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

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...

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Main Authors: Keisuke Yoshikiyo, Hidehisa Shimizu, Edward G. Nagato, Satoshi Ishizuka, Tatsuyuki Yamamoto
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/2/281
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author Keisuke Yoshikiyo
Hidehisa Shimizu
Edward G. Nagato
Satoshi Ishizuka
Tatsuyuki Yamamoto
author_facet Keisuke Yoshikiyo
Hidehisa Shimizu
Edward G. Nagato
Satoshi Ishizuka
Tatsuyuki Yamamoto
author_sort Keisuke Yoshikiyo
collection DOAJ
description 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.
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spelling doaj-art-79e599b4f105470abaac75fdc7a015b42025-01-24T13:43:24ZengMDPI AGMolecules1420-30492025-01-0130228110.3390/molecules30020281Comparative Analysis of γ-Cyclodextrin, Perilla Oil, and Their Inclusion Complexes on Liver Injury and Dyslipidemia Associated with Elevated Gastrointestinal 12-Hydroxylated Bile Acid LevelsKeisuke Yoshikiyo0Hidehisa Shimizu1Edward G. Nagato2Satoshi Ishizuka3Tatsuyuki Yamamoto4Institute of Agricultural and Life Sciences, Academic Assembly, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Shimane, JapanInstitute of Agricultural and Life Sciences, Academic Assembly, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Shimane, JapanGraduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Shimane, JapanResearch Faculty of Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo 060-8589, Hokkaido, JapanInstitute of Agricultural and Life Sciences, Academic Assembly, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Shimane, JapanOur 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.https://www.mdpi.com/1420-3049/30/2/281Perilla oilγ-cyclodextrininclusion complex12-hydroxylated bile acidscholic acidα-linolenic acid
spellingShingle Keisuke Yoshikiyo
Hidehisa Shimizu
Edward G. Nagato
Satoshi Ishizuka
Tatsuyuki Yamamoto
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
Molecules
Perilla oil
γ-cyclodextrin
inclusion complex
12-hydroxylated bile acids
cholic acid
α-linolenic acid
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Perilla oil
γ-cyclodextrin
inclusion complex
12-hydroxylated bile acids
cholic acid
α-linolenic acid
url https://www.mdpi.com/1420-3049/30/2/281
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