Myeloperoxidase (MPO) is a heme-containing peroxidase, mainly expressed in neutrophils and, to a lesser extent, in monocytes. MPO is known to have a broad bactericidal ability via catalyzing the reaction of Cl⁻ with H₂O₂ to produce a strong oxidant, hypochlorous acid (HOCl). However, the overproduction of MPO-derived oxidants has drawn attention to its detrimental role, especially in diseases characterized by acute or chronic inflammation. Broadly speaking, MPO and its derived oxidants are involved in the pathological processes of diseases mainly through the oxidation of biomolecules, which promotes inflammation and oxidative stress. Meanwhile, some researchers found that MPO deficiency or using MPO inhibitors could attenuate inflammation and tissue injuries. Taken together, MPO might be a promising target for both prognostic and therapeutic interventions. Therefore, understanding the role of MPO in the progress of various diseases is of great value. This review provides a comprehensive analysis of the diverse roles of MPO in the progression of several diseases, including cardiovascular diseases (CVDs), neurodegenerative diseases, cancers, renal diseases, and lung diseases (including COVID-19). This information serves as a valuable reference for subsequent mechanistic research and drug development.

Wogonin is a natural anticancer candidate. The purpose of this study was to explore the pharmacokinetic profiles, tissue distribution, excretion and plasma protein binding of wogonin in Sprague—Dawley rats. A rapid, sensitive, and specific LC-MS/MS method has been developed for the determination of wogonin in different rat biological samples. After i.v. dosing of wogonin at different levels (10, 20 and 40 mg/kg) the elimination half-life was approximately 14 min, the AUC_0-∞ increased in a dose disproportional manner from 112.13 mg/L·min for 10 mg/kg to 758.19 mg/L·min for 40 mg/kg, indicating a non linear pharmacokinetic profile. After i.g. dosing at 100 mg/kg, plasma levels of wogonin peaked at 28 min with a C_max value of 300 ng/mL and a very low oral bioavailability (1.10%). Following i.v. single dose (20 mg/kg), wogonin was detected in all examined tissues (including testis) with the highest levels in kidney and liver. Approximately 21% of the administered dose was excreted as unchanged drug (mainly via non-biliairy fecal route (16.33%). Equilibrium dialysis was used to evaluate plasma protein binding of wogonin at three concentrations (0.1, 0.5 and 2 µg/mL). Results indicated a very high protein binding degree (over 90%), reducing substantially the free fraction of the compound.

Oxidative stress plays an important role in the pathogenesis of acute lung injury (ALI). As a typical post-translational modification triggered by oxidative stress, protein S-glutathionylation (PSSG) is regulated by redox signaling pathways and plays diverse roles in oxidative stress conditions. In this study, we found that GSTP downregulation exacerbated LPS-induced injury in human lung epithelial cells and in mice ALI models, confirming the protective effect of GSTP against ALI both in vitro and in vivo. Additionally, a positive correlation was observed between total PSSG level and GSTP expression level in cells and mice lung tissues. Further results demonstrated that GSTP inhibited KEAP1-NRF2 interaction by promoting PSSG process of KEAP1. By the integration of protein mass spectrometry, molecular docking, and site-mutation validation assays, we identified C434 in KEAP1 as the key PSSG site catalyzed by GSTP, which promoted the dissociation of KEAP1-NRF2 complex and activated the subsequent anti-oxidant genes. In vivo experiments with AAV-GSTP mice confirmed that GSTP inhibited LPS-induced lung inflammation by promoting PSSG of KEAP1 and activating the NRF2 downstream antioxidant pathways. Collectively, this study revealed the novel regulatory mechanism of GSTP in the anti-inflammatory function of lungs by modulating PSSG of KEAP1 and the subsequent KEAP1/NRF2 pathway. Targeting at manipulation of GSTP level or activity might be a promising therapeutic strategy for oxidative stress-induced ALI progression.