ABSTRACT
Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties. However, the potential effects of IXN on the alleviation of colitis and the action of the mechanism is rarely studied. Here, we found that administration of IXN (60 mg/kg/day, gavage) significantly attenuated dextran sodium sulfate (DSS)-induced colitis, evidenced by reduced DAI scores and histological improvements, as well as suppressed the pro-inflammatory Th17/Th1 cells but promoted the anti-inflammatory Treg cells. Mechanically, oral IXN regulated T cell development, including inhibiting CD4+ T cell proliferation, promoting apoptosis, and regulating Treg/Th17 balance. Furthermore, IXN relieved colitis by restoring gut microbiota disorder and increasing gut microbiota diversity, which was manifested by maintaining the ratio of Firmicutes/Bacteroidetes balance, promoting abundance of Bacteroidetes and Ruminococcus, and suppressing abundance of proteobacteria. At the same time, the untargeted metabolic analysis of serum samples showed that IXN promoted the upregulation of D-( +)-mannose and L-threonine and regulated pyruvate metabolic pathway. Collectively, our findings revealed that IXN could be applied as a functional food component and served as a therapeutic agent for the treatment of UC.
Subject(s)
Colitis , Dextran Sulfate , Gastrointestinal Microbiome , Mice, Inbred C57BL , Xanthones , Gastrointestinal Microbiome/drug effects , Animals , Xanthones/pharmacology , Mice , Male , Colitis/drug therapy , Colitis/chemically induced , Metabolic Diseases/drug therapy , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/chemically induced , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , Th17 Cells/drug effects , Th17 Cells/metabolism , Anti-Inflammatory Agents/pharmacology , Disease Models, AnimalABSTRACT
OBJECTIVE: To observe the proliferation inhibition, apoptosis, and cell proliferation cycle of human lung carcinoma cell line A549 treated with Inotodiol extracts from Inonotus obliquus and explore the possibility of Inotodiol extracts from Inonotus obliquus as a new tumor chemopreventive drug. METHODS: Human lung cancer cell line A549 was treated with different concentrations of Inotodiol, the effects of Inotodiol on cell apoptosis, the expression of Ki-67, Bcl-2, Bax, and p53 and cell cycle were detected by TUNEL assay, immunohistochemistry, and flow cytometry assay respectively. RESULTS: Inotodiol extracts had antiproliferation effect on human lung carcinoma cell line A549. The expression of Ki-67 decreased with the increase of Inotodiol concentration and exposure time (P<0.05), in a dose-dependent and time-dependent manner. The typical characteristics of the apoptosis of A549 cells treated with Inotodiol were observed, and the apoptotic rate of A549 cell at 48 h was the highest by TUNEL assay. Inotodiol arrested A549 cells in the S phase, and apoptotic peak was observed by flow cytometry. Immunocytochemistry indicated that the expression of Bcl-2 protein decreased, while the expression of p53 and Bax proteins increased in A549 cells treated with Inotodiol, compared with the control cells (P<0.05). CONCLUSION: Inotodiol can inhibit proliferation and induce the apoptosis of A549 cells, and its molecular mechanism may be associated with the up-regulating expression of p53 and bax proteins and down-regulating expression of Bcl-2 protein, which arrested A549 cells in S phase.
Subject(s)
Apoptosis/drug effects , Basidiomycota/chemistry , Cell Proliferation/drug effects , Drugs, Chinese Herbal/pharmacology , Lanosterol/analogs & derivatives , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Apoptosis/genetics , Cell Cycle/drug effects , Cell Line, Tumor , Drug Evaluation, Preclinical , Drugs, Chinese Herbal/therapeutic use , Gene Expression Regulation, Neoplastic/drug effects , Genes, bcl-2/drug effects , Genes, p53/drug effects , Humans , Ki-67 Antigen/metabolism , Lanosterol/pharmacology , Lanosterol/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Phytotherapy , bcl-2-Associated X Protein/geneticsABSTRACT
Inonotus obliquus has high nutritional and medicinal value, especially in treating malignant tumors, diabetes, cardiovascular disease and AIDS, attracting significant attention from scholars in recent years. In this paper, the biological characteristics, chemical composition and pharmacologic effects of Inonotus obliquus were summarized. And the applications in medicine and food were introduced. Future research on Inonotus obliquus was also discussed in order to make Inonotus obliquus obtain effective exploitation and satisfy people's demands.
