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Antistress and anti-aging activities of Caenorhabditis elegans were enhanced by Momordica saponin extract

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Abstract

Background

Momordica saponin extract (MSE) was found to not only improve longevity and neuroprotection but also alleviate fat accumulation in Caenorhabditis elegans in our previous study. However, the lipid-lowering activity of MSE alone could not fully explain its ability to improve health, so the antistress effects of MSE were further studied.

Methods

Using C. elegans as an in vivo animal, the lifespan of MSE-treated C. elegans under various stressors (H2O2, paraquat and heat) and normal conditions was studied. Furthermore, the antioxidant activities of MSE were discussed. To study the underlying mechanisms, the expression of stress resistance genes and the resistance of related mutants to H2O2 stress were tested.

Results

MSE significantly improved the lifespan of C. elegans under stress and normal conditions. Meanwhile, the mobility of C. elegans was also improved. Moreover, the activities of SOD and CAT and the ratio of GSH/GSSG were elevated. Consistently, the levels of ROS and lipid oxidation (the NEFA and MDA content) were reduced. Furthermore, MSE treatment upregulated the expression of the sod-3, sod-5, clt-1, clt-2, hsp-16.1 and hsp-16.2 genes. All biomarkers indicated that the antistress and anti-aging activities of MSE were due to its strong antioxidant activities. Finally, MSE induced nuclear DAF-16::GFP localization. Studies with mutants revealed that skn-1 and hsf-1 were involved in the activity of MSE, which might upregulate the expression of downstream stress-responsive genes.

Conclusions

Therefore, in addition to its lipid-lowering property, the ability of MSE to improve healthspan was also attributed to the stress resistance effect. Together, MSE might serve as a lead nutraceutical in geriatric research.

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Availability of data and materials

All data generated or analyzed during this study are included in this published article. The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Abbreviations

:

Amyloid-β

CAT:

Catalase

E. coli OP50:

Escherichia coli strain OP50

GFP:

Green fluorescent protein

GSH:

Reduced glutathione

GSH-Px:

Glutathione peroxidase

GSSG:

Oxidized glutathione

IIS:

Insulin/insulin-like growth factor signaling

HSF:

Heat shock transcription factor

HSP:

Heat shock protein

MDA:

Malondialdehyde

mL:

Milliliter

mol:

Molar

MSE:

Momordica saponins extract

NEFA:

Non-esterified fatty acids

NGM:

Nematode growth medium

polyQ:

Polyglutamine

qRT-PCR:

Quantitative reverse transcription-polymerase chain reaction

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

μL:

Microliter

References

  1. Rodriguez M, Snoek LB, De Bono M, Kammenga JE (2013) Worms under stress: C. elegans stress response and its relevance to complex human disease and aging. Trends Genet 29:367–374. https://doi.org/10.1016/j.tig.2013.01.010

    Article  CAS  PubMed  Google Scholar 

  2. Prahlad V, Morimoto RI (2009) Integrating the stress response: lessons for neurodegenerative diseases from C. elegans. Trends Cell Biol 19:52–61. https://doi.org/10.1016/j.tcb.2008.11.002

    Article  CAS  PubMed  Google Scholar 

  3. Lithgow GJ, Walker GA (2002) Stress resistance as a determinate of C. elegans lifespan. Mech Ageing Dev 123:765–771. https://doi.org/10.1016/s0047-6374(01)00422-5

    Article  PubMed  Google Scholar 

  4. Feng SL, Cheng HR, Xu Z, Yuan M, Huang Y, Liao JQ, Yang RW, Zhou LJ, Ding CB (2018) Panax notoginseng polysaccharide increases stress resistance and extends lifespan in Caenorhabditis elegans. J Funct Foods 45:15–23. https://doi.org/10.1016/j.jff.2018.03.034

    Article  CAS  Google Scholar 

  5. Ayuda-Duran B, Gonzalez-Manzano S, Miranda-Vizuete A, Duenas M, Santos-Buelga C, Gonzalez-Paramas AM (2019) Epicatechin modulates stress-resistance in C. elegans via insulin/IGF-1 signaling pathway. PLoS One 14:e0199483. https://doi.org/10.1371/journal.pone.0199483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Asthana J, Pant A, Yadav D, Lal RK, Gupta MM, Pandey R (2015) Ocimum basilicum (L.) and Premna integrifolia (L.) modulate stress response and lifespan in Caenorhabditis elegans. Ind Crop Prod 76:1086–1093. https://doi.org/10.1016/j.indcrop.2015.08.032

