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Therapeutic potential of curcumin in non-alcoholic steatohepatitis

Published online by Cambridge University Press:  14 December 2007

Haim Shapiro  and
Rafael Bruck
Haim Shapiro
Affiliation:
Clinical Hypnosis Unit, E. Wolfson Medical Center, Holon 58100, Israel
Rafael Bruck*
Affiliation:
Institute of Gastroenterology, Tel-Aviv Sourasky Medical Center, 6 Weizman Street, 64239, Tel-Aviv, Israel Sackler School of Medicinexg, Tel-Aviv University, Israel
*
*Corresponding author: Dr Rafael Bruck, fax + 972 3 6961222, email [email protected]
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Abstract

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Non-alcoholic steatohepatitis (NASH) may be associated with a number of clinical conditions, but it occurs most commonly in patients with insulin resistance. There is as yet no established disease-modifying treatment, and a safe and broadly available agent that targets hepatic steatosis, insulin resistance, inflammation and fibrosis is necessary. The polyphenolic compound curcumin exhibits antioxidant and anti-inflammatory properties, inhibits NF-κB and activates PPAR-γ. In rodents, curcumin prevents dietary-induced hepatic steatosis, hepatic stellate cell activation and production of fibrotic proteins, and ameliorates steatohepatitis induced by the intake of alcohol or a methionine–choline-deficient diet. Indirect evidence suggests that curcumin may improve insulin sensitivity in diabetes and inflammatory states. The present paper reviews the numerous cellular and animal studies indicating that curcumin attenuates many of the pathophysiological processes involved in the development and progression of NASH. It is suggested that basic and clinical studies on curcumin in the development and progression of NASH are indicated.

Keywords

DiferuloylmethaneCurcuminSteatosisOxidative stressFibrosisSteatohepatitis
Type
Research Article
Information
Nutrition Research Reviews , Volume 18 , Issue 2 , December 2005 , pp. 212 - 221
Copyright
Copyright © The Authors 2005

References

Abe, Y, Hashimoto, S & Horie, T (1999) Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages. Pharmacological Research 39, 41–47.CrossRefGoogle ScholarPubMed
Aggarwal, BB, Kumar, A & Bharti, AC (2003) Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Research 23, 363–398.Google ScholarPubMed
Albanis, E, Safadi, R & Friedman, SL (2003) Treatment of hepatic fibrosis: almost there. Current Gastroenterology Reports 5, 48–56.CrossRefGoogle ScholarPubMed
Angulo, P (2002) Nonalcoholic fatty liver disease. New England Journal of Medicine 346, 1221–1231.CrossRefGoogle ScholarPubMed
Asai, A & Miyazawa, T (2001) Dietary curcuminoids prevent high-fat diet-induced lipid accumulation in rat liver and epididymal adipose tissue. Journal of Nutrition 131, 2932–2935.CrossRefGoogle ScholarPubMed
Babu, PS & Srinivasan, K (1997) Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats. Molecular and Cellular Biochemistry 166, 169–175.CrossRefGoogle ScholarPubMed
Balla, J, Vercellotti, GM, Nath, K, Yachie, A, Nagy, E, Eaton, JW & Balla, G (2003) Haem, haem oxygenase and ferritin in vascular endothelial cell injury. Nephrology Dialysis Transplantation 18, 8–12.CrossRefGoogle ScholarPubMed
Balogun, E, Hoque, M, Gong, P, Killeen, E, Green, CJ, Foresti, R, Alam, J & Motterlini, R (2003) Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. Biochemical Journal 371, 887–895.CrossRefGoogle ScholarPubMed
