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STUDIES: Chronic Pain

Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research.

Curcuma longa (turmeric) has a long history of use in Ayurvedic medicine as a treatment for inflammatory conditions. Turmeric constituents include the three curcuminoids: curcumin (diferuloylmethane; the primary constituent and the one responsible for its vibrant yellow color), demethoxycurcumin, and bisdemethoxycurcumin, as well as volatile oils (tumerone, atlantone, and zingiberone), sugars, proteins, and resins. While numerous pharmacological activities, including antioxidant and antimicrobial properties, have been attributed to curcumin, this article focuses on curcumin's anti-inflammatory properties and its use for inflammatory conditions. Curcumin's effect on cancer (from an anti-inflammatory perspective) will also be discussed; however, an exhaustive review of its many anticancer mechanisms is outside the scope of this article. Research has shown curcumin to be a highly pleiotropic molecule capable of interacting with numerous molecular targets involved in inflammation. Based on early cell culture and animal research, clinical trials indicate curcumin may have potential as a therapeutic agent in diseases such as inflammatory bowel disease, pancreatitis, arthritis, and chronic anterior uveitis, as well as certain types of cancer. Because of curcumin's rapid plasma clearance and conjugation, its therapeutic usefulness has been somewhat limited, leading researchers to investigate the benefits of complexing curcumin with other substances to increase systemic bioavailability. Numerous in-progress clinical trials should provide an even deeper understanding of the mechanisms and therapeutic potential of curcumin.

Source: Jurenka JS. Altern Med Rev. 2009;14(2):141-53.


Mechanism of the Anti-inflammatory Effect of Curcumin: PPAR-gamma Activation.

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-gamma (PPAR-gamma) activation.

Source: Jacob A, Wu R, Zhou M, Wang P. PPAR Res. 2007;89369.


Curcumin as "Curecumin": from kitchen to clinic.

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 12g 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".

Source: Goel A, Kunnumakkara AB, Aggarwal BB. Biochem Pharmacol. 2008 Feb 15;75(4):787-809.


A Randomized, Pilot Study to Assess the Efficacy and Safety of Curcumin in Patients with Active Rheumatoid Arthritis.

In this study, 45 patients with rheumatoid arthritis were randomized into 3 groups, with patients receiving either BCM-95 curcumin 500 mg twice daily, the prescription drug diclofenac sodium (one brand name is Voltaren®) 50 mg twice daily, or a combination of the two. The results were judged using the clinically validated Disease Activity Score (DAS) 28 and also with the American College of Rheumatology (ACR) criteria and scores for pain and swelling in joints. Patients in all 3 groups improved. The curcumin group showed the greatest improvement, and the endpoint scores were significantly better than the patients in the drug group. Using both interventions concurrently did not show any additional benefit with regards to disease scores. Curcumin was found to be safe with no adverse effects in this study. In the drug group. 14% of the patients withdrew because of adverse effects

Source: Chandran B, Goel A. Phytother Res. 2012 Mar 9. doi: 10.1002/ptr.4639.


Clinical Evaluation of a herbal product in the management of knee osteoarthritis.

Originally presented at the Osteoarthritis Research Symposium Internationale (OARSI) Annual World Congress on Osteoarthritis, September 15-18, 2011. San Diego, CA. 28 subjects with diagnosed osteoarthritis of the knee were randomized to a 500 mg blend BCM-95 curcumin and Bospure® Boswellia twice a day or to the prescription drug celecoxib (one brand name is Celebrex®) 100 mg twice a day. Symptom scoring and clinical evaluation yielded superior results on pain relief and distance walked for the BCM-95 and Bospure blend compared to celecoxib. BCM-95 and Bospure equaled celecoxib on joint flexibility. No serious adverse effects noted.

Source: Antony B, Kizhakedath R, Benny M, Kuruvilla BT. Abstract 316. Osteoarthritis Cartilage. 2011;19(S1):S145-S146.


Human Clinical Study to evaluate the bioavailability of a high-absorption curcumin.  

15 healthy men and women ages 24-45; 8 assigned to plain curcumin and 7 assigned to BCM-95 curcumin. Results: overall, 7-fold increase over course of 12 hours. BCM-95 peak at 1600 ng/g; plain curcumin peak at ~230 ng/g. BCM-95 curcumin remained above 200 ng/g for 12 hours. Plain curcumin remained above 200 ng/g for less than 2 hours. Two hours after ingestion, BCM-95 levels are 10-fold over plain curcumin.

Source: Benny B, Antony B. Spice India. September, 2006:11-15.

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