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Betula utilis extract prolongs life expectancy, protects against amyloid-β toxicity and reduces Alpha Synuclien in Caenorhabditis elegans via DAF-16 and SKN-1.

Abstract

Betula utilis (BU), an important medicinal plant that grows in high altitudes of the Himalayan region, has been utilized traditionally due to it's antibacterial, hepatoprotective, and anti-tumor properties. Here, we demonstrated the longevity and amyloid-β toxicity attenuating activity of B. utilis ethanolic extract (BUE) in Caenorhabditis elegans. Lifespan of the worms was observed under both the standard laboratory and stress (oxidative and thermal) conditions. Effect of BUE was also observed on the attenuation of age-dependent physiological parameters. Further, gene-specific mutants and green fluorescent protein (GFP)-tagged strains were used to investigate the molecular mechanism underlying the beneficial effects mediated by BUE supplementation. Our results showed that BUE (50 μg/ml) extended the mean lifespan of C. elegans by 35.99% and increased its survival under stress conditions. The BUE also reduced the levels of intracellular reactive oxygen species (ROS) by 22.47%. A delayed amyloid-β induced paralyses was observed in CL4176 transgenic worms. Interestingly, the BUE supplementation was also able to reduce the α-synuclein aggregation in NL5901 transgenic strain. Gene-specific mutant studies suggested that the BUE-mediated lifespan extension was dependent on daf-16, hsf-1, and skn-1 but not on sir-2.1 gene. Furthermore, transgenic reporter gene expression assay showed that BUE treatment enhanced the expression of stress-protective genes such as sod-3 and gst-4. Present findings suggested that ROS scavenging activity, together with multiple longevity mechanisms, were involved in BUE-mediated lifespan extension. Thus, BUE might have potential to increase the lifespan and to attenuate neuro-related disease progression.

Authors+Show Affiliations

Microbial Technology Division, CSIR-National Botanical Research Institute, Lucknow 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.Department of Biotechnology, Koneru Lakshmaiah Education Foundation, Guntur 522502, Andhra Pradesh, India.Microbial Technology Division, CSIR-National Botanical Research Institute, Lucknow 226001, India.Plant Diversity, Systematics and Herbarium, CSIR-National Botanical Research Institute, Lucknow 226001, India.Central Instrumentation Facility, CSIR-National Botanical Research Institute, Lucknow 226001, India.Central Instrumentation Facility, CSIR-National Botanical Research Institute, Lucknow 226001, India.Central Instrumentation Facility, CSIR-National Botanical Research Institute, Lucknow 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.Plant Diversity, Systematics and Herbarium, CSIR-National Botanical Research Institute, Lucknow 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.Microbial Technology Division, CSIR-National Botanical Research Institute, Lucknow 226001, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: puneet@nbri.res.in.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31669661

Citation

Pandey, Swapnil, et al. "Betula Utilis Extract Prolongs Life Expectancy, Protects Against Amyloid-β Toxicity and Reduces Alpha Synuclien in Caenorhabditis Elegans Via DAF-16 and SKN-1." Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP, vol. 228, 2020, p. 108647.
Pandey S, Phulara SC, Mishra SK, et al. Betula utilis extract prolongs life expectancy, protects against amyloid-β toxicity and reduces Alpha Synuclien in Caenorhabditis elegans via DAF-16 and SKN-1. Comp Biochem Physiol C Toxicol Pharmacol. 2020;228:108647.
Pandey, S., Phulara, S. C., Mishra, S. K., Bajpai, R., Kumar, A., Niranjan, A., Lehri, A., Upreti, D. K., & Chauhan, P. S. (2020). Betula utilis extract prolongs life expectancy, protects against amyloid-β toxicity and reduces Alpha Synuclien in Caenorhabditis elegans via DAF-16 and SKN-1. Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP, 228, 108647. https://doi.org/10.1016/j.cbpc.2019.108647
Pandey S, et al. Betula Utilis Extract Prolongs Life Expectancy, Protects Against Amyloid-β Toxicity and Reduces Alpha Synuclien in Caenorhabditis Elegans Via DAF-16 and SKN-1. Comp Biochem Physiol C Toxicol Pharmacol. 2020;228:108647. PubMed PMID: 31669661.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Betula utilis extract prolongs life expectancy, protects against amyloid-β toxicity and reduces Alpha Synuclien in Caenorhabditis elegans via DAF-16 and SKN-1. AU - Pandey,Swapnil, AU - Phulara,Suresh Chandra, AU - Mishra,Shashank Kumar, AU - Bajpai,Rajesh, AU - Kumar,Anil, AU - Niranjan,Abhishek, AU - Lehri,Alok, AU - Upreti,Dalip Kumar, AU - Chauhan,Puneet Singh, Y1 - 2019/10/25/ PY - 2019/07/25/received PY - 2019/10/17/revised PY - 2019/10/22/accepted PY - 2019/11/2/pubmed PY - 2020/3/4/medline PY - 2019/11/1/entrez KW - Anti-aging KW - Antioxidant KW - Betula utilis KW - Caenorhabditis elegans KW - Neuroprotective SP - 108647 EP - 108647 JF - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP JO - Comp. Biochem. Physiol. C Toxicol. Pharmacol. VL - 228 N2 - Betula utilis (BU), an important medicinal plant that grows in high altitudes of the Himalayan region, has been utilized traditionally due to it's antibacterial, hepatoprotective, and anti-tumor properties. Here, we demonstrated the longevity and amyloid-β toxicity attenuating activity of B. utilis ethanolic extract (BUE) in Caenorhabditis elegans. Lifespan of the worms was observed under both the standard laboratory and stress (oxidative and thermal) conditions. Effect of BUE was also observed on the attenuation of age-dependent physiological parameters. Further, gene-specific mutants and green fluorescent protein (GFP)-tagged strains were used to investigate the molecular mechanism underlying the beneficial effects mediated by BUE supplementation. Our results showed that BUE (50 μg/ml) extended the mean lifespan of C. elegans by 35.99% and increased its survival under stress conditions. The BUE also reduced the levels of intracellular reactive oxygen species (ROS) by 22.47%. A delayed amyloid-β induced paralyses was observed in CL4176 transgenic worms. Interestingly, the BUE supplementation was also able to reduce the α-synuclein aggregation in NL5901 transgenic strain. Gene-specific mutant studies suggested that the BUE-mediated lifespan extension was dependent on daf-16, hsf-1, and skn-1 but not on sir-2.1 gene. Furthermore, transgenic reporter gene expression assay showed that BUE treatment enhanced the expression of stress-protective genes such as sod-3 and gst-4. Present findings suggested that ROS scavenging activity, together with multiple longevity mechanisms, were involved in BUE-mediated lifespan extension. Thus, BUE might have potential to increase the lifespan and to attenuate neuro-related disease progression. SN - 1532-0456 UR - https://www.unboundmedicine.com/medline/citation/31669661/Betula_utilis_extract_prolongs_life_expectancy_protects_against_amyloid_β_toxicity_and_reduces_Alpha_Synuclien_in_Caenorhabditis_elegans_via_DAF_16_and_SKN_1_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1532-0456(19)30363-1 DB - PRIME DP - Unbound Medicine ER -