Bierhaus, A, Zhang, Y, Quehenberger, P, Luther, T, Haase, M, Muller, M, Mackman, N, Ziegler, R & Nawroth, PP (1997) The dietary pigment curcumin reduces endothelial tissue factor gene expression by inhibiting binding of AP-1 to the DNA and activation of NF-kappa B. Thrombosis and Haemostasis 77, 772–782.Google Scholar
Browning, JD & Horton, JD (2004) Molecular mediators of hepatic steatosis and liver injury. Journal of Clinical Investigation 114, 147–152.CrossRefGoogle ScholarPubMed
Chan, MM (1995) Inhibition of tumor necrosis factor by curcumin, a phytochemical. Biochemical Pharmacology 49, 1551–1556.CrossRefGoogle ScholarPubMed
Chandra, V, Pandav, R, Dodge, HH, Johnston, JM, Belle, SH, DeKosky, ST & Ganguli, M (2001) Incidence of Alzheimer's disease in a rural community in India: the Indo-US study. Neurology 57, 985–989.CrossRefGoogle Scholar
Chen, A & Xu, J (2005) Activation of PPAR{gamma} by curcumin inhibits Moser cell growth and mediates the suppression of the gene expression of cyclin D1 and EGFR. American Journal of Physiology 288, G447–G456.Google ScholarPubMed
Chen, YR & Tan, TH (1998) Inhibition of the c-Jun N-terminal kinase (JNK) signaling pathway by curcumin. Oncogene 17, 173–178.CrossRefGoogle ScholarPubMed
Cheng, AL, Hsu, CH, Lin, JK, Hsu, MM, Ho, YF, Shen, TS, Ko, JY, Lin, JT, Lin, BR, Ming-Shiang, W, Yu, HS & Jee, SH, et al. (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Research 21, 2895–2900.Google ScholarPubMed
Choudhury, J & Sanyal, AJ (2004) Insulin resistance and the pathogenesis of nonalcoholic fatty liver disease. Clinics in Liver Disease 8, 575–594.CrossRefGoogle ScholarPubMed
Chuang, SE, Cheng, AL, Lin, JK & Kuo, ML (2000 a) Inhibition by curcumin of diethylnitrosamine-induced hepatic hyperplasia, inflammation, cellular gene products and cell-cycle-related proteins in rats. Food and Chemical Toxicology 38, 991–995.CrossRefGoogle ScholarPubMed
Chuang, SE, Kuo, ML, Hsu, CH, Chen, CR, Lin, JK, Lai, GM, Hsieh, CY & Cheng, AL (2000 b) Curcumin-containing diet inhibits diethylnitrosamine-induced murine hepatocarcinogenesis. Carcinogenesis 21, 331–335.CrossRefGoogle ScholarPubMed
Chun, KS, Keum, YS, Han, SS, Song, YS, Kim, SH & Surh, YJ (2003) Curcumin inhibits phorbol ester-induced expression of cyclooxygenase-2 in mouse skin through suppression of extracellular signal-regulated kinase activity and NF-kappaB activation. Carcinogenesis 24, 1515–1524.CrossRefGoogle ScholarPubMed
den Boer, M, Voshol, PJ, Kuipers, F, Havekes, LM & Romijn, JA (2004) Hepatic steatosis: a mediator of the metabolic syndrome. Lessons from animal models. Arteriosclerosis, Thrombosis and Vascular Biology 24, 644–649.CrossRefGoogle ScholarPubMed
Diehl, AM (2004) Tumor necrosis factor and its potential role in insulin resistance and nonalcoholic fatty liver disease. Clinics in Liver Disease 8, 619–638.CrossRefGoogle ScholarPubMed
Friedman, SL (2000) Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. Journal of Biological Chemistry 275, 2247–2250.CrossRefGoogle ScholarPubMed
Gaedeke, J, Noble, NA & Border, WA (2004) Curcumin blocks multiple sites of the TGF-beta signaling cascade in renal cells. Kidney International 66, 112–120.CrossRefGoogle ScholarPubMed
Gao, X, Kuo, J, Jiang, H, Deeb, D, Liu, Y, Divine, G, Chapman, RA, Dulchavsky, SA & Gautam, SC (2004) Immunomodulatory activity of curcumin: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production in vitro. Biochemical Pharmacology 68, 51–61.CrossRefGoogle ScholarPubMed
