Leonurine inhibits the TXNIP/NLRP3 and NF‐κB pathways via Nrf2 activation to alleviate carrageenan‐induced pleurisy in mice

Abstract

Oxidative stress and inflammation play important roles in pleurisy. Leonurine (Leo) has been confirmed to exert antioxidative and antiinflammatory effects in many preclinical experiments, but these effects have not been studied in pleurisy. The aim of this study was to explore the therapeutic effect and mechanism of Leo in a carrageenan (CAR)‐induced pleurisy model. In this study, we found that the increase of reactive oxygen species (ROS), myeloperoxidase (MPO), and malondialdehyde (MDA) and decrease of glutathione (GSH) induced by CAR could be reversed by the treatment of Leo. Leo effectively reduced the levels of proinflammatory cytokines interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF‐α), and the percentages of mature macrophages and increased the levels of antiinflammatory cytokines (IL‐10). Furthermore, Western blotting revealed that Leo significantly activated the Nrf2 pathway to restrain the thioredoxin‐interacting protein/NOD‐like receptor protein 3 (TXNIP/NLRP3) and nuclear factor kappa‐B (NF‐κB) pathways. However, the protective effect of Leo was significantly weakened in Nrf2‐deficient mice. These results indicate that Leo confers potent protection against CAR‐induced pleurisy by inhibiting the TXNIP/NLRP3 and NF‐κB pathways dependent on Nrf2, which may serve as a promising agent for attenuating pleurisy.

Assessment of the Effect of Leonurine Hydrochloride in a Mouse Model of PCOS by Gene Expression Profiling

“…Leonurine hydrochloride (Leo, 3,5-dimethoxy-4-hydroxybenzoic acid (4-guanidine)-1butyl ester) is isolated as an alkaloid and is one of the main active ingredients of Leonurus [10]. Due to its anti-inflammatory [11,12], antioxidant, anti-apoptotic [13,14], and immune functions, an increasing number of researchers have focused on Leo. The good protective effect of Leo on cerebrovascular and cardiovascular diseases has been proven by pharmacological studies [15,16], and recent studies have shown that Leo also has antitumour, antidepressant, and oestrogen-like effects [17,18].…”