Skip to main content

Advertisement

Log in

Fructus lycii oligosaccharide alleviates acute liver injury via PI3K/Akt/mTOR pathway

  • ORIGINAL ARTICLE
  • Published:
Immunologic Research Aims and scope Submit manuscript

Abstract

Regulating the immune-environment is essential for treating acute liver injury (ALI). However, the deficiency of an effective immune balancer restricted progress. Herein, we reported an oligosaccharide from Fructus lycii oligosaccharide (FLO). To investigate the effects of FLO, we adopted primary macrophages and LO2 for experiments in vitro. In vivo, we assessed the influence of FLO in ALI with histochemical staining and enzyme indicators detection. Following that, we clarified the underlying mechanisms using western blotting and immunofluorescence. Our results indicated that FLO (100 μg/mL) showed apparent inflammatory reversal effects by shifting the phenotype of macrophages from M1 to M2 without causing any cytotoxicity. Furthermore, CCl4-induced mice were significantly improved by FLO intragastric administration. Meanwhile, PI3K/AKT/mTOR pathway was confirmed for the up-regulation of IL-10 via M2 polarization of macrophages. Collectively, our findings highlight the beneficial effects of FLO on ALI therapy via M1 to M2 macrophage conversion.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

Data availability

Raw datasets used during the current study are stored and available from the corresponding author on reasonable request.

Abbreviations

ALI:

Acute liver injury

ALT:

Alanine transaminase

AST:

Aspartate transaminase

BSA:

Bovine serum albumin

DDW:

Double distill water

FBS:

Fetal bovine serum

FLO:

Fructus lycii oligosaccharide

FLP:

Fructus lycii polysaccharide

FLS:

Fructus lycii saccharide

FT-IR:

Fourier transform infrared spectroscopy

H&E,:

Hematoxylin and eosin

HPLC:

High-performance liquid chromatography

HRP:

Horseradish peroxidase

iNOS:

Inducible nitric oxide synthase

LO2 :

Human normal liver cells

LPS:

Lipopolysaccharide

NMR-C:

Nuclear magnetic resonance-C

NMR-H:

Nuclear magnetic resonance-H

PBS:

Phosphate buffer solution

PFA:

Paraformaldehyde

PVDF:

Polyvinylidene difluoride

SPF:

Specific pathogen free

UPLC-DAD-MS/MS:

High-performance liquid chromatography coupled with diode-array detection and electrospray ionization tandem mass spectrometry

References

  1. Trefts E, Gannon M, Wasserman DH. The liver. Curr Biol. 2017;27(21):R1147–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Xu L, Liu J, Lu M, Yang D, Zheng X. Liver injury during highly pathogenic human coronavirus infections. Liver Int. 2020;40(5):998–1004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Chang L, Xu D, Zhu J, Ge G, Kong X, Zhou Y. Herbal therapy for the treatment of acetaminophen-associated liver injury: recent advances and future perspectives. Front Pharmacol. 2020;11:313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. De Santa F, Vitiello L, Torcinaro A, Ferraro E. The role of metabolic remodeling in macrophage polarization and its effect on skeletal muscle regeneration. Antioxid Redox Signal. 2019;30(12):1553–98.

    Article  PubMed  Google Scholar 

  5. Muñoz J, Akhavan NS, Mullins AP, Arjmandi BH. Macrophage polarization and osteoporosis: a review. Nutrients. 2020;12(10):2999.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cheng P, Li S, Chen H. Macrophages in lung injury, repair, and fibrosis. Cells. 2021;10(2):436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Saradna A, Do DC, Kumar S, Fu Q-L, Gao P. Macrophage polarization and allergic asthma. Transl Res. 2018;191.

  8. Jin M, Huang Q, Zhao K, Shang P. Biological activities and potential health benefit effects of polysaccharides isolated from Lycium barbarum L. Int J Biol Macromol. 2013;54:16–23.