Ghoneim, AI, Abdel-Naim, AB, Khalifa, AE & El-Denshary, ES (2002) Protective effects of curcumin against ischaemia/reperfusion insult in rat forebrain. Pharmacological Research 46, 273–279.CrossRefGoogle ScholarPubMed
Gukovsky, I, Reyes, CN, Vaquero, EC, Gukovskaya, AS & Pandol, SJ (2003) Curcumin ameliorates ethanol and nonethanol experimental pancreatitis. American Journal of Physiology 284, G85–G95.Google ScholarPubMed
Heyninck, K, Wullaert, A & Beyaert, R (2003) Nuclear factor-kappa B plays a central role in tumour necrosis factor-mediated liver disease. Biochemical Pharmacology 66, 1409–1415.CrossRefGoogle Scholar
Iqbal, M, Sharma, SD, Okazaki, Y, Fujisawa, M & Okada, S (2003) Dietary supplementation of curcumin enhances antioxidant and phase 2 metabolizing enzymes in ddY male mice: possible role in protection against chemical carcinogenesis and toxicity. Pharmacology and Toxicology 92, 33–38.CrossRefGoogle ScholarPubMed
Ishida, J, Ohtsu, H, Tachibana, Y, Nakanishi, Y, Bastow, KF, Nagai, M, Wang, HK, Itokawa, H & Lee, KH, (2002) Antitumor agents. Part 214: synthesis and evaluation of curcumin analogues as cytotoxic agents. Bioorganic Medical Chemistry 10, 3481–3487.CrossRefGoogle ScholarPubMed
Joe, B, Lokesh, BR (1994) Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochimica et Biophysica Acta 1224, 255–263.CrossRefGoogle ScholarPubMed
Joe, B, Vijaykumar, M & Lokesh, BR (2004) Biological properties of curcumin-cellular and molecular mechanisms of action. Critical Review of Food Science and Nutrition 44, 97–111.CrossRefGoogle ScholarPubMed
Kang, HC, Nan, JX, Park, PH, Kim, JY, Lee, SH, Woo, SW, Zhao, YZ, Park, EJ & Sohn, DH (2002) Curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo and in-vitro. Journal of Pharmacy and Pharmacology 54, 119–126.CrossRefGoogle ScholarPubMed
Kempaiah, RK & Srinivasan, K (2004) Influence of dietary curcumin, capsaicin and garlic on the antioxidant status of red blood cells and the liver in high-fat-fed rats. Annals of Nutrition Metabolism 48, 314–320.CrossRefGoogle ScholarPubMed
Kumar, A, Dhawan, S, Hardegen, NJ & Aggarwal, BB (1998) Curcumin (Diferuloylmethane) inhibition of tumor necrosis factor (TNF)-mediated adhesion of monocytes to endothelial cells by suppression of cell surface expression of adhesion molecules and of nuclear factor-kappa B activation. Biochemical Pharmacology 55, 775–783.CrossRefGoogle Scholar
Leclercq, IA, Farrell, GC, Sempoux, C, Pena, AD & Horsmans, Y (2004) Curcumin inhibits NF-kappaB activation and reduces the severity of experimental steatohepatitis in mice. Journal of Hepatology 41, 926–934.CrossRefGoogle ScholarPubMed
Lee, JJ, Huang, WT, Shao, DZ, Liao, JF & Lin, MT, (2003) Blocking NF-kappaB activation may be an effective strategy in the fever therapy. Japanese Journal of Physiology 53, 367–375.Google ScholarPubMed
Leu, TH & Maa, MC (2002) The molecular mechanisms for the antitumorigenic effect of curcumin. Current Medicinal Chemistry – Anti-Cancer Agents 2, 357–370.Google ScholarPubMed
Li, L, Grenard, P, Nhieu, JT, Julien, B, Mallat, A, Habib, A & Lotersztajn, (2003) Heme oxygenase-1 is an antifibrogenic protein in human hepatic myofibroblasts. Gastroenterology 125, 460–469.CrossRefGoogle ScholarPubMed
Lim, GP, Chu, T, Yang, F, Beech, W, Frautschy, SA & Cole, GM (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. Journal of Neuroscience 21, 8370–8377.CrossRefGoogle Scholar
