Puerarin ameliorates acute lung injury by modulating NLRP3 inflammasome-induced pyroptosis

Abstract

We commenced to analyze putative anti-pyroptosis effects of puerarin (PU) as mediated by the PP2A-HDAC1-NLRP3 pathway in acute lung injury (ALI). ALI animal and cell models were constructed, followed by treatment of PU. Then, the effect of HDAC1, PP2A, and NLRP3 on cell inflammation and pyroptosis was explored. The interaction between HDAC1 and PP2A as well as between PP2A and NLRP3 was analyzed. Our findings suggested that PU downregulated HDAC1 expression to alleviate symptoms of ALI. HDAC1 overexpression promoted inflammation induced by LPS, which reversed the inhibitory effect of PU on ALI. HDAC1 overexpression also decreased PP2A expression, suggesting that PP2A was involved in the effects of HDAC1 on LPS-induced inflammation. PP2A exerted inhibitory effects on NLRP3. Meanwhile, PU hindered the progression of ALI by silencing HDAC1 or overexpressing PP2A both in vivo and in vitro. Taken together, PU restrained pyroptosis of cells induced by NLRP3 inflammasome to abate ALI.

The Absence of Gasdermin D Reduces Nuclear Autophagy in a Cecal Ligation and Puncture-Induced Sepsis-Associated Encephalopathy Mouse Model

“…Impaired energy metabolism, resulting in a depletion of cellular ATP, which is critical for normal brain function, is another consequence of mitochondrial damage [ 36 ]. Furthermore, mitochondrial dysfunction can contribute to the activation of apoptotic pathways, which worsen brain damage in SAE [ 41 ]. This damage may be a compensatory response to increased energy demands, and may contribute to cognitive and emotional dysfunction.…”

Natural Products for the Treatment of Pulmonary Hypertension: Mechanism, Progress, and Future Opportunities

“…A novel crystal type V (Puer-V) was found to have a better therapeutic effect than the crude form of puerarin, effectively alleviating abnormal structural changes and dysfunction in lung tissue and the right ventricle [ 78 ]. Puerarin also exhibited anti-inflammatory properties in rats with acute lung injury by modulating the renin–angiotensin system and NF-κB signaling pathway, modulating the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3 (NLRP3) inflammasome-induced pyroptosis, and reducing TNF-α, interleukin-6 (IL-6), and interleukin-1β (IL-1β) production [ 79 , 80 , 81 ].…”

“…In addition, clinical and preclinical evidence suggests that inflammasomes, particularly NLRP3 and its downstream cytokine products, are promising drug targets for PH [ 119 ]. Puerarin inhibits NLRP3 inflammasome-induced pyroptosis to improve acute lung injury [ 81 ]. Astragaloside IV has been shown to inhibit MCT-induced PH via the NLRP-3/calpain-1 pathway [ 90 ].…”

Puerarin mitigated LPS‐ATP or HG‐primed endothelial cells damage and diabetes‐associated cardiovascular disease via ROS‐NLRP3 signalling

“… 24 , 25 , 26 Notably, previous studies reported that Pue exerted antioxidant and anti‐inflammatory effects, especially for the inhibition of ROS and NLRP3 inflammasome. 27 , 28 The specificity of Pue in addressing diabetes‐associated cardiovascular disease requires further clarification. This inquiry seeks to establish a coherent understanding of the mechanisms by which Pue exerts its effects on oxidative stress, inflammasome activation and pyroptotic cell death specifically within the context of diabetic vascular complications.…”

“…[24][25][26] Notably, previous studies reported that Pue exerted antioxidant and anti-inflammatory effects, especially for the inhibition of ROS and NLRP3 inflammasome. 27,28 The specificity…”