Coriandrum sativum L. Leaf Extract Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by Modulating the AMPK Pathway in High Fat-Fed C57BL/6 Mice

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. In recent times, the term NAFLD has been modified to metabolic dysfunction-associated steatotic liver disease (MASLD), reflecting its comprehensive scope encompassing a range of metabolic abnormalities. Coriandrum sativum L. (CS) is a traditional medicine, although the preventive mechanism of CS extracts remains unclear.

Objective: This study evaluated the preventive effects of CS in high-fat diet (HFD)-induced MASLD mice by oral administration of 100 or 200 mg/kg/day of CS extracts for 12 weeks.

Results: The major CS extract compounds were chlorogenic acid, caffeic acid, rutin, and isoquercetin. The administration of CS extract suppressed HFD-induced weight gain, liver weight, and the liver/body weight ratio. It improved the mice's serum biological profiles and suppressed HFD-induced lipid droplet and lipid accumulation by inhibiting lipid accumulation-related gene expression in the liver. It modulated HFD-induced Ampk-Srebp1c pathways and suppressed HFD-induced NF-κB pathway activation in the liver. It regulated inflammation and the AMPK alpha signaling pathway in HFD-fed mice by reducing the accumulation of specific amino acids, leading to the amelioration of fatty liver.

Conclusions: The CS extract prevents HFD-induced MASLD and may help prevent or treat MASLD.

Keywords: Coriandrum sativum L. leaves; inflammation; lipid accumulation; metabolic dysfunction-associated fatty liver disease.

Figure 1

High-performance liquid chromatogram of CS extracts (A) and standard solution mixture (B). CS, Coriandrum sativum.

Figure 2

The effect of CS extract treatment on the body and liver weight and morphological change in the liver of HFD-induced MASLD mice. (A) Body weight change during the 12 weeks (B) Gross appearance of liver tissues (C) Weight gain (D) Food intake (E) Liver weight (F) Liver/body weight ratio. Values represent the mean ± standard error of the mean (SEM) (n = 6–9). # p < 0.05 and ### p < 0.001 vs. ND; * p < 0.05, ** p < 0.01 and *** p < 0.001 vs. HFD. ND: normal diet; HFD: high-fat diet; MASLD: metabolic dysfunction-associated steatotic liver disease; CS: Coriandrum sativum; MT: milk thistle.

Figure 3

The effect of CS extract treatment on the hepatic function of and metabolic parameters in the serum of HFD-induced MASLD mice. (A) Serum ALT (B) Serum AST (C) Serum LDH (D) Serum GLU (E) Serum insulin (F) HOMA-IR. Values represent the mean ± standard error of the mean (SEM) (n = 6–9). ## p < 0.01 and ### p < 0.001 vs. ND; * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. HFD. ND: normal diet; HFD: high-fat diet; MASLD: metabolic dysfunction-associated steatotic liver disease; CS: Coriandrum sativum; MT: milk thistle; ALT: alanine aminotransferase; AST: aspartate aminotransferase; LDH: lactate dehydrogenase; GLU: glucose; HOMA-IR: homeostatic index of insulin resistance.

Figure 4

The effect of CS extract treatment on lipid levels in the serum of HFD-induced MASLD mice. (A) Serum TG (B) Serum TCHO (C) Serum HDL (D) Serum LDL. Values represent the mean ± standard error of the mean (SEM) (n = 6–9). ## p < 0.01 and ### p < 0.001 vs. ND; * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. HFD. ND: normal diet; HFD: high-fat diet; MASLD: metabolic dysfunction-associated steatotic liver disease; CS: Coriandrum sativum; MT: milk thistle; TG: triglycerides; TCHO: total cholesterol; LDL: low-density lipoprotein cholesterol; HDL: high-density lipoprotein cholesterol.

Figure 5

The effect of CS extract treatment on histological alteration in HFD-induced MASLD mice. (A) Representative histological results based on hematoxylin and eosin (H&E) and Oil Red O staining (B) NAFLD acitivity score (C) Oil Red O positive area. Values represent the mean ± standard error of the mean (SEM) (n = 6–9). ### p < 0.001 vs. ND; *** p < 0.001 vs. HFD. ND: normal diet; HFD: high-fat diet; MASLD: metabolic dysfunction-associated steatotic liver disease; CS: Coriandrum sativum; MT: milk thistle; CV: central vein. Scale bar: 50 μm; yellow arrow: balloon cells; red arrow: steatosis; black arrow: inflammation.

Figure 6

The effect of CS extract treatment on lipid metabolism-related mRNA expression in HFD-induced MASLD mice. (A) Mttp: microsomal triglyceride transfer protein (B) ApoB: apolipoprotein B (C) CD36: cluster of differentiation 36 (D) Srebp1c: sterol regulatory element binding protein-1c (E) Fas: fatty acid synthesis (F) Scd1: stearoyl-CoA desaturase 1 (G) Lcn2: lipocalin 2 (H) Col1a1: collagen type1 alpha 1 (I) α-SMA: alpha smooth muscle actin. Values represent the mean ± standard error of the mean (SEM) (n = 6–9). # p < 0.05, ## p < 0.01 and ### p < 0.001 vs. ND; * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. HFD. ND: normal diet; HFD: high-fat diet; MASLD: metabolic dysfunction-associated steatotic liver disease; CS: Coriandrum sativum; MT: milk thistle.

Figure 7

The effect of CS extract treatment on lipid metabolism-related protein levels in HFD-induced MASLD mice. (A) p-AMPKα: phospho-AMP-activated protein kinase alpha (B) Srebp1c: sterol regulatory element binding protein-1c (C) Fas: fatty acid synthase (D) Scd1: stearoyl-CoA desaturase-1. Values represent the mean ± standard error of the mean (SEM) (n = 6–9). ## p < 0.01 and ### p < 0.001 vs. ND; ** p < 0.01 and *** p < 0.001 vs. HFD. ND: normal diet, HFD: high-fat diet, MASLD: metabolic dysfunction-associated steatotic liver disease, CS: Coriandrum sativum, MT: milk thistle.

Figure 8

The effect of CS extract treatment on inflammation-related protein levels in HFD-induced MASLD mice. (A) p-NFκB: phospho-nuclear factor kappa-B, (B) p-IκB: phospho-inhibitor of κB, (C) TNF-α: tumor necrosis factor-α, (D) IL-1β: Interleukin-1β. Values represent the mean ± standard error of the mean (SEM) (n = 6–9). ## p < 0.01 and ### p < 0.001 vs. ND; * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. HFD. ND: normal diet; HFD: high-fat diet; MASLD: metabolic dysfunction-associated steatotic liver disease, CS: Coriandrum sativum, MT: milk thistle.

Figure 9

(A) Heat map analysis of quantitative metabolite levels in mouse liver tissue. (B) Alterations in the fold-changes in each metabolite. The row represents the metabolites, and the column represents the sample. Significantly decreased and significantly increased metabolites are displayed in blue and red, respectively. The brightness of each color is the size of the difference compared to the average value of normal in HFD, and the CS100, CS200, and MT values are the size of the difference compared to the average value of HFD (n = 3). # p < 0.05 and ## p < 0.01 vs. Normal; * p < 0.05, ** p < 0.01, and *** p < 0.001 vs. HFD.