Ginsenoside Prolongs the Lifespan of C. elegans via Lipid Metabolism and Activating the Stress Response Signaling Pathway.

Panax ginseng is a valuable traditional Chinese medicine in Northeast China. Ginsenoside, the active component of ginseng, has not been investigated much for its effects on aging and its underlying mechanism(s) of action. Here, we investigated the effects of total ginsenoside (TG), a mixture of the primary active ginsenosides from Panax ginseng, on the lifespan of Caenorhabditis elegans (C. elegans). We found that TG extended the lifespan of C. elegans and reduced lipofuscin accumulation. Moreover, TG increased the survival of C. elegans in response to heat and oxidative stress via the reduction of ROS. Next, we used RNA-seq to fully define the antiaging mechanism(s) of TG. The KEGG pathway analysis showed that TG can prolong the lifespan and is involved in the longevity regulating pathway. qPCR showed that TG upregulated the expression of nrh-80, daf-12, daf-16, hsf-1 and their downstream genes. TG also reduced the fat accumulation and promoted lipid metabolism. Moreover, TG failed to extend the lifespan of daf-16 and hsf-1 mutants, highlighting their role in the antiaging effects of TG in C. elegans. The four main constitution of TG were then confirmed by HPLC and included ginsenoside Re, Rg1, Rg2 and Rd. Of the ginsenosides, only ginsenoside Rd prolonged the lifespan of C. elegans to levels comparable to TG. These findings provided mechanistic insight into the antiaging effects of ginsenoside in C. elegans.

Ferulic Acid Supplementation Increases Lifespan and Stress Resistance via Insulin/IGF-1 Signaling Pathway in C. elegans.

Ferulic acid (FA) is a naturally-occurring well-known potent antioxidant and free radical scavenger. FA supplementation is an effective strategy to delay aging, but the underlying mechanism remains unknown. In the present study, we examined the effects of FA on lifespan extension and its mechanism of FA in Caenorhabditis elegans (C. elegans). Results suggested that FA increased the lifespan of C. elegans, rather than altering the growth of E. coli OP50. Meanwhile, FA promoted the healthspan of C. elegans by improving locomotion and reducing fat accumulation and polyQ aggregation. FA increased the resistance to heat and oxidative stress through reducing ROS. The upregulating of the expression of the hlh-30, skn-1, and hsf-1 were involved in the FA-mediated lifespan extension. Furthermore, FA treatment had no impact on the lifespan of daf-2, hlh-30, skn-1, and hsf-1 mutants, confirming that insulin/IGF-1 signaling pathway and multiple longevity mechanisms were associated with the longevity mechanism of FA. We further found that mitochondrial signaling pathway was modulation involved in FA-mediated lifespan extension. With the results from RNA-seq results and mutants lifespan assay. These findings contribute to our knowledge of the lifespan extension and underlying mechanism of action of FA in C. elegans.

Diselenium-containing ultrathin polymer nanocapsules for highly efficient targeted drug delivery and combined anticancer effect.

The combination of selenium and pillararenes to prepare selenium-containing pillararene-based biomaterials is of great significance for the development of biomedicine. Herein, using a covalent self-assembly strategy, we successfully developed new diselenium-containing ultrathin polymer nanocapsules based on lateral cross-linked pillararenes. The new system exhibited a very potent anticancer effect; additionally, the incorporation of the cleavable redox diselenium bond into the polymer nanocapsules provided a smart nanocarrier for drug delivery. Moreover, the polymer nanocapsules were developed for anticancer drug targeting delivery by loading an anticancer drug and introducing the tumor-penetrating peptide RGD through the host-guest interaction strategy. The targeting DOX-loaded diselenium-containing polymer nanocapsules exhibited enhanced stability, self-anticancer effect, targeted delivery and controlled drug release, resulting in effective combined inhibition of tumor progression.

Molecular mechanisms of anti-oxidant and anti-aging effects induced by convallatoxin in Caenorhabditis elegans.

