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Published in: Journal of Natural Medicines 3/2018

01-06-2018 | Original Paper

Scutellaria baicalensis regulates FFA metabolism to ameliorate NAFLD through the AMPK-mediated SREBP signaling pathway

Authors: Qian Chen, Mengyang Liu, Haiyang Yu, Jian Li, Sijian Wang, Yi Zhang, Feng Qiu, Tao Wang

Published in: Journal of Natural Medicines | Issue 3/2018

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Abstract

Scutellaria baicalensis has been reported to improve the lipid metabolism of high-fat diet-induced liver dysfunction, but direct evidence is rare. This study aimed to explore the effects and mechanisms of S. baicalensis and its major constituent baicalin on hepatic lipotoxicity. KK-Ay mice and orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) rats were used to evaluate lipid metabolism regulatory effects. Sodium oleate-induced triglyceride-accumulated HepG2 cells were used for the mechanism study, pretreated with or without compound C or STO-609 or transfected with liver kinase B1 (LKB1) siRNA. In KK-Ay mice, S. baicalensis extract showed a decreased effect on serum and hepatic triglycerides, total cholesterols, and free fatty acid (FFA) levels after 8 weeks of treatment. In OA-induced NAFLD rats, 18 days of treatment with baicalin significantly inhibited hepatic lipid accumulation, attenuating hepatocyte hypertrophy, vacuolization and necrosis. S. baicalensis and baicalin treatment significantly suppressed the sterol regulatory element binding protein-1c (SREBP-1c) transcriptional program with downregulation of gene and protein expression of SREBP-1c (both precursor and mature fraction) and acetyl-CoA carboxylase, fatty acid synthase and stearoyl-CoA desaturase, and upregulation of AMP-activated protein kinase (AMPK), carnitine palmitoyl transferase 1 and nuclear respiratory factor 2 in the liver. Furthermore, activation of AMPK by baicalin was observed to be relative to the increase in phosphorylation of calmodulin-dependent protein kinase kinase. Taken together, S. baicalensis conferred preventive effects against FFA-induced lipotoxicity through the AMPK-mediated SREBP signaling pathway.
Literature
1.
go back to reference Lonardo A, Nascimbeni F, Maurantonio M, Marrazzo A, Rinaldi L, Adinolfi L (2017) Nonalcoholic fatty liver disease: evolving paradigms. World J Gastroenterol 23(36):6571–6592CrossRef Lonardo A, Nascimbeni F, Maurantonio M, Marrazzo A, Rinaldi L, Adinolfi L (2017) Nonalcoholic fatty liver disease: evolving paradigms. World J Gastroenterol 23(36):6571–6592CrossRef
2.
go back to reference Meng G, Zhang B, Yu F, Li C, Zhang Q, Liu L, Wu H, Xia Y, Bao X, Shi H, Su Q, Gu Y, Fang L, Yang H, Yu B, Sun S, Wang X, Zhou M, Jia Q, Jiao H, Wang B, Guo Q, Carvalhoa L, Sun Z, Song K, Yu M, Niu K (2017) Soft drinks consumption is associated with nonalcoholic fatty liver disease independent of metabolic syndrome in Chinese population. Eur J Nutr. https://doi.org/10.1007/s00394-017-1485-0 CrossRefPubMed Meng G, Zhang B, Yu F, Li C, Zhang Q, Liu L, Wu H, Xia Y, Bao X, Shi H, Su Q, Gu Y, Fang L, Yang H, Yu B, Sun S, Wang X, Zhou M, Jia Q, Jiao H, Wang B, Guo Q, Carvalhoa L, Sun Z, Song K, Yu M, Niu K (2017) Soft drinks consumption is associated with nonalcoholic fatty liver disease independent of metabolic syndrome in Chinese population. Eur J Nutr. https://​doi.​org/​10.​1007/​s00394-017-1485-0 CrossRefPubMed
3.
go back to reference Benedict M, Zhang X (2017) Non-alcoholic fatty liver disease: an expanded review. World J Hepatol 9(16):715–732CrossRef Benedict M, Zhang X (2017) Non-alcoholic fatty liver disease: an expanded review. World J Hepatol 9(16):715–732CrossRef
7.
go back to reference Li S, Brown MS (2010) Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis. Proc Natl Acad Sci USA 107(8):3441CrossRef Li S, Brown MS (2010) Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis. Proc Natl Acad Sci USA 107(8):3441CrossRef
8.
go back to reference Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, Mangelsdorf DJ (2000) Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Gene Dev 14(22):2819–2830CrossRef Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, Mangelsdorf DJ (2000) Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Gene Dev 14(22):2819–2830CrossRef
9.
go back to reference Javary Joaquim, Allain-Courtois Nathalie, Saucisse Nicolas, Costet Pierre, Heraud Capucine, Benhamed Fadila, Pierre Rémi, Bure Corinne, Pallares-Lupon Nestor, Cruzeiro Marcio Do, Postic Catherine, Cota Daniela, Dubus Pierre, Rosenbaum Jean, Benhamouche-Trouillet S (2017) Liver Reptin/RUVBL2 controls glucose and lipid metabolism with opposite actions on mTORC1 and mTORC2 signalling. Gut. https://doi.org/10.1136/gutjnl-2017-314208 CrossRefPubMed Javary Joaquim, Allain-Courtois Nathalie, Saucisse Nicolas, Costet Pierre, Heraud Capucine, Benhamed Fadila, Pierre Rémi, Bure Corinne, Pallares-Lupon Nestor, Cruzeiro Marcio Do, Postic Catherine, Cota Daniela, Dubus Pierre, Rosenbaum Jean, Benhamouche-Trouillet S (2017) Liver Reptin/RUVBL2 controls glucose and lipid metabolism with opposite actions on mTORC1 and mTORC2 signalling. Gut. https://​doi.​org/​10.​1136/​gutjnl-2017-314208 CrossRefPubMed
