Anti-aging activities of black highland barley bran, chrysoeriol, and its glucuronide derivative on Caenorhabditis elegans
Main Article Content
Keywords
Black highland barley bran; Caenorhabditis elegans; Longevity; IIS/DAF-16 pathway; Antioxidant
Abstract
The anti-aging activities and underlying mechanisms of black highland barley bran extract (BHBBE) and its major phenolic components, chrysoeriol (CHR) and chrysoeriol-7-O-β-D-glucuronide (CHRG), were investigated in Caenorhabditis elegans (C. elegans). The effects of BHBBE, CHR, and CHRG at different concentrations were evaluated on lifespan, reproduction, locomotion, stress resistance (heat and ultraviolet [UV] stress), and antioxidant activities (such as superoxide dismutase and catalase activities as well as reactive oxygen species (ROS) and malondialdehyde levels). Furthermore, the expression of longevity-associated genes was examined. Central gene, daf-16, in the anti-aging process of BHBBE, CHR, and CHRG was verified by comparing ROS levels in wild-type N2 C. elegans with daf-16(mu86) mutant strains. Nuclear translocation as a function of DAF-16 protein was assessed. BHBBE, CHR, and CHRG significantly extended C. elegans’ lifespan, improved locomotion, and enhanced stress resistance, without adversely affecting reproduction. Their anti-aging effects were primarily mediated by DAF-16 nuclear translocation via insulin/insulin-like growth factor 1 signaling (IIS). Furthermore, this IIS signaling pathway was associated with antioxidant capacity and stress resistance. Therefore, BHBB, a by-product of grain processing, provides a sustainable, safe, and efficient strategy for anti-aging applications.
References
Blandino M., Locatelli M., Gazzola A., Coïsson J. D., Giacosa S., Travaglia F., Bordiga M., Reyneri A., Rolle L., and Arlorio M. (2015) Hull-less barley pearling fractions: Nutritional properties and their effect on the functional and technological quality in bread-making. Journal of Cereal Science, 65, 48-56. https://doi.org/10.1016/j.jcs.2015.06.004.
Braeckman B. P., Houthoofd K., and Vanfleteren J. R. (2003) Energy metabolism, anti-oxidant defense and aging in Caenorhabditis elegans. In Model Systems in Aging, 99-144. https://doi.org/10.1007/978-3-540-37005-5_5.
Brintz C. (2020) Free-Radical Theory of Aging. In Encyclopedia of Behavioral Medicine,edited by Marc D. Gellman, 899-899. https://doi.org/10.1007/978-3-030-39903-0_191.
Brown M. K., Evans J. L., and Luo Y. (2006) Beneficial effects of natural antioxidants EGCG and α-lipoic acid on life span and age-dependent behavioral declines in Caenorhabditis elegans. Pharmacology Biochemistry and Behavior, 85, 620-628. https://doi.org/10.1016/j.pbb.2006.10.017.
da Costa J. P., Vitorino R., Silva G. M., Vogel C., Duarte A. C., and Rocha-Santos T. (2016) A synopsis on aging—Theories, mechanisms and future prospects. Ageing Research Reviews, 29, 90-112. https://doi.org/10.1016/j.arr.2016.06.005.
Damiano S., Muscariello E., La Rosa G., Di Maro M., Mondola P., and Santillo M. (2019) Dual Role of Reactive Oxygen Species in Muscle Function: Can Antioxidant Dietary Supplements Counteract Age-Related Sarcopenia? Int J Mol Sci, 20, 3815. https://doi.org/10.3390/ijms20153815.
Davis R. J. (2000) Signal transduction by the JNK group of MAP kinases. Cell, 103, 239-252. https://doi.org/10.1016/s0092-8674(00)00116-1.
Demirtas I., Erenler R., Elmastas M., and Goktasoglu A. (2013) Studies on the antioxidant potential of flavones of Allium vineale isolated from its water-soluble fraction. Food Chemistry, 136, 34-40. https://doi.org/10.1016/j.foodchem.2012.07.086.
