Polydatin suppresses the development of lung inflammation and fibrosis by inhibiting activation of the NACHT domain‐, leucine‐rich repeat‐, and pyd‐containing protein 3 inflammasome and the nuclear factor‐κB pathway after Mycoplasma pneumoniae infection

Abstract

Mycoplasma pneumoniae (MP) can infect both the upper and lower respiratory tracts. Polydatin (PD), a traditional Chinese medicine, is known to have anti-inflammation and antifibrosis properties. However, the protective effects of PD against MP pneumonia (MPP) remain unclear. So, the aim of this study was to describe the therapeutic effects and underlying mechanisms of PD against MPP. BALB/c mice were assigned to three groups: a normal control group, MP infection group, or PD-treated MP infection group. BEAS-2B cells transfected with or without NACHT domain-, leucine-rich repeat-, and pyd-containing protein 3 (NLRP3) were used to confirm the protective mechanisms of PD. Immunohistochemical analysis, Western blot analysis, enzyme-linked immunosorbent assay, and flow cytometry were used in this study. The results showed that PD treatment suppressed MP-induced lung injury in mice by suppressing the expression of inflammatory factors and inhibiting the development of pulmonary fibrosis. Meanwhile, PD treatment inhibited activation of the NLRP3 inflammasome and nuclear factor κB (NF-κB) pathway. Overexpression of NLRP3 reversed the protective effect of PD against MPinduced injury of BEAS-2B cells. Taken together, these results indicate that PD treatment suppressed the inflammatory response and the development of pulmonary fibrosis by inhibiting the NLRP3 inflammasome and NF-κB pathway after MP infection. K E Y W O R D S fibrosis, inflammation, Mycoplasma pneumoniae, NACHT domain-, leucine-rich repeat-, and pyd-containing protein 3, polydatin

Impaired inflammasome activation and bacterial clearance in G6PD deficiency due to defective NOX/p38 MAPK/AP-1 redox signaling

“…Although the induction of the NLRP3 inflammasome contributes to host defenses against infections, dysregulated inflammasomes are associated with many human diseases, such as cancer, autoimmune diseases, and inflammatory disorders [[29], [30], [31], [32],66]. Our findings that G6PD inhibition can attenuate inflammasome activation suggest a new approach for therapeutic intervention of inflammasome-associated diseases [67,68] with inflammasome as a target. Hence, a G6PD inhibitor such as Polydatin, might be considered as a therapeutic agent to attenuate inflammasome-associated diseases [67,68].…”

“…Our findings that G6PD inhibition can attenuate inflammasome activation suggest a new approach for therapeutic intervention of inflammasome-associated diseases [67,68] with inflammasome as a target. Hence, a G6PD inhibitor such as Polydatin, might be considered as a therapeutic agent to attenuate inflammasome-associated diseases [67,68].…”

Mycoplasma pneumoniae lipids license TLR-4 for activation of NLRP3 inflammasome and autophagy to evoke a proinflammatory response

“…An inflammasome represents a multi-protein complex that protects the host against the invading pathogens through induction of proinflammatory factors, among which the NLRP3 inflammasome plays the most important role [25,45,46]. The NLRP3 inflammasome complex is comprised of NLRP3, ASC and caspase-1 [45].…”

The upshot of Polyphenolic compounds on immunity amid COVID-19 pandemic and other emerging communicable diseases: An appraisal

“…A study has demonstrated that polydatin improves lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). In addition, polydatin has mediated Parkin-dependent mitophagy and protects against mitochondria-dependent apoptosis in ARDS [209,210] niae (MP) infection, MP can infect both the upper and lower respiratory tracts, was found to be suppressed by polydatin treatment through inhibition of the NACHT domain-, leucinerich repeat-, and pyd-containing protein 3 inflammasome (NLRP3) and the nuclear factor-κB pathway after MP infection [211]. Actually, several in vivo studies have reported an important protective role of polydatin treatment via different mechanisms in ovalbumin-induced bronchial asthma as well as in LPS-induced acute lung injury [212,213].…”