Sophocarpine attenuates septic liver injury through suppression of the NLRP3 inflammasome via autophagy‑mediated degradation

Abstract

Septic liver injury remains a challenge in sepsis treatment. Nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome activation has been suggested to be a major cause of hepatocyte cell death in liver diseases. However, insufficient research has been performed to explore the underlying mechanisms associated with this. In the present study, sophocarpine, a pharmaceutical monomer originally isolated from Sophora flavescens, was suggested to attenuate septic liver injury in a mouse cecal ligation and puncture (CLP) model. By utilizing western blotting, ELISA, H&E staining and immunohistochemistry, the results demonstrated that sophocarpine treatment reversed CLP-induced elevations in serum aspartate transaminase, alanine transaminase, interleukin (IL)-6 and IL-1β levels. Additionally, sophocarpine appeared to have suppressed the activation of the NLRP3 inflammasome, as indicated by observed reductions in liver IL-1β, NLRP3, caspase 1-p20 and gasdermin D-p30 protein levels. Further investigation suggested that sophocarpine-induced autophagy was essential for this suppression of NLRP3 inflammasome activation, the inhibition of which reversed the protective effects of sophocarpine on CLP-induced liver injury. Collectively, results from the present study suggested a protective role for sophocarpine against septic liver injury, where sophocarpine may suppress NLRP3 inflammasome activation by autophagy-mediated degradation.

YTHDF1 alleviates sepsis by upregulating WWP1 to induce NLRP3 ubiquitination and inhibit caspase-1-dependent pyroptosis

“…NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes can stimulate the inflammation and induce immune cell apoptosis to exacerbate the development of sepsis [ 11 ]. Moreover, inactivation of NLRP3 inflammasomes could alleviate septic liver injury through autophagy-mediated degradation [ 12 ]. As previously reported, pyroptosis induced by the NLRP3/caspase-1 pathway could affect cognitive deficits in mice with sepsis-related encephalopathy [ 12 ].…”

“…Moreover, inactivation of NLRP3 inflammasomes could alleviate septic liver injury through autophagy-mediated degradation [ 12 ]. As previously reported, pyroptosis induced by the NLRP3/caspase-1 pathway could affect cognitive deficits in mice with sepsis-related encephalopathy [ 12 ]. Additionally, NLRP3-dependent caspase-1/11-GSDMD pathway was previously demonstrated to mediate pyroptosis in the hippocampus of a sepsis model [ 13 ].…”

Systematic analysis of chemical profiles of Sophorae tonkinensis Radix et Rhizoma in vitro and in vivo using UPLC‐Q‐TOF‐MSE

“…The content of matrine and oxymatrine, the characteristic components of S. tonkinensis , is specified in Pharmacopoeia of the People's Republic of China (Pharmacopoeia of People's Republic of China, 2020). Modern pharmaceutical studies showed alkaloids such as cytisine, matrine, oxymatrine, and sophocarpine have displayed different biological activities, including antiviral (Ding et al, 2006), antipyretic (Cho et al, 1986), anti‐inflammatory (He et al, 2019; Hou et al, 2020), and hepato‐protective activities (Huang & Xu, 2020; Wan et al, 2009). Meanwhile, alkaloids in S. tonkinensis were found to exhibit toxicity (Li, Zhao, et al, 2021; Wang et al, 2017; Wang, Wang, et al, 2019).…”

“…The residue was redissolved in 200 μL of 80% methanol, and the supernatant was transferred into the UPLC sample vial for LC-MS analysis. et al, 2006), antipyretic (Cho et al, 1986), anti-inflammatory (He et al, 2019;Hou et al, 2020), and hepato-protective activities (Huang & Xu, 2020;Wan et al, 2009). Meanwhile, alkaloids in S. tonkinensis were found to exhibit toxicity (Li, Zhao, et al, 2021;Wang et al, 2017;.…”

Nutrition and autophagy deficiency in critical illness

“…Impairing acute hepatic autophagy activation via local genetic inactivation worsened hepatic mitochondrial damage/dysfunction and aggravated liver damage after CLP in mice [35]. In other CLP mouse studies, autophagy enhancement alleviated liver injury [36,37]. Autophagy regulation protects against liver injury evoked by liver surgery associated ischemia-reperfusion [38].…”