Abstract
Rosavin, a phenylpropanoid glycoside, is the specific index component and one of the main active components of Rhodiola rosea. Currently, there are few studies describing the antiaging effect of rosavin, and most of them are mainly based on in vitro antioxidant research. Our study aimed to investigate the antiaging activities and mechanisms of rosavin in Caenorhabditis elegans. Using Caenorhabditis elegans as the model, the lifespan of Caenorhabditis elegans under various stressors (heat and juglone) and normal conditions was studied, and the antioxidant activities of rosavin were discussed. To discover the underlying mechanisms, we analyzed daf-16 nuclear localization, the expression of the sod-3p::GFP fusion protein, mRNA levels, and loss-of-function mutants of IIS-associated genes. The results showed that rosavin significantly improved the lifespan of Caenorhabditis elegans under stress and normal conditions. Rosavin can increase the expression and activity of antioxidant enzymes and suppress the generation of malondialdehyde and ROS in nematodes. Additionally, it promotes the nuclear localization of daf-16 and improves the expression of the sod-3 gene in Caenorhabditis elegans. The data revealed that rosavin activated the insulin/IGF-1 signaling pathway by downregulating the upstream components daf-2 and age-1. In summary, these results verify that rosavin could increase the lifespan of Caenorhabditis elegans through the insulin/IGF-1 signaling pathway.
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References
Akhoon BA, Gupta SK, Tiwari S, Rathor L, Pant A, Singh N, Gupta SK, Dandekar T, Pandey R (2019) C. elegans protein interaction network analysis probes RNAi validated pro-longevity effect of nhr-6, a human homolog of tumor suppressor Nr4a1. Sci Rep 9:15711. https://doi.org/10.1038/s41598-019-51649-0
Berdichevsky A, Nedelcu S, Boulias K, Bishop NA, Guarente L, Horvitz HR (2010) 3-Ketoacyl thiolase delays aging of Caenorhabditis elegans and is required for lifespan extension mediated by sir-2.1. Proc Natl Acad Sci U S A 107:18927–18932. https://doi.org/10.1073/pnas.1013854107
Chiang WC, Tishkoff DX, Yang B, Wilson-Grady J, Yu X, Mazer T, Eckersdorff M, Gygi SP, Lombard DB, Hsu AL (2012) C. elegans SIRT6/7 homolog SIR-2.4 promotes daf-16 relocalization and function during stress. PLoS Genet 8:e1002948. https://doi.org/10.1371/journal.pgen.1002948
Chuang HS, Kuo WJ, Lee CL, Chu IH, Chen CS (2016) Exercise in an electrotactic flow chamber ameliorates age-related degeneration in Caenorhabditis elegans. Sci Rep 6:28064. https://doi.org/10.1038/srep28064
Ding XJ, Zhang ZY, Jin J, Han JX, Wang Y, Yang K, Yang YY, Wang HQ, Da XT, Yao C, Sun T, Zhu CB, Liu HJ (2020) Salidroside can target both P4HB-mediated inflammation and melanogenesis of the skin. Theranostics 10:11110–11126. https://doi.org/10.7150/thno.47413
Feng S, Zhang C, Chen T, Zhou L, Huang Y, Yuan M, Li T, Ding C (2021) Oleuropein enhances stress resistance and extends lifespan via insulin/IGF-1 and SKN-1/Nrf2 signaling pathway in Caenorhabditis elegans. Antioxidants (basel) 10:1697. https://doi.org/10.3390/antiox10111697
Gaballah M, Slisz M, Hutter-Lobo D (2012) Role of JNK-1 regulation in the protection of contact-inhibited fibroblasts from oxidative stress. Mol Cell Biochem 359:105–113. https://doi.org/10.1007/s11010-011-1004-1
Gruber J, Ng LF, Poovathingal SK, Halliwell B (2009) Deceptively simple but simply deceptive–Caenorhabditis elegans lifespan studies: considerations for aging and antioxidant effects. FEBS Lett 583:3377–3387. https://doi.org/10.1016/j.febslet.2009.09.051
Kang DZ, Hong HD, Kim KI, Choi SY (2015) Anti-fatigue effects of fermented Rhodiola rosea extract in mice. Prev Nutr Food Sci 20:38–42. https://doi.org/10.3746/pnf.2015.20.1.38
Kenyon C (2010) A pathway that links reproductive status to lifespan in Caenorhabditis elegans. Ann N Y Acad Sci 1204:156–162. https://doi.org/10.1111/j.1749-6632.2010.05640.x
Kreis P, Gallrein C, Rojas-Puente E, Mack TGA, Kroon C, Dinkel V, Willmes C, Murk K, tom-Dieck S, Schuman EM, Kirstein J, Eickholt BJ (2019) ATM phosphorylation of the actin-binding protein drebrin controls oxidation stress-resistance in mammalian neurons and C. elegans. Nat Commun 10:486. https://doi.org/10.1038/s41467-019-08420-w
