Background: Esculetin, 6,7-dihydroxycoumarin, is a bioactive compound found in various herbal plants, and is known to have health-beneficial properties including anti-obesity effects. However, there is a lack of in vivo studies to clearly determine esculetin’s role in lipid metabolism. Objectives: In this study, we studied esculetin’s effect on lipid accumulation using Caenorhabditis elegans and its underlying mechanisms. Methods: C. elegans were treated with esculetin (100 or 200 μM) for 48 h, and their triglyceride and protein levels were measured. Additionally, behavioral patterns such as pharyngeal pumping rate, body bending rate, body sizes, and locomotive activity were analyzed. Genetic dependencies were examined by utilizing mutant worms and testing relative gene expressions. Results: C. elegans treated with esculetin displayed significantly reduced fat accumulation compared to the controls without effects on the pharyngeal pumping rate, body bending rate, or locomotive activity. Esculetin’s fat-lowering effect was dependent on DAF-2 (insulin/insulin-like growth factor-1 [IGF-1] receptor homolog), DAF-16 (Forkhead box protein O homolog), and AAK-2 (5′-adenosine monophosphate-activated protein kinase [AMPK] catalytic subunit α2) in the mutant experiments. Esculetin also significantly increased the relative expression of downstream targets of DAF-16 (hsp-16.2 and sod-3), AMPK-related genes (aak-1 and aak-2), a sirtuin gene, sir-2.1, and a lipolysis-related gene, atgl-1. Conclusions: These findings suggest that esculetin inhibited fat accumulation in C. elegans and this effect was dependent on the insulin/IGF-1 and 5′-adenosine monophosphate-activated protein kinase signaling pathways.

Asthma is a chronic inflammatory disease involving structural changes to the respiratory system and severe immune responses mediated by allergic cytokines and pro-inflammatory mediators. Agarum cribrosum (AC) is a kind of seaweed which contains a phlorotannin, trifuhalol A. To evaluate its anti-allergic inflammatory effect against asthma, an ovalbumin inhalation-induced mouse asthma model was used. Histologic observations proved that trifuhalol A is minimizing the lung and tracheal structure changes as well as the infiltration of eosinophils and mast cells against ovalbumin inhalation challenge. From the serum and bronchoalveolar lavage fluid, ovalbumin-specific IgE and Th2-specific cytokines, IL-4, -5, and -13, were reduced with trifuhalol A treatment. In addition, IL-1β, IL-6, and TNF-α concentrations in lung homogenate were also significantly reduced via trifuhalol A treatment. Taken together, trifuhalol A, isolated from AC, was able to protect lung and airways from Th2-specific cytokine release, and IgE mediated allergic inflammation as well as the attenuation of IL-1β, IL-6, and TNF-α in lung, which results in the suppression of eosinophils and the mast cells involved asthmatic pathology.

Trifuhalol A supports vascular homeostasis by enhancing endothelial NO signaling and modulating ACE activity within the renin–angiotensin and kallikrein–kinin pathways.

Caenorhabditis elegans is a multi-organ nematode widely used in various research fields of life science. It is favored for its ease of handling, short life cycle with high reproductive capacity, low maintenance costs, availability of diverse mutants, and substantial genomic and proteomic similarity to mammals. Since research involving C. elegans typically does not require approval from the Institutional Animal Care and Use Committee, it serves as a valuable alternative to vertebrate animal models. Most importantly, lipid metabolism exhibits significant homology between C. elegans and mammals, making it a powerful in vivo model for studying many food-based bioactives that target lipid metabolism. This review briefly covers the basic physiology and genes involved in lipid metabolism in C. elegans, research procedures, and limitations of using its use in research. In addition to established models like mammalian tissue culture and rodents, utilizing C. elegans can be a valuable strategy for exploring the potential role of food-based bioactives in controlling obesity.