    Article  Google Scholar 

  7. El Batran SAS, El-Gengaihi SE, El Shabrawy OA (2006) Some toxicological studies of Momordica charantia L. on albino rats in normal and alloxan diabetic rats. J Ethnopharmacol 108:236–242. https://doi.org/10.1016/j.jep.2006.05.015

    Article  Google Scholar 

  8. Bortolotti M, Mercatelli D, Polito L (2019) Momordica charantia, a nutraceutical approach for inflammatory related diseases. Front Pharmacol. https://doi.org/10.3389/fphar.2019.00486

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wu SB, Yue GGL, To MH, Keller AC, Lau CBS, Kennelly EJ (2014) Transport in Caco-2 cell monolayers of antidiabetic cucurbitane triterpenoids from Momordica charantia fruits. Planta Med 80:907–911. https://doi.org/10.1055/s-0034-1382837

    Article  CAS  PubMed  Google Scholar 

  10. Lin C, Lin Y, Chen Y, Xu J, Li J, Cao Y, Su Z, Chen Y (2019) Effects of Momordica saponin extract on alleviating fat accumulation in Caenorhabditis elegans. Food Funct 10:3237–3251. https://doi.org/10.1039/c9fo00254e

    Article  CAS  PubMed  Google Scholar 

  11. Zhao LC, Zhang Y, He LP, Dai WJ, Lai YY, Yao XY, Cao Y (2014) Soy sauce residue oil extracted by a novel continuous phase transition extraction under low temperature and its refining process. J Agric Food Chem 62:3230–3235. https://doi.org/10.1021/jf405459v

    Article  CAS  PubMed  Google Scholar 

  12. Chen Y, Onken B, Chen H, Xiao S, Liu X, Driscoll M, Cao Y, Huang Q (2014) Mechanism of longevity extension of Caenorhabditis elegans induced by pentagalloyl glucose isolated from eucalyptus leaves. J Agric Food Chem 62:3422–3431. https://doi.org/10.1021/jf500210p

    Article  CAS  PubMed  Google Scholar 

  13. Saul N, Pietsch K, Menzel R, Steinberg CEW (2008) Quercetin-mediated longevity in Caenorhabditis elegans: is DAF-16 involved? Mech Ageing Dev 129:611–613. https://doi.org/10.1016/j.mad.2008.07.001

    Article  CAS  PubMed  Google Scholar 

  14. Lin C, Zhang X, Xiao J, Zhong Q, Kuang Y, Cao Y, Chen Y (2019) Effects on longevity extension and mechanism of action of carnosic acid in Caenorhabditis elegans. Food Funct 10:1398–1410. https://doi.org/10.1039/c8fo02371a

    Article  CAS  PubMed  Google Scholar 

  15. Lithgow GJ, White TM, Melov S, Johnson TE (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci USA 92:7540–7544. https://doi.org/10.2307/2368280

    Article  CAS  PubMed  Google Scholar 

  16. Herndon LA, Schmeissner PJ, Dudaronek JM, Brown PA, Listner KM, Sakano Y, Paupard MC, Hall DH, Driscoll M (2002) Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature 419:808–814. https://doi.org/10.1038/nature01135

    Article  CAS  PubMed  Google Scholar 

  17. Joseph JS, Wang H (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 27:612–616. https://doi.org/10.1016/S0891-5849(99)00107-0

    Article  PubMed  Google Scholar 

  18. Lin C, Su Z, Luo J, Jiang L, Shen S, Zheng W, Gu W, Cao Y, Chen Y (2019) Polysaccharide extracted from the leaves of Cyclocarya paliurus (Batal.) Iljinskaja enhanced stress resistance in Caenorhabditis elegans via skn-1 and hsf-1. Int J Biol Macromol 143:243–254. https://doi.org/10.1016/j.ijbiomac.2019.12.023

    Article  CAS  PubMed  Google Scholar 

  19. Henderson ST, Johnson TE (2001) daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr Biol 11:1975–1980. https://doi.org/10.1016/s0960-9822(01)00594-2

