Mephenesin

Isotope labeling, particularly with deuterium ( 2 H), plays a critical role in drug discovery due to its ease of incorporation and its potential to switch unwanted metabolic transformations. Deuterium incorporation can enhance drug stability, affect pharmacokinetics, and alter metabolism pathways. Current deuterium labeling methods focus on hydrogen isotope exchange (HIE), and typically rely on the use of transition metal catalysis. Herein, we present a metal‐free approach for aromatic HIE, utilizing photoexcitation in deuterated hexafluoroisopropanol (HFIP‐ d1 ). By exploiting the enhanced basicity of excited‐state aromatics, this method achieves selective deuteration at positions often inaccessible by traditional methods. The approach is efficient and was demonstrated across a broad number of complex drug molecules. Transient absorption spectroscopy confirms the formation of deuterated arenium ions.

Yinchenhao Tang (YCHT), a traditional Chinese medicine (TCM), consists of Yinchen, Zhizi, and Dahuang. For over a millennium, it has been widely used in the treatment of liver disorders and jaundice. Furthermore, numerous studies have highlighted its anti-inflammatory, immunomodulatory, and antiviral properties. However, the specific active constituents and the involvement response to influenza virus infection remain unclear.

The present study aims to explore the YCHT' s antiviral and anti-inflammatory abilities, and further clarify the possible mechanisms underlying such effects.

In vitro and in vivo studies were performed to confirm the anti-influenza and anti-inflammatory abilities of YCHT. Ultra-Performance Liquid Chromatography-Quadrupole Orbitrap High-Resolution Mass Spectrometry (UPLC-Q-Orbitrap HRMS) analysis was used to determine the active components and mechanism of YCHT. The potential mechanisms exert its anti-influenza virus effects were investigated via network pharmacology and molecular docking, and the results of cell cytokines and signaling pathways were elucidated by Western blot.

The findings showed that YCHT increased the survival rate of virus-infected mice, reduced viral titers in lung tissue and improved lung pathology. Moreover, in viral-infected A549 cells and pulmonary tissues, inflammatory cytokine expression was suppressed. A total of 26 active compounds were identified in the serum of infected mice in the YCHT treatment group. According to experimental research, molecular docking, and network pharmacology, YCHT inhibits the JAK/STAT signaling pathway to provide its anti-influenza effects.

This study verified YCHT could prevent the production of inflammatory cytokines after influenza A virus infection and relieve the pneumonia via the regulation of JAK/STAT signaling pathway.