Lukita-Atmadja, W, Ito, Y, Baker, GL & McCuskey, RS (2002) Effect of curcuminoids as anti-inflammatory agents on the hepatic microvascular response to endotoxin. Shock 17, 399–403.CrossRefGoogle ScholarPubMed
Madan, B & Ghosh, B (2003) Diferuloylmethane inhibits neutrophil infiltration and improves survival of mice in high-dose endotoxin shock. Shock 19, 91–96.CrossRefGoogle ScholarPubMed
Manach, C, Scalbert, A, Morand, C, Remesy, C & Jimenez, L (2004) Polyphenols: food sources and bioavailability. American Journal of Clinical Nutrition 79, 727–747.CrossRefGoogle ScholarPubMed
Medina, J, Fernandez-Salazar, LI, Garcia-Buey, L & Moreno-Otero, R (2004) Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis. Diabetes Care 27, 2057–2066.CrossRefGoogle Scholar
Miquel, J, Bernd, A, Sempere, JM, Diaz-Alperi, J & Ramirez, A (2002) The curcuma antioxidants: pharmacological effects and prospects for future clinical use. A review. Archives of Gerontology and Geriatrics 34, 37–46.CrossRefGoogle ScholarPubMed
Mishra, B, Priyadarsini, KI, Bhide, MK, Kadam, RM & Mohan, H (2004) Reactions of superoxide radicals with curcumin: probable mechanisms by optical spectroscopy and EPR. Free Radical Research 38, 355–362.CrossRefGoogle ScholarPubMed
Morikawa, T, Matsuda, H, Ninomiya, K & Yoshikawa, M (2002) Medicinal foodstuffs. 29. Potent protective effects of sesquiterpenes and curcumin from Zedoariae Rhizoma on liver injury induced by D-galactosamine/lipopolysaccharide or tumor necrosis factor-alpha. Biological and Pharmaceutical Bulletin 25, 627–631.CrossRefGoogle ScholarPubMed
Motterlini, R, Foresti, R, Bassi, R & Green, CJ (2000) Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radical Biology and Medicine 28, 1303–1312.CrossRefGoogle ScholarPubMed
Nakatani, Y, Kaneto, H, Kawamori, D, Hatazaki, M, Miyatsuka, T, Matsuoka, TA, Kajimoto, Y, Matsuhisa, M, Yamasaki, Y & Hori, M (2004) Modulation of the JNK pathway in liver affects insulin resistance status. Journal of Biological Chemistry 279, 45803–45809.CrossRefGoogle ScholarPubMed
Nanji, AA, Jokelainen, K, Tipoe, GL, Rahemtulla, A, Thomas, P & Dannenberg, AJ (2003) Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-kappa B-dependent genes. American Journal of Physiology 284, G321 – G327Google ScholarPubMed
National Institutes of Health (2004 a) Curcumin in patients with mild to moderate Alzheimer's disease. Accessed March 2005. http://clinicaltrials.gov/ct/show/NCT00099710?order=1.Google Scholar
National Institutes of Health (2004 b) Trial of curcumin in advanced pancreatic cancer. Accessed March 2005. http://clinicaltrials.gov/ct/show/NCT00094445?order=2.Google Scholar
Neuschwander-Tetri, BA & Caldwell, SH (2003) Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 37, 1202–1219.CrossRefGoogle ScholarPubMed
Nishiyama, T, Mae, T, Kishida, H, Tsukagawa, M, Mimaki, Y, Kuroda, M, Sashida, Y, Takahashi, K, Kawada, T, Nakagawa, K & Kitahara, M (2005) Curcuminoids and sesquiterpenoids in turmeric (Curcuma longa L.) suppress an increase in blood glucose level in type 2 diabetic KK-A(y) mice. Journal of Agricultural and Food Chemistry 53, 959–963.CrossRefGoogle ScholarPubMed
Oetari, S, Sudibyo, M, Commandeur, JN, Samhoedi, R & Vermeulen, NP, (1996) Effects of curcumin on cytochrome P450 and glutathione S-transferase activities in rat liver. Biochemical Pharmacology 51, 39–45.CrossRefGoogle ScholarPubMed
