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3β-Hydroxy-urs-12-en-28-oic Acid Modulates Dietary Restriction Mediated Longevity and Ameliorates Toxic Protein Aggregation in C. elegans.

ABSTRACT: Species from lower invertebrates to a spectrum of mammals show antiaging health benefits of phytochemical(s). Here, we explored the pro-longevity effects of a natural triterpenoid, ursolic acid (3β-hydroxy-urs-12-en-28-oic acid; UA) in Caenorhabditis elegans with maximal life span being evident at 25 µM UA. Similar to eat-2 mutants, UA uptake by worm results in reduced fat storage and attenuation of reactive oxygen species (ROS), independent of superoxide dismutase(s) activation. The genetic requirements for UA-mediated longevity are quite similar to dietary restriction (DR) achieved through SKN-1/NRF-2 exhibiting upregulation of downstream target genes gcs-1 and daf-9. Longevity mechanism was independent of PHA-4/FOXA and attributed to partial dependence on sir-2.1. Altogether, our study suggests differential use of UA-elicited signaling cascades in nutrient sensing for longevity. Both the redox state and the proteostasis of an organism play critical role in aging and disease resistance. Interestingly, we observed a reduction of toxic protein aggregation in transgenic polyglutamine (polyQ) C. elegans model and UA-mediated JNK-1 (c-Jun-NH2-terminal kinase) activation in wild-type animals. Thus, our study demonstrates a small extent of prevention against proteotoxic stress by UA coupled with positive aspects of DR-mediated longevity.

SUBMITTER: Negi H

PROVIDER: S-EPMC5861981 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (11αOH-KA) is a multifunctional biochemical found in some ferns, Pteris semipinnata, and its congeneric species. Although a number of therapeutic applications of 11αOH-KA have been proposed (e.g., anti-cancer, anti-inflammation, and skin whitening), the content of 11αOH-KA in these ferns is not high. Adenostemma lavenia (L.) O. Kuntze, an Asteraceae, has also been reported to contain 11αOH-KA. The decoction (hot water extract) of whole plants of A. lavenia is used as a folk remedy for inflammatory disorders, such as hepatitis and pneumonia, suggesting that 11αOH-KA may be the ingredient responsible for the medicinal properties of this plant. The anti-melanogenic activities of the water extracts of A. lavenia leaves and Pteris dispar Kunze (a cognate of P. semipinnata) leaves were compared in mouse B16F10 melanoma cells. The amount of 11αOH-KA was measured by using liquid chromatography spectrometry. C57BL/6J mice were treated with the water extract of A. lavenia leaf, and the blood concentration of 11αOH-KA was measured. The in vivo efficacy of the water extract of A. lavenia leaf was evaluated according to tis anti-melanogenic activity by monitoring hair color. Although both the extracts (A. lavenia and P. dispar Kunze) showed high anti-melanogenic activities, only A. lavenia contained a high amount of 11αOH-KA, approximately 2.5% of the dry leaf weight. 11αOH-KA can be purified from A. lavenia leaves in two steps: water extraction followed by chloroform distribution. The treatment of mice with the water extract of A. lavenia leaf suppresses pigmentation in their hairs. Despite the small number of mice examined, the present preliminary result of the suppressed hair pigmentation suggests that the water extract of A. lavenia leaf and the ingredient that is possibly responsible for this-11αOH-KA-are new materials for oral cosmetics. The results may also be helpful in the future development of functional foods and methods to treat patients suffering from hyperpigmentation disorders, such as melasma.

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3β-Hydroxy-urs-12-en-28-oic Acid Modulates Dietary Restriction Mediated Longevity and Ameliorates Toxic Protein Aggregation in C. elegans.

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