    Article  CAS  PubMed  Google Scholar 

  20. Libina N, Berman JR, Kenyon C (2003) Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell 115:489–502. https://doi.org/10.1016/s0092-8674(03)00889-4

    Article  CAS  PubMed  Google Scholar 

  21. Zhang P, Zhai Y, Cregg J, Ang KK, Arkin M, Kenyon C (2020) Stress resistance screen in a human primary cell line identifies small molecules that affect aging pathways and extend Caenorhabditis elegans' lifespan. G3 (Bethesda) 10:849–862. https://doi.org/10.1534/g3.119.400618

    Article  CAS  Google Scholar 

  22. Johnson TE, Cypser J, de Castro E, de Castro S, Henderson S, Murakami S, Rikke B, Tedesco P, Link C (2000) Gerontogenes mediate health and longevity in nematodes through increasing resistance to environmental toxins and stressors. Exp Gerontol 35:687–694. https://doi.org/10.1016/S0531-5565(00)00138-8

    Article  CAS  PubMed  Google Scholar 

  23. Saul N, Pietsch K, Menzel R, Sturzenbaum SR, Steinberg CEW (2009) Catechin induced longevity in C. elegans: from key regulator genes to disposable soma. Mech Ageing Dev 130:477–486. https://doi.org/10.1016/j.mad.2009.05.005

    Article  CAS  PubMed  Google Scholar 

  24. Murakami S, Murakami H (2005) The effects of aging and oxidative stress on learning behavior in C. elegans. Neurobiol Aging 26:899–905. https://doi.org/10.1016/j.neurobiolaging.2004.08.007

    Article  CAS  PubMed  Google Scholar 

  25. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247. https://doi.org/10.1038/35041687

    Article  CAS  PubMed  Google Scholar 

  26. Kitisin T, Suphamungmee W, Meemon K (2019) Saponin-rich extracts from Holothuria leucospilota mediate lifespan extension and stress resistance in Caenorhabditis elegans via daf-16. J Food Biochem 43:e13075. https://doi.org/10.1111/jfbc.13075

    Article  PubMed  Google Scholar 

  27. Zhou L, Huang PP, Chen LL, Wang P (2019) Panax notoginseng saponins ameliorate a β-mediated neurotoxicity in C. elegans through antioxidant activities. Evid Based Complement Alternat Med 2019:7621043. https://doi.org/10.1155/2019/7621043

    Article  PubMed  PubMed Central  Google Scholar 

  28. Chumphoochai K, Chalorak P, Suphamungmee W, Sobhon P, Meemon K (2019) Saponin-enriched extracts from body wall and Cuvierian tubule of Holothuria leucospilota reduce fat accumulation and suppress lipogenesis in Caenorhabditis elegans. J Sci Food Agric 99:4158–4166. https://doi.org/10.1002/jsfa.9646

    Article  CAS  PubMed  Google Scholar 

  29. Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress. Curr Biol 2:453–462. https://doi.org/10.1016/j.cub.2014.03.034

    Article  CAS  Google Scholar 

  30. Hong Y, Hu HY, Xie X, Li FM (2008) Responses of enzymatic antioxidants and non-enzymatic antioxidants in the cyanobacterium Microcystis aeruginosa to the allelochemical ethyl 2-methyl acetoacetate (EMA) isolated from reed (Phragmites communis). J Plant Physiol 165:1264–1273. https://doi.org/10.1016/j.jplph.2007.10.007

    Article  CAS  PubMed  Google Scholar 

  31. Armstrong RWB (1998) Reduced glutathione and glutathione disulfide. Free Radic Antioxid Protoc 108:347–352. https://doi.org/10.1385/0-89603-472-0:347

    Article  Google Scholar 

  32. Jones DP (2002) Redox potential of GSH/GSSG couple: assay and biological significance. Method Enzymol 348:93–112. https://doi.org/10.1016/S0076-6879(02)48630-2

    Article  CAS  Google Scholar 

  33. Jin XC, Ning Y (2012) Antioxidant and antitumor activities of the polysaccharide from seed cake of Camellia oleifera Abel. Int J Biol Macromol 51:364–368. https://doi.org/10.1016/j.ijbiomac.2012.05.033

