A polymeric nanoparticle formulation of curcumin (NanoCurc™) ameliorates CCl4-induced hepatic injury and fibrosis through reduction of pro-inflammatory cytokines and stellate cell activation

被引:95
作者
Bisht, Savita [1 ]
Khan, Mehtab A. [1 ]
Bekhit, Mena [1 ]
Bai, Haibo [1 ]
Cornish, Toby [1 ]
Mizuma, Masamichi [1 ]
Rudek, Michelle A. [2 ]
Zhao, Ming [2 ]
Maitra, Amarnath [3 ]
Ray, Balmiki [4 ]
Lahiri, Debomoy [4 ]
Maitra, Anirban [1 ,2 ]
Anders, Robert A. [1 ]
机构
[1] Johns Hopkins Sch Med, Dept Pathol, Div GI & Liver Pathol, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[3] Visvabharati Univ, Santini Ketan, W Bengal, India
[4] Indiana Univ Sch Med, Stark Neurosci Res Inst, Indianapolis, IN USA
基金
美国国家卫生研究院;
关键词
carbon tetrachloride; cirrhosis; curcumin; cytokines; liver fibrosis; myofibroblasts; NanoCurct (TM); polymeric nanoparticle; ATTENUATING OXIDATIVE STRESS; HUMAN CYTOCHROMES P450; RAT-LIVER INJURY; CARBON-TETRACHLORIDE; RECEPTOR-GAMMA; LIPID-PEROXIDATION; PANCREATIC-CANCER; DRUG-DELIVERY; IN-VITRO; GLUTATHIONE;
D O I
10.1038/labinvest.2011.86
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Plant-derived polyphenols such as curcumin hold promise as a therapeutic agent in the treatment of chronic liver diseases. However, its development is plagued by poor aqueous solubility resulting in poor bioavailability. To circumvent the suboptimal bioavailability of free curcumin, we have developed a polymeric nanoparticle formulation of curcumin (NanoCurct (TM)) that overcomes this major pitfall of the free compound. In this study, we show that NanoCurct (TM) results in sustained intrahepatic curcumin levels that can be found in both hepatocytes and non-parenchymal cells. NanoCurct (TM) markedly inhibits carbon tetrachloride-induced liver injury, production of pro-inflammatory cytokines and fibrosis. It also enhances antioxidant levels in the liver and inhibits pro-fibrogenic transcripts associated with activated myofibroblasts. Finally, we show that NanoCurct (TM) directly induces stellate cell apoptosis in vitro. Our results suggest that NanoCurct (TM) might be an effective therapy for patients with chronic liver disease. Laboratory Investigation (2011) 91, 1383-1395; doi: 10.1038/labinvest.2011.86; published online 20 June 2011
引用
收藏
页码:1383 / 1395
页数:13
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