Phyllodulcin from the hexane fraction of Hydrangea macrophylla inhibits glucose-induced lipid accumulation and reactive oxygen species generation in Caenorhabditis elegans.

We confirmed that the hexane layer of Hydrangea macrophylla leaf extract (HLH) is rich in phyllodulcin (PD), an alternative sweetener, through high performance liquid chromatography (HPLC) analysis. To investigate in vivo activity of HLH and its PD, acute toxicity and growth rate of Caenorhabditis elegans were tested and there are no clinical abnormalities at 125-500 µg/mL of HLH. HLH decreased the total lipid and triglyceride contents dose-dependently in glucose-induced obese worms. Also, HLH increased survival rates under oxidative and thermal stress and decreased body reactive oxygen species (ROS) contents significantly. Such antioxidant properties of HLH were attributed to the enhanced activity of the antioxidant enzyme catalase. To determine whether the effect of HLH was due to PD, worms were treated with PD (concentration contained in HLH), and inhibitory effects on total lipids and ROS were observed. Our results suggest that HLH and its PD as a natural alternative sweetener can be used as materials to improve metabolic diseases.

Chlorogenic Acid of Cirsium japonicum Resists Oxidative Stress Caused by Aging and Prolongs Healthspan via SKN-1/Nrf2 and DAF-16/FOXO in Caenorhabditis elegans.

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.

Indian Almond (Terminalia catappa Linn.) Leaf Extract Extends Lifespan by Improving Lipid Metabolism and Antioxidant Activity Dependent on AMPK Signaling Pathway in Caenorhabditis elegans under High-Glucose-Diet Conditions.

This study aimed to evaluate the antioxidant and antiaging effects of Indian almond (Terminalia catappa Linn.) leaf extract (TCE) on high-glucose (GLU)-induced obese Caenorhabditis elegans. Since TCE contains high contents of flavonoids and phenolics, strong radical scavenging activity was confirmed in vitro. The stress-resistance effect of TCE was confirmed under thermal and oxidative stress conditions at nontoxic tested concentrations (6.25, 12.5, and 25 µg/mL). GLU at 2% caused lipid and reactive oxygen species (ROS) accumulation in C. elegans, and TCE inhibited lipid and ROS accumulation under both normal and 2% GLU conditions in a concentration-dependent manner. In addition, TCE proved to be effective in prolonging the lifespan of C. elegans under normal and 2% GLU conditions. The ROS reduction effect of TCE was abolished in mutants deficient in daf-16/FOXO and skn-1/Nrf-2. In addition, the lifespan-extending effect of TCE in these two mutants disappeared. The lifespan-extending effect was abolished even in atgl-1/ATGL-deficiency mutants. The TCE effect was reduced in aak-1/AMPK-deficient mutants and completely abolished under 2% GLU conditions. Therefore, the effect of prolonging lifespan by inhibiting lipid and ROS accumulation under the high GLU conditions of TCE is considered to be the result of atgl-1, daf-16, and skn-1 being downregulated by aak-1. These results suggest that the physiological potential of TCE contributes to antiaging under metabolic disorders.