Ginsenosides Rb3 and Rd reduce polyps formation while reinstate the dysbiotic gut microbiota and the intestinal microenvironment in ApcMin/+ mice

Abstract

Studies showed that manipulation of gut microbiota (GM) composition through the treatment of prebiotics could be a novel preventive measure against colorectal cancer (CRC) development. In this study, for the first time, we assessed the non-toxic doses of the triterpene saponins (ginsenoside-Rb3 and ginsenoside-Rd) – as prebiotics – that effectively reinstated the dysbiotic-gut microbial composition and intestinal microenvironment in an ApcMin/+ mice model. Rb3 and Rd effectively reduced the size and the number of the polyps that accompanied with the downregulation of oncogenic signaling molecules (iNOS, STAT3/pSTAT3, Src/pSrc). Both the compounds improved the gut epithelium by promoting goblet and Paneth cells population and reinstating the E-cadherin and N-Cadherin expression. Mucosal immunity remodeled with increased in anti-inflammatory cytokines and reduced in pro-inflammatory cytokines in treated mice. All these changes were correlating with the promoted growth of beneficial bacteria such as Bifidobacterium spp., Lactobacillus spp., Bacteroides acidifaciens, and Bacteroides xylanisolvens. Whereas, the abundance of cancer cachexia associated bacteria, such as Dysgonomonas spp. and Helicobacter spp., was profoundly lower in Rb3/Rd-treated mice. In conclusion, ginsenosides Rb3 and Rd exerted anti-cancer effects by holistically reinstating mucosal architecture, improving mucosal immunity, promoting beneficial bacteria, and down-regulating cancer-cachexia associated bacteria.

The Microbiota and Cancer Cachexia

“…They administered triterpene saponins (specifically ginsenoside-Rb3 and ginsenoside-Rd) orally to mice and evaluated the downstream effect on gut epithelium, inflammatory markers and microbiota. Though they did not specifically evaluate the changes in body weight, they reported that mice receiving ginsenoside-Rb3 and ginsenoside-Rd had improvement in their gut epithelium and a decrease in pro-inflammatory markers and cachexia-associated bacteria [54]. Though this research is promising, there is a paucity of human data and further studies are needed to make definitive conclusions.…”

“…Conversely, the use of INU in this mouse model exhibited a decrease in hepatic cancer cell invasion [53]. Huang et al evaluated this concept using the Apc MIN/+ mouse model of colon cancer [54]. They administered triterpene saponins (specifically ginsenoside-Rb3 and ginsenoside-Rd) orally to mice and evaluated the downstream effect on gut epithelium, inflammatory markers and microbiota.…”

Colorectal carcinogenesis: Insights into the cell death and signal transduction pathways: A review

“…Researchers removed one allele of the APC gene, thus creating the APC min/+ mouse model. The APC min/+ model of intestinal/colorectal cancer has been extensively studied in the context of developing novel chemotherapeutic drugs[ 39 , 40 ].…”

Association between the gut microbiota and patient responses to cancer immune checkpoint inhibitors (Review)

“…In terms of small molecules, it has been demonstrated that curcumin may increase the abundance of bacteria, particularly Lactobacillus spp ( 74 ). Furthermore, ginsenosides may restore the structure of the intestinal mucosa and improve immunity in this tissue, thereby promoting the growth of beneficial bacteria and decreasing the growth of bacteria that results from cancer-associated cachexia ( 75 ). Berberine may increase the relative abundance of the thick-walled Mycoplasma spp., decrease the relative abundance of proteobacteria and decrease ileal inflammatory responses and intestinal mucosal damage ( 76 ).…”