Deng J. L., Xiang Z. Y., Lin C. B., Zhu Y. Q., Yang K. J., Liu T. H., Xia C., Chen J., Zhang W. H., Zhang Y. H., and Zhu B. Y. (2021) Identification and quantification of free, esterified, and insoluble-bound phenolics in grains of hulless barley varieties and their antioxidant activities. LWT, 151, 112001. https://doi.org/10.1016/j.lwt.2021.112001.
Deng J. L., Yu M. Y., Yang Y. H., Liu T. H., Xiang Z. Y., Chen J., Yang K. J., Zhan R. L., Zhu B. Y., Zhu Y. Q., Yang X., Wan Y., and Xia C. (2024) Studies of phytochemical constituents by UPLC-QTOF-MS/MS of black hulless barley bran and its antioxidation and α-glucosidase inhibition effect. Arabian Journal of Chemistry, 17, 105644. https://doi.org/10.1016/j.arabjc.2024.105644.
Di Rosa G., Brunetti G., Scuto M., Trovato Salinaro A., Calabrese E. J., Crea R., Schmitz-Linneweber C., Calabrese V., and Saul N. (2020) Healthspan Enhancement by Olive Polyphenols in C. elegans Wild Type and Parkinson’s Models. International Journal of Molecular Sciences, 21, 3893-3915. https://doi.org/10.3390/ijms21113893.
Ding A. J., Zheng S. Q., Huang X. B., Xing T. K., Wu G. S., Sun H. Y., Qi S. H., and Luo H. R. (2017) Current Perspective in the Discovery of Anti-aging Agents from Natural Products. Natural Products and Bioprospecting, 7, 335-404. https://doi.org/10.1007/s13659-017-0135-9.
Duangjan C., Rangsinth P., Gu X. J., Zhang S. X., Wink M., and Tencomnao T. (2019) Glochidion zeylanicum leaf extracts exhibit lifespan extending and oxidative stress resistance properties in Caenorhabditis elegans via DAF-16/FoxO and SKN-1/Nrf-2 signaling pathways. Phytomedicine, 64, 153061. https://doi.org/10.1016/j.phymed.2019.153061.
Geng L., Li M., Zhang G., and Ye L. (2022) Barley: a potential cereal for producing healthy and functional foods. Food Quality and Safety, 6, fyac012. https://doi.org/10.1093/fqsafe/fyac012.
Guo T., Horvath C., Chen L., Chen J., and Zheng B. (2020) Understanding the nutrient composition and nutritional functions of highland barley (Qingke): A review. Trends in Food Science & Technology, 103, 109-117. https://doi.org/10.1016/j.tifs.2020.07.011.
Herndon L. A., Schmeissner P. J., Dudaronek J. M., Brown P. A., Listner K. M., Sakano Y., Paupard M. C., Hall D. H., and 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.
Hideki Inoue, Naoki Hisamoto, Jae Hyung An, Riva P Oliveira, Eisuke Nishida, T Keith Blackwell, and Matsumoto K. (2005) The C. elegans p38 MAPK pathway regulates nuclear localization of the transcription factor SKN-1 in oxidative stress response. Genes Dev, 19, 2278-2283. https://doi.org/10.1101/gad.1324805.
Higgins-Chen A. T., Thrush K. L., and Levine M. E. (2021) Aging biomarkers and the brain. Seminars in Cell & Developmental Biology, 116, 180-193. https://doi.org/10.1016/j.semcdb.2021.01.003.
How C. M., Lin T.-A., and Liao V. H.-C. (2021) Early-life chronic di(2-ethylhexyl)phthalate exposure worsens age-related long-term associative memory decline associated with insulin/IGF-1 signaling and CRH-1/CREB in Caenorhabditis elegans. Journal of Hazardous Materials, 417, 126044. https://doi.org/10.1016/j.jhazmat.2021.126044.
