6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in wasabi (Wasabia japonica), which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties, including anti-inflammatory, antimicrobial, antiplatelet, and anticancer effects. We previously reported that 6-MSITC strongly suppresses cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and cytokines, which are important factors that mediate inflammatory processes. Moreover, molecular analysis demonstrated that 6-MSITC blocks the expressions of these factors by suppressing multiple signal transduction pathways to attenuate the activation of transcriptional factors. Structure-activity relationships of 6-MSITC and its analogues containing an isothiocyanate group revealed that methylsulfinyl group and the length of alkyl chain of 6-MSITC might be related to high inhibitory potency. In this paper, we review the anti-inflammatory properties of 6-MSITC and discuss potential molecular mechanisms focusing on inflammatory responses by macrophages. 1. Introduction Isothiocyanates (ITCs) are a group of naturally occurring sulfur compounds containing –N=C=S functional group, available often abundantly from many cruciferous vegetables. ITCs are stored as glucosinolate precursors in the plants. The damage of plant tissue such as chopping and mastication activates myrosinase which hydrolyses the glucosinolate (myrosinase-glucosinolate system), and the resultant ITCs play a key role in the defense against herbivores and pathogens [1, 2]. There are a significant number of naturally occurring and synthetic ITCs, and numerous studies have demonstrated the chemopreventive and anti-inflammatory properties of ITCs in vitro and in vivo [3–5]. Accumulating evidence suggests that ITCs exert their effects through a variety of signaling pathways involved in detoxification, inflammation, apoptosis, and cell cycle regulation, among others [4–6]. Wasabi (Wasabia japonica) is a member of the Brassicaceae family of vegetables, and its rhizome is a very popular pungent spice in Japan. Several studies have shown that wasabi has multiple physiological functions, such as appetite enhancement [7], antimicrobial activity [8], inhibition of platelet aggregation [9], and the suppression of N-methyl- -nitro-N-nitrosoguanidine-induced rat gastric carcinogenesis [10]. Wasabi differs from other Brassicaceae species in that it contains higher concentration of ITCs, especially long-chain ITCs. The bioactive components of wasabi have
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