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.

Mushroom polysaccharides and jiaogulan saponins exert cancer preventive effects by shaping the gut microbiota and microenvironment in ApcMin/+ mice.

The incidence of colorectal cancer (CRC) is alarming among younger peoples. While no effective chemopreventive drug available in the market, researchers have been searching for alternative strategies against CRC that are in demand. Therefore, we tested the cancer-preventive properties of Ganoderma lucidum (Lingzhi) polysaccharides (GLP), along with the saponins extracted from Gynostemma pentaphyllum (GpS), an herbal tea with prebiotic-like effects. Here, we report that saponins from Gynostemma pentaphyllum (GpS) and polysaccharides from Ganoderma lucidum (GLP together with GpS) profoundly improved the inflamed gut barrier of ApcMin/+ mice by reducing polyps, shifting colonic M1 to M2 macrophages, positively reverting E-cadherin/N-cadherin ratio, and downregulating oncogenic signaling molecules. The treatments also markedly promoted short-chain fatty acids (SCFAs)-producing bacteria and abridged sulfate-reducing bacteria in a time-dependent manner. G-protein coupled-receptors were significantly stimulated in the treated mice, accompanied by the modulated expressions of histone deacetylases, anti-cancer gut hormone PYY, and PPAPγ. These findings suggest that some of the herbal medicinal foods could modulate the relationship between the host and the gut microbiota (GM) to exert their beneficial properties to the host. Our study also implicates that these dietary mushroom polysaccharides and the Gp saponins have the potential to be developed as new preventive medicines against CRC.

The Protective Effects of Icariin against the Homocysteine-Induced Neurotoxicity in the Primary Embryonic Cultures of Rat Cortical Neurons.

Icariin, an ingredient in the medicinal herb Epimedium brevicornum Maxim (EbM), has been considered as a potential therapeutic agent for neurodegenerative diseases such as Alzheimer's disease (AD). Hyperhomocysteinaemia is a risk factor for AD and other associated neurological diseases. In this study we aim to investigate whether icariin can reverse homocysteine (Hcy)-induced neurotoxicity in primary embryonic cultures of rat cortical neurons. Our findings demonstrated that icariin might be able restore the cytoskeleton network damaged by Hcy through the modulation of acetyl-α-tubulin, tyrosinated-α-tubulin, and phosphorylation of the tubulin-binding protein Tau. In addition, icariin downregulated p-extracellular signal-regulated kinase (ERK) which is a kinase targeting tau protein. Furthermore, icariin effectively restored the neuroprotective protein p-Akt that was downregulated by Hcy. We also applied RT² Profiler PCR Arrays focused on genes related to AD and neurotoxicity to examine genes differentially altered by Hcy or icariin. Among the altered genes from the arrays, ADAM9 was downregulated 15 folds in cells treated with Hcy, but markedly restored by icariin. ADAM family, encoded α-secreatase, plays a protective role in AD. Overall, our findings demonstrated that icariin exhibits a strong neuroprotective function and have potential for future development for drug treating neurological disorders, such as AD.

Bifidobacterium animalis: the missing link for the cancer-preventive effect of Gynostemma pentaphyllum.

Colorectal cancer (CRC) ranks the third most common cancer type in both men and women. Besides the known genetic and epigenetic changes in the gut epithelial cells, we now know that disturbed gut microbes could also contribute to the onset and progression of CRC. Hence, keeping a balanced gut microbiota (GM) has become a novel pursue in the medical field, particularly in the area of gastrointestinal disorders. Gynostemma pentaphyllum (Gp) is a dietary herbal medicine. In our previous study, Gp saponins (GpS) displayed prebiotic and cancer-preventive properties through the modulation of GM in ApcMin/+ mice. However, the specific group(s) of GM links to the health effects of GpS remains unknown. To track down the missing link, we first investigated and found that inoculation with fecal materials from GpS-treated ApcMin/+ mice effectively reduces polyps in ApcMin/+ mice. From the same source of the fecal sample, we successfully isolated 16 bacterial species. Out of the 16 bacteria, Bifidobacterium animalis stands out as the responder to the GpS-growth stimulus. Biochemical and RNAseq analysis demonstrated that GpS enhanced expressions of a wide range of genes encoding biogenesis and metabolic pathways in B. animalis culture. Moreover, we found that colonization of B. animalis markedly reduces the polyp burden in ApcMin/+ mice. These findings reveal a mutualistic interaction between the prebiotic and a probiotic to achieve anticancer and cancer-preventive activities. Our result, for the first time, unveils the anticancer function of B. animalis and extend the probiotic horizon of B. animalis.

Correlation of gut microbial compositions to the development of Kawasaki disease vasculitis in children.

Aim: Here, we hypothesize that dysbiotic gut microbiota might contribute to the development of Kawasaki disease (KD), a pediatric disease with unknown etiology. This is the second report on gut microbiota composition in KD patients. Materials & results: 16S amplicon sequencing was performed on fecal DNA samples and revealed predominance of bacterial pathogens, such as Fusobacterium, Neisseria, Shigella and Streptococcus, in the gut of KD patients, but absent or suppressed after immunoglobulin/antibiotics therapy. In addition, beneficial bacteria propagated after the therapy. Conclusion: We conclude that prevalence of Fusobacteria, Shigella and Streptococcus might contribute to KD pathogenesis.

Far infrared radiation induces changes in gut microbiota and activates GPCRs in mice.

Far infrared radiation (FIR) has been widely used to treat chronic diseases and symptoms; however, the underlying mechanism remains unclear. As gut microbiota (GM) markedly impact the host's physiology, making GM a potential target for the therapeutic evaluation of FIR. C57BL/6J mice were exposed to five times of 2 min-FIR exposure on the abdomen, with a two-hour interval of each exposure within one day. Fecal samples were collected on day one and day 25 after the FIR/control treatment, and the extracted fecal DNAs were evaluated using ERIC-PCR and 16S amplicon sequencing. Host's G-protein coupled receptors (GPCR) were analyzed using qRT-PCR. FIR induced immediate changes in the GM composition. A prompt and significant (p < 0.05) reduction in the abundance of phylum Deferribacteres (comprised of several pathogens) was observed in the FIR-irradiated mice compared to the control group. Contrarily, FIR exposure induced beneficial genera such as Alistipes, Barnesiella, and Prevotella. The gut of FIR-irradiated mice was predominated by short-chain fatty acids (SCFAs) producers. Also, FIR stimulated the expression of SCFAs-sensing receptors, GPCR 41, 43, and 109 in the gut epithelial barrier. These findings provide the first-hand evidence in which the beneficial effects of FIR radiation might be partially through the modulation of GM.