A Polymeric Nanoparticle Formulation of Curcumin (NanoCurc™) Ameliorates CCl4-induced Hepatic Injury and Fibrosis Through Reduction of Pro-inflammatory Cytokines and Stellate Cell Activation

Overview

Journal Lab Invest

Specialty Pathology

Date 2011 Jun 22

PMID 21691262

Citations 44

Authors

Savita Bisht

Mehtab A Khan

Mena Bekhit

Haibo Bai

Toby Cornish

Masamichi Mizuma

Michelle A Rudek

Ming Zhao

Amarnath Maitra

Balmiki Ray

Debomoy Lahiri

Anirban Maitra

Robert A Anders

Affiliations

Soon will be listed here.

Abstract

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 (NanoCurc™) that overcomes this major pitfall of the free compound. In this study, we show that NanoCurc™ results in sustained intrahepatic curcumin levels that can be found in both hepatocytes and non-parenchymal cells. NanoCurc™ 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 NanoCurc™ directly induces stellate cell apoptosis in vitro. Our results suggest that NanoCurc™ might be an effective therapy for patients with chronic liver disease.

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References

Sinha R, Anderson D, McDonald S, Greenwald P . Cancer risk and diet in India. J Postgrad Med. 2003; 49(3):222-8. View

Volak L, Ghirmai S, Cashman J, Court M . Curcuminoids inhibit multiple human cytochromes P450, UDP-glucuronosyltransferase, and sulfotransferase enzymes, whereas piperine is a relatively selective CYP3A4 inhibitor. Drug Metab Dispos. 2008; 36(8):1594-605. PMC: 2574793. DOI: 10.1124/dmd.108.020552. View

van Vlerken L, Amiji M . Multi-functional polymeric nanoparticles for tumour-targeted drug delivery. Expert Opin Drug Deliv. 2006; 3(2):205-16. DOI: 10.1517/17425247.3.2.205. View

Friedman S, Roll F, Boyles J, BISSELL D . Hepatic lipocytes: the principal collagen-producing cells of normal rat liver. Proc Natl Acad Sci U S A. 1985; 82(24):8681-5. PMC: 391500. DOI: 10.1073/pnas.82.24.8681. View

Friedman S . Molecular mechanisms of hepatic fibrosis and principles of therapy. J Gastroenterol. 1997; 32(3):424-30. DOI: 10.1007/BF02934504. View

Sharma R, Steward W, Gescher A . Pharmacokinetics and pharmacodynamics of curcumin. Adv Exp Med Biol. 2007; 595:453-70. DOI: 10.1007/978-0-387-46401-5_20. View

Miyahara T, Schrum L, Rippe R, Xiong S, Yee Jr H, Motomura K . Peroxisome proliferator-activated receptors and hepatic stellate cell activation. J Biol Chem. 2000; 275(46):35715-22. DOI: 10.1074/jbc.M006577200. View

Kulkarni S, Bhutani M, Bishnoi M . Antidepressant activity of curcumin: involvement of serotonin and dopamine system. Psychopharmacology (Berl). 2008; 201(3):435-42. DOI: 10.1007/s00213-008-1300-y. View

Xu Y, Ku B, Yao H, Lin Y, Ma X, Zhang Y . The effects of curcumin on depressive-like behaviors in mice. Eur J Pharmacol. 2005; 518(1):40-6. DOI: 10.1016/j.ejphar.2005.06.002. View

10.

Park E, Jeon C, Ko G, Kim J, Sohn D . Protective effect of curcumin in rat liver injury induced by carbon tetrachloride. J Pharm Pharmacol. 2000; 52(4):437-40. DOI: 10.1211/0022357001774048. View

11.

Donatus I, Sardjoko , Vermeulen N . Cytotoxic and cytoprotective activities of curcumin. Effects on paracetamol-induced cytotoxicity, lipid peroxidation and glutathione depletion in rat hepatocytes. Biochem Pharmacol. 1990; 39(12):1869-75. DOI: 10.1016/0006-2952(90)90603-i. View

12.

Garcia-Trevijano E, Iraburu M, Fontana L, Dominguez-Rosales J, Auster A, Rojkind M . Transforming growth factor beta1 induces the expression of alpha1(I) procollagen mRNA by a hydrogen peroxide-C/EBPbeta-dependent mechanism in rat hepatic stellate cells. Hepatology. 1999; 29(3):960-70. DOI: 10.1002/hep.510290346. View

13.

Anders R, Subudhi S, Wang J, Pfeffer K, Fu Y . Contribution of the lymphotoxin beta receptor to liver regeneration. J Immunol. 2005; 175(2):1295-300. DOI: 10.4049/jimmunol.175.2.1295. View

14.

Radaeva S, Sun R, Jaruga B, Nguyen V, Tian Z, Gao B . Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor necrosis factor-related apoptosis-inducing ligand-dependent manners. Gastroenterology. 2006; 130(2):435-52. DOI: 10.1053/j.gastro.2005.10.055. View

15.

Li Z, Diehl A . Innate immunity in the liver. Curr Opin Gastroenterol. 2005; 19(6):565-71. DOI: 10.1097/00001574-200311000-00009. View

16.

Pan M, Huang T, Lin J . Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999; 27(4):486-94. View

17.

Kiso Y, Suzuki Y, Watanabe N, Oshima Y, Hikino H . Antihepatotoxic principles of Curcuma longa rhizomes. Planta Med. 1983; 49(3):185-7. DOI: 10.1055/s-2007-969845. View

18.

Ramadori G, Knittel T, Odenthal M, Schwogler S, Neubauer K, Meyer zum Buschenfelde K . Synthesis of cellular fibronectin by rat liver fat-storing (Ito) cells: regulation by cytokines. Gastroenterology. 1992; 103(4):1313-21. DOI: 10.1016/0016-5085(92)91522-6. View

19.

Bisht S, Feldmann G, Soni S, Ravi R, Karikar C, Maitra A . Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy for human cancer therapy. J Nanobiotechnology. 2007; 5:3. PMC: 1868037. DOI: 10.1186/1477-3155-5-3. View

20.

Vicent M, Duncan R . Polymer conjugates: nanosized medicines for treating cancer. Trends Biotechnol. 2005; 24(1):39-47. DOI: 10.1016/j.tibtech.2005.11.006. View