Skip to main content
SpringerLink
Log in

Long-term intake of sulforaphene alleviates d-galactose-induced skin senescence by activating AMPK-Sirt 1 pathway

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

d-Galactose (d-gal) accumulation triggers the generation of oxygen free radicals, resulting in skin aging. Sulforaphene (SFE), an isothiocyanate compound derived from radish seeds, possesses diverse biological activities, including protective effects against inflammation and oxidative damage. This investigation delves into the antioxidant impact of SFE on age-related skin injury. In vivo experiments demonstrate that SFE treatment significantly improves the macro- and micro-morphology of dorsal skin. It effectively diminishes the elevation of oxidative stress biomarkers in mice skin tissue treated with d-gal, concurrently enhancing the activity of antioxidant enzymes. Additionally, SFE mitigates collagen mRNA degradation, lowers pro-inflammatory cytokine levels, and downregulates MAPK-related protein expression in the skin. Moreover, SFE supplementation reduces lipid metabolite levels and elevates amino acid metabolites, such as l-cysteine and l-histidine. These findings suggest that SFE holds promise as a natural remedy to mitigate aging induced by oxidative stress.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

All data and material during the current study are available from the corresponding author on reasonable request.

Abbreviations

ROS:

Reactive oxygen species

D-gal:

d-Galactose

AGEs:

Advanced glycation end products

TNF-α:

Tumor necrosis factor-α

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

ITCs:

Isothiocyanates

SFE:

Sulforaphene

SFN:

Sulforaphane

Nrf2:

Nuclear factor erythroid 2-related factor 2

TβRII:

TGF-beta receptor 2

MDA:

Malondialdehyde

SOD:

Superoxide dismutase

CAT:

Catalase

AMPK:

AMP-activated protein kinase

SirT1:

Sirtuin 1

PGC-1α:

Peroxisome proliferator-activated receptor γ coactivator 1α

ERK:

Extracellular regulated protein kinases

JNK:

c-Jun N-terminal kinase

T-AOC:

Total antioxidant capacity

HYP:

Hydroxyproline

HA:

Hyaluronic acid

4-HNE:

4-Hydroxynonenal

LPS:

Lipopolysaccharide

MMP-3:

Matrix metallopeptidase-3

MMP-1:

Matrix metallopeptidase-1

TGF-β:

Transforming growth factor-β

IL-10:

Interlenkin-10

References

  1. Bagautdinova NG, Panasyuk MV, Pudovik EM, Gilmanova AA (2014) Multivariate statistic analysis of the world population ageing. Mediter J Soc Sci 5(28):50–55. https://doi.org/10.5901/mjss.2014.v5n28p50

    Article  Google Scholar 

  2. Uitto J (1989) Connective tissue biochemistry of the aging dermis. Age-associated alterations in collagen and elastin. Clin Geriatr Med 5(1):127–147. https://doi.org/10.1016/S0749-0690(18)30700-6

    Article  CAS  PubMed  Google Scholar 

  3. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194–1217. https://doi.org/10.1016/j.cell.2013.05.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gu Y, Han J, Jiang C, Zhang Y (2020) Biomarkers, oxidative stress and autophagy in skin aging. Ageing Res Rev 59:101036. https://doi.org/10.1016/j.arr.2020.101036

    Article  CAS  PubMed  Google Scholar 

  5. Liu Y, Long J, Liu J (2014) Mitochondrial free radical theory of aging: who moved my premise? Geriatr Gerontol Int 14(4):740–749. https://doi.org/10.1111/ggi.12296

    Article  PubMed  Google Scholar 

  6. Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29(3–4):222–230. https://doi.org/10.1016/s0891-5849(00)00317-8

    Article  CAS  PubMed  Google Scholar 

  7. Liaoa AM, Lyu X, Ma JR, Hou YC, Hui M, Liu N, Zhao Y, Cui YX, Huang JH (2023) Multi-protective effects of wheat embryo globulin on d-gal-induced aging mice. Food Sci Hum Well 12(4):1300–1308. https://doi.org/10.1016/j.fshw.2022.10.012

