Novel Combinatorial Regimen of Garcinol and Curcuminoids for Non-alcoholic Steatohepatitis (NASH) in Mice

被引:19
作者
Majeed, Muhammed [1 ,2 ,3 ]
Majeed, Shaheen [2 ]
Nagabhushanam, Kalyanam [3 ]
Lawrence, Lincy [1 ]
Mundkur, Lakshmi [1 ]
机构
[1] Sami Labs Ltd, Peenya Ind Area, Bangalore 560058, Karnataka, India
[2] Sabinsa Corp, 750 Innovat Circle, Payson, UT 84651 USA
[3] Sabinsa Corp, 20 Lake Dr, East Windsor, NJ 08520 USA
关键词
FATTY LIVER-DISEASE; ENDOPLASMIC-RETICULUM STRESS; GROWTH-FACTOR; 21; LIPID-ACCUMULATION; OXIDATIVE STRESS; PROTECTIVE MECHANISM; AMERICAN ASSOCIATION; INSULIN SENSITIVITY; HEPATIC STEATOSIS; FIBROSIS;
D O I
10.1038/s41598-020-64293-w
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Non-alcoholic steatohepatitis (NASH) is a progressive form of Non-alcoholic fatty liver disease (NAFLD), a chronic liver disease with a significant unmet clinical need. In this study, we examined the protective effects of Garcinia indica extract standardized to contain 20% w/w of Garcinol (GIE) and 95% Curcuminoids w/w from Curcuma longa (Curcuminoids) in a Stelic animal model (STAM) of NASH. The STAM mice developed steatosis, hepatocyte ballooning, and inflammation, which were significantly reduced by the combination of GIE and Curcuminoids, resulting in a lower NAFLD activity score. The treatment reduced fibrosis as observed by Sirius red staining, liver hydroxyproline content and mRNA levels of TGF- beta and collagen in the liver. Immunostaining with alpha-smooth muscle actin (alpha SMA) revealed a significant reduction in hepatic stellate cells. Intriguingly, the combination regimen markedly decreased the mRNA levels of MCP1 and CRP and both mRNA and protein levels of TNF-alpha. NF-kB, reduced the hepatic and circulating FGF21 levels and altered the nonenzymatic (glutathione) and enzymatic antioxidant markers (Glutathione peroxidase, and superoxide dismutase). Our results suggest that the combination of GIE and Curcuminoids can reduce the severity of NASH by reducing steatosis, fibrosis, oxidative stress, and inflammation. The results suggest that the combinatorial regimen could be an effective supplement to prevent the progression of liver steatosis to inflammation and fibrosis in NASH.
引用
收藏
页数:14
相关论文
共 83 条
[31]  
Hung WL, 2014, FOOD FUNCT, V5, P2883, DOI [10.1039/c4fo00342j, 10.1039/C4FO00342J]
[32]   Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis [J].
Kisseleva, Tatiana ;
Cong, Min ;
Paik, YongHan ;
Scholten, David ;
Jiang, Chunyan ;
Benner, Chris ;
Iwaisako, Keiko ;
Moore-Morris, Thomas ;
Scott, Brian ;
Tsukamoto, Hidekazu ;
Evans, Sylvia M. ;
Dillmann, Wolfgang ;
Glass, Christopher K. ;
Brenner, David A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (24) :9448-9453
[33]   Design and validation of a histological scoring system for nonalcoholic fatty liver disease [J].
Kleiner, DE ;
Brunt, EM ;
Van Natta, M ;
Behling, C ;
Contos, MJ ;
Cummings, OW ;
Ferrell, LD ;
Liu, YC ;
Torbenson, MS ;
Unalp-Arida, A ;
Yeh, M ;
McCullough, AJ ;
Sanyal, AJ .
HEPATOLOGY, 2005, 41 (06) :1313-1321
[34]   Prevalence of Nonalcoholic Fatty Liver Disease in the United States: The Third National Health and Nutrition Examination Survey, 1988-1994 [J].
Lazo, Mariana ;
Hernaez, Ruben ;
Eberhardt, Mark S. ;
Bonekamp, Susanne ;
Kamel, Ihab ;
Guallar, Eliseo ;
Koteish, Ayman ;
Brancati, Frederick L. ;
Clark, Jeanne M. .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 2013, 178 (01) :38-45
[35]   Curcumin and Curcuma longa L. extract ameliorate lipid accumulation through the regulation of the endoplasmic reticulum redox and ER stress [J].
Lee, Hwa-Young ;
Kim, Seung-Wook ;
Lee, Geum-Hwa ;
Choi, Min-Kyung ;
Chung, Han-Wool ;
Lee, Yong-Chul ;
Kim, Hyung-Ryong ;
Kwon, Ho Jeong ;
Chae, Han-Jung .
SCIENTIFIC REPORTS, 2017, 7
[36]   The role of the gut microbiota in NAFLD [J].
Leung, Christopher ;
Rivera, Leni ;
Furness, John B. ;
Angus, Peter W. .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2016, 13 (07) :412-425
[37]   Metabolically induced liver inflammation leads to NASH and differs from LPS- or IL-1 β-induced chronic inflammation [J].
Liang, Wen ;
Lindeman, Jan H. ;
Menke, Aswin L. ;
Koonen, Debby P. ;
Morrison, Martine ;
Havekes, Louis M. ;
van den Hoek, Anita M. ;
Kleemann, Robert .
LABORATORY INVESTIGATION, 2014, 94 (05) :491-502
[38]   Downregulation of miR-192 causes hepatic steatosis and lipid accumulation by inducing SREBF1: Novel mechanism for bisphenol A-triggered non-alcoholic fatty liver disease [J].
Lin, Yi ;
Ding, Dongxiao ;
Huang, Qiansheng ;
Liu, Qiong ;
Lu, Haoyang ;
Lu, Yanyang ;
Chi, Yulang ;
Sun, Xia ;
Ye, Guozhu ;
Zhu, Huimin ;
Wei, Jie ;
Dong, Sijun .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2017, 1862 (09) :869-882
[39]   Adiponectin Mediates the Metabolic Effects of FGF21 on Glucose Homeostasis and Insulin Sensitivity in Mice [J].
Lin, Zhuofeng ;
Tian, Haishan ;
Lam, Karen S. L. ;
Lin, Shaoqiang ;
Hoo, Ruby C. L. ;
Konishi, Morichika ;
Itoh, Nobuyuki ;
Wang, Yu ;
Bornstein, Stefan R. ;
Xu, Aimin ;
Li, Xiaokun .
CELL METABOLISM, 2013, 17 (05) :779-789
[40]   The role of fibroblast growth factor 21 in the pathogenesis of non-alcoholic fatty liver disease and implications for therapy [J].
Liu, Jia ;
Xu, Yuan ;
Hu, Yanjin ;
Wang, Guang .
METABOLISM-CLINICAL AND EXPERIMENTAL, 2015, 64 (03) :380-390