For the duration of the research we examined mice by colonoscopy to watch irritation and tumor growth. Repre sentative colonoscopic views of management mice, mice with colitis and mice with colonic tumors are proven in Fig ure 1D. Ginseng inhibits proliferation and increases apoptosis in AOM DSS tumors To elucidate the results of ginseng on proliferation and apoptotic cell death we examined tumors for Ki67 and TUNEL staining. As proven in Figure two, ginseng reduced proliferation and enhanced apoptotic cell death. Quanti tation of proliferation and cell death in colonic tumors are summarized in Table one. Ginseng caused just about a 50% reduction in proliferation and just about a 50% raise in apoptosis.
Effects of ginseng on EGFR signals and regulators of apoptosis To start to dissect molecular signals possibly contri buting to ginseng induced modifications in proliferation and cell death, we examined EGFR signals and apoptosis regulators. As proven in Figure three, colonic tumors induced by AOM DSS in mice on Western diet plan showed up rules of phospho lively EGFR, pErbB2, pERK, and pAKT. experienced Dietary ginseng selleckchem significantly decreased these activations in tumors. Ginseng also greater cell cycle and apoptosis regulat ing p21Waf1 in tumors that may be predicted to inhibit professional liferation and raise apoptosis. With respect to other apoptotic regulators, ginseng decreased anti apop totic Cox 2 and elevated professional apoptotic Bax, consistent with ginseng induced improved apoptosis. Quantitative densitometry values are summarized in Table 2. Absorption and biological results of ginseng metabolite compound K Quite a few metabolites of ginseng require colonic micro biota for biosynthesis.
In latest preliminary scientific studies we observed that whereas the ginsenoside Rb1 had limited anti proliferative and pro apoptotic action, 20 O b 20 protopanaxadiol or compound K, a microbial metabolite of Rb1 potently suppressed colon cancer cell proliferation in vitro. To immediately assess the anti tumor effects of compound K we examined the skill of this bacterial metabolite of ginseng to inhibit tumor xeno graft growth. The structure of compound K is shown in Further File one. As shown in Figure 4A, compound K potently suppressed development of HCT116 cells in immu nodeficient nude mice when administered by intraperitoneal route. To deal with a colonic bacterial necessity for com pound K synthesis we pretreated mice with metronida zole a broad spectrum antibiotic or vehicle. Following 5 days remedy we measured ginsenoside Rb1 and compound K during the sera by mass spectrometry. As proven in Figure 4B, Rb1 absorption was not influ enced by antibiotic therapy. In contrast, compound K was undetectable in antibiotic treated mice, but readily detected in mouse sera from vehicle treated mice.