ACE Reduces Metabolic Abnormalities in a High-Fat Diet Mouse Model

Abstract

The medicinal plants Artemisia iwayomogi (A. iwayomogi) and Curcuma longa (C. longa) radix have been used to treat metabolic abnormalities in traditional Korean medicine and traditional Chinese medicine (TKM and TCM). In this study we evaluated the effect of the water extract of a mixture of A. iwayomogi and C. longa (ACE) on high-fat diet-induced metabolic syndrome in a mouse model. Four groups of C57BL/6N male mice (except for the naive group) were fed a high-fat diet freely for 10 weeks. Among these, three groups (except the control group) were administered a high-fat diet supplemented with ACE (100 or 200 mg/kg) or curcumin (50 mg/kg). Body weight, accumulation of adipose tissues in abdomen and size of adipocytes, serum lipid profiles, hepatic steatosis, and oxidative stress markers were analyzed. ACE significantly reduced the body and peritoneal adipose tissue weights, serum lipid profiles (total cholesterol and triglycerides), glucose levels, hepatic lipid accumulation, and oxidative stress markers. ACE normalized lipid synthesis-associated gene expressions (peroxisome proliferator-activated receptor gamma, PPARγ; fatty acid synthase, FAS; sterol regulatory element-binding transcription factor-1c, SREBP-1c; and peroxisome proliferator-activated receptor alpha, PPARα). The results from this study suggest that ACE has the pharmaceutical potential reducing the metabolic abnormalities in an animal model.

Figure 1

Fingerprint analysis of ACE using high-performance thin-layer chromatography (HP-TLC). ACE and its two major components were analyzed using HP-TLC and compared with reference compounds. Scopoletin (SCL, 0.1 μg/μL (a)), Artemisia iwayomogi (AI, 10 μg/μL (a)), curcumin (CUR, 0.1 μg/μL (b)), Curcuma longa radix (CL, 10 μg/μL (b)), and ACE (10 μg/μL ((a) and (b))) were applied to prewashed silica gel 60 F254 TLC plates and then separated in the mobile phase (chloroform : ethyl acetate : methanol : water = 17 : 46 : 25 : 12). The migrated components were visualized under UV light at 254 nm (left) or 366 nm (right).

Figure 2

Histological findings of adipose tissues. Epididymal and retroperitoneal tissues were evaluated using hematoxylin and eosin (H&E) staining. All photographs are at ×200 magnification. Cell sizes of adipose tissues were quantified using computer image analysis. ^## P < 0.01 compared with naive group; ^∗ P < 0.05, ^∗∗ P < 0.01 compared with control group.

Figure 3

Histopathological findings and lipid profiles of liver tissue. (a) Hepatic tissues were evaluated using hematoxylin and eosin (H&E) staining (upper) and immunohistochemistry for 4-HNE (bottom). All photos are at ×200 magnification. Determination of hepatic cholesterol (b) and triglyceride (c) was performed. Data are expressed as mean ± standard deviation (SD). ^## P < 0.01 compared with naive group; ^∗ P < 0.05, ^∗∗ P < 0.01 compared with control group.

Figure 4

Gene expression levels in liver. Hepatic mRNA expression levels of FAS, PPAR-γ, SREBP-1c, and PPAR-α were determined using real-time polymerase chain reaction (qPCR). Data are expressed as average ± standard deviation (SD; fold change relative to naive group). ^## P < 0.01 compared with naive group; ^∗ P < 0.05, ^∗∗ P < 0.01 compared with control group.