American ginseng (Panax quinquefolius L.) is one of the most commonly used herbal medicines in the West. It has been reported to possess significant antitumor effects that inhibit the process of carcinogenesis. However, the mechanisms underlying its anticancer effects remain largely unresolved. In this study, we investigated the cancer chemopreventive effects of American ginseng on the progression of high fat (HF) diet-enhanced colorectal carcinogenesis with a genetically engineered Apc(Min/+) mouse model. The metabolic alterations in sera of experimental mice perturbed by HF diet intervention as well as the American ginseng treatment were measured by gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) analysis. American ginseng treatment significantly extended the life span of the Apc(Min/+) mouse. Significant alterations of metabolites involving amino acids, organic acids, fatty acids, and carbohydrates were observed in Apc(Min/+) mouse in sera, which were attenuated by American ginseng treatment and concurrent with the histopathological improvement with significantly reduced tumor initiation, progression and gut inflammation. These metabolic changes suggest that the preventive effect of American ginseng is associated with attenuation of impaired amino acid, carbohydrates, and lipid metabolism. It also appears that American ginseng induced significant metabolic alterations independent of the Apc(Min/+) induced metabolic changes. The significantly altered metabolites induced by American ginseng intervention include arachidonic acid, linolelaidic acid, glutamate, docosahexaenoate, tryptophan, and fructose, all of which are associated with inflammation and oxidation. This suggests that American ginseng exerts the chemopreventive effects by anti-inflammatory and antioxidant mechanisms.
Keywords: American ginseng; ApcMin/+ mice; GC-TOFMS; LC-TOFMS; colorectal cancer; gas chromatography time-of-flight mass spectrometry; inflammatory cytokines; liquid chromatography time-of-flight mass spectrometry; metabonomics.