Ogihara, T, Asano, T, Katagiri, H, Sakoda, H, Anai, M, Shojima, N, Ono, H, Fujishiro, M, Kushiyama, A, Fukushima, Y, Kikuchi, M & Noguchi, N, et al. (2004) Oxidative stress induces insulin resistance by activating the nuclear factor-kappa B pathway and disrupting normal subcellular distribution of phosphatidylinositol 3-kinase. Diabetologia 47, 794–805.CrossRefGoogle ScholarPubMed
Park, EJ, Jeon, CH, Ko, G, Kim, J & Sohn, DH (2000) Protective effect of curcumin in rat liver injury induced by carbon tetrachloride. Journal of Pharmacy and Pharmacology 52, 437–440.CrossRefGoogle ScholarPubMed
Park, SD, Jung, JH, Lee, HW, Kwon, YM, Chung, KH, Kim, MG & Kim, CH (2005) Zedoariae rhizoma and curcumin inhibits platelet-derived growth factor-induced proliferation of human hepatic myofibroblasts. International Immunopharmacology 5, 555–569.CrossRefGoogle ScholarPubMed
Pendurthi, UR, Williams, JT & Rao, LV (1997) Inhibition of tissue factor gene activation in cultured endothelial cells by curcumin. Suppression of activation of transcription factors Egr-1, AP-1, and NF-kappa B. Arteriosclerosis, Thrombosis and Vascular Biology 17, 3406–3413.CrossRefGoogle ScholarPubMed
Philip, S & Kundu, GC (2003) Osteopontin induces nuclear factor kappa B-mediated promatrix metalloproteinase-2 activation through I kappa B alpha/IKK signaling pathways, and curcumin (diferulolylmethane) down-regulates these pathways. Journal of Biological Chemistry 278, 14487–14497.CrossRefGoogle Scholar
Plummer, SM, Holloway, KA, Manson, MM, Munks, RJ, Kaptein, A, Farrow, S & Howells, L (1999) Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene 18, 6013–6020.CrossRefGoogle ScholarPubMed
Punithavathi, D, Venkatesan, N & Babu, M (2003) Protective effects of curcumin against amiodarone-induced pulmonary fibrosis in rats. British Journal of Pharmacology 139, 1342–1450.CrossRefGoogle ScholarPubMed
Quiles, JL, Aguilera, C, Mesa, MD, Ramirez-Tortosa, MC, Baro, L & Gil, A (1998) An ethanolic-aqueous extract of Curcuma longa decreases the susceptibility of liver microsomes and mitochondria to lipid peroxidation in atherosclerotic rabbits. Biofactors 8, 51–57.CrossRefGoogle ScholarPubMed
Quiles, JL, Mesa, MD, Ramirez-Tortosa, CL, Aguilera, CM, Battino, M, Gil, A & Ramirez-Tortosa, MC (2002) Curcuma longa extract supplementation reduces oxidative stress and attenuates aortic fatty streak development in rabbits. Arteriosclerosis, Thrombosis and Vascular Biology 22, 1225–1231.CrossRefGoogle ScholarPubMed
Rasyid, A & Lelo, A (1999) The effect of curcumin and placebo on human gall-bladder function: an ultrasound study. Alimentary Pharmacology and Therapeutics 13, 245–249.CrossRefGoogle ScholarPubMed
Rasyid, A, Rahman, AR, Jaalam, K & Lelo, A (2002) Effect of different curcumin dosages on human gall bladder. Asia Pacific Journal of Clinical Nutrition 11, 314–318.CrossRefGoogle ScholarPubMed
Reddy, AC & Lokesh, BR (1994) Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in the rat liver. Food and Chemical Toxicology 32, 279–283.CrossRefGoogle ScholarPubMed
Reddy, AC & Lokesh, BR, (1996) Effect of curcumin and eugenol on iron-induced hepatic toxicity in rats. Toxicology 107, 39–45.CrossRefGoogle ScholarPubMed
Rinella, ME & Green, RM (2004) The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance. Journal of Hepatology 40, 47–51.CrossRefGoogle Scholar
