of unphosphorylated IKK-β protein was increased in both (HT-29 and HCT 116) cell lines after maslinic acid treatment. Conclusions: Maslinic acid inhibits the growth of HT-29 and HCT 116 cells in a different manner, induces cell cycle arrest in HT-29 cells and causes apoptosis in HCT 116 cells partially via NF-κB pathway inhibition.