Dietary Ursolic Acid Prevents Alcohol-Induced Liver Injury via Gut-Liver Axis Homeostasis Modulation: The Key Role of Microbiome Manipulation

被引：22

作者：

Yan, Xin ^{[1
,2
]}

Ren, Xueyang ^{[1
,2
]}

Liu, Xiaoyun ^{[1
,2
]}

Wang, Yu ^{[1
,2
]}

Ma, Jiamu ^{[1
,2
]}

Song, Ruolan ^{[1
,2
]}

Wang, Xiuhuan ^{[1
,2
]}

Dong, Ying ^{[1
,2
]}

Fan, Qiqi ^{[1
,2
]}

Wei, Jing ^{[1
,2
]}

Yu, Axiang ^{[1
,2
]}

She, Gaimei ^{[1
,2
]}

机构：

[1] Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing 102488, Peoples R China

[2] Beijing Univ Chinese Med, Beijing Key Lab Qual Evaluat Chinese Mat Med, Beijing 102488, Peoples R China

来源：

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY | 2021年 / 69卷 / 25期

关键词：

ursolic acid; hepatoprotective effect; alcoholic liver injury; gut-liver axis; gut microbiota manipulation; OXIDATIVE STRESS; INTESTINAL BARRIER; ETHANOL; INFLAMMATION; CONSUMPTION; DISRUPTION; ACTIVATION; MONOLAYERS; INTEGRITY; PATHWAYS;

D O I：

10.1021/acs.jafc.1c02362

中图分类号：

S [农业科学];

学科分类号：

09 ;

摘要：

Ursolic acid (UA), a natural triterpenoid widely distributed within fruits and edible plants, has been proven to relieve alcoholic liver disease (ALD). However, the mechanisms involved largely remain unclear. This study investigated whether the beneficial effects of UA on ALD could be related to gut-liver axis (GLA) modulation. Special attention was paid to the contribution of gut microbiome manipulation. UA ameliorated intestinal oxidative stress and barrier dysfunction induced by alcohol. As a consequence of gut leakiness amelioration, the related endotoxemia-mediated liver toll-like receptor 4 pathway induction and the subsequent reactive oxygen species overproduction were reverted. UA also counteracted alcohol-induced gut dysbiosis. A fecal microbiota transplantation study indicated that liver injury as well as ileum oxidative stress and gut barrier dysfunction of recipient mice were partly ameliorated as a result of microbiome remodeling. These results suggest that dietary UA alleviates ALD through GLA homeostasis modulation. Gut microbiome manipulation contributes to the hepatoprotective activity and GLA modulating effect of UA.

引用

页码：7074 / 7083

页数：10

共 48 条

[1] Epidemiology of Alcohol Consumption and Societal Burden of Alcoholism and Alcoholic Liver Disease [J].

Axley, Page D. ;

Richardson, Crit Taylor ;

Singal, Ashwani K. .

CLINICS IN LIVER DISEASE, 2019, 23 (01) :39-+

[2] Alcohol, liver disease and the gut microbiota [J].

Bajaj, Jasmohan S. .

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2019, 16 (04) :235-246

[3] Evidence that nuclear factor-κB activation is critical in oxidant-induced disruption of the microtubule cytoskeleton and barrier integrity and that its inactivation is essential in epidermal growth factor-mediated protection of the monolayers of intestinal epithelia [J].

Banan, A ;

Farhadi, A ;

Fields, JZ ;

Mutlu, E ;

Zhang, L ;

Keshavarzian, A .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 306 (01) :13-28

[4]

Banan A, 1999, J PHARMACOL EXP THER, V291, P1075

[5]

Banan A, 2000, J PHARMACOL EXP THER, V294, P997

[6] Intestinal permeability - a new target for disease prevention and therapy [J].

Bischoff, Stephan C. ;

Barbara, Giovanni ;

Buurman, Wim ;

Ockhuizen, Theo ;

Schulzke, Joerg-Dieter ;

Serino, Matteo ;

Tilg, Herbert ;

Watson, Alastair ;

Wells, Jerry M. .

BMC GASTROENTEROLOGY, 2014, 14

[7] Metagenomic Analyses of Alcohol Induced Pathogenic Alterations in the Intestinal Microbiome and the Effect of Lactobacillus rhamnosus GG Treatment [J].

Bull-Otterson, Lara ;

Feng, Wenke ;

Kirpich, Irina ;

Wang, Yuhua ;

Qin, Xiang ;

Liu, Yanlong ;

Gobejishvili, Leila ;

Joshi-Barve, Swati ;

Ayvaz, Tulin ;

Petrosino, Joseph ;

Kong, Maiying ;

Barker, David ;

McClain, Craig ;

Barve, Shirish .

PLOS ONE, 2013, 8 (01)

[8] A simple GC-MS method for the screening of betulinic, corosolic, maslinic, oleanolic and ursolic acid contents in commercial botanicals used as food supplement ingredients [J].

Caligiani, Augusta ;

Malavasi, Giulia ;

Palla, Gerardo ;

Marseglia, Angela ;

Tognolini, Massimiliano ;

Bruni, Renato .

FOOD CHEMISTRY, 2013, 136 (02) :735-741

[9] Microbiota, a key player in alcoholic liver disease [J].

Cassard, Anne-Marie ;

Ciocan, Dragos .

CLINICAL AND MOLECULAR HEPATOLOGY, 2018, 24 (02) :100-107

[10]

Chen SY, 2018, FASEB J, V32, P1139, DOI [10.1096/fj.201700741RR, 10.1096/fj.201700741rr]

← 1 2 3 4 5 →