Hsu A.-L., Feng Z. Y., Hsieh M. Y., and Xu X. Z. S. (2009) Identification by machine vision of the rate of motor activity decline as a lifespan predictor in C. elegans. Neurobiology of Aging, 30, 1498-1503. https://doi.org/10.1016/j.neurobiolaging.2007.12.007.
Ke T., Antunes Soares F. A., Santamaría A., Bowman A. B., Skalny A. V., and Aschner M. (2020) N,N’ bis-(2-mercaptoethyl) isophthalamide induces developmental delay in Caenorhabditis elegans by promoting DAF-16 nuclear localization. Toxicology Reports, 7, 930-937. https://doi.org/10.1016/j.toxrep.2020.07.012.
Klaudia Jomova, Renata Raptova, Suliman Y Alomar, Saleh H Alwasel, Eugenie Nepovimova, Kamil Kuca, and Valko M. (2023) Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Arch Toxicol, 97, 2499-2574. https://doi.org/10.1007/s00204-023-03562-9.
Kobayashi Y., Furukawa-Hibi Y., Chen C., Horio Y., Isobe K., Ikeda K., and Motoyama N. (2005) SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress. International journal of molecular medicine, 16, 237-243. https://doi.org/10.3892/ijmm.16.2.237.
Li G., Gong J., Liu J., Liu J., Li H., Hsu A.-L., Liu J., and Xu X. Z. S. (2019) Genetic and pharmacological interventions in the aging motor nervous system slow motor aging and extend life span in C. elegans. Sci Adv, 5, eaau5041-eaau5053. https://doi.org/10.1126/sciadv.aau5041.
Li X., Du Y., Tu Z., Zhang C., and Wang L. (2022) Highland barley improves lipid metabolism, liver injury, antioxidant capacities and liver functions in high-fat/cholesterol diet mice based on gut microbiota and LC-MS metabonomics. Food Bioscience, 50, 102094-102094. https://doi.org/10.1016/j.fbio.2022.102094.
Lukinac J., and Jukić M. (2022) Barley in the Production of Cereal-Based Products. Plants, 11, 3519-3526. https://doi.org/10.3390/plants11243519.
Maglioni S., and Ventura N. (2016) C. elegans as a model organism for human mitochondrial associated disorders. Mitochondrion, 30, 117-125. https://doi.org/10.1016/j.mito.2016.02.003.
Meints B., Vallejos C., and Hayes P. (2021) Multi-use naked barley: A new frontier. Journal of Cereal Science, 102, 103370. https://doi.org/10.1016/j.jcs.2021.103370.
Mishra B., Priyadarsini K. I., Kumar M. S., Unnikrishnan M. K., and Mohan H. (2003) Effect of O-glycosilation on the antioxidant activity and free radical reactions of a plant flavonoid, chrysoeriol. Bioorganic & Medicinal Chemistry, 11, 2677-2685. https://doi.org/10.1016/S0968-0896(03)00232-3.
Morley J. F., Brignull H. R., Weyers J. J., and Morimoto R. I. (2002) The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America, 99, 10417-10422. https://doi.org/10.1073/pnas.152161099.
Motta H., Roos D., Tabarelli G., Rodrigues O., Avila D., and Quines C. (2020) Activation of SOD-3 is involved in the antioxidant effect of a new class of β-aryl-chalcogenium azide compounds in Caenorhabditis elegans. Anais da Academia Brasileira de Ciências, 92, e20181147. https://doi.org/10.1590/0001-3765202020181147.
Obadi M., Sun J., and Xu B. (2021) Highland barley: Chemical composition, bioactive compounds, health effects, and applications. Food Research International, 140, 110065. https://doi.org/10.1016/j.foodres.2020.110065.
Oh S. W., Mukhopadhyay A., Svrzikapa N., Jiang F., Davis R. J., and Tissenbaum H. A. (2005) JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proceedings of the National Academy of Sciences of the United States of America, 102, 4494-4499. https://doi.org/10.1073/pnas.0500749102.
