Skip to main content
SpringerLink
Log in

Enhancement of astaxanthin incorporation by pulsed high-intensity ultrasound in LPS-stimulated macrophages

  • Original Article—Physics & Engineering
  • Published:
Journal of Medical Ultrasonics Aims and scope Submit manuscript

Abstract

Purpose

Ultrasound (US) has been reported to improve the permeability of cell membranes to pharmaceuticals by causing cavitation. Astaxanthin (AX) potently terminates the induction of inflammation, but it has low oral bioavailability, which limits its incorporation in local cells and organs and its therapeutic potential. In this study, we aimed to investigate the contribution of US to AX incorporation to compensate for the limited incorporation of AX, and regulation of the pro-inflammatory factor interleukin-1β (IL-1β) by AX.

Methods

Murine bone marrow-derived macrophages were stimulated by lipopolysaccharide (LPS). After 2 h, cells were treated with 10 μM AX and/or pulsed high-intensity US irradiation. The cells were then incubated for another 3 h and harvested. AX incorporation in cells was measured by absorbance, and the expression of IL-1β was measured by qPCR. All values are expressed as means ± standard error of the mean.

Results

The combination of AX and US significantly increased AX incorporation in cells compared to AX alone (p < 0.05). In addition, this combination further suppressed the expression of IL-1β compared to AX alone (p < 0.05).

Conclusion

Pulsed high-intensity US irradiation combined with AX treatment promoted AX incorporation in cells and enhanced the anti-inflammatory effect on macrophages.

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

Similar content being viewed by others

References

  1. Miller D, Smith N, Bailey M, et al. Overview of therapeutic ultrasound applications and safety considerations. J Ultrasound Med. 2012;31:623–34.

    Article  Google Scholar 

  2. Fu H, Comer J, Cai W, et al. Sonoporation at small and large length scales: Effect of cavitation bubble collapse on membranes. J Phys Chem Lett. 2015;6:413–8.

    Article  CAS  Google Scholar 

  3. Taniyama Y, Tachibana K, Hiraoka K, et al. Development of safe and efficient novel nonviral gene transfer using ultrasound: Enhancement of transfection efficiency of naked plasmid DNA in skeletal muscle. Gene Ther. 2002;9:372–80.

    Article  CAS  Google Scholar 

  4. Phenix CP, Togtema M, Pichardo S, et al. High intensity focused ultrasound technology, its scope and applications in therapy and drug delivery. J Pharm Pharm Sci. 2014;17:136–53.

    Article  Google Scholar 

  5. Chang MX, Xiong F. Astaxanthin and its effects in inflammatory responses and inflammation-associated diseases: recent advances and future directions. Molecules. 2020;25:5342–414.

    Article  Google Scholar 

  6. Edwards JA, Bellion P, Beilstein P, et al. Review of genotoxicity and rat carcinogenicity investigations with astaxanthin. Regul Toxicol Pharmacol. 2016;75:5–19.

    Article  CAS  Google Scholar 

  7. Kishimoto Y, Yoshida H, Kondo K. Potential anti-atherosclerotic properties of astaxanthin. Mar Drugs. 2016;14:35.

    Article  Google Scholar 

  8. Ambati RR, Phang SM, Ravi S, et al. Astaxanthin: sources, extraction, stability, biological activities and its commercial applications—a review. Mar Drugs. 2014;12:128–52.

    Article  Google Scholar 

  9. Ciapara IH, Valenzuela LF, Goycoolea FM. Astaxanthin: a review of its chemistry and applications. Crit Rev Food Sci Nutr. 2006;46:185–96.

    Article  Google Scholar 

  10. Kubo H, Asai K, Kojima K, et al. Astaxanthin suppresses cigarette smoke-induced emphysema through Nrf2 activation in mice. Mar Drugs. 2019;17:673.

    Article  CAS  Google Scholar 

  11. Madhavi D, Kagan D, Seshadri S. A study on the bioavailability of a proprietary, sustained-release formulation of astaxanthin. Integr Med. 2018;17:38–42.

    Google Scholar 

  12. Funes SC, Rios M, Vera JE, et al. Implications of macrophage polarization in autoimmunity. Immunology. 2018;154:186–95.

    Article  CAS  Google Scholar 

  13. Moghaddam AS, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization and function in health and disease. J Cell Physiol. 2018;233:6425–40.

    Article  Google Scholar 

  14. Kishimoto Y, Tani M, Kondo HU, et al. Astaxanthin suppresses scavenger receptor expression and matrix metalloproteinase activity in macrophages. Eur J Nutr. 2010;49:119–26.

    Article  CAS  Google Scholar 

  15. Grebe A, Hoss F, Latz E. NLRP3 inflammasome and the IL-1 pathway in atherosclerosis. Circ Res. 2018;122:1722–40.

    Article  CAS  Google Scholar 

  16. Jinnouchi H, Guo L, Sakamoto A, et al. Diversity of macrophage phenotypes and responses in atherosclerosis. Cell Mol Life Sci. 2020;77:1919–32.

