Journal Article

Hibiscus sabdariffa L. extract prolongs lifespan and protects against amyloid-β toxicity in Caenorhabditis elegans: involvement of the FoxO and Nrf2 orthologues DAF-16 and SKN-1

Weldle, Nora, Koch, Karoline, Büchter, Christian, Wätjen, Wim, Baier, Sabrina

2020

Overview

Purpose Hibiscus sabdariffa L. is commonly used as an ingredient for herbal teas and food supplements. Several studies demonstrated the beneficial effects of Hibiscus sabdariffa L. extracts (HSE); however, the bioactive components and their mode of action still remain unclear. Caenorhabditis elegans ( C. elegans ) was used to study health-related effects and the underlying molecular mechanisms of HSE in this model organism as well as effects of hydroxycitric acid (HCA), a main compound of HSE, and its structural analogue isocitric acid (ICA). Methods Survival and locomotion were detected by touch-provoked movement. Thermotolerance was analysed using the nucleic acid stain SYTOX green, and intracellular ROS accumulation was measured via oxidation of H 2 DCF. Localisation of the transcription factors DAF-16 and SKN-1 was analysed in transgenic strains (DAF-16::GFP, SKN-1::GFP). The involvement of DAF-16 and SKN-1 was further investigated using loss-of-function strains as well as gene silencing by feeding RNAi-inducing bacteria. Protection against amyloid-β toxicity was analysed using a transgenic strain with an inducible expression of human amyloid-β peptides in body wall muscle cells (paralysis assay). Results HSE treatment resulted in a prominent extension of lifespan (up to 24%) and a reduction of the age-dependent decline in locomotion. HCA, a main compound of HSE increased lifespan too, but to a lesser extent (6%) while ICA was not effective. HSE and HCA did not modulate resistance against thermal stress conditions and did not exert antioxidative effects: HSE rather increased intracellular ROS levels, suggesting a pro-oxidative effect of the extract in vivo. HSE and HCA increased the nuclear localisation of the pivotal transcription factors DAF-16 and SKN-1 indicating an activation of these factors. Consistent with this result, lifespan prolongation by HSE was dependent on both transcription factors. In addition to the positive effect on lifespan, HSE treatment also elicited a (strong) protection against amyloid-ß induced toxicity in C. elegans in a DAF-16- and SKN-1-dependent manner. Conclusion Our results demonstrate that HSE increases lifespan and protects against amyloid-β toxicity in the model organism C. elegans . These effects were mediated, at least in parts via modulation of pathways leading to activation/nuclear localisation of DAF-16 and SKN-1. Since HCA, a main component of HSE causes only minor effects, additional bioactive compounds like flavonoids or anthocyanins as well as synergistic effects of these compounds should be investigated.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Age / Alzheimer's disease / amyloid beta-peptides / Amyloid beta-Peptides - drug effects / Animals / Anthocyanins / antioxidant activity / Antioxidants - pharmacology / bacteria / Bioactive compounds / Body wall / Caenorhabditis elegans / Caenorhabditis elegans - genetics / Caenorhabditis elegans - metabolism / Caenorhabditis elegans Proteins - drug effects / Caenorhabditis elegans Proteins - genetics / Caenorhabditis elegans Proteins - metabolism / Chemistry / Chemistry and Materials Science / Dietary supplements / DNA-Binding Proteins - drug effects / DNA-Binding Proteins - genetics / DNA-Binding Proteins - metabolism / Flavonoids / Forkhead protein / Forkhead Transcription Factors - drug effects / Forkhead Transcription Factors - genetics / Forkhead Transcription Factors - metabolism / Gene silencing / genetically modified organisms / heat tolerance / herbal tea / Hibiscus / Hibiscus sabdariffa / humans / ingredients / integument / Intracellular / Isocitric acid / Life span / Locomotion / longevity / Longevity - drug effects / Longevity - physiology / loss-of-function mutation / mechanism of action / Models, Animal / Molecular modelling / myocytes / Nematodes / NF-E2-Related Factor 2 - drug effects / NF-E2-Related Factor 2 - genetics / NF-E2-Related Factor 2 - metabolism / Nucleic acids / Nutrition / Original Contribution / Oxidation / Oxidation-Reduction - drug effects / Oxidative Stress - drug effects / Paralysis / Plant Extracts - pharmacology / Protective Agents / Reactive oxygen species / RNA-mediated interference / Strains (organisms) / synergism / thermal stress / Toxicity / Transcription factors / Transcription Factors - drug effects / Transcription Factors - genetics / Transcription Factors - metabolism