RESUMEN
Gamavuton-0 (GVT-0) is a curcumin analogue, which is synthesized from acetone and vanillin with chloride acid as a catalyst and ethanol as a solvent. The compound has been reported to have an anti-inflammatory effect related to its activity as COX-2 inhibitor, anti-oxydant, and radical scavanger. This study was aimed to investigate whether the GVT-0 has a suppressive effect on rheumatoid arthritis (RA) as one of chronic inflammatory disorders in a rat model. Wistar rats were immunized with Complete Freund’s Adjuvant (CFA). After a second CFA immunization, the rats were treated with GVT-0 orally at 10, 20, 40, 80 mg/kg BW once a day for 21 days, while the positive control received methotrexate 0.22 mg/kg BW. The animal paws were evaluated macroscopically for redness, swelling and deformities with Smit method to assess arthritic index. The anti-inflammatory effect of GVT-0 was evaluated using a plethismograph by measuring rat paw edema, while it’s effects on the level of TNF- and IL-1β in the ankle joints were examined using an ELISA method. The effect of GVT-0 on cartilage destruction was assesed histologically using Safranin-O staining. The acute toxicity test was also performed to assess the safety potential of the compound. The oral treatment of rats for 21 days with various doses of GVT-0 significantly suppressed the progession of RA indicated by the improvement of arthritic index and decreased the inflammation in rat paws. The compound also decreased the level of TNFα and IL-1β in ankle joints. The destruction of cartilage was significantly reduced in rats ankles after treatment with GVT-0. In toxicological assay, the apparent LD50 value of GT-0 was regarded as 7,29 g/kg BW and was classiefied to be practically non-toxic. The results suggest that GVT-0 is safe and potential to modify the progression of rheumatoid arthritis and can be developed as a new disease modifying anti rheumatoid arthritis drugs (DMARDs).
RESUMEN
Gamavuton-0 (GVT-0), a curcumin analogue, has been reported to have antiinflammatory and antioxidant activity, however, its analgesic activity has not yet been investigated. This research purpose is to study the effect of GVT-0 on acute and persistent pain using Modified Hot Plate (MHP) method and Formalin test, respectively, on male Swiss mice. In MHP method, the five groups of animals were pretreated with GVT-0 (10, 20, 40, and 80 mg/kg, orally) and indomethacin (4 mg/kgBB, i.p, for positive control), respectively, and immediately followed by stimulation with the carrageenan in sterile saline with a final volume of 50 μl in the left paw. The animals were then placed in hot plate (51oC). The latency time was determined at 90 min post-challenge. In the Formalin test, the six groups of animals were pretreated with GVT-0 (10, 20, 40 and 80 mg/kg, orally), morphine (5 mg/kgBB, i.p), and indomethacin (4 mg/kgBB, i.p) respectively, 60 min prior to the injection of 1.0% aqueous formalin (20 μl) administered by the intraplantar route into the right hindpaw. The licking time was measured at the first 5 min (initial phase, neurogenic) and 10-30 min after formalin injection (late phase, inflammatory). Result showed that GVT-0 has analgesic effect on acute pain using MHP method with ED50 of 27,69 mg/kgBW (p.o). While using Formalin test, GVT-0 showed analgesic activity with ED50 of 109,02 mg/kgBW (p.o) in initial phase, and ED50 of 13,53 mg/kgBW (p.o) in late phase. These results suggest that GVT-0 is a potential candidate for new antiinflammatory and analgesic agent that can be used for the treatment of different painful condition.