Ginseng polysaccharides ameliorate ulcerative colitis via regulating gut microbiota and tryptophan metabolism.

Ulcerative colitis (UC) is regarded as a recurring inflammatory disorder of the gastrointestinal tract, for which treatment approaches remain notably limited. In this study, we demonstrated that ginseng polysaccharides (GPs) could alleviate the development of dextran sulfate sodium (DSS)-induced UC as reflected by the ameliorated pathological lesions in the colon. GPs strikingly suppressed the expression levels of multiple inflammatory cytokines, as well as significantly inhibited the infiltration of inflammatory cells. Microbiota-dependent investigations by virtue of 16S rRNA gene sequencing, antibiotic treatment and fecal microbiota transplantation illustrated that GPs treatment prominently restored intestinal microbial balance predominantly through modulating the relative abundance of Lactobacillus. Additionally, GPs remarkably influenced the levels of microbial tryptophan metabolites, diminished the intestinal permeability and strengthened intestinal barrier integrity via inhibiting the 5-HT/HTR3A signaling pathway. Taken together, the promising therapeutic potential of GPs on the development of UC predominantly hinges on the capacity to suppress the expression of inflammatory cytokines as well as to influence Lactobacillus and microbial tryptophan metabolites.

Rosmarinic acid in combination with ginsenoside Rg1 suppresses colon cancer metastasis via co-inhition of COX-2 and PD1/PD-L1 signaling axis.

Metastasis of colorectal cancer (CRC) is a leading cause of mortality among CRC patients. Elevated COX-2 and PD-L1 expression in colon cancer tissue has been linked to distant metastasis of tumor cells. Although COX-2 inhibitors and immune checkpoint inhibitors demonstrate improved anti-tumor efficacy, their toxicity and variable therapeutic effects in individual patients raise concerns. To address this challenge, it is vital to identify traditional Chinese medicine components that modulate COX-2 and PD-1/PD-L1: rosmarinic acid (RA) exerts striking inhibitory effect on COX-2, while ginsenoside Rg1 (GR) possesses the potential to suppress the binding of PD-1/PD-L1. In this study we investigated whether the combination of RA and GR could exert anti-metastatic effects against CRC. MC38 tumor xenograft mouse model with lung metastasis was established. The mice were administered RA (100 mg·kg-1·d-1, i.g.) alone or in combination with GR (100 mg·kg-1·d-1, i.p.). We showed that RA (50, 100, 150 µM) or a COX-2 inhibitor Celecoxib (1, 3, 9 µM) concentration-dependently inhibited the migration and invasion of MC38 cells in vitro. We further demonstrated that RA and Celecoxib inhibited the metastasis of MC38 tumors in vitro and in vivo via interfering with the COX-2-MYO10 signaling axis and inhibiting the generation of filopodia. In the MC38 tumor xenograft mice, RA administration significantly decreased the number of metastatic foci in the lungs detected by Micro CT scanning; RA in combination with GR that had inhibitory effect on the binding of PD-1 and PD-L1 further suppressed the lung metastasis of colon cancer. Compared to COX-2 inhibitors and immune checkpoint inhibitors, RA and GR displayed better safety profiles without disrupting the tissue structures of the liver, stomach and colon, offering insights into the lower toxic effects of clinical traditional Chinese medicine against tumors while retaining its efficacy.

Ginseng polysaccharides: Potential antitumor agents.

As a famous herbal medicine in China and Asia, ginseng (Panax ginseng C. A. Meyer) is also known as the "King of All Herbs" and has long been used in medicine and healthcare. In addition to the obvious biological activities of ginsenosides, ginseng polysaccharides (GPs) exhibit excellent antitumor, antioxidant stress, and immunomodulatory effects. In particular, GPs can exert an antitumor effect and is a potential immunomodulator. However, due to the complexity and diversity in the structures and components of GPs, their specific physicochemical properties, and underlying mechanisms remain unclear. In this article, we have summarized the factors influencing the antitumor activity of GPs and their mechanism of action, including the stimulation of the immune system, regulation of the gut microbiota, and direct action on tumor cells.

Systemic pharmacological verification of Salvia miltiorrhiza-Ginseng Chinese herb pair in inhibiting spontaneous breast cancer metastasis.

Breast cancer is the most commonly diagnosed cancer in the world, and metastasis is often the main cause of death in breast cancer patients. Salvia miltiorrhiza -Ginseng (SG) herb pair is clinically used for the treatment of cardiovascular diseases and cancers. However, the pharmacological action of this pair on breast cancer is yet unclear. In this study, a spontaneous metastasis model of breast cancer was constructed to assess the therapeutic value of SG. After administration of different doses of SG, the results showed that although it did not significantly inhibit tumor growth, high-dose SG administration could inhibit tumor metastasis. Then, based on systematic pharmacology combined with Gene Expression Omnibus (GEO) database, potential targets of drugs were identified such as vascular endothelial growth factor A (VEGFA), matrix metalloproteinase (MMP9), prostaglandin endoperoxide synthase2 (PTGS2), etc. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis revealed that these targets were related to cytokine-mediated signaling pathway, cell migration and other biological processes and signaling pathways such as PI3K/Akt, etc. The systematic pharmacology analysis showed that SG effectively inhibited the VEGFA and MMP9-mediated biological events such as angiogenesis, epithelial-mesenchymal transition (EMT) and impaired tumor metastasis. Overall, our research aimed to provide new ideas for the treatment of breast cancer lung metastasis in traditional Chinese medicine.

Crosstalk between traditional Chinese medicine-derived polysaccharides and the gut microbiota: A new perspective to understand traditional Chinese medicine.

Polysaccharide is a kind of macromolecule polymer composed of monosaccharides connected by glycosidic bonds. Traditional Chinese medicine (TCM), composed of various bioactive ingredients, is usually rich in polysaccharides. In recent years, extensive research on TCM polysaccharides has demonstrated their pharmacological effects. Polysaccharides can hardly be catabolized by enzymes encoded by the human genome but can be degraded to absorbable metabolites by bacteria inhabiting the colon. Hence, the gut microbiota plays a vital role in degrading TCM polysaccharides into short-chain fatty acids (SCFAs) which exert physiological functions locally and systemically. Besides, TCM polysaccharides can also modulate the composition and activities of the gut microbiota by promoting the growth of beneficial bacteria and inhibiting the colonization of pathogenic bacteria, ultimately restoring gut homeostasis and improving human health. In this review, we discuss the extraction and pharmacological effects of TCM polysaccharides, various functions of the gut microbiota, and the interactions between TCM polysaccharides and the gut microbiota, illuminating the mechanisms of TCM polysaccharides modulating host physiology via the gut microbiota. To firmly establish the clinical efficacy of TCM polysaccharides, further high-quality studies especially clinical trials are needed. Generally, discussion on the interplay between TCM polysaccharides and the gut microbiota is expected to elucidate their application prospects and inspire new thoughts in the development of TCM.