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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.
Eur J Nutr 2019EJ

Abstract

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 H2DCF. 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-β 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.

Authors+Show Affiliations

Institute of Agricultural and Nutritional Sciences, Biofunctionality of Secondary Plant Compounds, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle/Saale, Germany.Institute of Agricultural and Nutritional Sciences, Biofunctionality of Secondary Plant Compounds, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle/Saale, Germany.Institute of Agricultural and Nutritional Sciences, Biofunctionality of Secondary Plant Compounds, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle/Saale, Germany.Institute of Agricultural and Nutritional Sciences, Biofunctionality of Secondary Plant Compounds, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle/Saale, Germany.Institute of Agricultural and Nutritional Sciences, Biofunctionality of Secondary Plant Compounds, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120, Halle/Saale, Germany. wim.waetjen@landw.uni-halle.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30710163

Citation

Koch, Karoline, et al. "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." European Journal of Nutrition, 2019.
Koch K, Weldle N, Baier S, et al. 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. Eur J Nutr. 2019.
Koch, K., Weldle, N., Baier, S., Büchter, C., & Wätjen, W. (2019). 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. European Journal of Nutrition, doi:10.1007/s00394-019-01894-w.
Koch K, et al. 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. Eur J Nutr. 2019 Feb 1; PubMed PMID: 30710163.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Koch,Karoline, AU - Weldle,Nora, AU - Baier,Sabrina, AU - Büchter,Christian, AU - Wätjen,Wim, Y1 - 2019/02/01/ PY - 2018/09/20/received PY - 2019/01/05/accepted PY - 2019/2/3/entrez KW - Alzheimer’s disease KW - Amyloid-β KW - Caenorhabditis elegans KW - Hibiscus sabdariffa L. KW - Hydroxycitric acid KW - Plant extract JF - European journal of nutrition JO - Eur J Nutr N2 - 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 H2DCF. 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-β 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. SN - 1436-6215 UR - https://www.unboundmedicine.com/medline/citation/30710163/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_ L2 - https://dx.doi.org/10.1007/s00394-019-01894-w DB - PRIME DP - Unbound Medicine ER -