## 1 Introduction  
Although inflammation is a defense response against harmful stimuli and injury, its continued reaction is associated with the development of chronic diseases such as obesity, inflammatory bowel disease, and several cancers [1; 2; 3]. Macrophage activation plays a key role in the progression of multiple inflammatory diseases by secreting pro-inflammatory cytokines (e.g., interleukin (IL)-6 and IL-1B) that recruit additional immune cells to the site of infection or tissue injury, releasing cytotoxic and inflammatory molecules (e.g., nitric oxide (NO)), and critical enzymes (e.g., inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2)) [4; 5]. In particular, lipopolysaccharide (LPS)-stimulated macrophages are mediated through the trans-membrane signaling receptor toll-like receptor 4 (TLR4). Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), a pivotal regulator in TLR4 pathways, plays a crucial role in most inflammatory responses by stimulating the expression of pro-inflammatory genes. The activation of NF-\(\kappa\)B is a consequence of degradation of inhibitors of \(\kappa\)B (I\(\kappa\)B) [6; 7]. In addition, the activation of MAPK (Mitogen-activated protein kinase) pathways including p38, JNK, and ERK, leads to the activation of NF-\(\kappa\)B [8]. The MAPK pathway also regulated another inflammatory key gene name AP-1 by phosphorylation [9]. The vertebrate zebrafish (Danio rerio) is a small tropical fish that serves as a model species in the fields of molecular genetics and developmental biology [10; 11]. The zebrafish is an especially informative tool for studying inflammation, because it has both innate and acquired immune systems that are very similar to the mammalian immune system [12]. A large number of cytokine genes and inflammatory gene, such as TNF-a, IFN, IL-1b, IL-8, and NF-\(\kappa\)B, which are related to the innate immune system, have been identified in zebrafish [13; 14; 15]. Ginseng is a perennial plant that grows in eastern Asia. Its root has been used traditionally as a folk medicine for improving physical stamina and modulating immune function [16; 17]. Ginseng is composed mainly of ginsenosides, which contain an aglycone with a dammarane skeleton and exhibit a variety of biological benefits, including anti-tumor, anti-cardiovascular disease, and anti-inflammatory properties [18; 19]. It was previously reported that the biotransformation of ginsenosides by human intestinal bacteria is closely related to the biological activity of ginsenosides. For example, protopanaxadiol is transformed to 20-O-\(\beta\)-D-glucopyranosyl-20(S)-protopanaxadiol (compound K) by human intestinal bacteria [20]. Compound K is one of the pharmacologic metabolite compounds biotransformed from ginsenosides, and it has been reported to induce health benefits through its anti-carcinogenic and anti-diabetic properties [21; 22]. [PERSON] et al. demonstrated the absorption, distribution, and metabolism of compound K in human. Compound K was absorbed into the blood 24 h after oral administration, with average values of 10.76 \(\pm\) 2.07 h (maximum drug concentration time; Tmax), 27.89 \(\pm\) 24.46 ng/mL (maximum drug concentration; Cmax), and 221.98 \(\pm\) 221.42 ug/mL (area under the blood concentration curve; AUC) respectively [23]. Moreover, [PERSON] et al. investigated the absorption of compound K in rat plasma [24]. In our previous studies, we showed that compound K inhibited NO and prostaglandin E2 production by suppression of iNOS and COX-2 enzymes, but the precise mechanisms of action remains unknown. In the present study, to obtain insight into the biological effects of compound K on the inflammatory response of macrophages, we also investigated whether compound K could inhibit inflammatory responses in LPS-treated zebrafish.