Resveratrol Suppresses “Metabolic Memory” by Inhibiting Inflammation and Apoptosis Through the ROS/TXNIP/NLRP3 Signaling Pathway

• Published in: Pharmacognosy Magazine Vol. 20; no. 3; pp. 898 - 907
• Main Authors: Jiang, Tingting, Gu, Junxiang, Chang, Qing
• Format: Journal Article
• Language: English
• Published: New Delhi, India SAGE Publications 01.09.2024
• Subjects: metabolic memory; diabetic retinopathy; thioredoxin-interacting protein (TXNIP); Resveratrol; NOD-like receptor family pyrin domain-containing 3 (NLRP3)
• ISSN: 0973-1296; 0976-4062
• DOI: 10.1177/09731296241229242

Aim This research endeavored to explore the impact and underlying mechanisms of resveratrol on the phenomenon of “metabolic memory” in cultured human retinal vascular endothelial cells (HRVECs) under high-glucose (HG) conditions. Materials and Methods According to the glucose level and treatment, cultured HRVECs were divided into seven groups: normal glucose (NG), HG, high glucose followed by NG (HN), mannitol (Man), resveratrol, thioredoxin-interacting protein (TXNIP)-small interfering ribonucleic acid (siRNA), and N-acetylcysteine (NAC). The expression levels of TXNIP, nucleotide oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, intercellular adhesion molecule 1 (ICAM-1), caspase-1, interleukin-1β (IL-1β), B-cell lymphoma 2 (Bcl-2), caspase-3, and Bcl-2-associated X (BAX), as well as reactive oxygen species (ROS) production, were measured. Cell apoptosis was assessed through a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Results In HRVECs from the HG group, expression levels of TXNIP, NLRP3, caspase-1, ICAM-1, and IL-1β were upregulated. However, in the HN group, the above upregulations were not reversed. After the administration of resveratrol, the expression levels of TXNIP, NLRP3, and other inflammatory cytokines were significantly reduced. Resveratrol mitigated the elevated ROS production induced by HG conditions. In the NAC group, the expression of TXNIP and inflammatory cytokines was downregulated. TXNIP-siRNA treatment showed similar effects. Resveratrol inhibited apoptosis as well as reversed the downregulation of BCL-2 and the upregulation of caspase-3 and BAX induced by HG conditions. Conclusion Resveratrol mitigated the HG-induced phenomenon of “metabolic memory” by inhibiting inflammation and apoptosis via modulation of the ROS/TXNIP/NLRP3 signaling pathway in cultured HRVECs. Therefore, resveratrol may have therapeutic potential to treat diabetic retinopathy and related metabolic memory complications.