hyodeoxycholic-acid and baicalin

The complexity of ingredients in traditional Chinese medical formulas and the limited consideration of toxicological responses are fundamental issues that hamper prognostic information of drug quality control.. A multidisciplinary approach for quality control of Qingkailing injection (QKL) regarding drug induced liver toxicity was described for the first time. High content image analysis (HCA) was combined with reverse-phase chromatographic separation and high-resolution MS detection technologies to provide the dynamic responses of drug induced HepG2 cell injury. Firstly, a simple and rapid method for simultaneous qualification and quantification of 21 major constituents in QKL was established and validated using ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap mass spectrometer (UHPLC-Q-Orbitrap), which were operated in full MS/dd-MS. The detection in polarity switching mode empowered the coverage of comprehensive constituents with different chemical properties. Satisfactory linearity precisions, repeatability, stability, and recovery were achieved. QKL injection significantly induced HepG2 cell injury above the concentration of 1.25% (v/v). Meanwhile, flavone glycosides (F3) and stinasterols (F4) fractions exhibited hepatotoxicity above 75μg/mL and 50μg/mL, respectively. Still further, baicalin originated from F3 significantly caused cell loss and glutathione (GSH) depletion. In parallel, hyodeoxycholic acid from F4 induced cell loss, nucleus condense, and GSH reduction as well.. Our work provides multiple perspectives based on injection-fractions-single compound format to improve QKL pharmacovigilance through revealing the potential hepatotoxic material basis. Additionally, our study provides an integrating paradigm for the comprehensive and systematic quality control of traditional Chinese medical formulas.

Topics: Biomarkers; Chemical and Drug Induced Liver Injury; Deoxycholic Acid; Drugs, Chinese Herbal; Flavonoids; Hep G2 Cells; Humans; Quality Control

A simple, rapid, and specific analytical method for simultaneous determination of geniposide, baicalin, cholic acid and hyodeoxycholic acid in 50 microL samples of rat serum was developed by high performance liquid chromatography-tandem mass spectrometry. The quantification of the target compounds was determined by multiple reaction monitoring (MRM) mode using electrospray ionization (ESI). The correlation coefficients of the calibration curves were better than 0.997. The intra- and inter-day accuracy, precision, and linear range had been investigated in detail. This method was subsequently applied to pharmacokinetic studies of geniposide, baicalin, cholic acid and hyodeoxycholic acid in rats successfully.

Topics: Animals; Calibration; Cholic Acid; Chromatography, High Pressure Liquid; Deoxycholic Acid; Flavonoids; Iridoids; Male; Pyrans; Rats; Rats, Wistar; Reference Standards; Spectrometry, Mass, Electrospray Ionization

To investigate the mechanism of Qingkailing (QKL) Injection in treating acute promyelocytic leukemia.. Using MTT technique, cell morphologic method, DNA gel electrophoresis and flow-cytometry to study the human acute promyelocytic leukemia (HL-60) cell apoptosis induced by QKL and its active principle.. QKL and its active principle, Baicalin and hyodeoxycholic acid, showed strong cytotoxicity in inhibiting HL-60 cell, the Bezoar cholic acid showed a weaker effect. Apoptosis could be induced after being treated for 6 hrs by the former three principles, showing a typical apoptosis peak under flow-cytometry, but could not be induced by the latter one.. QKL could induce leukemia cell apoptosis in vitro, which may be one of the mechanisms of QKLI in curing acute promyelocytic leukemia.

Topics: Apoptosis; Deoxycholic Acid; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Flavonoids; HL-60 Cells; Humans; Leukemia, Promyelocytic, Acute