Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells.

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G1-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION: Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.

[Modern research on Chinese medicine based on single-cell omics: technologies and strategies].

As one of the most advanced technologies, single-cell omics technology develops rapidly in recent years. Based on different technical strategies, it enables unbiased and high-throughput access to multiple omics information at single-cell resolution. So far, single-cell omics technology, by virtue of its great powder in resolving tissue heterogeneity, has become a revolutionary tool to deeply understand the functional structure of tissues, reveal complex disease processes, and elucidate drug mechanisms of action. In view of the technical challenges in deconstructing the complexity of Chinese medicine and clarifying the modern scientific connotation of traditional Chinese medicine(TCM) theory, single-cell omics technology has huge application potential in the discovery of pharmacodynamic substances, construction of action networks, and elucidation of integrated regulatory mechanisms, which brings new opportunities for modern research in TCM. The present study briefly introduced three representative single-cell omics technologies, i.e., single-cell transcriptome sequencing, spatial transcriptomics, and single-cell multimodal omics, and their main application patterns. On this basis, an outlook was proposed on the strategies and applications for modern research in TCM using single-cell omics technology.

[Mechanism of salvianolate in preventing postoperative intestinal adhesion in rats].

OBJECTIVE: To observe the effects of salvianolate on rats with postoperative intestinal adhesion and to explore the prevention mechanism. METHODS: Forty SD male rats with intestinal adhesion were randomly divided into four groups: untreated group, low-dose salvianolate-treated group (12 mg/kg), medium-dose salvianolate-treated group (24 mg/kg) and high-dose salvianolate-treated group (48 mg/kg), with another ten SD male rats as normal control. Intraperitoneal injection of glucose was administered to the rats in the normal control group and the untreated group, and intraperitoneal injection of salvianolate was administered to the rats in the low-, medium- and high-dose salvianolate-treated groups. They were all treated for 8 days and once a day. On the eighth day after surgery the blood samples of each group were collected. Grades of intestinal adhesion were ranked by macroscopic observation. The adhesive tissues between viscera and belly wall were taken for pathological observation. The levels of interleukin-1beta (IL-1beta), interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-alpha) were determined by enzyme linked immunosorbent assay. RESULTS: Salvianolate can significantly reduce the extent of postoperative intestinal adhesion, obviously decrease the levels of IL-1beta, TNF-alpha and inhibit the hyperplasy of fibrous connective tissue. However, there was no significant impact on the level of IL-4. CONCLUSION: Salvianolate can reduce the extent of postoperative intestinal adhesion, decrease the expression of IL-1beta and TNF-alpha and inhibit the hyperplasy of fibrous connective tissue. This may be the mechanism of salvianolate in preventing intestinal adhesion.