Post by David Feder on Mar 11, 2008 11:34:27 GMT -5
Curcumin: From ancient medicine to current clinical trialsH. Hatchera, R. Planalpb, J. Chob, F. M. Tortia,d,* and S. V. Tortic,d
Abstract. Curcumin is the active ingredient in the
traditional herbal remedy and dietary spice turmeric
(Curcuma longa). Curcumin has a surprisingly wide
range of beneficial properties, including anti-inflammatory,
antioxidant, chemopreventive and chemotherapeutic
activity. The pleiotropic activities of
curcumin derive from its complex chemistry as well
as its ability to influence multiple signaling pathways,
including survival pathways such as those regulated by
NF-kB, Akt, and growth factors; cytoprotective pathways
dependent on Nrf2; and metastatic and angiogenic
pathways. Curcumin is a free radical scavenger
and hydrogen donor, and exhibits both pro- and
antioxidant activity. It also binds metals, particularly
iron and copper, and can function as an iron chelator.
Curcumin is remarkably non-toxic and exhibits limited
bioavailability. Curcumin exhibits great promise
as a therapeutic agent, and is currently in human
clinical trials for a variety of conditions, including
multiple myeloma, pancreatic cancer, myelodysplastic
syndromes, colon cancer, psoriasis and Alzheimer's
disease.
Anti-inflammatory and antioxidant activities of
curcumin
Many of the activities associated with curcumin relate
to its ability to suppress acute and chronic inflammation
[8]. In vitro studies have shown that curcumin
inhibits lipo-oxygenase and cyclo-oxygenase activities
in phorbol 12-myristate 13-acetate (PMA)-induced
inflammation of mouse fibroblast cells [9], xanthine
oxygenase activities in NIH3T3 cells [10], nitric oxide
production in RAW264.7 murine macrophages [11,
12], and reactive oxygen species (ROS) generation in
activated rat peritoneal macrophages [13]. Curcumin
also inhibits the production of pro-inflammatory
monocyte/macrophage-derived cytokines [interleukin-
8 (IL-8), monocyte inflammatory protein-1
(MIP-1), monocyte chemotactic protein-1 (MCP-1),
interleukin-1b (IL-1b), and tumor necrosis factor-a
(TNF- a)] in PMA- or LPS-stimulated peripheral
blood monocytes and alveolar macrophages [14]. A
recent study revealed that oxidative stimulation of G
proteins in human brain membranes by metabolic prooxidants,
homocysteine and hydrogen peroxide, can
be significantly depressed by curcumin [15]. Curcumin
was shown to inhibit lipid peroxidation in a rat
livermicrosome preparation [16] as well as in rat brain
homogenates, where curcuminoids actually exhibited
more potent antioxidant activity than alpha-tocopherol
[17].
In vivo studies have also demonstrated an inhibitory
effect of curcumin on inflammation. For example,
curcumin inhibited inflammation induced by carrageenan
[18, 19] and acute lung injury induced by
cyclophosphamide [20]. In rats, curcumin had comparable
activity to phenylbutazone, a commonly used
anti-inflammatory agent [18]. Further, whereas phenylbutazone
produced a significant leukopenia and
lymphyocytopenia, curcumin did not [18]. Rats that
were fed curcumin for 7 days prior to being treated
with cyclophosphamide to induce lung injury, exhibited
an increase in antioxidant defense mechanisms
[20]. Topical application of curcumin markedly inhibited
TPA- and arachidonic acid-induced epidermal
inflammation (ear edema) in mice [21]. Thus, curcumin
exhibits substantial antioxidant properties in a
wide variety of experimental settings.
www.ncbi.nlm.nih.gov/pubmed/16718687?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Progressive nuclear factor-kappaB activation resistant to inhibition by contraction and curcumin in mdx mice.Durham WJ, Arbogast S, Gerken E, Li YP, Reid MB.
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. wdurham@bc.tmc.edu
Skeletal muscle of patients with Duchenne-type muscular dystrophy and mdx mice exhibits elevated activity of the transcription factor NF-kappaB (nuclear factor-kappaB), which may play a role in muscle catabolism. We measured skeletal muscle NF-kappaB activity in mdx mice at three ages (10 days, 4 weeks, and 8 weeks) to test the hypothesis that NF-kappaB activity is elevated in an age-dependent manner in these mice. In addition, we tested the hypothesis that NF-kappaB activity could be reduced in mdx skeletal muscle by dietary supplementation with curcumin (1% w/v) or by fatiguing muscle contractions. We found that NF-kappaB activity was elevated at 4 and 8 weeks of age but not at 10 days, and was resistant to inhibition by either fatiguing contractions or dietary curcumin. We conclude that NF-kappaB activity is elevated in dystrophic skeletal muscle in an age-related manner and is resistant to inhibition by physiological and pharmacological means. These findings are consistent with a role for NF-kappaB activation in dystrophic muscle wasting but suggest that predicted interventions such as exercise or inhibitors of the early steps in the NF-kappa activation pathway may not be effective and that targeted research is needed to identify novel therapeutic strategies
Abstract. Curcumin is the active ingredient in the
traditional herbal remedy and dietary spice turmeric
(Curcuma longa). Curcumin has a surprisingly wide
range of beneficial properties, including anti-inflammatory,
antioxidant, chemopreventive and chemotherapeutic
activity. The pleiotropic activities of
curcumin derive from its complex chemistry as well
as its ability to influence multiple signaling pathways,
including survival pathways such as those regulated by
NF-kB, Akt, and growth factors; cytoprotective pathways
dependent on Nrf2; and metastatic and angiogenic
pathways. Curcumin is a free radical scavenger
and hydrogen donor, and exhibits both pro- and
antioxidant activity. It also binds metals, particularly
iron and copper, and can function as an iron chelator.
