Polygonum multiflorum Thunb extract extended the lifespan and healthspan of Caenorhabditis elegans via DAF-16/SIR-2.1/SKN-1.

Polygonum multiflorum Thunb (PMT), as a traditional Chinese herbal medicine, has been widely used in the prevention and treatment of aging-related diseases, including Alzheimer's disease, Parkinson's disease, hyperlipidemia, atherosclerosis and inflammation. However, the effect of PMT on the lifespan and its molecular mechanisms are still unclear. Here we found that 60% ethanol refined fraction (PMT-E) of Polygonum multiflorum Thunb at 50 µg mL-1, which contained two main bioactive compounds, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside (TSG) and emodin-8-O-ß-D-glucoside (EG), could significantly increase the mean lifespan by 19.82%, delay the age-related decline of phenotypes, enhance stress resistance and reduce ROS accumulation in Caenorhabditis elegans. Moreover, we also found that the mitochondrial membrane potential (ΔΨ) and ATP content of worms treated with 50 µg mL-1 PMT-E were obviously improved. Further mechanistic studies revealed that DAF-16, SIR-2.1 and SKN-1 transcription factors were required for PMT-E-mediated lifespan extension. Finally, we found that PMT-E could significantly inhibit the toxicity induced by ß-amyloid (Aß) in Aß transgenic worms. Altogether, these findings laid the foundation for the use of Polygonum multiflorum Thunb to treat aging and age-related diseases.

Essential Oil of Acorus tatarinowii Schott Ameliorates Aß-Induced Toxicity in Caenorhabditis elegans through an Autophagy Pathway.

BACKGROUND: Acorus tatarinowii Schott [Shi Chang Pu in Chinese (SCP)] is a traditional Chinese medicine frequently used in the clinical treatment of dementia, amnesia, epilepsy, and other mental disorders. Previous studies have shown the potential efficacy of SCP against Alzheimer's disease (AD). Nevertheless, the active constituents and the modes of action of SCP in AD treatment have not been fully elucidated. PURPOSE: The aim of this study was to investigate the protective effects of SCP on abnormal proteins and clarify its molecular mechanisms in the treatment of AD by using a Caenorhabditis elegans (C. elegans) model. METHODS: This study experimentally assessed the effect of SCP-Oil in CL4176 strains expressing human Aß in muscle cells and CL2355 strains expressing human Aß in pan-neurons. Western blotting, qRT-PCR, and fluorescence detection were performed to determine the oxidative stress and signaling pathways affected by SCP-Oil in nematodes. RESULTS: SCP-Oil could significantly reduce the deposition of misfolded Aß and polyQ proteins and improved serotonin sensitivity and olfactory learning skill in worms. The analysis of pharmacological action mechanism of SCP-Oil showed that its maintaining protein homeostasis is dependent on the autophagy pathway regulated partly by hsf-1 and sir-2.1 genes. CONCLUSION: Our results provide new insights to develop treatment strategy for AD by targeting autophagy, and SCP-Oil could be an alternative drug for anti-AD.

Lonicera japonica extends lifespan and healthspan in Caenorhabditis elegans.

Lonicera japonica (LJ) is widely used as the local medicine to improve body and prevent ills in China, but mechanisms of its healthy beneficial effects remain largely unclear. Here, we evaluated the anti-aging and healthspan promoting activities of 75% ethanol extract of LJ (LJ-E) in the animal model Caenorhabditis elegans. Our results showed that LJ-E (500 µg/mL) treatment enhanced the mean lifespan of worms by over 21.87% and significantly improved age-associated physiological functions in C. elegans. The 500 µg/mL concentration of LJ-E enhanced the survival rates under oxidative and thermal stresses, and decreased reactive oxygen species (ROS) levels and fat accumulation in the worms. Gene-specific mutant studies showed that LJ-E-mediated lifespan extension was dependent on mev-1, daf-2, daf-16, and hsf-1, but not eat-2 genes. LJ-E could upregulate stress-inducible genes, viz., hsp-16.2, sod-3 and mtl-1. Moreover, we found that the D1086.10 protein interacted with superoxide dismutase (SOD)-3 by functional protein association networks analysis according to RNA-sequencing results. It was confirmed that D1086.10 was needed to promote longevity, and positively regulated expression of sod-3 by using D1086.10 mutants. Furthermore, LJ-E significantly delayed amyloid ß-protein induced paralysis in CL4176 strain. Given the important role of autophagy in aging and protein homeostasis, we observed that LJ-E could remarkably increase the mRNA expression of autophagy gene bec-1 in CL4176 strain, and decrease expression of autophagy substrate p62 protein by more than 40.0% in BC12921 strain. Finally, we found that combination composed of three major compounds (54 µg/mL chlorogenic acid, 15 µg/mL 1,5-dicaffeoylquinic acid and 7.5 µg/mL 1,3-dicaffeoylquinic acid) of 500 µg/mL LJ-E could significantly delay paralysis in CL4176 worms caused by Aß toxicity, comparable to that of LJ-E. Overall, our study may have important implications in using Lonicera japonica to promote healthy aging and have a potency to design therapeutics for age-related diseases.