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Diosgenin a phytosterol substitute for cholesterol, prolongs the lifespan and mitigates glucose toxicity via DAF-16/FOXO and GST-4 in Caenorhabditis elegans.
Biomed Pharmacother 2017; 95:1693-1703BP

Abstract

Caenorhabditis elegans is a sterol auxotroph requires minute amount of exogenous sterol for their growth and development. To culture the C. elegans, cholesterol was given as sterol molecule to maintain the optimum survival of worms. Diosgenin (DG), a plant derived steroidal saponin, structurally similar to cholesterol has been used as a precursor for the synthesis of steroidal hormones. In this study, worms were cultured with cholesterol (Cho+) and cholesterol-free (Cho-) medium with DG (5, 10 and 50μg/mL) at 20°C. It was observed that worms cultured in (Cho-) exhibits late egg production, reduced lipid level and short lifespan, while addition of DG overcomes all defective facts. Combinations of both cholesterol and DG further extend the lifespan (20.8%), hinder lipid level and resistance to oxidative, thermal and high glucose stress. The intracellular ROS quantification was done by flouroscenic probe H2DCF-DA and confirmed that DG had significantly reduced ROS level (35.85%). Increased lifespan of worms were observed in the medium treated with DG which activates the nuclear translocation of DAF-16/FOXO transcription factor, followed by downstream antioxidant gene sod-3 as evidenced by GFP tagged strain. The expression of Phase II detoxification enzyme GST-4 significantly (p<0.001) increased in transgenic worms exposed to DG with 50mM glucose, and storage of lipid in intestinal cells was reduced in N2 wild type worms. Genetic requirement of DG induced longevity was studied with different mutant strains of mev-1, daf-16, skn-1, and eat-2. These studies have proved that DG is a sterol source to worms and modulate the DAF-16, SOD-3 and GST-4 expression levels to extend the lifespan of worms. The present study has also highlighted the use of phytosterols as an alternative to cholesterol.

Authors+Show Affiliations

Unit of Nematology, Department of Zoology, Bharathiar University, Coimbatore, Tamilnadu, India.Unit of Nematology, Department of Zoology, Bharathiar University, Coimbatore, Tamilnadu, India.Unit of Nematology, Department of Zoology, Bharathiar University, Coimbatore, Tamilnadu, India.Department of Biotechnology, Kumaraguru College of Technology, Coimbatore, Tamilnadu, India.DBT Bioinformatics Center, Department of Bioinformatics, Bharathiar University, Coimbatore, Tamilnadu, India.DBT Bioinformatics Center, Department of Bioinformatics, Bharathiar University, Coimbatore, Tamilnadu, India.Unit of Nematology, Department of Zoology, Bharathiar University, Coimbatore, Tamilnadu, India. Electronic address: sunpalan@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28954389

Citation

Shanmugam, Govindan, et al. "Diosgenin a Phytosterol Substitute for Cholesterol, Prolongs the Lifespan and Mitigates Glucose Toxicity Via DAF-16/FOXO and GST-4 in Caenorhabditis Elegans." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 95, 2017, pp. 1693-1703.
Shanmugam G, Mohankumar A, Kalaiselvi D, et al. Diosgenin a phytosterol substitute for cholesterol, prolongs the lifespan and mitigates glucose toxicity via DAF-16/FOXO and GST-4 in Caenorhabditis elegans. Biomed Pharmacother. 2017;95:1693-1703.
Shanmugam, G., Mohankumar, A., Kalaiselvi, D., Nivitha, S., Murugesh, E., Shanmughavel, P., & Sundararaj, P. (2017). Diosgenin a phytosterol substitute for cholesterol, prolongs the lifespan and mitigates glucose toxicity via DAF-16/FOXO and GST-4 in Caenorhabditis elegans. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 95, pp. 1693-1703. doi:10.1016/j.biopha.2017.09.096.
Shanmugam G, et al. Diosgenin a Phytosterol Substitute for Cholesterol, Prolongs the Lifespan and Mitigates Glucose Toxicity Via DAF-16/FOXO and GST-4 in Caenorhabditis Elegans. Biomed Pharmacother. 2017;95:1693-1703. PubMed PMID: 28954389.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diosgenin a phytosterol substitute for cholesterol, prolongs the lifespan and mitigates glucose toxicity via DAF-16/FOXO and GST-4 in Caenorhabditis elegans. AU - Shanmugam,Govindan, AU - Mohankumar,Amirthalingam, AU - Kalaiselvi,Duraisamy, AU - Nivitha,Sundararaj, AU - Murugesh,Easwaran, AU - Shanmughavel,Piramanayagam, AU - Sundararaj,Palanisamy, Y1 - 2017/10/06/ PY - 2017/07/16/received PY - 2017/08/21/revised PY - 2017/09/18/accepted PY - 2017/9/29/pubmed PY - 2018/6/8/medline PY - 2017/9/29/entrez KW - Caenorhabditis elegans KW - Cholesterol KW - Diosgenin KW - daf-16 KW - gst-4 KW - sod-3 SP - 1693 EP - 1703 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 95 N2 - Caenorhabditis elegans is a sterol auxotroph requires minute amount of exogenous sterol for their growth and development. To culture the C. elegans, cholesterol was given as sterol molecule to maintain the optimum survival of worms. Diosgenin (DG), a plant derived steroidal saponin, structurally similar to cholesterol has been used as a precursor for the synthesis of steroidal hormones. In this study, worms were cultured with cholesterol (Cho+) and cholesterol-free (Cho-) medium with DG (5, 10 and 50μg/mL) at 20°C. It was observed that worms cultured in (Cho-) exhibits late egg production, reduced lipid level and short lifespan, while addition of DG overcomes all defective facts. Combinations of both cholesterol and DG further extend the lifespan (20.8%), hinder lipid level and resistance to oxidative, thermal and high glucose stress. The intracellular ROS quantification was done by flouroscenic probe H2DCF-DA and confirmed that DG had significantly reduced ROS level (35.85%). Increased lifespan of worms were observed in the medium treated with DG which activates the nuclear translocation of DAF-16/FOXO transcription factor, followed by downstream antioxidant gene sod-3 as evidenced by GFP tagged strain. The expression of Phase II detoxification enzyme GST-4 significantly (p<0.001) increased in transgenic worms exposed to DG with 50mM glucose, and storage of lipid in intestinal cells was reduced in N2 wild type worms. Genetic requirement of DG induced longevity was studied with different mutant strains of mev-1, daf-16, skn-1, and eat-2. These studies have proved that DG is a sterol source to worms and modulate the DAF-16, SOD-3 and GST-4 expression levels to extend the lifespan of worms. The present study has also highlighted the use of phytosterols as an alternative to cholesterol. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/28954389/Diosgenin_a_phytosterol_substitute_for_cholesterol_prolongs_the_lifespan_and_mitigates_glucose_toxicity_via_DAF_16/FOXO_and_GST_4_in_Caenorhabditis_elegans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(17)33518-7 DB - PRIME DP - Unbound Medicine ER -