Curcumin is remarkably non-toxic and exhibits limited
bioavailability. Curcumin exhibits great promise
as a therapeutic agent, and is currently in human
clinical trials for a variety of conditions, including
multiple myeloma, pancreatic cancer, myelodysplastic
syndromes, colon cancer, psoriasis and Alzheimer's
disease.
Anti-inflammatory and antioxidant activities of
curcumin
Many of the activities associated with curcumin relate
to its ability to suppress acute and chronic inflammation
[8]. In vitro studies have shown that curcumin
inhibits lipo-oxygenase and cyclo-oxygenase activities
in phorbol 12-myristate 13-acetate (PMA)-induced
inflammation of mouse fibroblast cells [9], xanthine
oxygenase activities in NIH3T3 cells [10], nitric oxide
production in RAW264.7 murine macrophages [11,
12], and reactive oxygen species (ROS) generation in
activated rat peritoneal macrophages [13]. Curcumin
also inhibits the production of pro-inflammatory
monocyte/macrophage-derived cytokines [interleukin-
8 (IL-8), monocyte inflammatory protein-1
(MIP-1), monocyte chemotactic protein-1 (MCP-1),
interleukin-1b (IL-1b), and tumor necrosis factor-a
(TNF- a)] in PMA- or LPS-stimulated peripheral
blood monocytes and alveolar macrophages [14]. A
recent study revealed that oxidative stimulation of G
proteins in human brain membranes by metabolic prooxidants,
homocysteine and hydrogen peroxide, can
be significantly depressed by curcumin [15]. Curcumin
was shown to inhibit lipid peroxidation in a rat
livermicrosome preparation [16] as well as in rat brain
homogenates, where curcuminoids actually exhibited
more potent antioxidant activity than alpha-tocopherol
[17].
In vivo studies have also demonstrated an inhibitory
effect of curcumin on inflammation. For example,
curcumin inhibited inflammation induced by carrageenan
[18, 19] and acute lung injury induced by
cyclophosphamide [20]. In rats, curcumin had comparable
activity to phenylbutazone, a commonly used
anti-inflammatory agent [18]. Further, whereas phenylbutazone
produced a significant leukopenia and
lymphyocytopenia, curcumin did not [18]. Rats that
were fed curcumin for 7 days prior to being treated
with cyclophosphamide to induce lung injury, exhibited
an increase in antioxidant defense mechanisms
[20]. Topical application of curcumin markedly inhibited
TPA- and arachidonic acid-induced epidermal
inflammation (ear edema) in mice [21]. Thus, curcumin
exhibits substantial antioxidant properties in a
wide variety of experimental settings.
www.ncbi.nlm.nih.gov/pubmed/16718687?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum
Progressive nuclear factor-kappaB activation resistant to inhibition by contraction and curcumin in mdx mice.Durham WJ, Arbogast S, Gerken E, Li YP, Reid MB.
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. wdurham@bc.tmc.edu
Skeletal muscle of patients with Duchenne-type muscular dystrophy and mdx mice exhibits elevated activity of the transcription factor NF-kappaB (nuclear factor-kappaB), which may play a role in muscle catabolism. We measured skeletal muscle NF-kappaB activity in mdx mice at three ages (10 days, 4 weeks, and 8 weeks) to test the hypothesis that NF-kappaB activity is elevated in an age-dependent manner in these mice. In addition, we tested the hypothesis that NF-kappaB activity could be reduced in mdx skeletal muscle by dietary supplementation with curcumin (1% w/v) or by fatiguing muscle contractions. We found that NF-kappaB activity was elevated at 4 and 8 weeks of age but not at 10 days, and was resistant to inhibition by either fatiguing contractions or dietary curcumin. We conclude that NF-kappaB activity is elevated in dystrophic skeletal muscle in an age-related manner and is resistant to inhibition by physiological and pharmacological means. These findings are consistent with a role for NF-kappaB activation in dystrophic muscle wasting but suggest that predicted interventions such as exercise or inhibitors of the early steps in the NF-kappa activation pathway may not be effective and that targeted research is needed to identify novel therapeutic strategies
