Curcumin Research & Science

Curcumin and Inflammation Abstract - Pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α) play a key role in the pathogenesis of osteoarthritis (OA). Once released, these cytokines are potent stimulators

for the de novo production of catabolic enzymes such as matrix metalloproteinases (MMPs) and cyclo-oxygenase-2 (COX-2). Anti-inflammatory agents capable of suppressing the production and catabolic actions of these cytokines may have therapeutic potential in the treatment of OA and a range of other osteoarticular disorders. The purpose of this study was to examine the therapeutic effect of Curcumin (diferuloylmethane), a pharmacologically safe phytochemical agent, on males and foals affected by degenerative joint diseases. Curcumin, in the form phytosome (CURCUVET®, Indena Spa, Milan, Italy) was administered to animals for fifteen days and gene expression was monitored before the treatment and after four, eight, and fifteen days. In mares, Curcumin inhibited the expression of COX-2, TNF-α, IL-1β, IL1RN, and IL6, even if only the downregulation of IL-1β and IL1RN were significant. In foals, Curcumin significantly inhibited the expression of COX-2, TNF-α, IL1RN and significantly increased that of IL6. These results indicate that Curcumin has nutritional potential as a natural anti-inflammatory agent for treating osteoarticular disorders through suppression of pro-inflammatory cytokines and catabolic enzymes.

Reference:
Farinaci,M. et al. Dietary Administration of Curcumin Modifies Transcriptional Profile of Genes Involved in Inflammatory Cascade in Horse Leukocytes, Ital.J.Anim.Sci. vol. 8 (Suppl. 2), 84-86, 2009

Curcumin Capabilities
Abstract:  Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in
turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research
over the last half century has revealed several important functions of curcumin. It binds to a
variety of proteins and inhibits the activity of various kinases. By modulating the activation
of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates
cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12 g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be ‘‘Curecumin’’.

Reference:
Goel A, et al., Curcumin as ‘‘Curecumin’’: From kitchen to clinic, Biochem Pharmacol (2007),
doi:10.1016/j.bcp.2007.08.016

Curcumin and Cancer
Abstract:  Carcinogenesis encompasses 3 closely associated stages: initiation, progression, and promotion. Phytochemicals are nonnutritive components of plants that are currently being studied in chemoprevention of various diseases for their pleiotropic effects and nontoxicity. Cancer chemoprevention involves the use of either natural or synthetic chemicals to prevent the initiation, promotion, or progression of cancer. Curcumin is the active constituent of turmeric, which is widely used as a spice in Indian cooking. It has been shown to possess antiinflammatory, antioxidant, and antitumor properties. Curcumin has also been shown to be benefi cial in all 3 stages of carcinogenesis. Much of its benefi cial effect is found to be due to its inhibition of the transcription factor nuclear factor kappa B (NF-kappaB) and subsequent
inhibition of proinfl ammatory pathways. This review summarizes the inhibition of NF-kappaB by curcumin and describes the recently identifi ed molecular targets of curcumin. It is hoped that continued research will lead to development of curcumin as an anticancer agent

Reference:
Thangapazham, R. et al., Multiple Molecular Targets in Cancer Chemoprevention by Curcumin, The AAPS Journal 2006; 8 (3) Article 52

Curcumin and Inflammation
Abstract:   Osteoarthritis (OA) and rheumatoid arthritis (RA) are characterised by joint inflammation and cartilage degradation. Although mesenchymal stem cell (MSC)-like progenitors are resident in the superficial zone of articular cartilage, damaged tissue does not possess the capacity for regeneration. The high levels of pro-inflammatory cytokines present in OA/RA joints may impede the chondrogenic differentiation of these progenitors. Interleukin (IL)-1β activates the transcription factor nuclear factor-κB (NF-κB), which in turn activates proteins involved in matrix degradation, inflammation and apoptosis. Curcumin is a phytochemical capable of inhibiting IL-1β-induced activation of NF-κB and expression of apoptotic and pro-inflammatory genes in chondrocytes. Therefore, the aim of the present study was to evaluate the influence of curcumin on IL-1β-induced NF-κB signalling pathway in MSCs during chondrogenic differentiation.  Curcumin treatment may help establish a microenvironment in which the effects of pro-inflammatory cytokines are antagonized, thus facilitating chondrogenesis of MSC-like progenitor cells in vivo. This strategy may support the regeneration of articular cartilage.

Reference:
Buhrmann, C. et al., Curcumin mediated suppression of nuclear factor-kappaB promotes
chondrogenic differentiation of mesenchymal stem cells in a high-density co-culture microenvironment, Arthritis Research & Therapy 2010, 12:R127 doi:10.1186/ar3065

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