This study explored the potential therapeutic effects of epigallocatechin gallate (EGCG) from green tea on non-alcoholic fatty liver disease (NAFLD). The results show that EGCG can alleviate NAFLD symptoms by inhibiting the expression and activity of dipeptidyl peptidase-4 (DPP4), leading to a significant reduction in liver fat content and improvement in liver function. The study provides strong evidence for EGCG as a new adjunctive therapy for NAFLD, with good safety and tolerance, and it is expected to become an ideal treatment option in the future.
Green tea is highly regarded for its distinct fragrance and health benefits. Since ancient times, people have recognized that drinking tea not only refreshes the mind but also offers health benefits such as lowering blood pressure and blood lipids. With the acceleration of modern life and increasing health awareness, people have become more attentive to the active ingredients in natural foods and their potential impact on health.
Recently, a study from China Medical University, through clinical randomized controlled trials, animal model experiments, and in vitro studies, discovered that green tea, rich in epigallocatechin gallate (EGCG), can alleviate the progression of non-alcoholic fatty liver disease (NAFLD). The study, titled Epigallocatechin gallate alleviates non-alcoholic fatty liver disease through the inhibition of the expression and activity of Dipeptide kinase 4, was published in Clinical Nutrition.
Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. Without timely intervention, it can evolve into more severe conditions such as hepatitis, cirrhosis, and even hepatocellular carcinoma. Given the strong correlation between NAFLD and metabolic diseases such as obesity and type 2 diabetes, the prevalence of NAFLD and late-stage liver disease is expected to increase significantly in the coming years, posing a heavy economic and clinical burden on society. Despite this serious situation, effective treatments for NAFLD are currently limited to lifestyle changes, with no specific medications approved for treatment.
In response to this challenge, researchers have focused on a remarkable compound found in nature—epigallocatechin gallate (EGCG), the most abundant polyphenol catechin in green tea. Previous studies have shown that EGCG not only improves liver anti-fat absorption activity but also prevents hepatic lipotoxicity by inhibiting mitochondrial reactive oxygen species-driven ferroptosis. Additionally, it helps prevent liver lipid accumulation and damage while regulating gut immunity. More importantly, dipeptidyl peptidase 4 (DPP4), also known as T-cell surface antigen CD26, plays a crucial role in the development of NAFLD, and EGCG appears to alleviate the symptoms of NAFLD by inhibiting the expression and activity of DPP4.
In this comprehensive study, researchers recruited 20 qualified NAFLD patients, each of whom was asked to take 300 mg of EGCG in gummy form daily for 24 weeks. Ultimately, 15 patients completed the entire treatment course and were evaluated at baseline, week 12, and week 24.
The researchers found that after 12 weeks of intervention, liver fat content did not significantly increase compared to baseline. However, after 24 weeks of EGCG treatment, liver fat content significantly decreased when compared to baseline. Two patients showed complete fatty liver regression at the end of the 24-week treatment, with an overall NAFLD improvement rate of 13.33%.
Figure 1: Changes in study endpoints relative to baseline after 12 and 24 weeks of EGCG treatment
Compared to baseline values, the 15 patients who received EGCG treatment had significantly reduced waist circumference and waist-to-hip ratio. Similarly, the total cholesterol levels of these participants also dropped significantly after 24 weeks. To assess the changes in DPP4 levels and determine whether EGCG could inhibit DPP4, the researchers quantified serum DPP4 levels. They found that, compared to the healthy group, NAFLD patients had significantly elevated DPP4 levels, and EGCG treatment reduced these DPP4 levels, with the most pronounced effect seen after 24 weeks of intervention.
In animal experiments, mice fed a high-fat diet (HFD) and treated with EGCG showed lower liver-to-body weight ratios (LW/BW) and reductions in serum triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and inflammatory factor IL-6 levels, along with a tendency for increased high-density lipoprotein cholesterol (HDL-C) levels. Further analysis revealed that EGCG helped correct metabolic disorders induced by a high-fat diet, including downregulating the expression of lipid synthesis-related gene Fasn and upregulating the expression of lipid oxidation-related genes, thereby improving liver lipid metabolism.
Figure 2: EGCG improves liver weight and metabolic disorders in HFD-induced mice
Next, the researchers examined the effects of EGCG on liver health and fat accumulation in mice fed a high-fat diet (HFD). The results were encouraging: mice treated with EGCG showed a significant reduction in liver steatosis, inflammation, and liver swelling. This suggests that EGCG can help protect the liver from damage caused by a high-fat diet.
More specifically, compared to mice that only consumed a high-fat diet, those that also received EGCG had significantly lower triglyceride (TG) fat content, indicating a reduction in harmful liver fat accumulation. Additionally, the liver function of the EGCG-treated mice improved, as evidenced by decreased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), two enzymes typically released into the bloodstream when the liver is damaged. Their decreased levels suggest that the liver was better protected and less damaged.
Figure 3: EGCG can alleviate liver damage caused by a high-fat diet and reduce hepatic lipid accumulation
Finally, to verify the specific mechanism by which EGCG affects DPP4, the researchers used the human liver cancer cell line HepG2 to establish an NAFLD model. They found that EGCG could indeed reduce intracellular lipid accumulation by inhibiting the expression and enzyme activity of DPP4, thereby improving lipid metabolism. Molecular docking analysis confirmed that EGCG could directly bind to and inhibit DPP4, offering a potential target for the development of new therapeutic strategies.
Figure 4: EGCG can improve lipid accumulation and lipid metabolism in cells by inhibiting the expression and activity of DPP4
In conclusion, this study not only demonstrated the significant potential of EGCG, a naturally occurring compound, in the prevention and treatment of NAFLD but also provided valuable insights into its underlying molecular mechanisms. EGCG is safe and well-tolerated, with no significant side effects, making it a promising adjunctive treatment option. With further research and validation, we may soon witness a simple cup of green tea becoming a secret weapon for protecting health, offering new hope for patients with NAFLD!