Mechanism of the Anti-inflammatory Effect of Curcumin: PPAR-<mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>γ</mml:mi></mml:math> Activation

Jacob, Asha; Wu, Rongqian; Zhou, Mian; Wang, Ping

doi:https://doi.org/10.1155/2007/89369

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Review Article | Open Access

Volume 2007 | Article ID 089369 | https://doi.org/10.1155/2007/89369

Mechanism of the Anti-inflammatory Effect of Curcumin: PPAR-γ Activation

Asha Jacob,^1,2Rongqian Wu,^1,2Mian Zhou,^1,2and Ping Wang^1,2

Academic Editor: John P. Vanden Heuvel

Received04 Jun 2007

Accepted21 Nov 2007

Published17 Jan 2008

Abstract

Curcumin, the phytochemical component in turmeric, is used as a dietary spice and a topical ointment for the treatment of inflammation in India for centuries. Curcumin (diferuloylmethane) is relatively insoluble in water, but dissolves in acetone, dimethylsulphoxide, and ethanol. Commercial grade curcumin contains 10–20% curcuminoids, desmethoxycurcumin, and bisdesmethoxycurcumin and they are as effective as pure curcumin. Based on a number of clinical studies in carcinogenesis, a daily oral dose of 3.6 g curcumin has been efficacious for colorectal cancer and advocates its advancement into Phase II clinical studies. In addition to the anticancer effects, curcumin has been effective against a variety of disease conditions in both in vitro and in vivo preclinical studies. The present review highlights the importance of curcumin as an anti-inflammatory agent and suggests that the beneficial effect of curcumin is mediated by the upregulation of peroxisome proliferator-activated receptor-γ (PPAR-γ) activation.

