Quercetin: A Promising Candidate for the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a chronic liver disease. The development of MASLD is influenced by a multitude of diseases associated with modern lifestyles, including but not limited to diabetes mellitus, hypertension, hyperlipidaemia and obesity. These conditions are often consequences of the adoption of unhealthy habits, namely a sedentary lifestyle, a lack of physical activity, poor dietary choices and excessive alcohol consumption. The treatment of MASLD is primarily based on modifying the patient's lifestyle and pharmacological intervention. Despite the absence of FDA-approved pharmacological agents for the treatment of MASLD, several potential therapeutic modalities have demonstrated efficacy in reversing the histopathological features of the disease. Among the botanical ingredients belonging to the flavonoid group is quercetin (QE). QE has been demonstrated to possess a number of beneficial physiological effects, including anti-inflammatory, anticancer and antifungal properties. Additionally, it functions as a natural antioxidant. Preclinical evidence indicates that QE may play a beneficial role in reducing liver damage and improving metabolic health. Early human studies also suggest that QE may be an effective treatment for MASLD due to its antioxidant, anti-inflammatory, and lipid-regulating properties. This review aims to summarize the available information on the therapeutic effects of QE in MASLD.

Keywords: antioxidants; functional food; metabolic dysfunction-associated steatotic liver disease (MASLD); nutraceuticals; oxidative stress; polyphenols; quercetin.

Figure 1

Chemical formula of quercetin.

Figure 2

Bidirectional relationship between MetS and MASLD. Abbreviations: HDL—high-density lipoproteins, HT—hypertension, MASLD—metabolic dysfunction-associated steatotic liver disease, MetS—metabolic syndrome, TG—triglycerides, T2DM—type 2 diabetes mellitus, WC—waist circumference.

Figure 3

Molecular mechanisms of quercetin action in MASLD. For further explanations please see text below. All of the abbreviations are listed in the end of manuscript.

Figure 4

Scheme of the mechanism of action of dietary polyphenols in the treatment of MASLD using quercetin as the example. Polyphenols attenuate MASLD by many pathways to inhibit mitochondrial malfunction and/or reduce the lipid accumulation. By maintaining proper Firmicutes to Bacterioidetes ratio, the correct ratio of SCFAs is preserved. SCFAs transported to the liver by the portal vein in appropriate amounts have beneficial effects on MASLD. Adopted and modified from the figures by Yang et al. 2022 [99]. Abbreviations: AMPK—AMP-activated protein kinase, MASLD—metabolic dysfunction-associated steatotic liver disease, SCFA—short-chain fatty acid.