    Article  CAS  PubMed  Google Scholar 

  34. Ayala A, Munoz MF, Arguelles S (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014:360438. https://doi.org/10.1155/2014/360438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Govindaraj J, Sorimuthu Pillai S (2015) Rosmarinic acid modulates the antioxidant status and protects pancreatic tissues from glucolipotoxicity mediated oxidative stress in high-fat diet: streptozotocin-induced diabetic rats. Mol Cell Biochem 404:143–159. https://doi.org/10.1007/s11010-015-2374-6

    Article  CAS  PubMed  Google Scholar 

  36. Flemming Nielsen BBM, Nielsen JB, Andersen HR, Grandjean P (1997) Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem 43(7):1209–1214. https://doi.org/10.1093/clinchem/43.7.1209

    Article  Google Scholar 

  37. Morley JF, Morimoto RI (2004) Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15:657–664. https://doi.org/10.1091/mbc.E03-07-0532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kaletsky R, Lakhina V, Arey R, Williams A, Landis J, Ashraf J, Murphy CT (2016) The C. elegans adult neuronal IIS/FOXO transcriptome reveals adult phenotype regulators. Nature 529:92–96. https://doi.org/10.1038/nature16483

    Article  CAS  PubMed  Google Scholar 

  39. Lin C, Xiao J, Xi Y, Zhang X, Zhong Q, Zheng H, Cao Y, Chen Y (2019) Rosmarinic acid improved antioxidant properties and healthspan via the IIS and MAPK pathways in Caenorhabditis elegans. BioFactors 45:774–787. https://doi.org/10.1002/biof.1536

    Article  CAS  PubMed  Google Scholar 

  40. Chen W, Muller D, Richling E, Wink M (2013) Anthocyanin-rich purple wheat prolongs the life span of Caenorhabditis elegans probably by activating the DAF-16/FOXO transcription factor. J Agric Food Chem 61:3047–3053. https://doi.org/10.1021/jf3054643

    Article  CAS  PubMed  Google Scholar 

  41. Kampkotter A, Nkwonkam CG, Zurawski RF, Timpel C, Chovolou Y, Watjen W, Kahl R (2007) Effects of the flavonoids kaempferol and fisetin on thermotolerance, oxidative stress and FoxO transcription factor DAF-16 in the model organism Caenorhabditis elegans. Arch Toxicol 81:849–858. https://doi.org/10.1007/s00204-007-0215-4

    Article  CAS  PubMed  Google Scholar 

  42. Kampkotter A, Timpel C, Zurawski RF, Ruhl S, Chovolou Y, Proksch P, Watjen W (2008) Increase of stress resistance and lifespan of Caenorhabditis elegans by quercetin. Biochem Mol Biol 149:314–323. https://doi.org/10.1016/j.cbpb.2007.10.004

    Article  CAS  Google Scholar 

  43. Tullet JM, Hertweck M, An JH, Baker J, Hwang JY, Liu S, Oliveira RP, Baumeister R, Blackwell TK (2008) Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell 132:1025–1038. https://doi.org/10.1016/j.cell.2008.01.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Seo K, Choi E, Lee D, Jeong DE, Jang SK, Lee SJ (2013) Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell 12:1073–1081. https://doi.org/10.1111/acel.12140

    Article  CAS  PubMed  Google Scholar 

  45. Koneri RB, Samaddar S, Ramaiah CT (2014) Antidiabetic activity of a triterpenoid saponin isolated from Momordica cymbalaria Fenzl. Indian J Exp Biol 52:46–52. https://doi.org/10.3109/03630269.2013.855936

    Article  CAS  PubMed  Google Scholar 

  46. Ali L, Khan AK, Mamun MI, Mosihuzzaman M, Nahar N, Nur-e-Alam M, Rokeya B (1993) Studies on hypoglycemic effects of fruit pulp, seed, and whole plant of Momordica charantia on normal and diabetic model rats. Planta Med 59:408–412. https://doi.org/10.1055/s-2006-959720

    Article  CAS  PubMed  Google Scholar 

  47. Koneri RB, Samaddar S, Simi SM, Rao ST (2014) Neuroprotective effect of a triterpenoid saponin isolated from Momordica cymbalaria Fenzl in diabetic peripheral neuropathy. Indian J Pharmacol 46:76–81. https://doi.org/10.4103/0253-7613.125179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Popovich DG, Li L, Zhang W (2010) Bitter melon (Momordica charantia) triterpenoid extract reduces preadipocyte viability, lipid accumulation and adiponectin expression in 3T3-L1 cells. Food Chem Toxicol 48:1619–1626. https://doi.org/10.1016/j.fct.2010.03.035

