Nectandrin B significantly increases the lifespan of Drosophila - Nectandrin B for longevity

Abstract

Phytochemicals are increasingly recognized in the field of healthy aging as potential therapeutics against various aging-related diseases. Nutmeg, derived from the Myristica fragrans tree, is an example. Nutmeg has been extensively studied and proven to possess antioxidant properties that protect against aging and alleviate serious diseases such as cancer, heart disease, and liver disease. However, the specific active ingredient in nutmeg responsible for these health benefits has not been identified thus far. In this study, we present evidence that Nectandrin B (NecB), a bioactive lignan compound isolated from nutmeg, significantly extended the lifespan of the fruit fly Drosophila melanogaster by as much as 42.6% compared to the control group. NecB also improved age-related symptoms including locomotive deterioration, body weight gain, eye degeneration, and neurodegeneration in aging D. melanogaster. This result represents the most substantial improvement in lifespan observed in animal experiments to date, suggesting that NecB may hold promise as a potential therapeutic agent for promoting longevity and addressing age-related degeneration.

Keywords: Myristica fragrans; Nectandrin B; lifespan; longevity; nutmeg.

Figure 1

NecB increased the lifespan of Drosophila melanogaster. (A) Oregon-RC males, (B) Oregon-RC females, (C) DGRP-100 males and (D) DGRP-100 females. Ctrl represents standard cornmeal medium; Rap-50 represents cornmeal medium supplemented with Rapamycin at 50 μg/mL; Rap-200 represents cornmeal medium supplemented with Rapamycin at 200 μg/mL; NecB-50 represents cornmeal medium supplemented with NecB at 50 μg/mL; and NecB-200 represents cornmeal medium supplemented with NecB at 200 μg/mL (Supplementary Table 1). For the lifespan assay, the survival rate of 150 flies from each group was monitored with medium change every 2 days. Comparisons were made using log-rank tests. The p values (log-rank tests) for each strain and each sex were as follows. (A) Oregon-RC male flies: Ctrl versus RAP-50 (p = 0.004), RAP-200 (p < 0.0001), NecB-50 (p < 0.0001), and NecB-200 (p < 0.0001), respectively. (B) Oregon-RC female flies: Ctrl versus Rap-50 (p = 0.0015), Rap-200 (p < 0.0001), NecB-50 (p < 0.0001), and NecB-200 (p < 0.0001), respectively. (C) DGRP-100 male flies: Ctrl versus RAP-50 (p = 0.0006), Rap-200 (p < 0.0001), NecB-50 (p < 0.0001), and NecB-200 (p < 0.0001), respectively. (D) DGRP-100 female flies: CTRL versus Rap-50 (p < 0.0001), Rap-200 (p < 0.0001), NecB-50 (p < 0.0001), and NecB-200 (p < 0.0001), respectively. The percentage of surviving flies is shown along with the maximum lifespan in each group (n = 150).

Figure 2

NecB improved the locomotion activity of D. melanogaster. (A) Oregon-RC males, (B) Oregon-RC females, (C) DGRP-100 males and (D) DGRP-100 females. Ctrl represents standard cornmeal medium; Rap-50 represents cornmeal medium supplemented with Rapamycin at 50 μg/mL; Rap-200 represents cornmeal medium supplemented with Rapamycin at 200 μg/mL; NecB-50 represents cornmeal medium supplemented with NecB at 50 μg/mL; and NecB-200 represents cornmeal medium supplemented with NecB at 200 μg/mL (Supplementary Table 1). The locomotor activity was observed on the 30th, 60th, and 90th day and indicated as performance index. The data are from three independent experiments, and values are shown as mean ± s.e.m. An unpaired Student’s t-test was used for the statistical analysis; n = 15, ^*p < 0.05, ^**p < 0.01, ^***p < 0.001.

Figure 3

The effects of NecB on changes in the body weights of D. melanogaster. (A) Oregon-RC males, (B) Oregon-RC females, (C) DGRP-100 males and (D) DGRP-100 females. Ctrl represents standard cornmeal medium; Rap-50 represents cornmeal medium supplemented with Rapamycin at 50 μg/mL; Rap-200 represents cornmeal medium supplemented with Rapamycin at 200 μg/mL; NecB-50 represents cornmeal medium supplemented with NecB at 50 μg/mL; and NecB-200 represents cornmeal medium supplemented with NecB at 200 μg/mL (Supplementary Table 1). The body weights were measured on the 30th, 60th, and 90th day. The data are from three independent experiments, and values are shown as mean ± s.e.m. An unpaired Student’s t-test was used for the statistical analysis; n = 30, ^*p < 0.05, ^**p < 0.01, ^***p < 0.001.

Figure 4

NecB suppressed the developmental eye defects in D. melanogaster. (A) Oregon-RC males, (B) Oregon-RC females, (C) DGRP-100 males and (D) DGRP-100 females. Ctrl represents standard cornmeal medium; Rap-50 represents cornmeal medium supplemented with Rapamycin at 50 μg/mL; Rap-200 represents cornmeal medium supplemented with Rapamycin at 200 μg/mL; NecB-50 represents cornmeal medium supplemented with NecB at 50 μg/mL; and NecB-200 represents cornmeal medium supplemented with NecB at 200 μg/mL (Supplementary Table 1). Light microscopy studies of the Drosophila compound eyes were performed at the 30th, 60th and 90th days post-eclosion, and the eye damages are indicated as arrows.

Figure 5

NecB inhibited age-related neurodegeneration in D. melanogaster’s brain morphology. Ctrl represents standard cornmeal medium; Rap-50 represents cornmeal medium supplemented with Rapamycin at 50 μg/mL; Rap-200 represents cornmeal medium supplemented with Rapamycin at 200 μg/mL; NecB-50 represents cornmeal medium supplemented with NecB at 50 μg/mL; and NecB-200 represents cornmeal medium supplemented with NecB at 200 μg/mL (Supplementary Table 1). A histological analysis was performed by H&E staining to examine the neurodegeneration of the Drosophila brains at the 90th days post-eclosion. n = 100; scale bars: 100 μm.

Figure 6

NecB suppressed age-dependent increase in vacuole area in D. melanogaster’s brain. (A) Oregon-RC males, (B) Oregon-RC females, (C) DGRP-100 males and (D) DGRP-100 females. Ctrl represents standard cornmeal medium; Rap-50 represents cornmeal medium supplemented with Rapamycin at 50 μg/mL; Rap-200 represents cornmeal medium supplemented with Rapamycin at 200 μg/mL; NecB-50 represents cornmeal medium supplemented with NecB at 50 μg/mL; and NecB-200 represents cornmeal medium supplemented with NecB at 200 μg/mL (Supplementary Table 1). The quantification of the neurodegeneration and vacuolar lesions based on the histological analysis of the Drosophila brains were observed at the 90th days post-eclosion. The data are from three independent experiments, and values are shown as mean ± s.e.m. Statistical significance was analyzed with an unpaired Student’s t-test and indicated as ^*p < 0.05, ^**p < 0.01, and ^***p < 0.001 from three independent experiments (n = 30).