The gastrointestinal microbiota and host co-evolve into a complex ‘super-organism,’ and this relationship plays a vital role in many physiological processes, such as drug metabolism. Ginseng is an important medicinal resource and the main ingredients are ginsenosides, which are less polar, difficult to absorb, and have low bioavailability. However, studies have shown that the biological activity of ginsenosides such as compound K (CK), ginsenoside Rg3 (Rg3), ginsenoside Rh2 (Rh2), 20(S)-protopanaxatriol (20(S)-PPT), and 20(S)-protopanaxadiol (20(S)-PPD) is closely related to the gastrointestinal microbiota. In this paper, the metabolic pathway of gastrointestinal microbiota-generated ginsenosides and the main pharmacological effects of these metabolites are discussed. Furthermore, our study provides a new insight into the discovery of novel drugs. Specifically, in new drug screening process, candidates with low biological activity and bioavailability should not be excluded. Because their metabolites may exhibit good pharmacological effects due to the involvement of the gastrointestinal microbiota. In addition, in further research studies to develop probiotics, a combination of agents could exert greater efficacy than single agents. Moreover, differences in lifestyle and diet lead to differences in the gastrointestinal microbiota in the human body. Therefore, administration of the same drug dose to different individuals could elicit different therapeutic effects, owing to the involvement of the gastrointestinal microbiota. Thus, treatment accuracy could be achieved by detecting the gastrointestinal microbiota before drug treatment.

Colorectal cancer (CRC) is a common malignant tumor with a high global incidence, metastasis rate and low cure rate. Changes in lipid metabolism-related genes can affect the occurrence and development of CRC, and may be a potential therapeutic target for CRC. Therefore, starting from lipid metabolism-related genes to find natural medicines for tumor treatment may become a new direction in CRC research. This study aimed to investigate the effect of PLA2G16, a key gene involved in lipid metabolism, on the biological function of CRC, and whether the anti-CRC effect of GCK is related to PLA2G16. To explore the role of PLA2G16 in CRC in vitro and in vivo, we performed cell proliferation, migration, invasion and nude mice tumorigenesis assays. As for the mechanism, we designed RNA-seq analysis and verified by western blotting and immunofluorescence experiments. Subsequently, we found the anti-CRC effect of GCK is related to PLA2G16 through western blotting and rescue experiments. We showed that PLA2G16 was significantly higher in CRC tissues than the adjacent normal appearing tissues, and high PLA2G16 expression correlates with unfavorable prognosis of CRC patients. Further, PLA2G16 promoted the malignant progression of CRC by inhibiting the Hippo signaling pathway determined by RNA-seq analysis, and GCK exerted anti-CRC effects by inhibiting the protein expression of PLA2G16 in vitro and in vivo. Our results suggested that PLA2G16 promote the malignant progression of CRC by inhibiting the Hippo signaling pathway and the anti-CRC effect of GCK is through inhibiting the protein expression of PLA2G16.

Colorectal cancer (CRC) has become one of the most important diseases due to its increasing morbidity and mortality. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is reported to be overexpressed in multiple cancers, but their role remains poorly understood. In this study, we explored the role of LPCAT1 in the progression of CRC and the possible underlying mechanism. Bioinformatics analysis was used to search for the association between target gene LPCAT1 and CRC. LPCAT1 expression was measured in CRC and paired para cancerous tissues. The role of LPCAT1 was investigated both in vitro and in vivo. iTRAQ-based quantitative proteomics was used to explore the mechanism of LPCAT1 in CRC progression. TCGA and GEO database analysis showed that LPCAT1 was upregulated in CRC. LPCAT1 was upregulated in CRC tissues and the IHC score was also correlated with tumor stage. The depletion of LPCAT1 not only abrogated cell proliferation, migration and invasion in vitro, but also arrested tumor growth in vivo. The proteomic results showed that differentially expressed proteins were enriched in multiple pathways after LPCAT1 knockdown, and the extracellular matrix (ECM) receptor interaction pathway was the most significant. The ECM is involved in the process by which LPCAT1 promotes CRC metastasis and invasion.

Bisphenol A (BPA), a pervasive environmental pollutant, is increasingly associated with osteoarthritis (OA) development, yet its molecular mechanisms remai