10.
go back to reference Schultze S, Hemmings B, Niessen M, Tschopp O (2012) PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis. Expert Rev Mol Med 14:e1CrossRef Schultze S, Hemmings B, Niessen M, Tschopp O (2012) PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis. Expert Rev Mol Med 14:e1CrossRef
16.
18.
go back to reference Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226(1):497–509PubMed Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226(1):497–509PubMed
22.
go back to reference Burnett BP, Silva S, Mesches MH, Wilson S, Jia Q (2007) Safety evaluation of a combination, defined extract of Scutellaria baicalensis and Acacia catechu. J Food Biochem 31(6):797–825CrossRef Burnett BP, Silva S, Mesches MH, Wilson S, Jia Q (2007) Safety evaluation of a combination, defined extract of Scutellaria baicalensis and Acacia catechu. J Food Biochem 31(6):797–825CrossRef
24.
go back to reference Qing-ming C, Xin-li H, Yan-mei L, Zhang K, Akao T, Tori MH (2001) Studies on metabolites of baicalin in human urine. China J Chin Mater Med 26(11):768–769 Qing-ming C, Xin-li H, Yan-mei L, Zhang K, Akao T, Tori MH (2001) Studies on metabolites of baicalin in human urine. China J Chin Mater Med 26(11):768–769
25.
26.
go back to reference Malhi H, Gores G (2008) Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease. Semin Liver Dis 28(4):360–369CrossRef Malhi H, Gores G (2008) Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease. Semin Liver Dis 28(4):360–369CrossRef
27.
go back to reference Leamy A, Egnatchik R, Young J (2013) Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease. Prog Lipid Res 52(1):165–174CrossRef Leamy A, Egnatchik R, Young J (2013) Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease. Prog Lipid Res 52(1):165–174CrossRef
29.
go back to reference Neuschwander-Tetri B (2010) Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites. Hepatology 52(2):774–788CrossRef Neuschwander-Tetri B (2010) Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites. Hepatology 52(2):774–788CrossRef
30.
go back to reference Akao T, Kawabata K, Yanagisawa E, Ishihara K, Mizuhara Y, Wakui Y, Sakashita Y, Kobashi K (2000) Baicalin, the predominant flavone glucuronide of scutellariae radix, is absorbed from the rat gastrointestinal tract as the aglycone and restored to its original form. J Pharm Pharmacol 52(12):1563–1568CrossRef Akao T, Kawabata K, Yanagisawa E, Ishihara K, Mizuhara Y, Wakui Y, Sakashita Y, Kobashi K (2000) Baicalin, the predominant flavone glucuronide of scutellariae radix, is absorbed from the rat gastrointestinal tract as the aglycone and restored to its original form. J Pharm Pharmacol 52(12):1563–1568CrossRef
34.
go back to reference Li J, Liu X, Ran X, Chen J, Li X, Wu W, Huang H, Huang H, Long Y, Liang J, Cheng J, Tian H (2010) Sterol regulatory element-binding protein-1c knockdown protected INS-1E cells from lipotoxicity. Diabetes Obes Metab 12(1):35–46CrossRef Li J, Liu X, Ran X, Chen J, Li X, Wu W, Huang H, Huang H, Long Y, Liang J, Cheng J, Tian H (2010) Sterol regulatory element-binding protein-1c knockdown protected INS-1E cells from lipotoxicity. Diabetes Obes Metab 12(1):35–46CrossRef
37.
go back to reference Zeng X, Yang J, Hu O, Huang J, Ran L, Chen M, Zhang Y, Zhou X, Zhu J, Zhang Q, Yi L, Mi M (2018) Dihydromyricetin ameliorates nonalcoholic fatty liver disease by improving mitochondrial respiratory capacity and redox homeostasis through modulation of SIRT3 signaling. Antioxid Redox Sign. https://doi.org/10.1089/ars.2017.7172 CrossRef Zeng X, Yang J, Hu O, Huang J, Ran L, Chen M, Zhang Y, Zhou X, Zhu J, Zhang Q, Yi L, Mi M (2018) Dihydromyricetin ameliorates nonalcoholic fatty liver disease by improving mitochondrial respiratory capacity and redox homeostasis through modulation of SIRT3 signaling. Antioxid Redox Sign. https://​doi.​org/​10.​1089/​ars.​2017.​7172 CrossRef
Metadata
Title
Scutellaria baicalensis regulates FFA metabolism to ameliorate NAFLD through the AMPK-mediated SREBP signaling pathway
Authors
Qian Chen
Mengyang Liu
Haiyang Yu
Jian Li
Sijian Wang
Yi Zhang
Feng Qiu
Tao Wang
Publication date
01-06-2018
Publisher
Springer Singapore
Published in
Journal of Natural Medicines / Issue 3/2018
Print ISSN: 1340-3443
Electronic ISSN: 1861-0293
DOI
https://doi.org/10.1007/s11418-018-1199-5

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