20 KEY INGREDIENTS side-effects linked to prolonged ficantly decreased pain responses treatment with nimesulide, as with in two validated pain tests: the hot- other NSAIDs, such as diclofenac plate and formalin test. Given that or ibuprofen and so many others, soft tissue injury is associated with have been reported with increased inflammatory pain, the anti-inflam- risks of developing gastrointestinal matory effect of the mangosteen damage (16). With similar efficacy, extract was examined in an animal 5 days’ supplementation with man- model of LPS-induced systemic gosteen extract, 600 mg daily, was inflammation. Mice pre-treated effective in significantly relieving with the extract 30 minutes before pain (-37.4%). Despite the fact injection with LPS displayed a si- that nimesulide appeared to be a gnificantly lower level of TNF-α in slightly more efficient solution for plasma (-69%) when compared to the management of acute pain in LPS-treated mice. the short period of treatment, the mangosteen extract provided the The role of TNF-α in inflammato- same benefits as the NSAID in the ry pain has been brought to light subgroup of volunteers suffering in studies showing a strong cor- from chronical pain, who showed relation between levels of TNF-α respective averaged pain scores and pain intensity (18). Evidence of 3.8 (n=4) and 4.25 (n=5) suggested that a TNF-α-induced (p=0.38) (data not shown). mechanism of pain might be eli- cited through direct and indirect This suggests that the extract of pathways. The latter includes ac- mangosteen, in the absence of tivation of COX-2 expression and any side or unwanted effects, the subsequent release of the may have the ability to provide a mediator of central pain, PGE2 comparatively better risk-benefit (19)Numerous authors have also . balance for the management of highlighted the modulation of pain chronic pain,.Analgesic activity of through a direct sensitization of active compounds extracted from nociceptors, suggesting a key mangosteen has previously been role of TNF-α in pain initiation demonstrated in a model of pain and sustained pain (20). Accor- in mice (17)in which pretreatment dingly,the significant decrease with either α- or γ-mangostin signi- in LPS-induced release of TNF-α