A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan, and reduces amyloid β peptide toxicity in Caenorhabditis elegans

Abstract

Lactoferrin is a highly multifunctional glycoprotein involved in many physiological functions, including regulation of iron absorption and immune responses. Moreover, there is increasing evidence for neuroprotective effects of lactoferrin. We used Caenorhabditis elegans as a model to test the protective effects, both on phenotype and transcriptome, of a nutraceutical product based on lactoferrin liposomes. In a dose-dependent manner, the lactoferrin-based product protected against acute oxidative stress and extended lifespan of C. elegans N2. Furthermore, Paralysis of the transgenic C. elegans strain CL4176, caused by Aβ1-42 aggregates, was clearly ameliorated by treatment. Transcriptome analysis in treated nematodes indicated immune system stimulation, together with enhancement of processes involved in the oxidative stress response. The lactoferrin-based product also improved the protein homeostasis processes, cellular adhesion processes, and neurogenesis in the nematode. In summary, the tested product exerts protection against aging and neurodegeneration, modulating processes involved in oxidative stress response, protein homeostasis, synaptic function, and xenobiotic metabolism. This lactoferrin-based product is also able to stimulate the immune system, as well as improving reproductive status and energy metabolism. These findings suggest that oral supplementation with this lactoferrin-based product could improve the immune system and antioxidant capacity. Further studies to understand the molecular mechanisms related with neuronal function would be of interest.

Keywords: Alzheimer's disease; Caenorhabditis elegans; immune system; lactoferrin; neuroprotection.

Figures

Figure 1

Measurement of body paralysis of C. elegans CL 4176 nematodes fed with LfCD product (25, 50, 100, and 150 μL) after temperature up‐shift. Gingko biloba extract (1 μg/mL) was used as positive control. Worms without temperature‐induction were included as negative control. Time refers to hours after Aβ42 induction by temperature up‐shift. Data are the average of two independent experiments.

Figure 2

Survival of the C. elegans N2 nematodes treated with 2 mmol/L H2O2 on nematode growth medium plates in a worm population fed with different doses of the LfCD product. Vitamin C (10 μg/mL) was used as positive control. ***Significant at P ≤ 0.001. **Significant at P ≤ 0.01. NS: not significant. Data are the average of four independent experiments.

Figure 3

Survival curves of C. elegans wild‐type strain N2 fed with nematode growth medium (NGM) medium (control) or with LfCD product during 24 h from adult stage with (A) 25 μL of LfCD; (B) 50 μL of LfCD. Two hundred worms per condition were used in two independent experiments. Mean lifespan, indicating the time in days where half of the worm population is still alive, is shown on the X‐axis. P‐values are shown in each curve comparison between control NGM and LfCD‐treated nematodes. NS: no significant differences.

Figure 4

Model for the mechanism of action of LfCD product based on the different metabolic pathways targeted in C. elegans.