References

H. P. T. Ammon and M. A. Wahl, “Pharmacology of Curcuma longa,” Planta Medica, vol. 57, no. 1, pp. 1–7, 1991.
View at: Publisher Site | Google Scholar
B. B. Aggarwal, A. Kumar, and A. C. Bharti, “Anticancer potential of curcumin: preclinical and clinical studies,” Anticancer Research, vol. 23, no. 1 A, pp. 363–398, 2003.
View at: Google Scholar
R. A. Sharma, A. J. Gescher, and W. P. Steward, “Curcumin: the story so far,” European Journal of Cancer, vol. 41, no. 13, pp. 1955–1968, 2005.
View at: Publisher Site | Google Scholar
S. V. Jovanovic, C. W. Boone, S. Steenken, M. Trinoga, and R. B. Kaskey, “How curcumin works preferentially with water soluble antioxidants,” Journal of the American Chemical Society, vol. 123, no. 13, pp. 3064–3068, 2001.
View at: Publisher Site | Google Scholar
Y.-J. Wang, M.-H. Pan, A.-L. Cheng et al., “Stability of curcumin in buffer solutions and characterization of its degradation products,” Journal of Pharmaceutical and Biomedical Analysis, vol. 15, no. 12, pp. 1867–1876, 1997.
View at: Publisher Site | Google Scholar
M.-T. Huang, N. Ma, Y.-P. Lu et al., “Effects of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin on 12- $O$ -tetradecanoylphorbol-13-acetate-induced tumor promotion,” Carcinogenesis, vol. 16, no. 10, pp. 2493–2497, 1995.
View at: Publisher Site | Google Scholar
B. Wahlstrom and G. Blennow, “A study on the fate of curcumin in the rat,” Acta Pharmacologica et Toxicologica, vol. 43, no. 2, pp. 86–92, 1978.
View at: Google Scholar
V. Ravindranath and N. Chandrasekhara, “Absorption and tissue distribution of curcumin in rats,” Toxicology, vol. 16, no. 3, pp. 259–265, 1980.
View at: Publisher Site | Google Scholar
V. Ravindranath and N. Chandrasekhara, “In vitro studies on the intestinal absorption of curcumin in rats,” Toxicology, vol. 20, no. 2-3, pp. 251–257, 1981.
View at: Publisher Site | Google Scholar
G. M. Holder, J. L. Plummer, and A. J. Ryan, “The metabolism and excretion of curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) in the rat,” Xenobiotica, vol. 8, no. 12, pp. 761–768, 1978.
View at: Google Scholar
G. Shoba, D. Joy, T. Joseph, M. Majeed, R. Rajendran, and P. S. S. R. Srinivas, “Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers,” Planta Medica, vol. 64, no. 4, pp. 353–356, 1998.
View at: Publisher Site | Google Scholar
A.-L. Chen, C.-H. Hsu, J.-K. Lin et al., “Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions,” Anticancer Research, vol. 21, no. 4 B, pp. 2895–2900, 2001.
View at: Google Scholar
R. A. Sharma, H. R. McLelland, K. A. Hill et al., “Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer,” Clinical Cancer Research, vol. 7, no. 7, pp. 1894–1900, 2001.
View at: Google Scholar
R. A. Sharma, S. A. Euden, S. L. Platton et al., “Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance,” Clinical Cancer Research, vol. 10, no. 20, pp. 6847–6854, 2004.
View at: Publisher Site | Google Scholar
S. Shishodia, G. Sethi, and B. B. Aggarwal, “Curcumin: getting back to the roots,” Annals of the New York Academy of Sciences, vol. 1056, pp. 206–217, 2005.
View at: Publisher Site | Google Scholar
M.-T. Huang, Y.-R. Lou, W. Ma, H. L. Newmark, K. R. Reuhl, and A. H. Conney, “Inhibitory effects of dietary curcumin on forestomach, duodenal, and colon carcinogenesis in mice,” Cancer Research, vol. 54, no. 22, pp. 5841–5847, 1994.
View at: Google Scholar
K. M. Mohandas and D. C. Desai, “Epidemiology of digestive tract cancers in India. V. Large and small bowel,” Indian Journal of Gastroenterology, vol. 18, no. 3, pp. 118–121, 1999.
View at: Google Scholar
G. S. Sidhu, A. K. Singh, D. Thaloor et al., “Enhancement of wound healing by curcumin in animals,” Wound Repair and Regeneration, vol. 6, no. 2, pp. 167–177, 1998.
View at: Publisher Site | Google Scholar
J. Folkman and Y. Shing, “Angiogenesis,” The Journal of Biological Chemistry, vol. 267, no. 16, pp. 10931–10934, 1992.
View at: Google Scholar
J. Folkman, “Angiogenesis in cancer, vascular, rheumatoid and other disease,” Nature Medicine, vol. 1, no. 1, pp. 27–31, 1995.
View at: Publisher Site | Google Scholar
D. Thaloor, A. K. Singh, G. S. Sidhu, P. V. Prasad, H. K. Kleinman, and R. K. Maheshwari, “Inhibition of angiogenic differentiation of human umbilical vein endothelial cells by curcumin,” Cell Growth and Differentiation, vol. 9, no. 4, pp. 305–312, 1998.
View at: Google Scholar
J. L. Arbiser, N. Klauber, R. Rohan et al., “Curcumin is an in vivo inhibitor of angiogenesis,” Molecular Medicine, vol. 4, no. 6, pp. 376–383, 1998.
View at: Google Scholar
S. Toda, T. Miyase, H. Arichi, H Tanizawa, and Y. Takino, “Natural antioxidants. III. Antioxidative components isolated from rhizome of Curcuma longa L,” Chemical and Pharmaceutical Bulletin, vol. 33, no. 4, pp. 1725–1728, 1985.
View at: Google Scholar
J. P. Gaddipati, S. V. Sundar, J. Calemine, P. Seth, G. S. Sidhu, and R. K. Maheshwari, “Differential regulation of cytokines and transcription factors in liver by curcumin following hemorrhage/resuscitation,” Shock, vol. 19, no. 2, pp. 150–156, 2003.
View at: Publisher Site | Google Scholar
S. D. Deodhar, R. Sethi, and R. C. Srimal, “Preliminary study on antirheumatic activity of curcumin (diferuloyl methane),” The Indian Journal of Medical Research, vol. 71, pp. 632–634, 1980.
