Methylophiopogonanone A is a naturally occurring broad-spectrum inhibitor against human UDP-glucuronosyltransferases: Inhibition behaviours and implication in herb-drug interactions.

Methylophiopogonanone A (MOA) is an abundant homoisoflavonoid in the Chinese herb Ophiopogonis Radix. Recent investigations revealed that MOA inhibited several human cytochrome P450 enzymes (CYPs) and stimulated OATP1B1. However, the inhibitory effects of MOA on phase II drug-metabolizing enzymes, such as human UDP-glucuronosyltransferases (hUGTs), have not been well investigated. Herein, the inhibition potentials of MOA on hUGTs were assessed. The results clearly demonstrated that MOA dose-dependently inhibited all tested hUGTs including UGT1A1 (IC50 = 1.23 µM), one of the most important detoxification enzymes in humans. Further investigations showed that MOA strongly inhibited UGT1A1-catalysed NHPH-O-glucuronidation in a range of biological settings including hUGT1A1, human liver microsomes (HLM) and HeLa cells overexpressing UGT1A1. Inhibition kinetic analyses demonstrated that MOA competitively inhibited UGT1A1-catalysed NHPH-O-glucuronidation in both hUGT1A1 and HLM, with Ki values of 0.52 and 1.22 µM, respectively. Collectively, our findings expanded knowledge of the interactions between MOA and human drug-metabolizing enzymes, which would be very helpful for guiding the use of MOA-related herbal products in clinical settings.

A new dicyanoisophorone-based ratiometric and colorimetric near-infrared fluorescent probe for specifically detecting hypochlorite and its bioimaging on a model of acute inflammation.

To explore how hypochlorous acid (HClO) affects human health, a highly sensitive, selective, and trace detection method for hypochlorite (ClO-) is crucial for determining its non-negligible function in both environment and living systems. Herein, a dicyanoisophorone-phenylboronic acid-based novel ratiometric near-infrared fluorescent probe (Probe 1) was designed for the rapid and specific detection of ClO- based on the intramolecular charge transfer (ICT) mechanism. Excess addition of HClO to the Probe 1 solution, 186-times ratio (I652/I582) augment were gained. And this probe provided a colorimetric and ratiometric fluorescence response to ClO- with a high selectivity, a rapid response (within 30 s), and had an extremely low detection limit (15.7 nM). In addition, owing to the good sensing properties and low cytotoxicity of Probe 1, it can be used to expediently visualize exogenous ClO- in HepG2 cells and endogenous ClO- in RAW264.7 macrophage cells. Furthermore, the probe was successfully used for the bioimaging of zebrafish with an acute inflammation. Thus, Probe 1 is a promising vehicle to identify the level of HClO in animals with associated diseases.

A Ratiometric and Colorimetric Hemicyanine Fluorescent Probe for Detection of SO2 Derivatives and Its Applications in Bioimaging.

Based upon the intramolecular charge transfer (ICT) mechanism, a novel ratiometric fluorescent probe EB was developed to detect SO32-/HSO3-. The probe displayed both colorimetric and ratiometric responses toward SO32-/HSO3-. It displayed a quick response (within 60 s), good selectivity and high sensitivity (a detection limit of 28 nM) towards SO32-/HSO3-. The SO32-/HSO3- sensing mechanism was confirmed as the Michael addition reaction by ESI-MS. Moreover, the probe could be applied to measure the level of sulfite in real samples, like sugar and chrysanthemum, and it could also be used to detect SO32-/HSO3- in HepG2 cells through confocal fluorescence microscopy, which proved its practical application in clinical diagnosis.