Published online Nov 28, 2021. doi: 10.3748/wjg.v27.i44.7669
Peer-review started: May 17, 2021
First decision: June 26, 2021
Revised: July 9, 2021
Accepted: September 10, 2021
Article in press: September 10, 2021
Published online: November 28, 2021
Acute lung injury (ALI) is a common and life-threatening complication of severe acute pancreatitis (SAP). There are currently limited effective treatment options for SAP and associated ALI. Calycosin (Cal), a bioactive constituent extracted from the medicinal herb Radix astragali exhibits potent anti-inflammatory properties, but its effect on SAP and associated ALI has yet to be determined.
To determine the effect of Cal on the SAP-ALI and its underlying mechanism.
To identify the roles of Cal in SAP-ALI and the underlying mechanism.
SAP was induced via two intraperitoneal injections of L-arginine (L-arg: 4g/kg). Cal-treated mice received intraperitoneal injections of Cal (25 or 50 mg/kg) 1 h prior to the first L-arg challenge. Mice were sacrificed 72 h after the second L-arg challenge and indices of SAP and associated ALI were examined histologically and biochemically. An in vitro model of lipopolysaccharide (LPS)-induced ALI was established using A549 cells. Cells were either fixed for immunofluorescence analysis or protein extracted for western blot assessment of High Mobility Group Box 1(HGMB1) and nuclear factor-kappa B (NF-κB) expression, respectively. Molecular docking analyses were conducted to examine the interaction of Cal with HMGB1.
Cal treatment significantly reduced serum amylase levels and alleviated histopathological injury associated with SAP and ALI. Neutrophil infiltration and lung tissue levels of the neutrophil mediator myeloperoxidase (MPO) were reduced in line with the protective effects of Cal against ALI in SAP. Cal treatment also attenuated the serum levels and mRNA expression of pro-inflammatory cytokines in lung tissue. Cal treatment markedly suppressed the expression of HMGB1 and phosphorylated NF-κB p65 in lung tissues and in an in vitro model of LPS-induced ALI in A549 cells. Furthermore, molecular docking analysis provided evidence for the direct interaction of Cal with HGMB1.
Cal protects mice against L-arg-induced SAP and associated ALI by attenuating local and systemic neutrophil infiltration and the inflammatory response via inhibition of HGMB1 and the NF-κB signaling pathway.
Cal may be used as a potential medicine in SAP-ALI therapy.