Natural Compounds for Counteracting Nonalcoholic Fatty Liver Disease (NAFLD): Advantages and Limitations of the Suggested Candidates

Abstract

The booming prevalence of nonalcoholic fatty liver disease (NAFLD) in adults and children will threaten the health system in the upcoming years. The "multiple hit" hypothesis is the currently accepted explanation of the complex etiology and pathophysiology of the disease. Some of the critical pathological events associated with the development of NAFLD are insulin resistance, steatosis, oxidative stress, inflammation, and fibrosis. Hence, attenuating these events may help prevent or delay the progression of NAFLD. Despite an increasing understanding of the mechanisms involved in NAFLD, no approved standard pharmacological treatment is available. The only currently recommended alternative relies on lifestyle modifications, including diet and physical activity. However, the lack of compliance is still hampering this approach. Thus, there is an evident need to characterize new therapeutic alternatives. Studies of food bioactive compounds became an attractive approach to overcome the reticence toward lifestyle changes. The present study aimed to review some of the reported compounds with beneficial properties in NAFLD; namely, coffee (and its components), tormentic acid, verbascoside, and silymarin. We provide details about their protective effects, their mechanism of action in ameliorating the critical pathological events involved in NAFLD, and their clinical applications.

Keywords: NAFLD; NASH; caffeic acid; caffeine; chicoric acid; coffee; silymarin; tormentic acid; verbascoside.

Figure 1

Pathophysiological mechanisms of NAFLD and some critical events counteracted by the compounds. Adipose tissue expansion, insulin resistance, and caloric surplus can lead to free fatty acid accumulation in the liver, which inhibits VLDL synthesis, and thus increases the TG intrahepatic pool. These events, along with impaired with β-oxidation, promote steatosis. Lipotoxic species can then cause oxidative stress, inflammation, and fibrosis. The activation of hepatic stellate cells marks the promotion of NASH fibrosis. Nonhepatic players can also contribute directly or indirectly to NASH progression. Changes in gut microbiota composition can yield toxic microbiota products, or even form a leaky gut to release LPS or bacteria, all of which could contribute to hepatic inflammation. The compounds’ beneficial effects on NAFLD can be attributed to counteracting these critical pathological events and other nonhepatic players. Abbreviations: DAG, diacylglycerol; ECM, extracellular matrix; FFA, free fatty acids; IL-6, interleukin-6; IL-8, interleukin-8; IR, insulin resistance; IGF-1, insulin-like growth factor 1; LPS, lipopolysaccharides; PDGF, platelet-derived growth factor; TLR, toll-like receptor; TGF-β, transforming growth factor beta; TNF-α, tumor necrosis—alpha; VLDL, very-low-density lipoprotein.