Isoeugenol (IEG), a natural component of clove oil, possesses antioxidant, anti-inflammatory, and antibacterial properties. However, the effects of IEG on adipogenesis have not yet been elucidated. Here, we showed that IEG blocks adipogenesis in 3T3-L1 cells at an early stage. IEG inhibits lipid accumulation in adipocytes in a concentration-dependent manner and reduces the expression of mature adipocyte-related factors including PPARγ, C/EBPα, and FABP4. IEG treatment at different stages of adipogenesis showed that IEG inhibited adipocyte differentiation by suppressing the early stage, as confirmed by lipid accumulation and adipocyte-related biomarkers. The early stage stimulates growth-arrested preadipocytes to enter mitotic clonal expansion (MCE) and initiates their differentiation into adipocytes by regulating cell cycle-related factors. IEG arrested 3T3-L1 preadipocytes in the G₀/G₁ phase of the cell cycle and attenuated cell cycle-related factors including cyclinD1, CDK6, CDK2, and cyclinB1 during the MCE stage. Furthermore, IEG suppresses reactive oxygen species (ROS) production during MCE and inhibits ROS-related antioxidant enzymes, including superoxide dismutase1 (SOD1) and catalase. The expression of cell proliferation-related biomarkers, including pAKT and pERK1/2, was attenuated by the IEG treatment of 3T3-L1 preadipocytes. These findings suggest that it is a potential therapeutic agent for the treatment of obesity.

Chronic kidney disease (CKD) gradually leads to loss of renal function and is associated with inflammation and fibrosis. Chrysanthemum coronarium L., a leafy vegetable, possesses various beneficial properties, including anti-oxidative, anti-inflammatory, and antiproliferative effects. In this study, we investigated the renoprotective effect of Chrysanthemum coronarium L. extract (CC) on adenine (AD)-induced CKD in mice. CKD was induced by feeding mice with an AD diet (0.25% w/w) for 4 weeks. Changes in renal function, histopathology, inflammation, and renal interstitial fibrosis were analyzed. The adenine-fed mice were characterized by increased blood urea nitrogen, serum creatinine, and histological changes, including inflammation and fibrosis; however, these changes were significantly restored by treatment with CC. Additionally, CC inhibited the expression of the inflammatory markers, monocyte chemoattractant protein-1, interleukins-6 and -1β, intercellular adhesion molecule-1, and cyclooxygenase 2. Moreover, CC suppressed the expression of the fibrotic markers, type IV collagen, and fibronectin. Furthermore, CC attenuated the expression of profibrotic genes (tumor growth factor-β and α-smooth muscle actin) in AD-induced renal injury mice. Thus, our results suggest that CC has the potential to attenuate AD-induced renal injury and might offer a new option as a renoprotective agent or functional food supplement to manage CKD.

Tissue homeostasis requires a delicate balance between stem cell self-renewal, proliferation, and differentiation. Essential to this process is glycosylation, with both intra-and extra-cellular glycosylation being required for stem cell homeostasis. However, it remains unknown how intracellular glycosylation, O-GlcNAcylation, interfaces with cellular components of the extracellular glycosylation machinery, like the cytosolic N-glycanase NGLY1. In this study, we utilize the Drosophila gut and uncover a pathway in which O-GlcNAcylation cooperates with the NGLY1 homologue PNG1 to regulate proliferation in intestinal stem cells (ISCs) and apoptosis in differentiated enterocytes. Further, the CncC antioxidant signaling pathway and ENGase, an enzyme involved in the processing of free oligosaccharides in the cytosol, interact with O-GlcNAc and PNG1 through regulation of protein aggregates to contribute to gut maintenance. These findings reveal a complex coordinated regulation between O-GlcNAcylation and the cytosolic glycanase PNG1 critical to balancing proliferation and apoptosis to maintain gut homeostasis.

The intestines play important roles in responding immediately and dynamically to food intake, environmental stress, and metabolic dysfunction, and they are involved in various human diseases and aging. A key part of their function is governed by intestinal stem cells (ISCs); therefore, understanding ISCs is vital. Dysregulation of ISC activity, which is influenced by various cell signaling pathways and environmental signals, can lead to inflammatory responses, tissue damage, and increased cancer susceptibility. Aging exacerbates these dynamics and affects ISC function and tissue elasticity. Additionally, proliferation and differentiation profoundly affect ISC behavior and gut health, highlighting the complex interplay between environmental factors and gut homeostasis. Drosophila models help us understand the complex regulatory networks in the gut, providing valuable insights into disease mechanisms and therapeutic strategies targeting human intestinal diseases.

Stem cells are essential for tissue maintenance but are highly sensitive to oxidative and metabolic stress. Here, we show that Drosophila Gpxl, the ortholog of mammalian GPX4, preserves intestinal stem cell (ISC) function by coupling nutrient-sensing O-GlcNAcylation to the DNA damage response (DDR) during aging and oxidative stress. In ISCs/enteroblasts of aged or oxidative stressed Drosophila midguts and in aged mouse intestine, expression of Gpxl (Drosophila) and GPX4 (mammals) was increased, coincident with ISC hyperproliferation, elevated O-GlcNAcylation, and enhanced ATM/ATR activity. Under oxidative-stress-induced hyperproliferation, ISCs/EBs-specific Gpxl knockdown attenuated the proliferative response. Moreover, loss of Gpxl suppressed O-GlcNAcase (OGA) knockdown-induced hyperproliferation and dysplasia, suggesting that Gpxl functionally interacts with O-GlcNAc cycling and may exert cell-type-specific actions in stem and differentiated cells. Together, these findings define a Gpxl-O-GlcNAc-DDR axis that integrates lipid-peroxidation defense with nutrient and stress signaling to maintain epithelial homeostasis during aging and oxidative stress. By identifying Gpxl as a required node in O-GlcNAc-dependent proliferative programs, our work nominates this axis as a tractable therapeutic target for age-associated intestinal dysfunction and neoplastic progression.

Hyun-Jin Na and Mi Jeong Sung. Prev Nutr Food Sci 2025;30:444-9. https://doi.org/10.3746/pnf.2025.30.5.444