Robinson, TP, Ehlers, T, Hubbard, RB IV, Bai, X, Arbiser, JL, Goldsmith, DJ & Bowen, JP (2003) Design, synthesis, and biological evaluation of angiogenesis inhibitors: aromatic enone and dienone analogues of curcumin. Bioorganic Medical Chemistry Letter 13, 115–117.CrossRefGoogle ScholarPubMed
Rukkumani, R, Aruna, K, Varma, PS & Menon, VP (2004 a) Curcumin influences hepatic expression patterns of matrix metalloproteinases in liver toxicity. Italian Journal of Biochemistry 43, 61–66.Google Scholar
Rukkumani, R, Aruna, K, Varma, PS, Rajasekaran, KN & Menon, VP (2004 b) Comparative effects of curcumin and an analog of curcumin on alcohol and PUFA induced oxidative stress. Journal of Pharmacy and Pharmaceutical Sciences 7, 274–283.Google Scholar
Rukkumani, R, SriBalasubashini, M & Menon, VP (2003) Protective effects of curcumin and photo-irradiated curcumin on circulatory lipids and lipid peroxidation products in alcohol and polyunsaturated fatty acid-induced toxicity. Phytotherapy Research 17, 925–929.CrossRefGoogle ScholarPubMed
Rukkumani, R, SriBalasubashini, M, Vishwanathan, P & Menon, VP (2002) Comparative effects of curcumin and photo-irradiated curcumin on alcohol- and polyunsaturated fatty acid-induced hyperlipidemia. Pharmacogical Research 46, 257–264.Google ScholarPubMed
Sahai, A, Malladi, P, Melin-Aldana, H, Green, RM & Whitington, PF (2004) Upregulation of osteopontin expression is involved in the development of nonalcoholic steatohepatitis in a dietary murine model. American Journal of Physiology 287, G264–G273.Google Scholar
Sass, DA, Chang, P & Chopra, KB (2005) Nonalcoholic fatty liver disease: a clinical review. Digestive Diseases and Science 50, 171–180.CrossRefGoogle ScholarPubMed
Satapathy, SK, Garg, S, Chauhan, R, Sakhuja, P, Malhotra, V, Sharma, BC & Sarin, SK (2004) Beneficial effects of tumor necrosis factor-alpha inhibition by pentoxifylline on clinical, biochemical, and metabolic parameters of patients with nonalcoholic steatohepatitis. American Journal of Gastroenterology 99, 1946–1952.CrossRefGoogle ScholarPubMed
Scapagnini, G, Foresti, R, Calabrese, V, Green, CJ & Motterlini, R (2002) Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers. Molecular Pharmacology 61, 554–561.CrossRefGoogle ScholarPubMed
Sharma, RA, Euden, SA, Platton, SL, Cooke, DN, Shafayat, A, Hewitt, HR, Marczylo, TH, Morgan, B, Hemingway, D, Plummer, SM, Pirmohamed, M & Gescher, AJ, et al. (2004) Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clinical Cancer Research 10, 6847–6854.CrossRefGoogle ScholarPubMed
Sharma, RA, Ireson, CR, Verschoyle, RD, Hill, KA, Williams, ML, Leuratti, C, Manson, MM, Marnett, LJ, Steward, WP & Gescher, A (2001 a) Effects of dietary curcumin on glutathione S-transferase and malondialdehyde-DNA adducts in rat liver and colon mucosa: relationship with drug levels. Clinical Cancer Research 7, 1452–1458.Google ScholarPubMed
Sharma, RA, McLelland, HR, Hill, KA, Ireson, CR, Euden, SA, Manson, MM, Pirmohamed, M, Marnett, LJ, Gescher, AJ & Steward, WP (2001 b) Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clinical Cancer Research 7, 1894–1900.Google ScholarPubMed
Shishodia, S, Potdar, P, Gairola, CG & Aggarwal, BB (2003) Curcumin (diferuloylmethane) down-regulates cigarette smoke-induced NF-kappaB activation through inhibition of IkappaBalpha kinase in human lung epithelial cells: correlation with suppression of COX-2, MMP-9 and cyclin D1. Carcinogenesis 24, 1269–1279.CrossRefGoogle ScholarPubMed
