In the chronic phase, our data show that ginseng treatment very significantly reduced colon tumor number and load. The H&E staining histological observations support these pharmacological observations. We used HPLC analysis to determine the major ginsenosides in the AG used in this study. Previously, we evaluated the effects of another herb in the ginseng family, notoginseng,

on experimental colitis for up to 14 days. We reported that notoginseng attenuated the acute colitis [34] comparable to what was observed using AG in this study. Although the ginseng saponin profiles are different between AG and notoginseng, the two botanicals also share a number of common ginsenosides. It would be interesting to identify which is/are see more the key ginsenoside(s) responsible for the observed effects reported in these two studies. AG and Asian ginseng are two major ginseng species. These two ginsengs, especially Asian ginseng, are the most studied TSA HDAC in vitro natural products in the world [35] and [36]. It is generally accepted that the main bioactive constituents of both ginsengs are ginsenosides [37] and [38]. Over 80 ginsenosides have been identified, and nearly all these ginsenosides can be found in the two species. However, the ginsenoside profile between the two ginseng species is different, and this difference may contribute to their different pharmacological effects [18] and [35]. Of note, AG has approximately two times higher total

ginsenoside content than Asian ginseng, largely due to its obvious high levels of Rb1, Re,

and Rd [35]. Using the extract of AG, Cui et al [39] showed that the extract suppressed colon cancer associated with colitis in the AOM/DSS model. In clonidine particular, these authors investigated the molecular mechanisms of ginseng’s anticancer effects using antibody array observations on colon cells isolated at a precancerous stage. Our study also used oral ginseng administration, and it is likely that enteric microbiome plays a role in ginseng metabolism and bioavailability. After AG is ingested orally, the bioavailability of its saponins is low. This is due to incomplete absorption of the parent compounds and their conversion into metabolites by the enteric microbiome, mainly via step-wise cleavage of sugar moieties [35] and [40]. The ginseng metabolites may possess more significant pharmacological benefits than their parent compounds such as Rb1 [41], including the effects observed in this study. Because the diarrhea induced by DSS is likely to affect the activity and/or profile of enteric microbiome, AOM/DSS-induced, colitis-associated colorectal carcinogenesis may not be an ideal in vivo model to study the botanical chemoprevention of colorectal cancer in relation to the enteric microbiome. Future study should be extended to other colon cancer animal models, especially the APC mutant Min (multiple intestinal neoplasia) mice with detailed mechanisms of action [42] and [43].