Antistress and anti-aging activities of Caenorhabditis elegans were enhanced by Momordica saponin extract.

BACKGROUND: Momordica saponin extract (MSE) was found to not only improve longevity and neuroprotection but also alleviate fat accumulation in Caenorhabditis elegans in our previous study. However, the lipid-lowering activity of MSE alone could not fully explain its ability to improve health, so the antistress effects of MSE were further studied. METHODS: Using C. elegans as an in vivo animal, the lifespan of MSE-treated C. elegans under various stressors (H2O2, paraquat and heat) and normal conditions was studied. Furthermore, the antioxidant activities of MSE were discussed. To study the underlying mechanisms, the expression of stress resistance genes and the resistance of related mutants to H2O2 stress were tested. RESULTS: MSE significantly improved the lifespan of C. elegans under stress and normal conditions. Meanwhile, the mobility of C. elegans was also improved. Moreover, the activities of SOD and CAT and the ratio of GSH/GSSG were elevated. Consistently, the levels of ROS and lipid oxidation (the NEFA and MDA content) were reduced. Furthermore, MSE treatment upregulated the expression of the sod-3, sod-5, clt-1, clt-2, hsp-16.1 and hsp-16.2 genes. All biomarkers indicated that the antistress and anti-aging activities of MSE were due to its strong antioxidant activities. Finally, MSE induced nuclear DAF-16::GFP localization. Studies with mutants revealed that skn-1 and hsf-1 were involved in the activity of MSE, which might upregulate the expression of downstream stress-responsive genes. CONCLUSIONS: Therefore, in addition to its lipid-lowering property, the ability of MSE to improve healthspan was also attributed to the stress resistance effect. Together, MSE might serve as a lead nutraceutical in geriatric research.

Effect of Momordica saponin- and Cyclocarya paliurus polysaccharide-enriched beverages on oxidative stress and fat accumulation in Caenorhabditis elegans.

BACKGROUND: As an edible and medicinal herb in Chinese folk medicine, Cyclocarya paliurus (Batal.) Iljinskaja leaves are traditionally widely used in the treatment of metabolic disorders. The vegetable Momordica charantia L. has been consumed worldwide for thousands of years as a traditional drug due to its activities against obesity and diabetes. In view of the therapeutic value of Momordica saponins (MSs) and C. paliurus polysaccharides (CPPs), an independently developed MSs- and CPPs-containing beverage (MC) was evaluated for its efficacy in controlling oxidative stress and obesity in Caenorhabditis elegans. RESULTS: First, we found that MC could promote the nuclear localization of DAF-16 and the translation of SOD-3. Further exploring its antioxidant properties, the oxidative stress by-products reactive oxygen species, malondialdehyde, and nonesterified fatty acids were significantly inhibited in C. elegans. Moreover, damage due to diseases related to oxidative stress (age pigments and neurodegenerative diseases) was alleviated. Furthermore, fat accumulation was significantly reduced in normal and high-fat models. Finally, the lipid-lowering effects of MC might involve reductions in the size and number of lipid droplets without impairing basic physiological functions in C. elegans. CONCLUSION: These results provide promising data indicating MC as an innovative health beverage for the pharmacological management of oxidative stress and obesity. © 2020 Society of Chemical Industry.

Anti-fat effect and mechanism of polysaccharide-enriched extract from Cyclocarya paliurus (Batal.) Iljinskaja in Caenorhabditis elegans.

Obesity is a global epidemic. Recent studies have shown that Cyclocarya paliurus (C. paliurus) leaves have the potential to alleviate fat deposits. However, the fat-reducing mechanism of it remains unclear. Using Caenorhabditis elegans (C. elegans) as a model, we found that C. paliurus polysaccharide (CPP) significantly decreased fat storage in both normal and high-fat worms without affecting the movement. Moreover, the size and number of lipid droplets were reduced in CPP-treated ZXW618 worms. In energy metabolism, CPP decreased Escherichia coli (E. coli) OP50 growth and pharyngeal pumping and increased the expression of vit-2. In lipid metabolism, CPP down-regulated the expression of the sbp-1 and nhr-49 genes by modulating mdt-15 to prevent the expression of the Δ9-desaturase genes (fat-5, fat-6 and fat-7). Meanwhile, the expression of the acs-2 genes, the downstream of nhr-49, was suppressed by CPP. These findings provided insights into the CPP-induced anti-fat mechanisms, which contributed to the application of CPP in anti-obesity drugs.

Effects of Momordica saponin extract on alleviating fat accumulation in Caenorhabditis elegans.

Momordica saponins have diverse biological activities and are widely used to improve obesity. Here, we investigated the alleviation of fat accumulation and mechanism of action of the saponin-enriched ethanol extract from Momordica charantia (MSE) in Caenorhabditis elegans (C. elegans). First, MSE had a strong fat-reduction capacity in normal and high-fat worms. Second, MSE significantly increased the proportion of small lipid droplets and reduced the average particle size in ZXW618. Meanwhile, it improved lifespan and healthspan and physiological functions, such as age pigmentation and neuroprotection. Furthermore, MSE mediated fat reduction gets involved neither in energy intake nor in energy expenditure. Finally, MSE might down-regulate sbp-1 and nhr-49 via mdt-15, and up regulate age-1 via daf-2. And these targets genes together down-regulated the expression of fat-5, fat-6 and fat-7 to decrease fat accumulation. Our results provided new insights into the inhibition of fat accumulation and underlying mechanisms of Momordica saponins in C. elegans, which might be developed into a nutraceutical to ameliorate obesity.