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.

Parkinson’s disease (PD) is a prevalent neurodegenerative disease for which no effective treatment currently exists. In this study, we identified formononetin (FMN), a neuroprotective component found in herbal medicines such as Astragalus membranaceus and Glycyrrhiza uralensis, as a potential agent targeting multiple pathways involved in PD. To investigate the anti-PD effects of FMN, we employed Caenorhabditis elegans (C. elegans) PD models, specifically the transgenic strain NL5901 and the MPP(+)-induced strain BZ555, to investigate the effects of FMN on the key pathological features of PD, including dyskinesia, dopamine neuron damage, and reactive oxygen species (ROS) accumulation. The MPP(+)-induced SH-SY5Y cell PD model was utilized to evaluate the effects of FMN on cell viability, ROS accumulation, and mitochondrial dysfunction. The signaling pathway induced by FMN was analyzed using transcriptomic techniques and subsequently validated in vitro. Our results indicate that FMN significantly reduced ROS accumulation and improved both dopaminergic neuron vitality and dyskinesia in the C. elegans PD models. In the cell PD model, FMN significantly reduced ROS accumulation and enhanced mitochondrial membrane potential (MMP) and cell viability. A transcriptomic analysis suggested that the effects of FMN are associated with Nrf2 activation. Furthermore, ML385, a specific Nrf2 inhibitor, blocked the beneficial effects of FMN in vitro, indicating that FMN ameliorates dyskinesia and protects dopaminergic neurons through Nrf2 signaling pathway activation. In addition, the effects of FMN on ameliorating dyskinesia and protecting dopamine neurons were comparable to those of the Nrf2 agonist of sulforaphane (SFN) in vivo. The results of this study confirm that FMN exerts significant anti-PD effects primarily through the Nrf2 signaling pathway. These findings provide crucial insights for the development of anti-PD therapies.