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

OBJECTIVE

Previous studies have indicated that clinical hypogonadism is common among males with type 2 diabetes mellitus (T2DM). However, the reported prevalence varies due to the diverse diagnostic criteria used in these studies. This study aims to determine the prevalence of clinical hypogonadism among Malaysian T2DM males and their associated factors.

A total of 360 participants who fulfilled the inclusion criteria were included in this study. Their socio-demographic and clinical parameters were documented and a total testosterone level was sampled from a morning fasting serum. Patients with serum total testosterone of 8-12 nmol/L had their serum total testosterone repeated and their symptoms assessed with the Aging Male Symptoms (AMS) scale. Clinical hypogonadism was diagnosed with total testosterone 26.

The prevalence of clinical hypogonadism among Malaysian T2DM males was 17.5% (n = 63), with 55.6% of them having hypogonadotropic hypogonadism. There is a significant association between clinical hypogonadism with waist circumference > 94 cm (p < 0.001), obesity (p < 0.001), hypertension (p = 0.010), coronary artery disease (p = 0.014) and peripheral artery disease (p = 0.022). There is a significant difference in the weight (p = 0.001), BMI (p < 0.001), waist circumference P < 0.001), serum HDL-C levels (p < 0.001), serum triglycerides levels (p = 0.001) and serum TyG index (p < 0.001). Diabetic males with increasing age (adjusted OR = 1.070, 95% CI 1.004-1.146, p = 0.038), presence of coronary artery diseases (adjusted OR = 2.08, 95% CI 1.220-10.219, p = 0.020) and low total testosterone (adjusted OR = 2.451, 95% CI 1.908-3.155, p < 0.001) are at higher risk of developing clinical hypogonadism.

This study is the first in the Asian region to use stricter criteria for diagnosing hypogonadism. Despite these stringent criteria, the prevalence of hypogonadism remains significantly high among Malaysian T2DM males. It is particularly common in diabetic males over 35 years old with coronary artery disease, regardless of A1c control and the duration of diabetes.

Managing a patient with both pituitary hypersecretory and hyposecretory manifestations may be perplexing. We report a 14-year-old female who presented with weight gain, polyuria and polydipsia. Biochemical results were consistent with Cushing disease with central diabetes insipidus. Pituitary magnetic resonance imaging showed right adenoma with stalk thickening. The immunohistochemistry staining of both adenomas was positive for adrenocorticotropic hormone, thyroid stimulating hormone, growth hormone and luteinizing hormone. Postoperatively, the patient developed panhypopituitarism with persistent diabetes insipidus. The coexistence of double adenomas can pose diagnostic and management challenges and is a common cause of surgical failure. Intraoperative evaluation is important in the identification of double or multiple pituitary adenomas in a patient presenting with multiple secretory manifestations.
Pituitary ACTH Hypersecretion ; Cushing disease ; Diabetes Insipidus

Mullerian agenesis or Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH) Type-II is a congenital defect in the Mullerian duct that results in the absence of a uterus in women. The aetiology of this syndrome is unknown and has been considered a sporadic genetic disease. MRKH, together with anorectal anomaly, is an extremely rare condition and has only been reported in a few cases without any information on genetic analysis. This study investigated the mutational profile of a girl diagnosed with MRKH and anorectal anomalies with rectovaginal fistula. The whole exome sequencing (WES) trio-genetic analysis of a 5-year-old Malaysian girl diagnosed with MRKH (having anorectal anomaly with rectovaginal fistula) was performed together with her normal parents, using the Ion AmpliSeq Exome RDY kit (ThermoFisher Scientific, USA). Data were analysed using Torrent Suite v.5.0.4 and annotated using ANNOVAR. Single nucleotide polymorphisms (SNPs) with an allele frequency >0.01 were excluded, and the remaining variants were filtered based on de novo mutations, autosomal recessive, and autosomal recessive genetic traits. Related genes were analysed by biological pathway analysis (g:Profiler) and protein-protein interaction (HIPPIE v.2.3, STRING v.11.5, dan GeneMANIA). A total of 36 mutations were identified, and two of them, the LHX5 (p.P358Q), inherited from the father, and CFTR (p.R1158X), inherited from the mother. There were 28 de-novo mutations from 28 genes. All genes were involved in 27 biological processes that connected with 23 interactions, and are likely to cause MRKH syndrome in this patient.

Introduction: The consumption of sugar-sweetened beverages (SSBs) among young adults in Malaysia has witnessed a notable increase in recent years, giving rise to concerns regarding the potential adverse health effects, including obesity and diabetes. Despite the urgent need for targeted interventions, there is a dearth of research examining the knowledge, attitudes, and practices (KAP) related to SSBs among Malaysian young adults. To address this research gap, the present study aims to assess the level of KAP concerning SSB intake and its associated factors in this specific population. Methods: A cross-sectional study was conducted involving 408 Malaysian young adults aged between 15 and 29 years. Respondents completed an online questionnaire survey, which encompassed the assessment of socio-demographic characteristics and KAP regarding SSB consumption. The collected data were analyzed using IBM’s Statistical Package for the Social Sciences (SPSS) version 22.0. Spearman correlation tests were performed at a significance level of 0.05. Results: The majority of respondents demonstrated moderate knowledge (60%) and practices (60%), while exhibiting a high positive attitude (100%) towards reducing SSB consumption. Significant correlations were observed between knowledge and attitude (p = 0.003, rs = 0.148) and between knowledge and practice (p = 0.005, rs = 0.138). Moreover, the attitude scores were found to be significantly associated with gender (χ2 (1, N = 408) = 10.421, p = 0.001) and locality (χ2 (1, N = 408) = 4.106, p = 0.043), while the practice scores exhibited a significant association with ethnicity (p = 0.006). Conclusion: This study provides valuable insights into the relationship between KAP related to SSB consumption and socio-demographic factors among Malaysian young adults. The findings underscore the importance of utilizing these insights to develop strategic interventions that aim to curtail SSB consumption and promote a healthy lifestyle, ultimately contributing to the reduction of non-communicable diseases. Health authorities are encouraged to capitalize on these findings to design targeted interventions tailored to the unique needs and circumstances of this population.