Okoro N. O., Odiba A. S., Osadebe P. O., Omeje E. O., Liao G., Fang W., Jin C., and Wang B. (2021) Bioactive Phytochemicals with Anti-Aging and Lifespan Extending Potentials in Caenorhabditis elegans. Molecules 26 (23): 7323-7323. https://doi.org/10.3390/molecules26237323.
Park S., Kim B.-K., and Park S.-K. (2021) Supplementation with phosphatidylethanolamine confers anti-oxidant and anti-aging effects via hormesis and reduced insulin/IGF-1-like signaling in C. elegans. Mechanisms of Ageing and Development, 197, 111498. https://doi.org/10.1016/j.mad.2021.111498.
Rodrigues L. P., Teixeira V. R., Alencar-Silva T., Simonassi-Paiva B., Pereira R. W., Pogue R., and Carvalho J. L. (2021) Hallmarks of aging and immunosenescence: Connecting the dots. Cytokine & Growth Factor Reviews, 59, 9-21. https://doi.org/10.1016/j.cytogfr.2021.01.006.
Salmon A. B., Richardson A., and Pérez V. I. (2010) Update on the oxidative stress theory of aging: Does oxidative stress play a role in aging or healthy aging? Free Radical Biology and Medicine, 48, 642-655. https://doi.org/10.1016/j.freeradbiomed.2009.12.015.
Son L. T., Ko K.-M., Cho J. H., Singaravelu G., Chatterjee I., Choi T.-W., Song H.-O., Yu J.-R., Park B.-J., Lee S.-K., and Ahnn J. (2011) DHS-21, a dicarbonyl/l-xylulose reductase (DCXR) ortholog, regulates longevity and reproduction in Caenorhabditis elegans. FEBS Letters, 585, 1310-1316. https://doi.org/10.1016/j.febslet.2011.03.062.
Song Y. M., Liu D. Y., Xie J. Y., Xie J. H., Chen Y., Chen X. Y., Hu X. B., and Yu Q. (2024) Protective effects of EGCG on acrolein-induced Caenorhabditis elegans and its mechanism of life extension. Food & Function, 15, 5855-5867. https://doi.org/10.1039/d3fo05394f.
Sun X. J., Chen W. D., and Wang Y. D. (2017) DAF-16/FOXO Transcription Factor in Aging and Longevity. Front Pharmacol, 8, 548. https://doi.org/10.3389/fphar.2017.00548.
Takasawa R., Takahashi S., Saeki K., Sunaga S., Yoshimori A., and Tanuma S.-i. (2008) Structure–activity relationship of human GLO I inhibitory natural flavonoids and their growth inhibitory effects. Bioorganic & Medicinal Chemistry, 16, 3969-3975. https://doi.org/10.1016/j.bmc.2008.01.031.
Tanaka-Hino M., Sagasti A., Hisamoto N., Kawasaki M., Nakano S., Ninomiya-Tsuji J., Bargmann C. I., and Matsumoto K. (2002) SEK-1 MAPKK mediates Ca2+ signaling to determine neuronal asymmetric development in Caenorhabditis elegans. Embo Reports, 3, 56-62. https://doi.org/10.1093/embo-reports/kvf001.
van der Hoeven R., McCallum K. C., Cruz M. R., and Garsin D. A. (2011) Ce-Duox1/BLI-3 Generated Reactive Oxygen Species Trigger Protective SKN-1 Activity via p38 MAPK Signaling during Infection in C. elegans. PLOS Pathogens, 7, e1002453. https://doi.org/10.1371/journal.ppat.1002453.
Wang H., Li T., Chen L., Zheng B. S., and Liu R. H. (2020) Effects of Orange Extracts on Longevity, Healthspan, and Stress Resistance in Caenorhabditis elegans. Molecules, 25, 351-368. https://doi.org/10.3390/molecules25020351.
Wang H. L., Liu J., Li T., and Liu R. H. (2018) Blueberry extract promotes longevity and stress tolerance via DAF-16 in Caenorhabditis elegans. Food & function, 9, 5273-5282. https://doi.org/10.1039/c8fo01680a.
