Comparative Analysis of γ-Cyclodextrin, Perilla Oil, and Their Inclusion Complexes on Liver Injury and Dyslipidemia Associated with Elevated Gastrointestinal 12-Hydroxylated Bile Acid Levels

Abstract

Our previous study demonstrated that γ-cyclodextrin (γ-CD)-perilla oil inclusion complexes increase plasma α-linolenic acid and eicosapentaenoic acid levels in healthy rats without adverse effects. The present study examined the effects of perilla oil, γ-CD, and their inclusion complexes on rats fed cholic acid (CA) to mimic the elevated gastrointestinal 12-hydroxylated (12OH) bile acid levels in high-fat diet-fed rats. Rats fed CA (CA group) tended to have higher AST, ALT, plasma total cholesterol (T-CHO), and triglyceride (TG) levels compared to controls fed a standard diet without CA. Rats fed CA and perilla oil (CA+LP group) showed a tendency for lower AST and plasma TG levels than those in the CA group. Rats fed CA and γ-CD (CA+CD group) had significantly higher AST, ALT, plasma T-CHO, and TG levels than the controls, indicating severe liver injury and dyslipidemia. Rats fed CA and the γ-CD-perilla oil inclusion complex (CA+IC group) had significantly lower AST and ALT levels than the CA+CD rats, with a trend towards lower plasma T-CHO and TG levels. Plasma α-linolenic acid and eicosapentaenoic acid levels were significantly higher in the CA+LP and CA+IC groups than in the controls and CA+CD groups. However, the CA+IC group tended to have lower α-linolenic acid levels and significantly lower eicosapentaenoic acid levels than the CA+LP group. This suggests an accelerated conversion of α-linolenic acid to eicosapentaenoic acid in the CA+IC group, which may contribute to the attenuation of liver injury and dyslipidemia. These findings suggest that γ-CD may exacerbate liver injury and dyslipidemia caused by elevated gastrointestinal 12OH bile acid levels, whereas γ-CD-perilla oil inclusion complexes may ameliorate these effects by altering fatty acid metabolism. Furthermore, we recommend evaluating γ-CD safety in both healthy and pathological models and carefully selecting compounds co-ingested with γ-CD.

Keywords: 12-hydroxylated bile acids; Perilla oil; cholic acid; dyslipidemia; eicosapentaenoic acid; fatty acid; inclusion complex; liver injury; α-linolenic acid; γ-cyclodextrin.

Figure 1

General observations of test animals. (A) Food consumption, (B) body weight gain, (C) relative epididymal fat weight to body weight, and (D) relative liver weight to body weight in the five feeding groups. Mean values are significantly different (p < 0.05) for groups with different letters.

Figure 2

Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). (A) AST and (B) ALT of 5 feeding groups. Mean values are significantly different (p < 0.05) for groups with different letters.

Figure 3

Plasma levels of total cholesterol (T-CHO), triglycerides (TG), and glucose (Glu). (A) T-CHO, (B) TG, and (C) Glu in five feeding groups. Mean values are significantly different (p < 0.05) for groups with different letters.