    Article  CAS  Google Scholar 

  17. Pereira CPM, Souza ACR, Vasconcelos AR, et al. Antioxidant and anti-inflammatory mechanisms of action of astaxanthin in cardiovascular diseases (review). Int J Mol Med. 2021;47:37–48.

    Article  CAS  Google Scholar 

  18. Kobayashi EH, Suzuki T, Funayama R, et al. Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Commun. 2016;7:11624.

    Article  CAS  Google Scholar 

  19. Langston PK, Nambu A, Jung J, et al. Glycerol phosphate shuttle enzyme GPD2 regulates macrophage inflammatory responses. Nat Immunol. 2019;20:1186–95.

    Article  CAS  Google Scholar 

  20. Maeshige N, Langston PK, Yuan ZM, et al. High-intensity ultrasound irradiation promotes the release of extracellular vesicles from C2C12 myotubes. Ultrasonics. 2021;110:106243.

    Article  CAS  Google Scholar 

  21. Astaxanthin manufactures' Association [homepage on the Internet]. Japan: The Association [cited 25 Feb 2012]. Astaxanthin Quality Standards [about 3 screens]. Available from: http://www.asta-ma.jp/haematococcus/index.html.

  22. Postema M, Gilja OH. Ultrasound-directed drug delivery. Curr Pharm Biotechnol. 2007;8:355061.

    Article  Google Scholar 

  23. Nan C, Zheng Y, Fan H, et al. Antitumorigenic effect of hsp90 inhibitor snx-2112 on tongue squamous cell carcinoma is enhanced by low-intensity ultrasound. Onco Targets Ther. 2020;13:7907–19.

    Article  CAS  Google Scholar 

  24. Maeshige N, Koga Y, Tanaka M, et al. Low-Intensity ultrasound enhances histone acetylation and inhibition of interleukin 6 messenger RNA expression by the histone deacetylase inhibitor sodium butyrate in fibroblasts. J Ultrasound Med. 2017;36:879–85.

    Article  Google Scholar 

  25. Riley JS, Tait SW. Mitochondrial DNA in inflammation and immunity. EMBO Rep. 2020;21:e49799.

    Article  CAS  Google Scholar 

  26. Kim SH, Kim H. Inhibitory effect of astaxanthin on oxidative stress-induced mitochondrial dysfunction—a mini-review. Nutrients. 2018;10:1137.

    Article  Google Scholar 

  27. Hayes BT, Merrick MA, Sandrey MA, et al. Three-MHz ultrasound heats deeper into the tissues than originally theorized. J Athl Train. 2004;39:230–4.

    PubMed  PubMed Central  Google Scholar 

  28. Grumelli S, Corry DB, Song LZ, et al. An immune basis for lung parenchymal destruction in chronic obstructive pulmonary disease and emphysema. PLoS Med. 2004;1:e8.

    Article  Google Scholar 

  29. Vonlaufen A, Apte MV, Imhof BA, et al. The role of inflammatory and parenchymal cells in acute pancreatitis. J Pathol. 2007;213:239–48.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We appreciate the members of our laboratory for their thoughtful technical advice. This study was supported by JSPS KAKENHI [grant numbers 21H03852, 20KK0227, and 19H03989].

Author information

Authors and Affiliations

  1. Department of Rehabilitation Science, Kobe University Graduate School of Health Sciences, 7-10-2 Tomogaoka, Kobe, Hyogo, 654-0142, Japan

    Xiaoqi Ma, Atomu Yamaguchi, Noriaki Maeshige, Mikiko Uemura, Hikari Noguchi & Hidemi Fujino

  2. Department of Food Science and Nutrition, Nagoya Women’s University, Nagoya, Japan

    Hiroyo Kondo

Authors
  1. Xiaoqi Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Atomu Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noriaki Maeshige
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mikiko Uemura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hikari Noguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hiroyo Kondo
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hidemi Fujino
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

This paper was coauthored by Xiaoqi Ma, Atomu Yamaguchi, Noriaki Maeshige, Mikiko Uemura, Hikari Noguchi, Hiroyo Kondo, and Hidemi Fujino. XM, NM, and HF conceived and designed the experiments. XM, NM, and AY performed the experiments. XM, NM, HN, MU, and HF analyzed the data. NM, MU, HK, and HF contributed by providing reagents, materials, and analysis tools. XM, NM, AY, MU, HK, and HF interpreted the data and wrote the paper. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Noriaki Maeshige.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical statements

This study was approved by the Institutional Animal Care and Use Committee and was performed according to the Kobe University Animal Experimentation Regulations.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 157 KB)

Supplementary file2 (DOCX 436 KB)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ma, X., Yamaguchi, A., Maeshige, N. et al. Enhancement of astaxanthin incorporation by pulsed high-intensity ultrasound in LPS-stimulated macrophages. J Med Ultrasonics 49, 125–132 (2022). https://doi.org/10.1007/s10396-022-01189-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10396-022-01189-4

Keywords

Search

Navigation