Abstract
The problem of an aging society is becoming increasingly acute. Diseases related to aging also come with it. There are some diseases that people can’t treat fundamentally. Therefore, people try to find a natural ingredient from natural medicine to treat these diseases and improve the quality of life of the elderly. With the screening of a large number of traditional Chinese medicines, we found that polysaccharides from Rehmannia glutinous (PRG) can prolong the lifespan of Caenorhabditis elegans (C. elegans). Neutral polysaccharide is the main component of PRG. In the present study, we used a C. elegans model to illustrate the stress resistance and lifespan extension effect and mechanism of two kinds of neutral polysaccharide fractions from Rehmannia glutinosa (NPRG), respectively called NPRRP and NPRR. Our data showed that two kinds of neutral polysaccharides fractions could extend the lifespan and delay senescence of wild-type worms. Moreover, the mechanism study revealed that NPRG was able to promote the nuclear localization of DAF-16 resulting in the activation of antioxidant enzymatic systems under oxidative stress. We also observed that NPRG didn’t increase the lifespan of mutants with daf-16 portion loss of function, suggesting NPRG prolonging the lifespan partially required the daf-16 gene on the insulin/IGF-1 signaling pathway (IIS). NPRG was found to have no effect on Escherichia coli OP50 (E. coli OP50) growth and pharyngeal pump movement of nematodes, indicating that the anti-aging effect of NPRG is not realized by the caloric restriction. However, mRNA levels of daf-2 were remarkably decreased after NPRG treatment. Thus daf-2 lost its inhibitory effect on the expression of daf-16 and had a continuous stimulation effect on the IIS, then prolonged the life of nematodes. Overall, our results illustrated the potential utilization of NPRG as a functional pharmaceutical ingredient to increase stress resistance and extend the life of C. elegans via the IIS, which could be developed as a natural supplement agent.
Highlights
Rehmannia glutinosa is a member of the Scrophulariaceae family
When nematodes are subjected to external heat and oxidative stress, daf-16 will rapidly transfer to the nucleus under the stimulation of these stress signals and induce the high expression of these downstream effector elements so as to resist the pressure caused by external stress and extend the lifespan of nematodes [25,26,27,28]
Through the RT-PCR experiment, we found that polysaccharides from Rehmannia glutinous (PRG) could significantly inhibit the transcriptional activity of daf-2 but had little effect on other genes, which indicates that neutral polysaccharide fractions from Rehmannia glutinosa (NPRG) could inhibit the negative regulation of the insulin signal receptor daf-2 on the insulin/IGF-1 signaling pathway (IIS) in nematodes by inhibiting the expression of daf-2, thereby extending the lifespan of nematodes
Summary
Rehmannia glutinosa is a member of the Scrophulariaceae family. It is a traditional Chinese medicinal herb which is widely used in China, Japan, Korea and other Asian countries. Its steamed roots have been used for different medical purposes as traditional Chinese medicine (TCM) for thousands of years. Polysaccharide abundant in Rehmannia glutinosa is one important active ingredient and has a wide range of pharmacological activity. Lots of data has shown that it exerts an anti-inflammatory, anti-bacterial, and anti-tumor effect and that it protects cardiovascular function [1]. Accumulating evidence demonstrates that polysaccharides from natural sources, such as fungi, plants and marine
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