Adaptogenic flower buds exert cancer preventive effects by enhancing the SCFA-producers, strengthening the epithelial tight junction complex and immune responses.

Microbiome therapy has attracted a keen interest from both research and business sectors. Our lab has been applying this "second genome" platform to assess the functionality of herbal medicines with fulfilling results. In this study, we applied this platform to assess the potential cancer-preventive effects of three selected adaptogenic plants. The flower buds from these plants were used to constitute Preparations SL and FSP according to the receipts of two commonly consumed Chinese medicinal decoctions for gastrointestinal discomfort. Preparation SL contains Sophorae japonica and Lonicerae Japonicae, and Preparation FSP contains Sophorae japonica and Gardenia Jasminoides. SL and FSP extracts significantly (p < 0.001) lowered the polyp burden, as well as the expressions of oncogenic signaling molecules, such as MAPK/ERK, PI3K/AKT, and STAT3 in ApcMin/+ mice. The inflamed gut was alleviated by shifting M1 to M2 macrophage phenotypes and the associated immune cytokines. The other remarkable change was on the extracellular tight junction protein complex, where the occludin, ZO-1, ICAM-1, E-cadherin were significantly (p < 0.05) upregulated while the N-cadherin and ß-catenin were downregulated in the treated mice. The above physiological changes in the gut epithelial barrier were companied with the changes in gut microbiome. The 16S Sequencing data revealed a marked decrease in the potential pathogens (especially Helicobacter species and hydrogen sulfide producing-bacteria) and the increase in beneficial bacteria (especially for species from the genera of Akkermansia, Barnesiella, Coprococcus, Lachnoclostridium, and Ruminococcus). The majority of which were the short-chain fatty acids (SCFAs) producers. Meanwhile SCFAs-sensing G protein-coupled receptors (GPCRs), including GPR41, GPR43, and GPR109a were also significantly upregulated. In a recent report, we proved that the bacteria-derived SCFAs plays an essential role to the anti-cancer effects of the mushroom polysaccharides and saponins in ApcMin/+ mice. In this study, we further demonstrated that butyrate treatment could enhance the extracellular tight junction protein complex as effective as the treatments with SL and FSP to the ApcMin/+ mice. Our findings provide strong evidence of the vital role of the SCFA-producers and their metabolites to the cancer-preventive properties of the SL and FSP preparations.

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

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.