Lee EB, Kim JH, Kim YJ, Noh YJ, Kim SJ, Hwang IH, Kim DK (2018) Lifespan-extending property of 6-shogaol from Zingiber officinale Roscoe in Caenorhabditis elegans. Arch Pharm Res 41:743–752. https://doi.org/10.1007/s12272-018-1052-0
Leite NR, de Araújo LCA, Rocha PS, Agarrayua DA, Ávila DS, Carollo CA, Silva DB, Estevinho LM, Souza KP, Santos EL (2020) Baru Pulp (Dipteryx alata Vogel): Fruit from the brazilian savanna protects against oxidative stress and increases the life expectancy of Caenorhabditis elegans via sod-3 and daf-16. Biomolecules 10:E1106. https://doi.org/10.3390/biom10081106
Li H, Su L, Chen S, Zhao L, Wang H, Ding F, Chen H, Shi R, Wang Y, Huang Z (2018) Physicochemical characterization and functional analysis of the polysaccharide from the edible microalga Nostoc sphaeroides. Molecules 23:508. https://doi.org/10.3390/molecules23020508
Liu C, Tang Y, Gao Y, Li Y, Chen X (2021) Antioxidative effect of velvet antler extracts in vitro and in vivo. J Shenyang Pharm Univ 38:1061–1067. https://doi.org/10.14066/j.cnki.cn21-1349/r.2020.0176
Lyu SY, Park WB (2012) Photoprotective potential of anthocyanins isolated from Acanthopanax divaricatus Var. albeofructus fruits against UV irradiation in human dermal fibroblast cells. Biomol Ther (seoul) 20:201–206. https://doi.org/10.4062/biomolther.2012.20.2.201
Moskalev AA, Shaposhnikov MV, Plyusnina EN, Zhavoronkov A, Budovsky A, Yanai H, Fraifeld VE (2013) The role of DNA damage and repair in aging through the prism of Koch-like criteria. Ageing Res Rev 12:661–684. https://doi.org/10.1016/j.arr.2012.02.001
Ogawa T, Kodera Y, Hirata D, Blackwell TK, Mizunuma M (2016) Natural thioallyl compounds increase oxidative stress resistance and lifespan in Caenorhabditis elegans by modulating SKN-1/Nrf. Sci Rep 6:21611. https://doi.org/10.1038/srep21611
Qin Y, Djabou ASM, An F, Li K, Li Z, Yang L, Wang X, Chen S (2017) Proteomic analysis of injured storage roots in cassava (Manihot esculenta Crantz) under postharvest physiological deterioration. PLoS ONE 12:e0174238. https://doi.org/10.1371/journal.pone.0174238
Reiter RJ, Tan DX, Rosales-Corral S, Galano A, Zhou XJ, Xu B (2018) Mitochondria: central organelles for melatonin’s antioxidant and Anti-aging actions. Molecules 23:E509. https://doi.org/10.3390/molecules23020509
Sasako T, Ueki K (2016) Insulin/IGF-1 signaling and aging. Nihon Rinsho 74:1435–1440
Shibuya S, Sakaguchi I, Ito S, Kato E, Watanabe K, Izuo N, Shimizu T (2017) Topical application of trisodium ascorbyl 6-palmitate 2-phosphate actively supplies ascorbate to skin cells in an ascorbate transporter-independent manner. Nutrients 9:E645. https://doi.org/10.3390/nu9070645
Singh NK, Sonani RR, Awasthi A, Prasad B, Patel AR, Kumar J, Madamwar D (2016) Phycocyanin moderates aging and proteotoxicity in Caenorhabditis elegans. J Appl Phycol 28:2407–2417. https://doi.org/10.1007/s10811-015-0772-5
Squiban B, Leopold Kurz C (2011) C. elegans: an all in one model for antimicrobial drug discovery. Curr Drug Targets 12:967–977. https://doi.org/10.2174/138945011795677854
Sun Q, Liu C, Jiang K, Fang Y, Kong C, Fu J, Liu Y (2021) A preliminary study on the neurotoxic mechanism of harmine in Caenorhabditis elegans. Comp Biochem Physiol C Toxicol Pharmacol 245:109038. https://doi.org/10.1016/j.cbpc.2021.109038
Tamagno WA, Santini W, Santos A, Alves C, Bilibio D, Sutorillo NT, Zamberlan DC, Kaizer RR, Barcellos LJG (2022) Pitaya fruit extract ameliorates the healthspan on copper-induced toxicity of Caenorhabditis elegans. J Food Biochem 46:e14050. https://doi.org/10.1111/jfbc.14050
Tullet JMA, Araiz C, Sanders MJ, Au C, Benedetto A, Papatheodorou I, Clark E, Schmeisser K, Jones D, Schuster EF, Thornton JM, Gems D (2014) daf-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans. PLoS Genet 10:e1004109. https://doi.org/10.1371/journal.pgen.1004109
Wang E, Wink M (2016) Chlorophyll enhances oxidative stress tolerance in Caenorhabditis elegans and extends its lifespan. PeerJ 4:e1879. https://doi.org/10.7717/peerj.1879
Wang J, Deng N, Wang H, Li T, Chen L, Zheng B, Liu RH (2020) Effects of orange extracts on longevity, healthspan, and stress resistance in Caenorhabditis elegans. Molecules 25:351. https://doi.org/10.3390/molecules25020351
