Baicalin and its nanoliposomes ameliorates nonalcoholic fatty liver disease via suppression of TLR4 signaling cascade in mice

被引:50
作者
Liu, Jin [1 ,2 ]
Yuan, Yinglin [2 ,3 ]
Gong, Xia [4 ]
Zhang, Liangke [5 ]
Zhou, Qin [6 ]
Wu, Shengwang [3 ]
Zhang, Xue [4 ]
Hu, Jun [2 ]
Kuang, Ge [2 ]
Yin, Xinru [7 ]
Wan, Jingyuan [2 ]
Yuan, Yonghua [1 ]
机构
[1] Chongqing Med Univ, Dept Clin Pharm, Chongqing, Peoples R China
[2] Chongqing Med Univ, Dept Pharmacol, Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing, Peoples R China
[3] Army Med Univ, Xinqiao Hosp, Dept Hematol, Chongqing, Peoples R China
[4] Chongqing Med Univ, Dept Anat, Chongqing, Peoples R China
[5] Chongqing Med Univ, Dept Pharm, Chongqing, Peoples R China
[6] Army Med Ctr PLA, Chongqing, Peoples R China
[7] Army Med Univ, Daping Hosp, Inst Surg Res, Dept Gastroenterol, Chongqing, Peoples R China
基金
中国国家自然科学基金;
关键词
Nonalcoholic fatty liver disease; Baicalin; Nanoliposomes; Inflammation; Toll-like receptor 4; TOLL-LIKE RECEPTORS; OXIDATIVE STRESS; INFLAMMATION; INJURY; PHARMACOKINETICS;
D O I
10.1016/j.intimp.2020.106208
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
As a natural flavonoid compound, baicalin(BA)has been reported to exhibit hepatoprotective and anti-inflammatory properties. However, the characteristic of poor solubility and low bioavailability greatly limits its application. In addition, the effects and underlying mechanisms of BA in nonalcoholic fatty liver disease (NAFLD) remain elusive. In this study, Methionine and choline deficient diet (MCD)-induced NAFLD mice were treated with baicalin or baicalin-loaded nanoliposomes (BA-NL), then hepatic histopathological changes, biochemical parameters and inflammatory molecules were observed. We found that mice in MCD group showed significant increases in plasma transaminase, hepatocyte apoptosis, hepatic lipid accumulation, liver fibrosis, and infiltration of neutrophils and macrophages compared with control group, however, BA and BA-NL markedly attenuated MCD-induced the above changes. Besides, further analysis indicated that BA and BA-NL also inhibited the up-regulation of toll-like receptor 4 (TLR4) signal and the production of inflammatory mediators in MCD mice. Importantly, BA-NL was found to be more effective than baicalin on MCD-induced NAFLD in mice. These data suggested that BA and its nanoliposomes BA-NL could effectively protect mice against MCD-induced NAFLD, which might be mediated through inhibiting TLR4 signaling cascade.
引用
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页数:9
相关论文
共 47 条
[1]  
Ahmad S., 2018, INT J MOL SCI, V19
[2]   Toll-like receptor signalling [J].
Akira, S ;
Takeda, K .
NATURE REVIEWS IMMUNOLOGY, 2004, 4 (07) :499-511
[3]   Innate Immunity and Inflammation in NAFLD/NASH [J].
Arrese, Marco ;
Cabrera, Daniel ;
Kalergis, Alexis M. ;
Feldstein, Ariel E. .
DIGESTIVE DISEASES AND SCIENCES, 2016, 61 (05) :1294-1303
[4]   Burden of liver diseases in the world [J].
Asrani, Sumeet K. ;
Devarbhavi, Harshad ;
Eaton, John ;
Kamath, Patrick S. .
JOURNAL OF HEPATOLOGY, 2019, 70 (01) :151-171
[5]   Kupffer cells in non-alcoholic fatty liver disease: The emerging view [J].
Baffy, Gyoergy .
JOURNAL OF HEPATOLOGY, 2009, 51 (01) :212-223
[6]   The innate immune response during liver inflammation and metabolic disease [J].
Bieghs, Veerie ;
Trautwein, Christian .
TRENDS IN IMMUNOLOGY, 2013, 34 (09) :446-452
[7]   Deficiency in myeloid differentiation factor-2 and toll-like receptor 4 expression attenuates nonalcoholic steatohepatitis and fibrosis in mice [J].
Csak, Timea ;
Velayudham, Arumugam ;
Hritz, Istvan ;
Petrasek, Jan ;
Levin, Ivan ;
Lippai, Dora ;
Catalano, Donna ;
Mandrekar, Pranoti ;
Dolganiuc, Angela ;
Kurt-Jones, Evelyn ;
Szabo, Gyongyi .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2011, 300 (03) :G433-G441
[8]  
Hatamipour M., 2019, ANTICANCER AGENTS ME
[9]   Pharmacokinetics and Bioavailability Enhancement of Baicalin: A Review [J].
Huang, Ting ;
Liu, Yanan ;
Zhang, Chengliang .
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS, 2019, 44 (02) :159-168
[10]   Toll-like receptors and liver disease [J].
Kesar, Vivek ;
Odin, Joseph A. .
LIVER INTERNATIONAL, 2014, 34 (02) :184-196