NAD+ enhancer ameliorates DSS-induced colitis in mice
To investigate the anti-inflammatory effect of LMT503 on IBD in vivo , mouse DSS-induced colitis model was used in this study. Mice received DSS for 5 days followed by oral treatment with LMT503 or tofacitinib from day 5 when DSS was replaced by normal drinking water. LMT503 treated mice showed alleviated body weight loss, which was comparable to an IBD therapeutic JAK-inhibitor tofacitinib (Figure 2a) (Sandborn et al., 2014). LMT503 treated mice also showed reduced disease activity index (Figure 2b), recovered colon length (Figure 2c), and bacterial translocation in mesenteric lymph nodes compared to mice in the vehicle control group (Figure 2d). H&E staining of colon tissues showed reduced inflammation in LMT503 treated groups (Figure 2e). Pro-inflammatory cytokines TNF, MCP-1, and IL-1β were also significantly reduced in LMT503 treated groups (Figure 2f).
To further evaluate inflammation in colon tissues, innate immune cell infiltration was analyzed. Percentage and absolute numbers of CD11b+Ly6G+ neutrophils and CD11b+Ly6C+ monocytes were decreased significantly in LMT503 treated groups (Figure 3a-d). However, macrophage and dendritic cell percentage did not differ between LMT503 treated groups and vehicle control groups (Figures 3e,f and Figure S1a,b).