Zerumbone suppresses high glucose and LPS-induced inflammation in THP-1-derived macrophages by inhibiting the NF-κB/TLR signaling pathway

• Published in: Nutrition research (New York, N.Y.) N.Y.), 2022-04, Vol.100, p.58-69
• Main Authors: Kim, Arang, Gwon, Min-Hee, Lee, Wooje, Moon, Ha-Rin, Yun, Jung-Mi
• Format: Article
• Language: English
• Subjects: Diabetes mellitus; Glucose - pharmacology; Humans; Inflammation; Inflammation - drug therapy; Inflammation - metabolism; Lipopolysaccharides - pharmacology; Macrophages; NF-kappa B - metabolism; Sesquiterpenes; Signal Transduction; Sirtuin; Sirtuins - metabolism; Sirtuins - pharmacology; Toll-like receptor; Zerumbone
• ISSN: 0271-5317; 1879-0739
• DOI: 10.1016/j.nutres.2022.01.002

Diabetes mellitus is characterized by hyperglycemia. Low-grade bacterial infection with hyperglycemia in patients with diabetes is associated with atherosclerosis development. Therefore, this study hypothesized that macrophages lead to more severe diabetic complications under combined conditions of high glucose and lipopolysaccharide (LPS)-induced inflammation than under normoglycemic conditions. Zerumbone is the main component of Zingiber zerumbet Smith essential oil, a type of wild ginger. It possesses various biomedical activities, including antibacterial, antioxidant, anti-inflammatory, and anticancer activities; however, the precise mechanism of its anti-inflammatory and epigenetic effects is not fully understood. In this study, the effects of zerumbone on the secretion of proinflammatory cytokines and its underlying regulatory mechanism were investigated in THP-1-derived macrophages exposed to high glucose and LPS. THP-1-derived macrophages were cultured under normoglycemic (5.5 mmol/L glucose) or hyperglycemic (25 mmol/L glucose) conditions in the absence or presence of zerumbone (5-50 μM) for 48 hours and then treated with 100 ng/mL LPS for 6 hours. Zerumbone (25 and 50 μM) suppressed the production of tumor necrosis factor-α and interleukin-6 and the activation of cyclooxygenase-2, nuclear factor-κB, histone deacetylases 3 proteins, and Toll-like receptor messenger RNA (mRNA) and increased the transcription of the sirtuin 1 (SIRT1), SIRT3, and SIRT6 mRNAs. Taken together, our results suggest that zerumbone may exert beneficial effects on diabetes and its complications. High glucose and lipopolysaccharide (LPS) induce inflammation in THP-1 macrophages. High glucose and LPS activate Toll-like receptor 2 (TLR2) and TLR4, followed by myeloid differentiation factor 88. Subsequently, activated nuclear factor-κB (NF-κB) increases the secretion of inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α, resulting in an inflammatory reaction. However, zerumbone suppressed inflammation by inhibiting NF-κB and TLR under high glucose and LPS-induced inflammation. Zerumbone is a promising dietary component for the treatment and prevention of diabetes and its related complications. [Display omitted]