    Article  CAS  Google Scholar 

  8. Lei M, Hua X, Xiao M, Ding J, Han Q, Hu G (2008) Impairments of astrocytes are involved in the d-galactose-induced brain aging. Biochem Biophys Res Commun 369(4):1082–1087. https://doi.org/10.1016/j.bbrc.2008.02.151

    Article  CAS  PubMed  Google Scholar 

  9. Yu Y, Bai F, Wang W, Liu Y, Yuan Q, Qu S, Zhang T, Tian G, Li S, Li D, Ren G (2015) Fibroblast growth factor 21 protects mouse brain against d-galactose induced aging via suppression of oxidative stress response and advanced glycation end products formation. Pharmacol Biochem Behav 133:122–131. https://doi.org/10.1016/j.pbb.2015.03.020

    Article  CAS  PubMed  Google Scholar 

  10. Lu J, Wu DM, Zheng YL, Hu B, Zhang ZF, Ye Q, Liu CM, Shan Q, Wang YJ (2010) Ursolic acid attenuates d-galactose-induced inflammatory response in mouse prefrontal cortex through inhibiting AGEs/RAGE/NF-κB pathway activation. Cereb Cortex 20(11):2540–2548. https://doi.org/10.1093/cercor/bhq002

    Article  PubMed  Google Scholar 

  11. Bharath LP, Agrawal M, McCambridge G, Nicholas DA, Hasturk H, Liu J, Jiang K, Liu R, Guo Z, Deeney J, Apovian CM, Snyder-Cappione J, Hawk GS, Fleeman RM, Pihl RMF, Thompson K, Belkina AC, Cui L, Proctor EA, Kern PA, Nikolajczyk BS (2020) Metformin enhances autophagy and normalizes mitochondrial function to alleviate aging-associated inflammation. Cell Metab 32(1):44–55. https://doi.org/10.1016/j.cmet.2020.04.015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Commission CP (2020) Pharmacopoeia of the People’s Republic of China, vol 1. China Medical Science Publisher, Beijing

    Google Scholar 

  13. Ko MO, Kim MB, Lim SB (2016) Relationship between chemical structure and antimicrobial activities of isothiocyanates from cruciferous vegetables against oral pathogens. J Microbiol Biotechnol 26(12):2036–2042. https://doi.org/10.4014/jmb.1606.06008

    Article  CAS  PubMed  Google Scholar 

  14. Bao C, Kim MC, Chen J, Song J, Ko HW, Lee HJ (2016) Sulforaphene interferes with human breast cancer cell migration and invasion through inhibition of hedgehog signaling. J Agric Food Chem 64(27):5515–5524. https://doi.org/10.1021/acs.jafc.6b02195

    Article  CAS  PubMed  Google Scholar 

  15. Yang W, Liu Y, Xu QQ, Xian YF, Lin ZX (2020) Sulforaphene ameliorates neuroinflammation and hyperphosphorylated tau protein via regulating the PI3K/Akt/GSK-3β pathway in experimental models of Alzheimer’s disease. Oxid Med Cell Longev 2020:4754195. https://doi.org/10.1155/2020/4754195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chen J, Bao C, Kim JT, Cho JS, Qiu S, Lee HJ (2018) Sulforaphene inhibition of adipogenesis via hedgehog signaling in 3T3-L1 adipocytes. J Agric Food Chem 66(45):11926–1134. https://doi.org/10.1021/acs.jafc.8b04330

    Article  CAS  PubMed  Google Scholar 

  17. Govindan S, Johnson EE, Christopher J, Shanmugam J, Thirumalairaj V, Gopalan J (2016) Antioxidant and anti-aging activities of polysaccharides from Calocybe indica var. APK2. Exp Toxicol Pathol 68(6):329–334. https://doi.org/10.1016/j.etp.2016.04.001

    Article  CAS  PubMed  Google Scholar 

  18. Kim DB, Shin GH, Kim JM, Kim YH, Lee JH, Lee JS, Song HJ, Choe SY, Park IJ, Cho JH, Lee OH (2016) Antioxidant and anti-ageing activities of citrus-based juice mixture. Food Chem 194:920–927. https://doi.org/10.1016/j.foodchem.2015.08.094

