ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Dingxin Recipe â ¢ (DXR â ¢) is a traditional Chinese medicine compound used for hyperlipidemia treatment in clinical practice. However, its curative effects and pharmacological mechanisms in hyperlipidemia have not been clarified to date. AIM OF THE STUDY: Studies have demonstrated that gut barrier was strongly implicated in lipid deposition. Based on gut barrier and lipid metabolism, this study examined the effects and molecular mechanisms of DXR â ¢ in hyperlipidemia. MATERIALS AND METHODS: The bioactive compounds of DXR â ¢ were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and its effects were evaluated in high-fat diet-fed rats. Specifically, the serum levels of lipids and hepatic enzymes were measured using the appropriate kits; colon and liver sections were obtained for histological analyses; gut microbiota and metabolites were analyzed by 16S rDNA sequencing and liquid chromatography-MS/MS; and the expression of genes and proteins was determined by real-time quantitative polymerase chain reaction and western blotting and immunohistochemistry, respectively. The pharmacological mechanisms of DXR â ¢ were further explored by fecal microbiota transplantation and short-chain fatty acid (SCFAs)-based interventions. RESULTS: DXR â ¢ treatment significantly downregulated serum lipid levels, mitigated hepatocyte steatosis and improved lipid metabolism. Moreover, DXR â ¢ improved the gut barrier, specifically by improving the physical barrier in the colon, causing part composition changes in the gut microbiota, and increasing the serum SCFAs level. DXR â ¢ also upregulated the expression of colon GPR43/GPR109A. Fecal microbiota transplantation from rats treated with DXR â ¢ downregulated part hyperlipidemia-related phenotypes, while the SCFAs intervention significantly improved most of the hyperlipidemia-related phenotypes and upregulated the expression of GPR43. Moreover, both DXR â ¢ and SCFAs upregulated the expression of colon ABCA1. CONCLUSION: DXR â ¢ protects against hyperlipidemia by improving the gut barrier, particularly the SCFAs/GPR43 pathway.
Subject(s)
Hyperlipidemias , Rats , Animals , Hyperlipidemias/drug therapy , Rats, Sprague-Dawley , Tandem Mass Spectrometry , Lipids , Fatty Acids, Volatile/metabolismABSTRACT
PROBLEM: We aimed to investigate the modulatory effects of vitamin D on peripheral blood cellular immune response in patients with recurrent miscarriage (RM). METHOD OF STUDY: The effect of vitamin D on the number of peripheral blood cells, T helper 1 (Th1) cytokines, and NK cytotoxicity was measured in 99 women with RM. RESULTS: The percentage of CD19+ B cells and NK cytotoxicity at an effector-to-target cell (E:T) ratio of 50:1, 25:1, and 12.5:1 were significantly higher in the vitamin D insufficiency group (VDI) than in the vitamin D normal group (VDN) (P<.05 each). The proportion of TNF-α-expressing Th cells was significantly higher in the vitamin D deficiency group (VDD) than in VDN (P<.05). However, there were no significant differences between VDI and VDD. This dysregulation was significantly reduced with 1,25(OH)2 D supplementation. CONCLUSION: The data suggest that the abnormalities of cellular immune response were observed in RM patients with a low vitamin D level, which could be regulated to some extent with 1,25(OH)2 D supplementation.
Subject(s)
Abortion, Habitual/immunology , Calcitriol/administration & dosage , Immunologic Factors/administration & dosage , Vitamin D Deficiency/immunology , Abortion, Habitual/diet therapy , Abortion, Habitual/genetics , Abortion, Habitual/pathology , Administration, Oral , Adult , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , B-Lymphocytes/pathology , Case-Control Studies , Cytotoxicity, Immunologic , Female , Gene Expression , Humans , Immunophenotyping , Interferon-gamma/genetics , Interferon-gamma/immunology , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Killer Cells, Natural/pathology , Pregnancy , Th1 Cells/drug effects , Th1 Cells/immunology , Th1 Cells/pathology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology , Vitamin D Deficiency/diet therapy , Vitamin D Deficiency/genetics , Vitamin D Deficiency/pathologyABSTRACT
Three new unusual 23-spirocholestane derivatives, ypsilanogenin (1), ypsilanogenin 3-O-ß-D-glucopyranoside (2), and 4'-acetylypsilanogenin 3-O-ß-D-glucopyranoside (3), were isolated from the whole plants of Ypsilandra thibetica. The structures of compounds 1-3 were deduced by spectroscopic and chemical methods, and the structure of 1 was further confirmed by a single-crystal diffraction analysis. All isolates were evaluated for their inhibitory activities against HIV-1.