    Article  CAS  PubMed  Google Scholar 

  49. Jung K, Chin YW, Yoon K, Chae HS, Kim CY, Yoo H, Kim J (2013) Anti-inflammatory properties of a triterpenoidal glycoside from Momordica cochinchinensis in LPS-stimulated macrophages. Immunopharmacol Immunotoxicol 35:8–14. https://doi.org/10.3109/08923973.2012.715165

    Article  CAS  PubMed  Google Scholar 

  50. Elekofehinti OO, Ariyo EO, Akinjiyan MO, Olayeriju OS, Lawal AO, Adanlawo IG, Rocha JBT (2018) Potential use of bitter melon (Momordica charantia) derived compounds as antidiabetics: in silico and in vivo studies. Pathophysiology 25:327–333. https://doi.org/10.1016/j.pathophys.2018.05.003

    Article  CAS  PubMed  Google Scholar 

  51. Kulkarni P, Lohidasan S, Mahadik K (2019) Isolation, characterisation and investigation of in vitro antidiabetic and antioxidant activity of phytoconstituents from fruit of Momordica charantia Linn. Nat Prod Res 2019:1–3. https://doi.org/10.1080/14786419.2019.1613400

    Article  CAS  Google Scholar 

  52. Wang ZH, Ah Kang K, Zhang R, Piao MJ, Jo SH, Kim JS, Kang SS, Lee JS, Park DH, Hyun JW (2010) Myricetin suppresses oxidative stress-induced cell damage via both direct and indirect antioxidant action. Environ Toxicol Phar 29:12–18. https://doi.org/10.1016/j.etap.2009.08.007

    Article  CAS  Google Scholar 

  53. Piao MJ, Kang KA, Zhang R, Ko DO, Wang ZH, You HJ, Kim HS, Kim JS, Kang SS, Hyun JW (2008) Hyperoside prevents oxidative damage induced by hydrogen peroxide in lung fibroblast cells via an antioxidant effect. Biochim Biophys Acta 1780:1448–1457. https://doi.org/10.1016/j.bbagen.2008.07.012

    Article  CAS  PubMed  Google Scholar 

  54. Fonte V, Kipp DR, Yerg J 3rd, Merin D, Forrestal M, Wagner E, Roberts CM, Link CD (2008) Suppression of in vivo beta-amyloid peptide toxicity by overexpression of the HSP-16.2 small chaperone protein. J Biol Chem 283:784–791. https://doi.org/10.1074/jbc.M703339200

    Article  CAS  PubMed  Google Scholar 

  55. Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300:1142–1145. https://doi.org/10.1126/science.1083701

    Article  CAS  PubMed  Google Scholar 

  56. Landis GN, Tower J (2005) Superoxide dismutase evolution and life span regulation. Mech Ageing Dev 126:365–379. https://doi.org/10.1016/j.mad.2004.08.012

    Article  CAS  PubMed  Google Scholar 

  57. Hanmei Li MR, Cheng X, Zhang S, Cheng H, Wink M (2019) Pro-oxidant and lifespan extension effects of caffeine and related methylxanthines in Caenorhabditis elegans. Food Chem X 1:1–9. https://doi.org/10.1016/j.fochx.2019.100005

    Article  CAS  Google Scholar 

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Acknowledgements

Strain N2, GR1307, CF1553 and TK22 were provided by the Caenorhabditis Genetics Center at University of Minnesota. Strain TJ356, EU1 and PS3551 were provided by Prof. Qinghua Zhou (Biomedical Translational Research Institute, Jinan University, Guangdong Province, China).

Funding

This research was supported by the National Natural Science Foundation of China (31700501); The Science and Technology Planning Project of Guangdong Province, China (2017A020208042); The National Key R&D Program (2016YFD0600806).

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Lin, C., Chen, Y., Lin, Y. et al. Antistress and anti-aging activities of Caenorhabditis elegans were enhanced by Momordica saponin extract. Eur J Nutr 60, 1819–1832 (2021). https://doi.org/10.1007/s00394-020-02338-6

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