3ß-Hydroxy-12-oleanen-27-oic Acid Exerts an Antiproliferative Effect on Human Colon Carcinoma HCT116 Cells via Targeting FDFT1.

3ß-hydroxy-12-oleanen-27-oic acid (ATA), a cytotoxic oleanane triterpenoid with C14-COOH isolated from the rhizome of Astilbe chinensis, has been previously proven to possess antitumor activity and may be a promising antitumor agent. However, its molecular mechanisms of antitumor action were still unclear. This study explored the underlying mechanisms of cytotoxicity and potential target of ATA against human colorectal cancer HCT116 cells via integrative analysis of transcriptomics and network pharmacology in combination with in vitro and in vivo experimental validations. ATA significantly inhibited the proliferation of HCT116 cells in a concentration- and time-dependent manner and induced the cell cycle arrest at the G0/G1 phase, apoptosis, autophagy, and ferroptosis. Transcriptomic analysis manifested that ATA regulated mRNA expression of the genes related to cell proliferation, cell cycle, and cell death in HCT116 cells. The integrated analysis of transcriptomics, network pharmacology, and molecular docking revealed that ATA exerted cytotoxic activity via interactions with FDFT1, PPARA, and PPARG. Furthermore, FDFT1 was verified to be an upstream key target mediating the antiproliferative effect of ATA against HCT116 cells. Of note, ATA remarkably suppressed the growth of HCT116 xenografts in nude mice and displayed an apparent attenuation of FDFT1 in tumor tissues accompanied by the alteration of the biomarkers of autophagy, cell cycle, apoptosis, and ferroptosis. These results demonstrate that ATA exerted in vitro and in vivo antiproliferative effects against HCT116 cells through inducing cell apoptosis, autophagy, and ferroptosis via targeting FDFT1.

Herba Origani alleviated DSS-induced ulcerative colitis in mice through remolding gut microbiota to regulate bile acid and short-chain fatty acid metabolisms.

This study aimed to investigate the protective effect of Herba Origani, the dried whole herb of Origanum vulgare L., on dextran sodium sulfate (DSS)-induced ulcerative colitis in mice and explore its mechanisms of action through analyzing the intestinal microbiota in cecum contents and metabolites in colonic tissues. HOEP alleviated colitis symptoms, colonic inflammation and pathological injury as well as repaired intestinal barrier function in DSS-induced UC mice. The intestinal microbiota analysis showed that HOEP restored the gut microbiota dysbiosis in DSS-treated mice by increasing the alpha diversity of the intestinal microbiota, increasing the abundance of the Bacteroidota community and adjusting short-chain fatty acids (SCFAs), which maintain mucosal immunity and intestinal barrier. Metabolomic analysis revealed that HOEP promoted bile acids absorption and regulated bile acids metabolism in the intestine, thereby maintaining intestinal mucosal immune homeostasis. In addition, HOEP might also regulate the intestinal immune system through the phosphatidylinositol signaling system. These findings suggested that HOEP exerted promising protection against DSS-induced ulcerative mice through remolding gut microbiota to regulate bile acid and SCFA metabolism, and that HOEP have a potential to be utilized for the treatment of inflammatory intestinal diseases.