Liquiritigenin attenuates high glucose-induced mesangial matrix accumulation, oxidative stress, and inflammation by suppression of the NF-κB and NLRP3 inflammasome pathways.

Abstract

Oxidative stress, inflammation, and hyperglycemia are considered to play crucial roles in the pathogenesis and progression of diabetic nephropathy (DN). Liquiritigenin, one of the flavonoid compounds, has been shown to possess anti-inflammatory, anti-hyperlipidemic, and anti-oxidative properties. Our study aimed to explore the effects of liquiritigenin on high glucose (HG)-induced extracellular matrix (ECM) accumulation, oxidative stress and inflammatory response and delineate the underlying mechanism. In our study, glomerular mesangial cells (HBZY-1) were co-treated with various doses of liquiritigenin and HG. We found that HG, but not normal glucose or mannitol, promoted the proliferation of HBZY-1 cells, which was suppressed by liquiritigenin. Liquiritigenin inhibited HG-induced ECM accumulation in HBZY-1 cells by reducing the expressions and production of collagen IV (Col IV) and fibronectin (FN). Moreover, liquiritigenin attenuated HG-induced oxidative stress, as evidenced by the decreased MDA content and NADPH oxidase 4 (NOX4) expression, and the increased SOD activity in HBZY-1 cells. Liquiritigenin suppressed HG-induced inflammatory response, as demonstrated by the reduced expressions and secretion of interleukin (IL)-6 and IL-1β in HBZY-1 cells. Furthermore, we found that liquiritigenin inhibited HG-induced activation the nuclear factor-kappa B (NF-κB) and nod-like receptor protein 3 (NLRP3) inflammasome pathways. In conclusion, these results demonstrated that liquiritigenin attenuated HG-induced ECM accumulation, oxidative stress, and inflammation by suppression of the NF-κB and NLRP3 inflammasome pathways, suggesting that liquiritigenin might be a promising therapeutic agent for preventing the development of DN.

• Authors: Xiaoguang Zhu, Jun Shi, Huicong Li
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 106 Pg. 976-982 (Oct 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 30119269 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Flavanones
• Inflammasomes
• Inflammation Mediators
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, rat
• Glucose
• liquiritigenin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Cell Line
• Cell Proliferation (drug effects)
• Cytoprotection
• Diabetic Nephropathies (immunology, metabolism, pathology, prevention & control)
• Dose-Response Relationship, Drug
• Extracellular Matrix (drug effects, metabolism, pathology)
• Flavanones (pharmacology)
• Glomerulonephritis (immunology, metabolism, pathology, prevention & control)
• Glucose (toxicity)
• Inflammasomes (drug effects, immunology, metabolism)
• Inflammation Mediators (metabolism)
• Mesangial Cells (drug effects, immunology, metabolism, pathology)
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Oxidative Stress (drug effects)
• Rats
• Signal Transduction (drug effects)