Reshaping the gut microbiome and bile acid composition by Gyejibongnyeong-hwan ameliorates western diet-induced dyslipidemia

Gyejibongnyeong-hwan (GBH), a traditional Chinese medicine, is used in clinical practice to treat blood stasis in metabolic diseases. Herein, we examined the effects of GBH on dyslipidemia and investigated the underlying mechanisms by focusing on modulation of the gut microbiota-bile acid axis by GB...

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Main Authors: So Min Lee, You Mee Ahn, Seong-Hwan Park, Sarah Shin, Jeeyoun Jung
Format: Article
Language:English
Published: Elsevier 2023-07-01
Series:Biomedicine & Pharmacotherapy
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0753332223006169
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author So Min Lee
You Mee Ahn
Seong-Hwan Park
Sarah Shin
Jeeyoun Jung
author_facet So Min Lee
You Mee Ahn
Seong-Hwan Park
Sarah Shin
Jeeyoun Jung
author_sort So Min Lee
collection DOAJ
description Gyejibongnyeong-hwan (GBH), a traditional Chinese medicine, is used in clinical practice to treat blood stasis in metabolic diseases. Herein, we examined the effects of GBH on dyslipidemia and investigated the underlying mechanisms by focusing on modulation of the gut microbiota-bile acid axis by GBH. We utilized a Western diet-induced dyslipidemia mouse model and divided animals into the following four groups (n = 5 each): the normal chow diet, vehicle control (WD), simvastatin (Sim, 10 mg/kg/day simvastatin; positive control), and GBH (GBH, 300 mg/kg/day) groups. The drugs were administered for 10 weeks, and morphological changes in the liver and aorta were analyzed. The mRNA expression of genes related to cholesterol metabolism, gut microbiota, and bile acid profiles were also evaluated. The GBH group showed significantly lower levels of total cholesterol, accumulation of lipids, and inflammatory markers in the liver and aorta of Western diet-fed mice. Low-density lipoprotein cholesterol levels were significantly lower in the GBH group than in the WD group (P < 0.001). The expression of cholesterol excretion-associated genes such as liver X receptor alpha and ATP-binding cassette subfamily G member 8, as well as the bile acid synthesis gene cholesterol 7 alpha-hydroxylase, which lowers cholesterol in circulation, was increased. Furthermore, GBH inhibited the intestinal farnesoid X receptor (FXR)-fibroblast growth factor 15 signaling pathway through the interactions of gut microbiota with bile acids acting as FXR ligands, which included chenodeoxycholic acid and lithocholic acid. Overall, GBH improved dyslipidemia induced by a Western diet by modulating the gut microbiota-bile acid axis.
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spelling doaj.art-07735d8388ba494e92c111f8f5def2b92023-05-23T04:21:13ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-07-01163114826Reshaping the gut microbiome and bile acid composition by Gyejibongnyeong-hwan ameliorates western diet-induced dyslipidemiaSo Min Lee0You Mee Ahn1Seong-Hwan Park2Sarah Shin3Jeeyoun Jung4KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of KoreaKM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of KoreaKM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of KoreaKM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of KoreaKM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Republic of Korea; Correspondence to: KM Science Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-Gu, Daejeon 34054, Republic of Korea.Gyejibongnyeong-hwan (GBH), a traditional Chinese medicine, is used in clinical practice to treat blood stasis in metabolic diseases. Herein, we examined the effects of GBH on dyslipidemia and investigated the underlying mechanisms by focusing on modulation of the gut microbiota-bile acid axis by GBH. We utilized a Western diet-induced dyslipidemia mouse model and divided animals into the following four groups (n = 5 each): the normal chow diet, vehicle control (WD), simvastatin (Sim, 10 mg/kg/day simvastatin; positive control), and GBH (GBH, 300 mg/kg/day) groups. The drugs were administered for 10 weeks, and morphological changes in the liver and aorta were analyzed. The mRNA expression of genes related to cholesterol metabolism, gut microbiota, and bile acid profiles were also evaluated. The GBH group showed significantly lower levels of total cholesterol, accumulation of lipids, and inflammatory markers in the liver and aorta of Western diet-fed mice. Low-density lipoprotein cholesterol levels were significantly lower in the GBH group than in the WD group (P < 0.001). The expression of cholesterol excretion-associated genes such as liver X receptor alpha and ATP-binding cassette subfamily G member 8, as well as the bile acid synthesis gene cholesterol 7 alpha-hydroxylase, which lowers cholesterol in circulation, was increased. Furthermore, GBH inhibited the intestinal farnesoid X receptor (FXR)-fibroblast growth factor 15 signaling pathway through the interactions of gut microbiota with bile acids acting as FXR ligands, which included chenodeoxycholic acid and lithocholic acid. Overall, GBH improved dyslipidemia induced by a Western diet by modulating the gut microbiota-bile acid axis.http://www.sciencedirect.com/science/article/pii/S0753332223006169DyslipidemiaHypercholesterolemiaGut microbiomeBile acidFXR-FGF15 signalGyejibongnyeong-hwan (GBH)
spellingShingle So Min Lee
You Mee Ahn
Seong-Hwan Park
Sarah Shin
Jeeyoun Jung
Reshaping the gut microbiome and bile acid composition by Gyejibongnyeong-hwan ameliorates western diet-induced dyslipidemia
Biomedicine & Pharmacotherapy
Dyslipidemia
Hypercholesterolemia
Gut microbiome
Bile acid
FXR-FGF15 signal
Gyejibongnyeong-hwan (GBH)
title Reshaping the gut microbiome and bile acid composition by Gyejibongnyeong-hwan ameliorates western diet-induced dyslipidemia
title_full Reshaping the gut microbiome and bile acid composition by Gyejibongnyeong-hwan ameliorates western diet-induced dyslipidemia
title_fullStr Reshaping the gut microbiome and bile acid composition by Gyejibongnyeong-hwan ameliorates western diet-induced dyslipidemia
title_full_unstemmed Reshaping the gut microbiome and bile acid composition by Gyejibongnyeong-hwan ameliorates western diet-induced dyslipidemia
title_short Reshaping the gut microbiome and bile acid composition by Gyejibongnyeong-hwan ameliorates western diet-induced dyslipidemia
title_sort reshaping the gut microbiome and bile acid composition by gyejibongnyeong hwan ameliorates western diet induced dyslipidemia
topic Dyslipidemia
Hypercholesterolemia
Gut microbiome
Bile acid
FXR-FGF15 signal
Gyejibongnyeong-hwan (GBH)
url http://www.sciencedirect.com/science/article/pii/S0753332223006169
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