Protective Effects of Plum on Liver and Gut Injury in Metabolic Dysfunction-Associated Fatty Liver Disease

Abstract

Metabolic dysfunction-associated fatty liver disease (MASLD), a persistent liver condition associated with metabolic syndrome, is primarily caused by excessive fructose intake and a typical Western diet. Because there is currently only one approved treatment, lifestyle and dietary interventions are crucial. This study assessed the effects of dietary intervention involving freeze-dried plum (FDP), a natural source of antioxidants containing diverse polyphenols. This study aimed to assess its potential as a protective agent against the gut-liver axis and its therapeutic effects on liver injury and gut permeability issues associated with MASLD. We indicate that 10% FDP intake restored gut barrier proteins and reduced serum endotoxin levels in the MASLD mouse models. Additionally, 10% FDP intake significantly reduced hepatic oxidative stress, lipid metabolism, and fibrosis marker levels. Interestingly, FDP intake significantly reduced the levels of inflammatory cytokine tumor necrosis factor-α and markers of liver damage, such as serum alanine aminotransferase/aspartate aminotransferase and hepatic triglycerides. These results highlight that dietary intervention with FDP that acts as a natural antioxidant may be a significant protective and therapeutic agent against liver and gut damage caused by MASLD.

Keywords: freeze-dried plum (FDP); gut damage; liver damage; metabolic dysfunction-associated fatty liver disease (MASLD).

Figure 1

This summary highlights the protective effects of plum against oxidative stress, intestinal permeability, and liver fibrosis induced by diet high in fat, fructose, and cholesterol. The left and right illustrations indicate an increase in these parameters in the metabolic dysfunction-associated fatty liver disease mouse model and a decrease in each parameter owing to the plum diet, respectively. Upward and downward arrows also represent increase and decrease, respectively.

Figure 2

Effect of freeze-dried plum (FDP) diet on body weight, glucose metabolism, and inflammation markers in metabolic dysfunction-associated fatty liver disease (MASLD) mice. (A) Schematic representation to study the effects of plum diet against MASLD mice. (B) The representative body weight. (C) The representative liver weight. (D) Glucose tolerance testing of the area under the curve for MASLD mice. (E) Tumor necrosis factor-alpha levels are measured using enzyme-linked immunosorbent assay. * p < 0.05, between CON and high-fat, -fructose, and -cholesterol (FFC) groups; # p < 0.05, ## p < 0.01 between FFC and FFC + 10% FDP groups. The significance of mean values for each group is determined using Student’s t-test.

Figure 3

Freeze-dried plum (FDP) diet attenuated high-fat, -fructose, and -cholesterol (FFC)-induced liver injury in metabolic dysfunction-associated fatty liver disease mice. (A) Representative hematoxylin and eosin-stained liver sections for CON, FFC, FFC + 10% FDP group, as indicated. The levels of (B) serum alanine aminotransferase, (C) aspartate aminotransferase, and (D) hepatic triglycerides are presented. Immunoblot analyses for (E) oxidative stress markers (cytochrome P450 2E1, inducible nitric oxide synthase, and 3-nitrotyrosine) and (F) apoptosis markers (Bax, cleaved caspase 3, and phosphorylated c-Jun N-terminal kinase) for the indicated groups. Densitometric analysis of immunoblotting for each protein is demonstrated relative to the glyceraldehyde 3-phosphate dehydrogenase loading control. * p < 0.05, ** p < 0.01, and *** p < 0.001 between CON and FFC groups; # p < 0.05, ## p < 0.01, and ### p < 0.001 between FFC and FFC + 10%.

Figure 4

Freeze-dried plum (FDP) diet attenuated high-fat, -fructose, and -cholesterol (FFC)-induced liver fibrosis in metabolic dysfunction-associated fatty liver disease mice. (A) Representative Sirius Red-stained liver sections for CON, FFC, FFC + 10% FDP, as indicated. Immunoblot results for (B–D) various liver lipid metabolism markers (fatty acid synthase, sterol regulatory element-binding protein 1, and peroxisome proliferator-activated receptor gamma) or fibrosis markers (collagen type I alpha [COL/A], Pro-COL/A2, transforming growth factor beta, matrix metalloproteinase 2-, MMP-9, and alpha-smooth muscle actin) for the indicated groups. Densitometric analysis of immunoblotting for each protein is demonstrated relative to the glyceraldehyde 3-phosphate dehydrogenase loading control. * p < 0.05, ** p < 0.01, and *** p < 0.001 between CON and FFC groups; # p < 0.05, ## p < 0.01, between FFC and FFC + 10% FDP groups. The significance of mean values for each group is determined using Student’s t-test.

Figure 5

Freeze-dried plum (FDP) diet prevented high-fat, -fructose, and -cholesterol (FFC)-induced leaky gut in metabolic dysfunction-associated fatty liver disease mice. (A) Representative sections of the small intestine stained with hematoxylin and eosin for CON, FFC, FFC + 10% FDP, as indicated. (B) Serum endotoxin levels. (C) Levels of oxidative stress protein markers (cytochrome P450 2E1, inducible nitric oxide synthase, and 3-nitrotyrosine). (D) Levels of gut tight junction proteins (zonula occludens-1, claudin-4, and occludin) or (E) adherens junction proteins (E-cadherin, β-catenin, and α-tubulin). Densitometric analysis of immunoblotting for each protein is demonstrated relative to the glyceraldehyde 3-phosphate dehydrogenase loading control. * p < 0.05, ** p < 0.01, and *** p < 0.001 between CON and FFC groups; # p < 0.05, ## p < 0.01, and ### p < 0.001 between FFC and FFC + 10% FDP groups. The significance of mean values for each group is determined using Student’s t-test.