Comprehensive Metabolomics Analysis of Xueshuan Xinmaining Tablet in Blood Stasis Model Rats Using UPLC-Q/TOF-MS
MOLECULES
Authors: Tan, Jing; Wang, Cuizhu; Zhu, Hailin; Zhou, Baisong; Xiong, Lingxin; Wang, Fang; Li, Pingya; Liu, Jinping
Abstract
Blood stasis syndrome (BSS) is one of the most common Chinese medicine patterns in coronary heart disease. Our previous work proved that Xueshuan Xinmaining Tablet (XXT) could treat blood stasis through regulating the expression of F13a1, Car1 and Tbxa2r. In the current study, the effect and mechanism of XXT on BSS was comprehensively and holistically investigated based on a metabolomics approach. Urine and plasma samples of 10 BBS rats treated with XXT (XT), 9 BSS model rats (BM) and 11 normal control (NC) rats were collected and then determined by UPLC-Q/TOP-MS. Multivariate analyses were applied to distinguish differentiate urinary and plasma metabolite patterns between three groups. Results showed that a clear separation of three groups was achieved. XT group was located between BM group and NC group, and showing a tendency of recovering to NC group, which was consistent with the results of hemorheological studies. Some significantly changed metabolites like cortexolone, 3 alpha,21-dihydroxy-5 beta-pregnane-11,20-dione and 19S-hete and leukotriene A4, chiefly involved in steroid hormone biosynthesis, arachidonic acid metabolism and lipid metabolism, were found and identified to explain the mechanism. These potential markers and their corresponding pathways will help explain the mechanism of BSS and XXT treatment. This work also proves that metabolomics is effective in traditional Chinese medicinal research.
Coagulation factor XIII gene variation, oral contraceptives, and risk of ischemic stroke
BLOOD
Authors: Martijn, D.; Pruissen, O.; Slooter, Arjen J. C.; Rosendaal, Frits R.; van der Graaf, Yolanda; Algra, Ale
Abstract
Prothrombotic conditions are associated with ischemic stroke in young women. In particular, the combination of oral contraceptive use and prothrombotic genetic variants appears to increase the risk of ischemic stroke. We performed a population-based case-control study in 190 women aged 20 to 49 years with ischemic stroke and 767 women without cardiovascular disease stratified for age, calendar year of the index event, and residence. A total of 4 variants of coagulation factor XIII subunit A and B genes (F13A1 and F13B) were investigated. The Phe allele of the F13A1 Tyr204Phe variant was present in 59 (31%) patients and 43 (6%) controls; the odds ratio for ischemic stroke was 9.1 for Phe/Phe and Phe/Tyr versus Tyr/Tyr genotype; the 95% confidence interval was 5.5 to 15. Homozygous genotypes (Phe/Phe) conferred a higher risk (odds ratio, 77; 95% confidence interval, 7.0-848) than heterozygous (Tyr/Phe) genotypes (odds ratio, 8.2; 95% confidence interval, 4.9-14). The risk of ischemic stroke was further increased in carriers of the 204Phe allele using oral contraceptives (odds ratio, 20; 95% confidence interval, 9-46) compared with non-users with Tyr/Tyr genotype. In conclusion, the F13A1 204Phe allele was strongly associated with ischemic stroke in young women. Oral contraceptive use further increased the risk of ischemic stroke.