    Article  CAS  PubMed  Google Scholar 

  19. Chawalitpong S, Ichikawa S, Uchibori Y, Nakamura S, Katayama S (2019) Long-term intake of glucoraphanin-enriched kale suppresses skin aging via activating Nrf2 and the TβRII/Smad pathway in SAMP1 mice. J Agric Food Chem 67(35):9782–9788. https://doi.org/10.1021/acs.jafc.9b02725

    Article  CAS  PubMed  Google Scholar 

  20. Kuang P, Song D, Yuan Q, Lv X, Zhao D, Liang H (2013) Preparative separation and purification of sulforaphene from radish seeds by high-speed countercurrent chromatography. Food Chem 136(2):309–315. https://doi.org/10.1016/j.foodchem.2012.08.042

    Article  CAS  PubMed  Google Scholar 

  21. Chung JH, Seo JY, Choi HR, Lee MK, Youn CS, Rhie G, Cho KH, Kim KH, Park KC, Eun HC (2001) Modulation of skin collagen metabolism in aged and photoaged human skin in vivo. J Invest Dermatol 117(5):1218–1224. https://doi.org/10.1046/j.0022-202x.2001.01544.x

    Article  CAS  PubMed  Google Scholar 

  22. Brosnan JT, Brosnan ME (2006) The sulfur-containing amino acids: an overview. J Nutr 136(6):1636S – 1640. https://doi.org/10.1093/jn/136.6.1636S

    Article  CAS  PubMed  Google Scholar 

  23. Bansal A, Simon MC (2018) Glutathione metabolism in cancer progression and treatment resistance. J Cell Biol 217(7):2291–2298. https://doi.org/10.1083/jcb.201804161

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Block G, Patterson B, Subar A (1992) Fruit, vegetables, and cancer prevention: a review of the epidemiological evidence. Nutr Cancer 18(1):1–29. https://doi.org/10.1080/01635589209514201

    Article  CAS  PubMed  Google Scholar 

  25. Voorrips LE, Goldbohm RA, van Poppel G, Sturmans F, Hermus RJ, van den Brandt PA (2000) Vegetable and fruit consumption and risks of colon and rectal cancer in a prospective cohort study: the Netherlands cohort study on diet and cancer. Am J Epidemiol 152(11):1081–1092. https://doi.org/10.1093/aje/152.11.1081

    Article  CAS  PubMed  Google Scholar 

  26. Nandini DB, Rao RS, Deepak BS, Reddy PB (2020) Sulforaphane in broccoli: the green chemoprevention!! Role in cancer prevention and therapy. J Oral Maxillofac Pathol 24(2):40. https://doi.org/10.4103/jomfp.JOMFP_126_19

    Article  Google Scholar 

  27. Liu X, Dilxat T, Shi Q, Qiu T, Lin J (2022) The combination of nicotinamide mononucleotide and lycopene prevents cognitive impairment and attenuates oxidative damage in d-galactose induced aging models via Keap1-Nrf2 signaling. Gene 822:146348. https://doi.org/10.1016/j.gene.2022.146348

    Article  CAS  PubMed  Google Scholar 

  28. Bukhari SNA, Roswandi NL, Waqas M, Habib H, Hussain F, Khan S, Sohail M, Ramli NA, Thu HE, Hussain Z (2018) Hyaluronic acid, a promising skin rejuvenating biomedicine: a review of recent updates and pre-clinical and clinical investigations on cosmetic and nutricosmetic effects. Int J Biol Macromol 120:1682–1695. https://doi.org/10.1016/j.ijbiomac.2018.09.188

    Article  CAS  PubMed  Google Scholar 

  29. Sun G, Dang Y, Lin Y, Zeng W, Wu Z, Zhang X, Dong D, Wu B (2022) Scutellaria baicalensis Georgi regulates REV-ERBα/BMAL1 to protect against skin aging in mice. Front Pharmacol 13:991917. https://doi.org/10.3389/fphar.2022.991917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhou XX, Yang Q, Xie YH, Sun JY, Qiu PC, Cao W, Wang SW (2013) Protective effect of tetrahydroxystilbene glucoside against d-galactose induced aging process in mice. Phytochem Lett 6:372–378. https://doi.org/10.1016/j.intimp.2018.03.017

