Plant-Based Foods and Their Bioactive Compounds on Fatty Liver Disease: Effects, Mechanisms, and Clinical Application

Abstract

Fatty liver disease (FLD), including nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD), is a serious chronic metabolic disease that affects a wide range of people. Lipid accumulation accompanied by oxidative stress and inflammation in the liver is the most important pathogenesis of FLD. The plant-based, high-fiber, and low-fat diet has been recommended to manage FLD for a long time. This review discusses the current state of the art into the effects, mechanisms, and clinical application of plant-based foods in NAFLD and AFLD, with highlighting related molecular mechanisms. Epidemiological evidence revealed that the consumption of several plant-based foods was beneficial to alleviating FLD. Further experimental studies found out that fruits, spices, teas, coffee, and other plants, as well as their bioactive compounds, such as resveratrol, anthocyanin, curcumin, and tea polyphenols, could alleviate FLD by ameliorating hepatic steatosis, oxidative stress, inflammation, gut dysbiosis, and apoptosis, as well as regulating autophagy and ethanol metabolism. More importantly, clinical trials confirmed the beneficial effects of plant-based foods on patients with fatty liver. However, several issues need to be further studied especially the safety and effective doses of plant-based foods and their bioactive compounds. Overall, certain plant-based foods are promising natural sources of bioactive compounds to prevent and alleviate fatty liver disease.

Figure 1

Bioactive compounds from plant-based foods relevant to FLD.

Figure 2

The molecular mechanisms of plant-based foods in the alleviation of NAFLD. The major molecular mechanisms include the alleviation of hepatic steatosis, oxidative stress, inflammation, gut dysbiosis, and the regulation of autophagy. To be specific, fruits, spices, and teas alleviated hepatic steatosis by activating AMPK, PPAR-α, SIRT1, and FXR and inhibiting PPAR-γ pathways. Besides, the antioxidative stress property of such plants was mainly associated with the activation of the Nrf2 pathway. Moreover, plant-based foods could alleviate inflammation by activating SIRT1, while inhibiting NF-κB pathways. Furthermore, these plants alleviated gut dysbiosis by regulating the abundance of Akkermansia, Bacteroides, Firmicutes, and Lactobacillus. Also, such plants could regulate autophagy by inhibiting the Akt pathway and reducing the production of autophagic biomarkers. Akt: protein kinase B; AMPK: adenosine 5′-monophosphate-activated protein kinase; ARE: Nrf2-antioxidant response element; CYP2E1: cytochrome P450 2E1; FAS: fatty acid synthase; FXR: farnesoid X receptor; IL-1β/6/8: interleukin-1β/6/8; LXRα: liver X receptor α; mTOR: mammalian target rapamycin; NF-κB: nuclear factor kappa-B; Nrf2: nuclear factor erythroid 2-related factor 2; PGC-1α: peroxisomal proliferator-activated receptor-gamma coactivator-1α; PKA: protein kinase A; PPAR-α/γ: peroxisome proliferator-activated receptor-α/γ; ROS: reactive oxygen species; SIRT1: sirtuin 1; SOD: superoxide dismutase; SREBP-1c: sterol regulatory element-binding transcription factor 1c; TNF-α: tumor necrosis factor-α.

Figure 3

The molecular mechanisms of plant-based foods in the alleviation of AFLD. The major molecular mechanisms include the promotion of ethanol metabolism and inhibition of apoptosis, hepatic steatosis, oxidative stress, inflammation, and gut dysbiosis. First of all, plant-based foods accelerated ethanol metabolism by increasing the activities of ALD and ALDH. Also, these plants inhibited apoptosis by activating the SIRT1 pathway. Moreover, they could alleviate hepatic steatosis by activating the AMPK-PPAR-α pathway and regulating lipid homeostasis-related genes (like HNF4A and PTP1B). Furthermore, the antioxidative effect of such plants was related to the upregulation of the Nrf2 pathway. Besides, edible plants ameliorated inflammation by inhibiting TLR4 and NF-κB pathways. Additionally, these plants attenuated gut dysbiosis by regulating the abundance of Bacteroides and Firmicutes. AMPK: adenosine 5′-monophosphate-activated protein kinase; ARE: Nrf2-antioxidant response element; CPT-1: carnitine palmitoyltransferase 1; CYP2E1: cytochrome P450 2E1; FAS: fatty acid synthase; IL-1β/6/8: interleukin-1β/6/8; NF-κB: nuclear factor kappa-B; Nrf2: nuclear factor erythroid 2-related factor 2; PPAR-α: peroxisome proliferator-activated receptor-α; ROS: reactive oxygen species; SOD: superoxide dismutase; SREBP-1c: sterol regulatory element-binding transcription factor 1c; TNF-α: tumor necrosis factor-α.