Benefits of Combining Sonchus brachyotus DC. Extracts and Synbiotics in Alleviating Non-Alcoholic Fatty Liver Disease

Abstract

Non-alcoholic fatty liver disease, commonly abbreviated to NAFLD, is a pervasive ailment within the digestive system, exhibiting a rising prevalence, and impacting individuals at increasingly younger ages. Those afflicted by NAFLD face a heightened vulnerability to the onset of profound liver fibrosis, cardiovascular complications, and malignancies. Currently, NAFLD poses a significant threat to human health, and there is no approved therapeutic treatment for it. Recent studies have shown that synbiotics, which regulate intestinal microecology, can positively impact glucolipid metabolism, and improve NAFLD-related indicators. Sonchus brachyotus DC., a Chinese herb, exhibits hepatoprotective and potent antioxidant properties, suggesting its potential therapeutic use in NAFLD. Our preclinical animal model investigation suggests that the synergy between Sonchus brachyotus DC. extracts and synbiotics is significantly more effective in preventing and treating NAFLD, compared to the isolated use of either component. As a result, this combination holds the potential to introduce a fresh and encouraging therapeutic approach to addressing NAFLD.

Keywords: NAFLD; Sonchus brachyotus DC. extracts; gut microbiota; synbiotics.

Figure 1

The second-hit pathogenesis of NAFLD. A genetic predisposition coupled with an unhealthy diet leads to an excessive accumulation of fatty acids in the liver. Concurrently, the heightened insulin resistance in the adipose tissue initiates an inflammatory response, prompting the release of adipocytokines. These cytokines activate hepatic stellate cells, initiating a cascade that culminates in hepatic fibrosis and fatty liver, constituting the “first hit”. Subsequently, this sets the stage for persistent hepatocyte damage, stress responses, and hepatocyte apoptosis, collectively manifesting as liver hepatitis, or the “second hit”.

Figure 2

Gut microbiota and NAFLD. Obesity or a high-fat diet can trigger an imbalance in the intestinal microecology, and disrupt the function of the intestinal barrier. This disruption allows pathogenic bacteria and harmful metabolites to migrate to the liver. Consequently, this can lead to apoptosis in the liver parenchymal cells, and the activation of non-parenchymal immune cells within the liver. These cascading effects ultimately give rise to liver lesions and the progression of NAFLD.

Figure 3

Effects of a synbiotic and SBE compound on NAFLD. After administration in mice, the changes in (A) body weight, (B) fasting blood glucose (FBG), (C) serum insulin concentration (INS), (D) total cholesterol (TC), (E) triglycerides (TG), and (F) alanine aminotransferase are shown. The representative results from three independent experiments are included. NS, no significance; * p < 0.05; ** p < 0.01. n = 3 biological replicates/group; one-way ANOVA. All analyses were performed using the GraphPad Prism 8 software (Version 8.0.2; GraphPad Software, Inc., San Diego, CA, USA).

Figure 4

The potential mechanisms of synbiotics in NAFLD. The therapeutic impacts of synbiotics on NAFLD encompass three key aspects. Firstly, the catabolism of prebiotics results in the generation of SCFAs. These SCFAs enter hepatocytes via the MCP1 transporter and, subsequently, bind to PPAR, effectively inhibiting leptin signaling. Secondly, the catabolism of prebiotics yields active acidic substances (such as H₂O₂ and SCFAs), along with antibacterial agents (including bacteriocin and bacteriophages). This dual action serves to impede the proliferation of detrimental bacteria. Lastly, the influence of probiotics is manifested in their ability to enhance the maintenance of the intestinal barrier integrity. This is achieved through mechanisms involving the TLR- or DN-SIGN-mediated regulation of tight junctions. DC-SIGN, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin; IECs, intestinal epithelial cells; MCP1, monocyte chemoattractant protein 1; SCFAs, short-chain fatty acids; TLR, toll-like receptor.