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As the most important marker component in Carthamus tinctorius L., hydroxysafflor yellow A (HSYA) was widely used in the prevention and treatment of cardiovascular diseases, due to its effect of improving blood supply, suppressing oxidative stress, and protecting against ischemia/reperfusion. In this paper, both an in vitro microsomal incubation and an in vivo animal experiment were conducted, along with an LC-Q-TOF/MS instrument and a 3-step protocol, to further explore the metabolism of HSYA. As a result, a total of 10 metabolites were searched and tentatively identified in plasma, urine, and feces after intravenous administration of HSYA to male rats, although no obvious biotransformation was found in the simulated rat liver microsomal system. The metabolites detected involving both phase I and phase II metabolism including dehydration, deglycosylation, methylation, and glucuronic acid conjugation. A few of the metabolites underwent more than one-step metabolic reactions, and some have not been reported before. The study would contribute to a further understanding of the metabolism of HSYA and provide scientific evidence for its pharmacodynamic mechanism research and clinical use. [ABSTRACT FROM AUTHOR]

Xin-Sheng-Hua granule, a representative formula for postpartum hemorrhage, has been used clinically to treat postpartum diseases. Its main bioactive components comprise aromatic acids, phthalides, alkaloids, flavonoids, and gingerols among others. To investigate the changes in main bioactive constituents in its seven single herbs before and after compatibility, a rapid, simple, and sensitive method was developed for comparative analysis of 27 main bioactive components by using ultrahigh-performance liquid chromatography with triple quadrupole electrospray tandem mass spectrometry for the first time. The sufficient separation of 27 target constituents was achieved on a Thermo Scientific Hypersil GOLD column (100 mm × 3 mm, 1.9 μm) within 20 min under the optimized chromatographic conditions. Compared with the theoretical content, the observed content of each analyte showed remarkable differences in Xin-Sheng-Hua granule except thymine, p-coumaric acid, senkyunolide I, senkyunolide H, and ligustilide; the total contents of 27 components increased significantly, and the content variation degrees for the different components were gingerols > flavonoids > aromatic acids > alkaloids > phthalides. The results could provide a good reference for the quality control of Xin-Sheng-Hua granule and might be helpful to interpret the drug interactions based on variation of bioactive components in formulae. [ABSTRACT FROM AUTHOR]

Dysregulation of mitotic processes can induce chromosome instability, which results in aneuploidy, tumorigenesis, and chemo-resistance. Thyroid hormone receptor interactor 13 (TRIP13) is a critical mitosis regulator, and recent studies suggest that it functions as an oncogene in multiple cancers. However, the role of TRIP13 in bladder cancer (BC) is still unknown. In this study, our analysis of RNA-sequencing data from the Cancer Genome Atlas and Gene expression profiling databases showed that TRIP13 expression was upregulated in BC tissues, and overexpression of TRIP13 was significantly associated with poor prognosis of BC patients. In addition, we found a remarkable elevation of TRIP13 in BC samples compared to normal controls by immunohistochemistry. Furthermore, our in vitro functional assays showed that overexpression of TRIP13 promoted the growth/viability, colony formation ability by inducing cell cycle arrest in G2/M phase, as well as enhancing drug resistance of BC cells to cisplatin and doxorubicin. Conversely, knockdown of TRIP13 inhibited cell growth and induced apoptosis of BC cells. Furthermore, TRIP13 acted as an oncogene in BC by inhibiting spindle assembly checkpoint signaling by targeting mitotic arrest deficient 2 (MAD2) protein. TRIP13 overexpression also alleviated cisplatin- and doxorubicin-induced DNA damage and enhanced DNA repair as evidenced by the reduced expression of γH2AX and enhanced expression of RAD50 in drug-treated BC cells. In conclusion, TRIP13 may be a novel target for the treatment of BC., Competing Interests: None.