Convallatoxin is widely used as a cardiac glycoside in acute and chronic congestive heart-failure and paroxysmal tachycardia, with many effects and underlying protective mechanisms on inflammation and cellular proliferation. However, convallatoxin has not been investigated in its antioxidant effects and lifespan extension in Caenorhabditis elegans. In this study, we found that convallatoxin (20 µM) could significantly prolong the lifespan of wild-type C. elegans up to 16.3% through daf-16, but not sir-2.1 signalling and increased thermotolerance and resistance to paraquat-induced oxidative stress. Convallatoxin also improved pharyngeal pumping, locomotion, reduced lipofuscin accumulation and reactive oxygen species levels in C. elegans, which were attributed to hormesis, free radical-scavenging effects in vivo, and up-regulation of stress resistance-related proteins, such as SOD-3 and HSP-16.1. Furthermore, aging-associated genes daf-16, sod-3, and ctl-2 also appeared to contribute to the stress-resistance effect of convallatoxin. In summary, this study demonstrates that convallatoxin can protect against heat and oxidative stress and extend the lifespan of C. elegans, pointing it as a potential novel drug for retarding the aging process in humans.

A deuterohemin peptide extends lifespan and increases stress resistance in Caenorhabditis elegans.

This group has invented a novel deuterohemin containing peptide deuterohemin-AlaHisThrValGluLys (DhHP-6), which has various biological activities including protection of murine ischemia reperfusion injury, improving cell survival and preventing apoptosis. It was hypothesized that DhHP-6 is beneficial on the lifespan of Caenorhabditis elegans (C. elegans) and increases their resistance to heat and oxidative stress. C. elegans were treated with different concentrations of DhHP-6. Survival time and sensitivity to heat and paraquat were investigated. The data demonstrated that the mean survival time of C. elegans was significantly increased (p < 0.05) in the DhHP-6 treated group compared with the control group. The maximum lifespan was not affected by DhHP-6 treatment. DhHP-6 improved the survival rate of C. elegans in the acute heat stress (35 degrees C) and rescued the C. elegans' sensitivity to paraquat in acute oxidative stress. Superoxide dismutase 3 (SOD-3) protein was up-regulated by DhHP-6 treatment. It was further demonstrated that stress resistance genes such as hsp-16.1, hsp-16.49 and sir-2.1 were regulated by DhHP-6. DAF-16 and SIR-2.1 genes are essential for the beneficial effect of DhHP-6. Therefore, the investigation into the beneficial effect of DhHP-6 on C. elegans' lifespan has the potential to develop novel drugs to prevent ageing.

Immunological adjuvant effect of Japanese ginseng saponins (JGS) on specific antibody and cellular response to ovalbumin and its haemolytic activities.

In this study, the saponins (JGS) extracted from the rhizoma of Japanese ginseng were evaluated for their haemolytic activities and their potential ability as adjuvants on the immune responses to ovalbumin (OVA) in mice. The haemolytic activity of JGS was determined using 0.5% rabbit red blood cell, with its HD(50) value being 177.78+/-6.77microg/mL. ICR mice were immunized subcutaneously with OVA 100microg alone or with OVA 100microg dissolved in saline containing Alum (200microg), QuilA (10 and 20microg) or JGS (50, 100 or 200microg) on Days 1 and 15. Two weeks later (Day 28), concanavalin A (ConA)-, lipopolysaccharide (LPS)-, OVA-stimulated splenocyte proliferation and OVA-specific antibodies in serum were measured. JGS significantly enhanced the ConA-, LPS-, and OVA-induced splenocyte proliferation in the OVA-immunized mice especially at a dose of 100microg (P<0.05 or P<0.01). The OVA-specific IgG, IgG1 and IgG2b antibody levels in serum were also significantly enhanced by JGS compared with OVA control group (P<0.01). The results suggest that JGS showed a slight haemolytic effect and enhanced significantly a specific antibody and cellular response against OVA in mice.