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. 2015 Aug;5(4):177-183.
doi: 10.1007/s13659-015-0064-4. Epub 2015 Jun 26.

The Lifespan-Promoting Effect of Otophylloside B in Caenorhabditis elegans

Jie Yang #  1   2   3 , Qin-Li Wan #  1   2 , Quan-Zhang Mu  1 , Chun-Feng Wu  1 , Ai-Jun Ding  1   2 , Zhong-Lin Yang  1   2 , Ming-Hua Qiu  1 , Huai-Rong Luo  1
Affiliations

The Lifespan-Promoting Effect of Otophylloside B in Caenorhabditis elegans

Jie Yang et al. Nat Prod Bioprospect. 2015 Aug.

Abstract

Aging is the major risk factor for many human diseases and degeneration. Thus, clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted. In traditional Chinese medicine (TCM), some were claimed to slow down aging. Qingyangshen (Cynanchum otophyllum schneid) is such a TCM. Here, we assayed the longevity effect of compound Otophylloside B (Ot B), a C-21 steroidal glycoside isolated from Qingyangshen, in Caenorhabditis elegans, which is a popular model for aging research. Our results showed that Ot B could modestly extend the lifespan of C. elegans, delay the age-related decline of body movement and improve the stress resistance. Further investigating the molecular mechanism of lifespan extension effect revealed that Ot B could activate the FOXO transcription factor DAF-16. Ot B could not further extend the lifespan of long-lived mutant of insulin/IGF-1-like receptor (daf-2). In addition, Ot B also requires SIR-2.1 and CLK-1 which is an enzyme in ubiquinone synthesis, for lifespan extension.

Keywords: Aging; Caenorhabditis elegans; DAF-16/FOXO; IIS signaling pathway; Otophylloside B.

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Figures

Fig. 1
Fig. 1
Otophylloside (Ot B) extended adult lifespan in C. elegans. a Chemical structure of Ot B. b Survival curves of wild-type (N2) animals raised at 20 °C on nematode growth media plates containing either no Ot B or different concentrations of Ot B(5, 20, 50, 200, and 500 μM). c Doseage–response analysis of Ot B. Wild-type (N2) animals was treated with 5, 20, 50, 200, and 500 μM Ot B. The average percentage change in lifespan of at least two independent experiments was plotted as a function of dosage. d Survival curves of wild-type (N2) animals raised on 0 (black) and 50 μM (red) Ot B plates at 20 °C. All experiments the treatments were initiated from the first day of adulthood and continued until death. Statistical details and repetition of this experiment are summarized in Table S1 (Supplementary information)
Fig. 2
Fig. 2
Otophylloside (Ot B) delayed age-associated body movement changes and improved thermotolerance. a Age-related movement of worms non-treated and treated with 50 μM Ot B. The movement was assorted as fast movement and not fast movement. The mean fast body movement span was identified as a phenotype of age, Table S3 (supplementary information). b The survival percentage of WT worms cultured at 35 °C non-treated and treated with 50 μM Ot B. The figures showed the mean lifespan of at least three independent experiments, and error bars represented standard deviation (SD). In each experiment, the P values were calculated by K–M method log rank test and P < 0.001. The statistical details are summarized in the Table S2 (Supplementary information)
Fig. 3
Fig. 3
Otophylloside (Ot B) extended adult lifespan in a DAF-16-dependent manner. a Survival curves of daf-16 mutants grown on 0 (black) and 50 μM (red) Ot B plates at 20 °C, Ot B could not further extend mean lifespan of daf-16 mutants. In all cases, these data represent the results of a single trial. Repetition of this experiment and statistical details are summarized in Table S1 (supplementary information). b sod-3 mRNA was increased 1.4-fold in treated with 50 μM Ot B worms compared with non-treated worms. The results presented correspond to the mean and SEM of two independent experiments: **P = 0.007643 in t test. c Ot B could cause DAF-16 nuclear localization. DAF16::GFP-expressing worms were placed on 0 and 50 μM Ot B plates at 20 °C for 24 h. RNA interference treatment by feeding of akt-1 was performed as a positive control
Fig. 4
Fig. 4
Lifespan extension by Otophylloside (Ot B) was mediated by IIS signaling pathway. Survival curves of a daf-2(e1370) III, b skn-1(zu67) IV grown on plates containing 0 (black) and 50 μM (red) Ot B at 20 °C. Ot B could not further extend the lifespan of daf-2(e1370) III, but could extend the lifespan of skn-1(zu67) IV. All drug treatments were initiated from the first day of adulthood and continued until death. In all cases, these data represent the results of a single trial. Repetition of this experiment and statistical details are summarized in Table S1 (supplementary information)
Fig. 5
Fig. 5
Otophylloside (Ot B)-related lifespan extension required for SIR-2.1 and reduction of mitochondrial respiration, but could not further extend the lifespan of eat-2. Survival curves of a sir-2.1(ok434) IV, b eat-2(ad1116) II, c clk-1(e2519) III. Ot B could not further extend mean lifespan of sir-2.1(ok434) IV and clk-1(e2519) III, but could further extend lifespan of eat-2. In all cases, these data represent the results of a single trial. Repetition of this experiment and statistical details are summarized in Table S1 (supplementary information)
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