Suppression by Curcuma comosa Roxb. of pro-inflammatory cytokine secretion in phorbol-12-myristate-13-acetate stimulated human mononuclear cells Amorntus Sodsai a , Pawinee Piyachaturawat b , Samaisukh Sophasan b , Apichart Suksamrarn c , Molvibha Vongsakul d, ⁎ a Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok 10400, Thailand b Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand c Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok 10240, Thailand d Department of Microbiology, Faculty of Science, Mahidol University, Rama 6 Rd, Bangkok 10400, Thailand Received 7 October 2006; received in revised form 14 December 2006; accepted 26 December 2006 Abstract Curcuma comosa Roxb. is a medicinal plant that has traditionally been used in Thailand for treatment of inflammation in postpartum uterine bleeding. The purpose of this study was to evaluate its anti-inflammatory effects using peripheral blood mononuclear cells (PBMC) and human pro-monocytic cell line (U937). Pretreatment with hexane or ethanol extract or two diarylhepatanoids (5-hydroxy-7-(4-hydroxyphenyl)-1-phenyl-(1E)-1-heptene and 7-(3,4-dihydroxyphenyl)-5-hydroxy-1-phenyl- (1E)-1-heptene) of C. comosa significantly decreased the release of pro-inflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin-1β, from phorbol-12-myristate-13-acetate (PMA)-stimulated PBMC and U937 cells. In PMA-stimulated U937 cells, the two C. comosa diarylhepatanoids reduced the expression of TNF-α and suppressed expression of IκB kinase and activation of nuclear factor kappa B. These results indicated that C. comosa and its diarylheptanoids have anti-inflammatory properties which could be exploited for clinical use. © 2007 Elsevier B.V. All rights reserved. Keywords: Curcuma comosa; Diarylheptanoids; Anti-inflammation; NF-κB; TNF-α 1. Introduction Nuclear factor kappa B (NF-κB) is a key transcrip- tion factor activated by several cellular signal transduc- tion pathways involved in host defense, inflammation, apoptosis, tumorigenesis and various autoimmune diseases [1,2]. In the cytoplasm it exists as an inactive heterotrimer consisting of p50 and p65 bound by members of the inhibitory IκB protein family. Various inflammatory stimuli, including a variety of pathogens, stress-inducing agents and phorbol-12-myristate-13- acetate (PMA), activate monocyte and macrophage to secrete pro-inflammatory cytokines [3,4]. PMA acti- vates protein kinase C (PKC) to initiate a cascade of responses, leading to phosphorylation and inactivation of IκB and resulting in translocation of NF-κB (p50/ p65) from cytosol to nucleus, where it binds to its cognate element and induces expression of a number of immediate-early genes involved in inflammatory and International Immunopharmacology 7 (2007) 524 – 531 www.elsevier.com/locate/intimp ⁎ Corresponding author. Tel.: +66 2 201 5679; fax: +66 2 644 5411. E-mail address: scmvs2@yahoo.com (M. Vongsakul). 1567-5769/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.intimp.2006.12.013