Wang W, Feng X, Du Y, Liu C, Pang X, Jiang K, Wang X, Liu Y (2021) Synthesis of novel pinocembrin amino acid derivatives and their antiaging effect on Caenorhabditis elegans via the modulating daf-16/FOXO. Drug Des Devel Ther 15:4177–4193. https://doi.org/10.2147/DDDT.S330223
Wawrzyniak MK, Kalemba EM, Ratajczak E, Chmielarz P (2020) Oxidation processes related to seed storage and seedling growth of Malus sylvestris, Prunus avium and Prunus padus. PLoS ONE 15:e0234510. https://doi.org/10.1371/journal.pone.0234510
Wyss-Coray T (2016) Ageing, neurodegeneration and brain rejuvenation. Nature 539:180–186. https://doi.org/10.1038/nature20411
Yoon DS, Cha DS, Choi Y, Lee JW, Lee MH (2019) MPK-1/ERK is required for the full activity of resveratrol in extended lifespan and reproduction. Aging Cell 18:e12867. https://doi.org/10.1111/acel.12867
Zeng C, Feng S (2020) The Antioxidant Capacity In Vitro and In Vivo of Polysaccharides From Bergenia emeiensis. Int J Mol Sci 21:E7456. https://doi.org/10.3390/ijms21207456
Zhang Y, Chen D, Ennis AC, Polli JR, Xiao P, Zhang B, Stellwag EJ, Overton A, Panet X (2013) Chemical dispersant potentiates crude oil impacts on growth, reproduction, and gene expression in Caenorhabditis elegans. Arch Toxicol 87:371–382. https://doi.org/10.1007/s00204-012-0936-x
Zhang N, Jiao S, Jing P (2021a) Red cabbage rather than green cabbage increases stress resistance and extends the lifespan of Caenorhabditis elegans. Antioxidants (basel) 10:930. https://doi.org/10.3390/antiox10060930
Zhang Y, Jiang W, Hao X, Tan J, Wang W, Yu M, Zhang G, Zhang Y (2021b) Preparation of the enzymatic hydrolysates from chlorella vulgaris protein and assessment of their antioxidant potential using Caenorhabditis elegans. Mol Biotechnol 63:1040–1048. https://doi.org/10.1007/s12033-021-00361-4
Zheng S, Liao S, Zou Y, Qu Z, Liu F (2014) ins-7 Gene expression is partially regulated by the daf-16/IIS signaling pathway in Caenorhabditis elegans under celecoxib intervention. PLoS ONE 9:e100320. https://doi.org/10.1371/journal.pone.0100320
Zhong L, Peng L, Fu J, Zou L, Zhao G, Zhao J (2020) Phytochemical, antibacterial and antioxidant activity evaluation of Rhodiola crenulata. Molecules 25:E3664. https://doi.org/10.3390/molecules25163664
Zhong T, Hu Y, Su J, Yang S, He B, Zhang Y (2021) Synthesis research of active constituent rosavin from Rhodiola rosea. Mod Chin Med 23:781–785+806. https://doi.org/10.13313/j.issn.1673-4890.20200530002
Zhou M, Zhu J, Yu H, Yin X, Sabour PM, Zhao L, Chen W, Gong J (2014) Investigation into in vitro and in vivo models using intestinal epithelial IPEC-J2 cells and Caenorhabditis elegans for selecting probiotic candidates to control porcine enterotoxigenic Escherichia coli. J Appl Microbiol 117:217–226. https://doi.org/10.1111/jam.12505
Zhou L, Liu J, Bu LL, Liao DF, Cheng SW, Zheng XL (2021) Curcumin acetylsalicylate extends the lifespan of Caenorhabditis elegans. Molecules 26:6609. https://doi.org/10.3390/molecules26216609
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This research was funded by the Central University Scientific Research Fund of the People’s Republic of China (2020-JYB-ZDGG-040) and the National Science and Technology Ministry of Science and Technology of the People’s Republic of China (2018YFC1706505).
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Conceptualization: B.W., Y.L., and Y.Z.; methodology: Y.L.; validation: L.L. and X.F.; formal analysis: T.Z.; investigation: L.L., X.F., Y.G., and X.C.; resources: Y.G. and X.C.; data curation: T.Z.; writing—original draft preparation: L.L. and T.Z.; writing—review and editing: Y.Z.; visualization: T.Z.; supervision: Y.Z.; project administration: B.W. and Y.L.; funding acquisition: Y.L. The authors declare that all data were generated in-house and that no paper mill was used. All authors have read and agreed to the published version of the manuscript.
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Liang, L., Zheng, T., Fan, X. et al. Rosavin extends lifespan via the insulin/IGF-1 signaling pathway in Caenorhabditis elegans. Naunyn-Schmiedeberg's Arch Pharmacol 397, 5275–5287 (2024). https://doi.org/10.1007/s00210-024-02952-9
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DOI: https://doi.org/10.1007/s00210-024-02952-9