Wang X., Yang K., Liu T., Xie S., Wang W., Zhao J., Liu G., and Xia C. (2023) Structural Analysis of Functional Factors and Antioxidant Function of BlackBarley Bran. Food Science and Technology, 48, 142-148. https://doi.org/10.13684/j.cnki.spkj.2023.07.021.
Wu H., Zhao Y., Guo Y., Xu L., and Zhao B. L. (2012) Significant longevity-extending effects of a tetrapeptide from maize on Caenorhabditis elegans under stress. Food Chemistry, 130, 254-260. https://doi.org/10.1016/j.foodchem.2011.07.027.
Xiang Z. Y., Deng J. L., Yang K. J., Zhu Y. Q., Xia C., Chen J., and Liu T. H. (2021) Effect of processing on the release of phenolic compounds and antioxidant activity during in vitro digestion of hulless barley. Arabian Journal of Chemistry, 14, 103447. https://doi.org/10.1016/j.arabjc.2021.103447.
Xiao Y., Zhang Y., Li L., Jiang N., Yu C., Li S., Zhu X., Liu F., and Liu Y. (2024) Cynaroside extends lifespan and improves the neurondegeneration diseases via insulin/IGF-1 signaling pathway in Caenorhabditis elegans. Archives of Gerontology and Geriatrics, 122, 105377. https://doi.org/10.1016/j.archger.2024.105377.
Yang L., Ye Q., Zhang X. G., Li K., Liang X. S., Wang M., Shi L. R., Luo S. H., Zhang Q., and Zhang X. M. (2021) Pyrroloquinoline quinone extends Caenorhabditis elegans' longevity through the insulin/IGF1 signaling pathway-mediated activation of autophagy. Food Funct, 12, 11319-11330. https://doi.org/10.1039/d1fo02128a.
Yang Y., Fan B., Mu Y. W., Li Y., Tong L. T., Wang L. L., Liu L. Y., Li M. M., Sun P. P., Sun J., and Wang F. Z. (2023) A comparative metabolomics study of polyphenols in highland barley (Hordeum vulgare L.) grains with different colors. Food Research International, 174, 113672. https://doi.org/10.1016/j.foodres.2023.113672.
Zečić A., and Braeckman B. P. (2020) DAF-16/FoxO in Caenorhabditis elegans and Its Role in Metabolic Remodeling. Cells, 9, 109-125. https://doi.org/10.3390/cells9010109.
Zhang L., Cui D., Ma X., Han B., and Han L. (2023) Comparative analysis of rice reveals insights into the mechanism of colored rice via widely targeted metabolomics. Food Chemistry, 399, 133926. https://doi.org/10.1016/j.foodchem.2022.133926.
Zhang S. W., Li F., Zhou T., Wang G. X., and Li Z. (2020) Caenorhabditis elegans as a Useful Model for Studying Aging Mutations. Front Endocrinol (Lausanne), 11, 554994-555003. https://doi.org/10.3389/fendo.2020.554994.
Zhang Y. Z., Yin L. Q., Huang L., Tekliye M., Xia X. D., Li J. Z., and Dong M. S. (2021) Composition, antioxidant activity, and neuroprotective effects of anthocyanin-rich extract from purple highland barley bran and its promotion on autophagy. Food Chemistry, 339, 127849-127860. https://doi.org/10.1016/j.foodchem.2020.127849.
Zhu Y., Li T., Fu X., Abbasi A. M., Zheng B., and Liu R. H. (2015) Phenolics content, antioxidant and antiproliferative activities of dehulled highland barley (Hordeum vulgare L.). Journal of Functional Foods, 19, 439-450. https://doi.org/10.1016/j.jff.2015.09.053.
Ziv E., and Hu D. (2011) Genetic variation in insulin/IGF-1 signaling pathways and longevity. Ageing Research Reviews, 10, 201-204. https://doi.org/10.1016/j.arr.2010.09.002.