Shoskes, DA (1998) Effect of bioflavonoids quercetin and curcumin on ischemic renal injury: a new class of renoprotective agents. Transplantation 66, 147–152.CrossRefGoogle ScholarPubMed
Shukla, Y & Arora, A (2003) Suppression of altered hepatic foci development by curcumin in Wistar rats. Nutrition and Cancer 45, 53–59.CrossRefGoogle ScholarPubMed
Singh, S & Aggarwal, BB (1995) Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). Journal of Biological Chemistry 270, 24995–25000.CrossRefGoogle ScholarPubMed
Stravitz, RT & Sanyal, AJ (2003) Drug-induced steatohepatitis. Clinics in Liver Disease 7, 435–451.CrossRefGoogle ScholarPubMed
Syng-Ai, C, Kumari, AL & Khar, A (2004) Effect of curcumin on normal and tumor cells: role of glutathione and bcl-2. Molecular Cancer Therapeutics 3, 1101–1108.CrossRefGoogle ScholarPubMed
Venkatesan, N (1998) Curcumin attenuation of acute adriamycin myocardial toxicity in rats. British Journal of Pharmacology 124, 425–427.CrossRefGoogle ScholarPubMed
Venkatesan, N, Punithavathi, D & Arumugam, V (2000) Curcumin prevents adriamycin nephrotoxicity in rats. British Journal of Pharmacology 129, 231–234.CrossRefGoogle ScholarPubMed
Venkatesan, P & Rao, MN (2000) Structure-activity relationships for the inhibition of lipid peroxidation and the scavenging of free radicals by synthetic symmetrical curcumin analogues. Journal of Pharmacy and Pharmacology 52, 1123–1128.CrossRefGoogle ScholarPubMed
Watanabe, S & Fukui, T (2000) Suppressive effect of curcumin on trichloroethylene-induced oxidative stress. Journal of Nutritional Science and Vitaminology (Tokyo) 46, 230–234.CrossRefGoogle ScholarPubMed
World Health Organization (2000) Evaluation of Certain Food Additives: 51st Report of the Joint FAO/WHO Expert Committee on Food Additives, WHO Technical Report no. 891. Geneva: WHO.Google Scholar
Xu, J, Fu, Y & Chen, A (2003) Activation of peroxisome proliferator-activated receptor-gamma contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth. American Journal of Physiology 285, G20–G30.Google Scholar
Xu, YX, Pindolia, KR, Janakiraman, N, Chapman, RA & Gautam, SC (1997–1998) Curcumin inhibits IL1 alpha and TNF-alpha induction of AP-1 and NF-kB DNA-binding activity in bone marrow stromal cells. Hematopathology and Molecular Hematology 11, 49–62.Google ScholarPubMed
Yao, QH, Wang, DQ, Cui, CC, Yuan, ZY, Chen, SB, Yao, XW, Wang, JK & Lian, JF (2004) Curcumin ameliorates left ventricular function in rabbits with pressure overload: inhibition of the remodeling of the left ventricular collagen network associated with suppression of myocardial tumor necrosis factor-alpha and matrix metalloproteinase-2 expression. Biological and Pharmaceutical Bulletin 27, 198–202.CrossRefGoogle ScholarPubMed
Yeon, JE, Choi, KM, Baik, SH, Kim, KO, Lim, HJ, Park, KH, Kim, JY, Park, JJ, Kim, JS, Bak, YT, Byun, KS & Lee, CH (2004) Reduced expression of peroxisome proliferator-activated receptor-alpha may have an important role in the development of non-alcoholic fatty liver disease. Journal of Gastroenterology and Hepatology 19, 799–804.CrossRefGoogle ScholarPubMed
Zheng, S & Chen, A (2004) Activation of PPARgamma is required for curcumin to induce apoptosis and to inhibit the expression of extracellular matrix genes in hepatic stellate cells in vitro. Biochemical Journal 384, 49–57.CrossRefGoogle ScholarPubMed
Zuckerbraun, BS & Billiar, TR (2003) Heme oxygenase-1: a cellular Hercules. Hepatology 37, 742–743.CrossRefGoogle ScholarPubMed