Sinomenine attenuates lipopolysaccharide‐induced inflammation and apoptosis of WI‐38 cells by reducing glutathione S‐transferase M1 expression

Abstract

Pediatric pneumonia is an infectious lung disease with high morbidity and mortality. Sinomenine, an alkaloid extracted from Caulis Sinomenii, exerts anti‐inflammatory and anti‐apoptotic activities. Lipopolysaccharide (LPS) is widely used for the establishment of an inflammatory model. This research aimed to explore the influences of sinomenine on LPS‐caused inflammatory injuries in fetal lung WI‐38 cells. WI‐38 cells were treated with LPS to establish a cellular model of pediatric pneumonia. Cell viability was evaluated using CCK‐8 assay. Apoptosis was evaluated using TUNEL staining and caspase‐3 activity assays. Inflammatory cytokines and NF‐κB p65 phosphorylation levels were measured by Enzyme‐Linked Immunosorbent Assay. Glutathione S‐transferase M1 (GSTM1) expression was detected by western blotting. Results showed that LPS reduced WI‐38 cell viability, and sinomenine protected cells against LPS‐induced viability reduction. Sinomenine concentration‐dependently attenuated LPS‐induced inflammation by reducing TNF‐α, IL‐1β and MCP‐1, and increasing IL‐10 levels. Sinomenine mitigated LPS‐induced apoptosis. GSTM1 was screened by matching the targets of sinomenine and pediatric pneumonia. GSTM1 was upregulated in LPS‐treated WI‐38 cells, and this effect was attenuated after sinomenine treatment. GSTM1 was upstream of NF‐κB pathway. Overexpression of GSTM1 reversed the suppressive functions of sinomenine on LPS‐stimulated inflammation and apoptosis. Overall, sinomenine attenuates inflammation and apoptosis in WI‐38 cells stimulated by LPS via inhibiting GSTM1 expression, indicating the therapeutic potential of sinomenine in pediatric pneumonia.

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review

“…Y. Liu and team reported on the treatment of SIN in children with pneumonia. Their results showed that SIN (5–20 µM) inhibited glutathione S-transferase M1 (GSTM1), decreased TNF-α, IL-1β, and MCP-1, and increased IL-10, thereby alleviating inflammation and apoptosis in lipopolysaccharide (LPS)-stimulated WI-38 cells [ 130 ].…”

Curcumin inhibits malignant behavior of colorectal cancer cells by regulating M2 polarization of tumor‐associated macrophages and metastasis associated in colon cancer 1 (MACC1) expression

“…Activation of the caspase-3 pathway has been considered a pivotal event during cell apoptosis (Y. Liu et al, 2022;Singh et al, 2023) A permeable fluorogenic caspase substrate, Su-perView™ 488 Caspase-3 Assay Kit for Live Cells (Yeasen Biotechnology, China), can detect caspase-3 within live cells. Transfected or non-transfected SW620 or HCT 116 cells were cultured in black 96-well plates with the addition of curcumin or not for 72 h. Then, a fresh medium containing 5 μM SuperView 488 Substrate was added to replace the old medium.…”