Curcumin spices up OA treatment

Janis Kelly

February 06, 2006

February 6, 2006


Tel Aviv, Israel - Turmeric, a component of curry spice mixtures, has long been used for anti-inflammatory treatment in traditional Chinese and Ayurevedic medicine. The active ingredient in turmeric is curcumin, and Dr Nadir Arber (Sourasky Medical Center, Tel Aviv, Israel) reports in the February 2006 issue of Rheumatology that curcumin not only has anti-inflammatory properties but also synergistically potentiates the beneficial effects of celecoxib (Celebrex, Pfizer) [ 1 ].

"The effects of curcumin are due to inhibition of COX-2, resulting in a 95% reduction in production of prostaglandins, but also to non-COX-2 processes. The synergy with celecoxib in vitro was so striking that we think adding curcumin might permit the use of much lower doses of celecoxib, thereby reducing the risk of side effects such as cardiovascular problems," Arber told rheumawire. "Consequently, we have begun a double-blind, randomized, placebo-controlled trial of celecoxib with and without curcumin in patients with knee osteoarthritis [OA]."

Curcumin inhibits COX-2 at the translational level and has been the subject of considerable interest in cancer treatment and prevention. Arber reasoned that combining curcumin with a COX-2 inhibitor with a different mechanism of action might also be useful for treating joint inflammation such as OA or rheumatoid arthritis (RA).

The synergy with celecoxib in vitro was so striking that we think adding curcumin might permit the use of much lower doses of celecoxib, thereby reducing the risk of side effects.

Arber used bits of human synovial tissue collected during total-knee-replacement surgery to prepare cultures of OA synovial adherent cells. These cells were then exposed to different concentrations of celecoxib (0-40 mol/L) and curcumin (0-20 mol/L) and combinations of the two. Apoptosis was measured with flow cytometry, and COX-2 activity was measured as production of prostaglandin E2.

"A synergistic effect was observed in inhibition of cell growth when the cells were exposed to various concentrations of celecoxib combined with curcumin," Arber writes. The inhibition of cell growth was associated with increased apoptosis, and the synergy was mediated "through a mechanism that involves inhibition of COX-2 activity."

Arber hopes that this might mean that the combination will permit the use of celecoxib at lower and safer concentrations. He and Dr Dan Caspi (Sackler School of Medicine, Tel Aviv, Israel) have begun testing this possibility in a double-blind, placebo-controlled, randomized crossover trial of patients with knee OA. Arber said that 10 of the anticipated 100 patients have already entered the study. Patients will be randomized to four weeks of celecoxib (100 mg bid) with either placebo or curcumin (1.5-2.0 g bid) and then will cross over to another four weeks of celecoxib plus the opposite treatment.

Outcome measures are self-assessment of knee pain using 100-mm visual analog scale (VAS), self-assessment of knee function using 100-mm VAS, patient global assessment, physician global assessment, knee swelling (measured as knee circumference at the mid-patellar region), and Western Ontario and McMaster Universities osteoarthritis index (WOMAC).

Although Arber's studies use pharmaceutical-grade curcumin obtained from Merck, clinicians might also face questions from patients interested in taking nonprescription curcumin dietary supplements or just in eating more curry.

"I myself believe that this combination will work, but what I believe does not matter. Only the data from a proper randomized trial matter. So my advice is, wait for the data!" Arber said.

The effects of curcumin are only partly due to reductions in COX-2 activity. Curcumin affects numerous molecular targets, including transcription factors such as NF- B, cell-cycle proteins such as cyclin D1 and p21, and cytokines such as TNF, IL-1, and IL-6. It also appears able to directly protect cartilage from inflammation-related damage. Shakibaei et al found that curcumin protected cultured human chondrocytes from IL-1- B (IL-1b)-induced degradation by preventing activation of matrix-degrading enzymes, preventing downregulation of matrix production, and reducing chondrocyte apoptosis [ 2 ].

Sources

  1. Lev-Ari S, Strier L, Kazanov D, et al. Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells. Rheumatology 2006; 4:171-177. Abstract

  2. Shakibaei M, Schulze-Tanzil G, John T, et al. Curcumin protects human chondrocytes from IL-1-beta-induced inhibition of collagen type II and beta-1-integrin expression and activation of caspase-3: an immunomorphological study. Ann Anat 2005; 187:487-497. Abstract


 

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....