There is still no approved drug to treat nonalcoholic fatty liver disease (NAFLD), even though enormous research has highlighted its protective effects. Therefore, this study aimed to determine whether Panax ginseng can protect against nonalcoholic fatty liver disease (NAFLD) in preclinical studies.

In recent years, intrahepatic and extrahepatic mechanisms have contributed to the development of NAFLD (e.g., inflammation, oxidative stress, mitochondrial dysfunction, ER stress). However, even though numerous clinical trials are underway, there is still no approved drug for NAFLD due to the heterogeneous nature of the disease pathogenesis.

The most common chronic liver disease, nonalcoholic fatty liver disease (NAFLD), develops into a continuum of hepatic dysfunction ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), resulting in fibrosis and hepatocellular carcinoma (HCC).

As a description of NASH pathogenesis in 1988, Day and James proposed the “two-hit” theory. According to this theory, intrahepatic triglyceride accumulation is the liver’s first hit, making it more vulnerable to damage from “second hits, ” such as inflammation, oxidative stress, and mitochondrial dysfunction.

As a result, NAFLD is highly related to metabolic syndromes, such as obesity, insulin resistance, type 2 diabetes, and dyslipidemia. NAFLD incidence has increased worldwide as a result of the COVID-19 pandemic and obesity epidemic, however. 

However, there is no approved drug to treat the disease, and lifestyle interventions are the first line of therapy. There is, therefore, an urgent need for a drug that can address the different pathogenic mechanisms associated with NAFLD.

Panax ginseng is one of the world’s oldest and most famous herbal medicines. Panax ginseng contains approximately 300 substances, including ginsenosides, polysaccharides, polyacetylenes, amino acids, and peptides.

Panax ginseng has been shown to have antioxidant, anti-inflammatory, and anti-microbial properties in animal models of liver disease, cardiovascular disease, diabetes mellitus, and neurological disease.

Furthermore, Panax ginseng can be well tolerated for 24 weeks or 12 months in healthy individuals or Sprague Dawley rats, respectively, when administered orally.

As a result of these findings and systematic reviews and meta-analyses, more than 100 clinical trials targeting metabolic syndrome, neurological diseases, and cardiovascular diseases have been registered with Panax ginseng on the WHO international clinical trials registry platform.

Methodolgy & Results

Based on a search of the PubMed, Web of Science, and Cochrane Library databases, 41 studies were identified for this study. In addition, methodological quality was assessed using the risk of bias tool from the Systematic Review Center for Laboratory Animal Experimentation.

Using the standardized mean difference (SMD) with a 95% confidence interval, the random effects model was used to examine the effectiveness or heterogeneity of the treatment, and Egger’s test was used to assess publication bias.

Alanine aminotransferase, aspartate aminotransferase, triglycerides, total cholesterol, low-density lipoprotein, and fasting glucose levels were significantly reduced by Panax ginseng treatment in NAFLD, regardless of animal model or species, while high-density lipoprotein levels were increased.

It is unclear what protective mechanisms Panax ginseng has on NAFLD, but this meta-analysis suggests that it is beneficial intra- and extrahepatic.

There was considerable heterogeneity and publication bias in the included studies, so the results should be interpreted cautiously.

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