To evaluate the value of Cirsium japonicum (CJ; thistle) as a material for functional foods, we studied the functional composition of cultivated CJ and the in vitro and in vivo antioxidant activity of the functional substance. The detected phenolics in farmed CJ were chlorogenic acid (CA), linarin (LIN), and pectolinarin (PLIN) by HPLC analysis. As a result of the antioxidant activity of CJ and its phenolics by DPPH and ABTS method, CA had shown the greatest antioxidant activity. We employed Caenorhabditis elegans to validate that in vitro effects of CA are shown in vivo. CA delayed reduction in pumping rate and progeny production during aging of C. elegans. Under both normal and oxidative stress conditions, CA reduced the production of reactive oxygen species (ROS) in worms and increased their lifespan. In particular, CA showed the reducing effect of ROS accumulation due to aging in aged worms (8 days old). To gain insight into the mechanism, we used skn-1/Nrf2 and daf-16/FOXO transformed worms. The CA effects (on catalase activity and lifespan extension) in the wild-type (WT) decreased in skn-1 and daf-16 mutants. In particular, CA strongly relied on daf-16 under mild oxidative condition and skn-1 under overall (from mild to strong) oxidative stress to reduce ROS and extend healthspan. Thus, we conclude that CA, a key bioactive phenolic of CJ, reduces ROS production and ultimately extends healthspan, and this effect is the result of actions of daf-16 or skn-1 at different stages depending on the degree of oxidation or aging. Our results suggest that CJ containing CA can be used as an antiaging material due to its antioxidant properties.

In this study, we investigated the effects of MG4244 on intestinal permeability, oxidative stress, and lipid accumulation in Caenorhabditis elegans with metabolic inflammation induced by Pseudomonas aeruginosa (PA) and a high-glucose diet (HGD). The worms infected with PA exhibited increased intestinal permeability and reactive oxygen species (ROS) production, which were improved upon MG4244 treatment. Also, MG4244 inhibited lipid and ROS accumulation induced by an HGD. In addition, MG4244-treated worms showed extended lifespans under various conditions. To elucidate the mechanism of the MG4244 effects, we conducted further investigation using mutant strains with knockdown of genes associated with the AMP-activated protein kinase (AMPK) and mitogen-activated protein kinase (MAPK) pathways. The results demonstrated that the MG4244 effect on lipid metabolism was primarily mediated through the AMPK signaling pathway. Furthermore, MG4244 enhanced pathogen resistance by MAPK signaling pathways, mitigating stress responses, and maintaining intestinal integrity. In further studies, combined treatment with PA and an HGD significantly increased intestinal permeability, lipid, and ROS levels, confirming their negative synergistic effects. However, MG4244 under PA and HGD co-treatment conditions effectively mitigated these health disruptions, suggesting a protective role of MG4244. This study provides an in vivo platform using C. elegans to evaluate probiotic efficacy related to the intestinal environment. Also, our results highlight the therapeutic potential of MG4244 in improving resilience to metabolic inflammation through gut-targeted mechanisms.