    Article  CAS  Google Scholar 

  31. Ramana KV, Srivastava S, Singhal SS (2013) Lipid peroxidation products in human health and disease. Oxid Med Cell Longev 2013:583438. https://doi.org/10.1155/2013/583438

    Article  PubMed  PubMed Central  Google Scholar 

  32. Lin LZ, Yang K, Zheng L, Zhao MM, Sun WZ, Zhu QY (2018) Anti-aging effect of sea cucumber (Cucumaria frondosa) hydrolysate on fruit flies and d-galactose-induced aging mice. J Funct Foods 47:11–18. https://doi.org/10.1016/j.jff.2018.05.033

    Article  CAS  Google Scholar 

  33. Zhuang Y, Ma Q, Guo Y, Sun L (2017) Protective effects of rambutan (Nephelium lappaceum) peel phenolics on H2O2-induced oxidative damages in HepG2 cells and d-galactose-induced aging mice. Food Chem Toxicol 108:554–562. https://doi.org/10.1016/j.fct.2017.01.022

    Article  CAS  PubMed  Google Scholar 

  34. Ke R, Xu Q, Li C, Luo L, Huang D (2018) Mechanisms of AMPK in the maintenance of ATP balance during energy metabolism. Cell Biol Int 42(4):384–392. https://doi.org/10.1002/cbin.10915

    Article  CAS  PubMed  Google Scholar 

  35. Lee G, Uddin MJ, Kim Y, Ko M, Yu I, Ha H (2019) PGC-1α, a potential therapeutic target against kidney aging. Aging Cell 18(5):e12994. https://doi.org/10.1111/acel.12994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nwomeh BC, Liang HX, Diegelmann RF, Cohen IK, Yager DR (1998) Dynamics of the matrix metalloproteinases MMP-1 and MMP-8 in acute open human dermal wounds. Wound Repair Regen 6(2):127–130. https://doi.org/10.1046/j.1524-475x.1998.60206.x

    Article  CAS  PubMed  Google Scholar 

  37. Martindale JL, Holbrook NJ (2002) Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol. 192(1):1–15. https://doi.org/10.1002/jcp.10119

    Article  CAS  PubMed  Google Scholar 

  38. Solano F (2020) Metabolism and functions of amino acids in the skin. Adv Exp Med Biol 1265:187–199. https://doi.org/10.1007/978-3-030-45328-2_11

    Article  CAS  PubMed  Google Scholar 

  39. Fujii J, Ito JI, Zhang X, Kurahashi T (2011) Unveiling the roles of the glutathione redox system in vivo by analyzing genetically modified mice. J Clin Biochem Nutr 49(2):70–78. https://doi.org/10.3164/jcbn.10-138SR

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by the Key Research and Development Program of Guangdong Province (Grant No. 2022B1111080003), the National Natural Science Foundation of China (Grant Nos. 22238001, 22078011), and Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (Grant No. TSBICIP-KJGG-009).

Author information

Author notes

  1. Bo Zhang and Pengtao Liu have contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China

    Bo Zhang, Pengtao Liu, Huakang Sheng, Yongzhi Han & Qipeng Yuan

Authors
  1. Bo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pengtao Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Huakang Sheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yongzhi Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qipeng Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The work was conceived and experiments planned by Bo Zhang, Yongzhi Han, Huakang Sheng, and Pengtao Liu; experiments were performed by Bo Zhang; and the manuscript was written by Bo Zhang and Pengtao Liu, with additional input from Qipeng Yuan. All authors reviewed the manuscript.

Corresponding author

Correspondence to Qipeng Yuan.

Ethics declarations

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, B., Liu, P., Sheng, H. et al. Long-term intake of sulforaphene alleviates d-galactose-induced skin senescence by activating AMPK-Sirt 1 pathway. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-04965-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11010-024-04965-7

Keywords

Search

Navigation