View at: Google Scholar
B. Lal, A. K. Kapoor, P. K. Agrawal, O. P. Asthana, and R. C. Srimal, “Role of curcumin in idiopathic inflammatory orbital pseudotumours,” Phytotherapy Research, vol. 14, no. 6, pp. 443–447, 2000.
View at: Publisher Site | Google Scholar
B. Lal, A. K. Kapoor, O. P. Asthana et al., “Efficacy of curcumin in the management of chronic anterior uveitis,” Phytotherapy Research, vol. 13, no. 4, pp. 318–322, 1999.
View at: Publisher Site | Google Scholar
R. R. Satoskar, S. J. Shah, and S. G. Shenoy, “Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with postoperative inflammation,” International Journal of Clinical Pharmacology, Therapy, and Toxicology, vol. 24, no. 12, pp. 651–654, 1986.
View at: Google Scholar
R. C. Srimal and B. N. Dhawan, “Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent,” The Journal of Pharmacy and Pharmacology, vol. 25, no. 6, pp. 447–452, 1973.
View at: Google Scholar
A. M. Siddiqui, X. Cui, R. Wu et al., “The anti-inflammatory effect of curcumin in an experimental model of sepsis is mediated by up-regulation of peroxisome proliferator-activated receptor- $?$ ,” Critical Care Medicine, vol. 34, no. 7, pp. 1874–1882, 2006.
View at: Publisher Site | Google Scholar
B. M. Forman, J. Chen, and R. M. Evans, “The peroxisome proliferator-activated receptors: ligands and activators,” Annals of the New York Academy of Sciences, vol. 804, no. 1, pp. 266–275, 1996.
View at: Publisher Site | Google Scholar
B. Zingarelli, M. Sheehan, P. W. Hake, M. O'Connor, A. Denenberg, and J. A. Cook, “Peroxisome proliferator activator receptor-gamma ligands, 15-deoxy-Delta(12,14)-prostaglandin J2 and ciglitazone, reduce systemic inflammation in polymicrobial sepsisby modulation of signal transduction pathways,” Journal of Immunology, vol. 171, no. 12, pp. 6827–6837, 2003.
View at: Google Scholar
M. Ricote, A. C. Li, T. M. Willson, C. J. Kelly, and C. K. Glass, “The peroxisome proliferator-activated receptor- $γ$ is a negative regulator of macrophage activation,” Nature, vol. 391, no. 6662, pp. 79–82, 1998.
View at: Publisher Site | Google Scholar
C. Jiang, A. T. Ting, and B. Seed, “PPAR- $γ$ agonists inhibit production of monocyte inflammatory cytokines,” Nature, vol. 391, no. 6662, pp. 82–86, 1998.
View at: Publisher Site | Google Scholar
F. Chen, M. Wang, J. P. O'Connor, M. He, T. Tripathi, and L. E. Harrison, “Phosphorylation of PPAR $γ$ via active ERK1/2 leads to its physical association with p65 and inhibition of NF- $κ β$ ,” Journal of Cellular Biochemistry, vol. 90, no. 4, pp. 732–744, 2003.
View at: Publisher Site | Google Scholar
A. B. Kunnumakkara, S. Guha, S. Krishnan, P. Diagaradjane, J. Gelovani, and B. B. Aggarwal, “Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor- $κ β$ -regulated gene products,” Cancer Research, vol. 67, no. 8, pp. 3853–3861, 2007.
View at: Publisher Site | Google Scholar
G. C. Jagetia and B. B. Aggarwal, ““Spicing up” of the immune system by curcumin,” Journal of Clinical Immunology, vol. 27, no. 1, pp. 19–35, 2007.
View at: Publisher Site | Google Scholar
M. Hu, Q. Du, I. Vancurova et al., “Proapoptotic effect of curcumin on human neutrophils: activation of the p38 mitogen-activated protein kinase pathway,” Critical Care Medicine, vol. 33, no. 11, pp. 2571–2578, 2005.
View at: Publisher Site | Google Scholar
D. C. Angus, W. T. Linde-Zwirble, J. Lidicker, G. Clermont, J. Carcillo, and M. R. Pinsky, “Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care,” Critical Care Medicine, vol. 29, no. 7, pp. 1303–1310, 2001.
View at: Publisher Site | Google Scholar
A. Ayala, C.-S. Chung, J. L. Lomas et al., “Shock-induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency,” American Journal of Pathology, vol. 161, no. 6, pp. 2283–2294, 2002.
View at: Google Scholar
R. Taneja, J. Parodo, S. H. Jia, A. Kapus, O. D. Rotstein, and J. C. Marshall, “Delayed neutrophil apoptosis in sepsis is associated with maintenance of mitochondrial transmembrane potential and reduced caspase-9 activity,” Critical Care Medicine, vol. 32, no. 7, pp. 1460–1469, 2004.
View at: Publisher Site | Google Scholar
M. Collin, N. S. Patel, L. Dugo, and C. Thiemermann, “Role of peroxisome proliferator-activated receptor- $γ$ in the protection afforded by 15-deoxy $Δ^{12, 14}$ prostaglandin J2 against the multiple organ failure caused by endotoxin,” Critical Care Medicine, vol. 32, no. 3, pp. 826–831, 2004.
View at: Publisher Site | Google Scholar
M. Abdelrahman, A. Sivarajah, and C. Thiemermann, “Beneficial effects of PPAR- $γ$ ligands in ischemia-reperfusion injury, inflammation and shock,” Cardiovascular Research, vol. 65, no. 4, pp. 772–781, 2005.
View at: Publisher Site | Google Scholar
M. Abdelrahman, M. Collin, and C. Thiemermann, “The peroxisome proliferator-activated receptor- $γ$ ligand 15-deoxy $Δ^{12, 14}$ prostaglandin J2 reduces the organ injury in hemorrhagic shock,” Shock, vol. 22, no. 6, pp. 555–561, 2004.
View at: Publisher Site | Google Scholar

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Copyright © 2007 Asha Jacob et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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