Pulsatilla chinensis saponins improve SCFAs regulating GPR43-NLRP3 signaling pathway in the treatment of ulcerative colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulsatilla decoction has been extensively used to treat ulcerative colitis (UC) in recent years. Pulsatilla chinensis saponin (PRS), the active ingredient of its monarch medicine Pulsatilla chinensis (Bunge) Regel, plays a crucial role in the treatment of UC, but its specific mechanism of action has not been fully elucidated. AIM OF THE STUDY: This study aims to investigate the protective effect and possible mechanism of PRS on DSS-induced ulcerative colitis in rats. MATERIALS AND METHODS: In this study, the DSS-induced colitis model was used to explore the metabolism and absorption of PRS under UC, detect the content of short-chain fatty acids (SCFAs) in colon tissue, the expression of receptor G Protein-Coupled Receptor 43 (GPR43) protein and inflammasome NLRP3, and observe the expression level of IL-1ß, IL-6 and TNF-α in colon tissue. The protective effect of the PRS was also observed. RESULTS: It was found that in the UC group, the absorption rate and extent of drugs increased, and the elimination was accelerated. Compared with the control group, PRS increased the content of short-chain fatty acids (SCFAs) in colon tissue, promoted the expression of SCFAs receptor GPR43 protein, inhibited the activation of the NLRP3 inflammasome, and decreased the content of IL-1ß, IL-6 and TNF-α. PRS protects the colon in DSS-induced inflammatory bowel disease by increasing the content of SCFAs, promoting the expression of GPR43 protein, inhibiting the activation of the NLRP3 inflammasome, and reversing the increase in IL-1ß, IL-6 and TNF-α levels. CONCLUSIONS: PRS can increase the content of colonic SCFAs, activate the GPR43-NLRP3 signaling pathway, and reduce the levels of pro-inflammatory cytokines, thereby improving the symptoms of DSS-induced colitis.

Isobaric tags for relative and absolute quantitation-based proteomics analysis of the effect of ginger oil on bisphenol A-induced breast cancer cell proliferation.

Several chemicals in the environment, particularly those with estrogenic activity and small amounts (micromolar or lower) of environmental estrogen can cause changes in cell function and interfere with endocrine functions of animals and humans. These compounds enter the human body and increase the load of estrogen in the body, leading to an increasing incidence of estrogen-related tumors in breast cancer, ovarian cancer and endometrial cancer. Previous studies have demonstrated that ginger can inhibit the expression of estrogen receptors, while the bioactive ingredients of ginger sig-nificantly inhibit proliferation and promote the apoptosis of breast cancer cells. In the present study, a quantitative proteomics technique based on relative and absolute quanti-tative isobaric labeling was used to determine the effect of ginger essential oil (GEO) and BPA combined treatment on the proteomic characteristics of MCF-7 cells. In total, 5,084 proteins were detected. Proteins that were upregulated >1.2-fold and downregu-lated by >0.8-fold were differentially expressed. Overall, 528 differentially expressed proteins were identified. Compared with the control group, MCF-7 cells treated with GEO, BPA and GEO-BPA resulted in 45 (14 up- and 31 downregulated), 481 (141 up- and 340 downregulated) and 34 (13 up- and 21 downregulated) differentially ex-pressed proteins, respectively. Compared with the BPA group, MCF- 7 cells treated with GEO-BPA resulted in 210 (117 up- and 93 downregulated) differentially expressed proteins, among the 210 differentially expressed proteins in the GEO-BPA group, 10 proteins were associated with oxidative phosphorylation pathways, while succinate dehydrogenase (ubiquinone) iron-sulfur subunit (SDHB), succinate dehydrogenase cytochrome b560 subunit, mitochondrial (SDHC), cytochrome c oxidase subunit 2 and superoxide dismutase (Mn), mitochondrial (SOD2) expression was decreased with GEO-BPA combined treatment. Through the analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, the cellular localization, functional annotation and biological pathways of differentially expressed proteins were ex-amined. The results indicated that GEO-BPA may act through the oxidative phosphory-lation pathway, decreased the expression of SDHB and SDHC, affected the tricarbox-ylic acid cycle and decreased the expression of SOD2. This may have led to oxidative stress and the death of breast cancer cells, and the SDH signaling pathway may be an important mediator of the inhibitory effects of GEO in MCF-7 breast cancer cells. GEO can inhibit the proliferation of breast cancer MCF-7 cells induced by BPA, and the underlying mechanism may be associated with oxidative phosphorylation. These results may aid the development of future treatment strategies for breast cancer caused by environmental estrogen exposure.

In Vivo Toxicity of Solasonine and Its Effects on cyp450 Family Gene Expression in the Livers of Male Mice from Four Strains.

Solasonine was reported to inhibit tumour cell growth in several different models. The in vivo toxicity of solasonine, the effects of genetic background on its toxicity, and its possible roles in regulating the expression of cyp450 family genes were still unclear and required characterisation. Here, Horn's assays were performed on male mice from four different strains, and the expression of cyp450 family genes in their livers was examined by RT-PCR and ELISA. Mice treated by intraperitoneal injection with high levels of solasonine showed immediate post-excitatory depression, intraperitoneal tissue adhesion, and dissolving of cells in the liver. Furthermore, these four mouse strains showed different toxicological sensitivity to solasonine. The strains, in decreasing order of LD50 value, rescuing speed of body weight, and more severe pathological symptoms, were KM, ICR, C57BL/6, and BALB/c. Interestingly, more cyp450 genes were downregulated at the mRNA and/or protein level in the livers of male mice from C57BL/6 or BALB/c strains than those from KM or ICR strains. These results suggest that (1) Solasonine has hepatic toxicity and downregulates cyp450 genes expression at transcriptional and/or post-transcriptional levels; (2) Genetic background is an important factor which can affect the in vivo toxicity; (3) Downregulation of cyp450 gene expression in the liver may be a clue to help understand whether or not a given strain is sensitive to solasonine; (4) Influences on the expression of cyp450 genes should be considered when using solasonine alone, or in combination with other drugs.

Trifluoperazine prevents FOXO1 nuclear excretion and reverses doxorubicin-resistance in the SHG44/DOX drug-resistant glioma cell line.

As a tumor suppressor, Forkhead box O1 (FOXO1) is located in the nucleus where it regulates gene expression and inhibits tumor progression. However, the antitumor effects of FOXO1 are attenuated in several tumors due to its translocation from the nucleus to the cytoplasm. Trifluoperazine (TFP) is able to reverse tumor drug resistance by inhibiting multidrug resistance (MDR), however, the detailed molecular mechanisms by which this occurs remain to be fully elucidated. In the present study, the doxorubicin (DOX)­resistant SHG44/DOX glioma cell line was established. The results showed that TFP promoted DOX­induced cytotoxicity, cell cycle arrest and early apoptosis using a Cell Counting Kit­8 and flow cytometry. In vivo experiments also demonstrated that DOX combined with TFP reduced tumor volumes and proliferation indices, and led to higher protein levels of FOXO1. In addition, TFP inhibited the nuclear exclusion of FOXO1, contributing toward the downregulation of MDR genes and an increase in intracellular DOX concentrations by reverse transcription­quantitative polymerase chain reaction, western blot analysis, immunofluorescence and spectrophotometer analysis. Therefore, TFP may inhibit DOX resistance by stimulating FOXO1 nuclear translocation and suppressing MDF genes in SHG44/DOX cells, contributing to promising clinical prospects for tumor chemotherapy.