    Article  CAS  PubMed  Google Scholar 

  9. Masci A, Carradori S, Casadei MA, et al. Lycium barbarum polysaccharides: extraction, purification, structural characterisation and evidence about hypoglycaemic and hypolipidaemic effects. A review. Food Chem. 2018;254:377–89.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang F, Zhang X, Gu Y, et al. Hepatoprotection of lycii fructus polysaccharide against oxidative stress in hepatocytes and larval zebrafish. Oxid Med Cell Longev. 2021;2021:3923625.

    PubMed  PubMed Central  Google Scholar 

  11. Cheng D, Kong H. The effect of Lycium barbarum polysaccharide on alcohol-induced oxidative stress in rats. Molecules. 2011;16(3):2542–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Xiao J, Liong EC, Ching YP, et al. Lycium barbarum polysaccharides protect mice liver from carbon tetrachloride-induced oxidative stress and necroinflammation. J Ethnopharmacol. 2012;139(2):462–70.

    Article  CAS  PubMed  Google Scholar 

  13. Manthey AL, Chiu K, So K-F. Effects of Lycium barbarum on the visual system. Int Rev Neurobiol. 2017;135:1–27.

    Article  PubMed  Google Scholar 

  14. Zheng Y, Pang X, Zhu X, et al. Lycium barbarum mitigates radiation injury via regulation of the immune function, gut microbiota, and related metabolites. Biomed Pharmacother = Biomed Pharmacother. 2021;139:111654.

  15. Xiao Z, Deng Q, Zhou W, Zhang Y. Immune activities of polysaccharides isolated from Lycium barbarum L. What do we know so far? Pharmacol Ther. 2022;229:107921.

    Article  CAS  PubMed  Google Scholar 

  16. Chen X, Fu X, Huang L, Xu J, Gao X. Agar oligosaccharides: a review of preparation, structures, bioactivities and application. Carbohydr Polym. 2021;265:118076.

    Article  CAS  PubMed  Google Scholar 

  17. Courtois J. Oligosaccharides from land plants and algae: production and applications in therapeutics and biotechnology. Curr Opin Microbiol. 2009;12(3):261–73.

    Article  CAS  PubMed  Google Scholar 

  18. Sun Y, Diao F, Niu Y, et al. Apple polysaccharide prevents from colitis-associated carcinogenesis through regulating macrophage polarization. Int J Biol Macromol. 2020;161:704–11.

    Article  CAS  PubMed  Google Scholar 

  19. Li X-Y, Wang Y-J, Chen S, et al. Polysaccharide suppresses atherosclerosis via regulating autophagy-mediated macrophage polarization. J Agric Food Chem. 2022;70(12):3633–43.

    Article  CAS  PubMed  Google Scholar 

  20. Zhao S-J, Kong F-Q, Jie J, et al. Macrophage MSR1 promotes BMSC osteogenic differentiation and M2-like polarization by activating PI3K/AKT/GSK3β/β-catenin pathway. Theranostics. 2020;10(1):17–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gao Z, Yuan F, Li H, et al. The ameliorations of Ganoderma applanatum residue polysaccharides against CCl induced liver injury. Int J Biol Macromol. 2019;137:1130–40.

    Article  CAS  PubMed  Google Scholar 

  22. Zeng P, Li J, Chen Y, Zhang L. The structures and biological functions of polysaccharides from traditional Chinese herbs. Prog Mol Biol Transl Sci. 2019;163:423–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gao Y, Wei Y, Wang Y, Gao F, Chen Z. Lycium barbarum: a traditional Chinese herb and a promising anti-aging agent. Aging Dis. 2017;8(6):778–91.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Liu R-J, He Y-J, Liu H, Zheng D-D, Huang S-W, Liu C-H. Protective effect of Lycium barbarum polysaccharide on di-(2-ethylhexyl) phthalate-induced toxicity in rat liver. Environ Sci Pollut Res Int. 2021;28(18):23501–9.

    Article  CAS  PubMed  Google Scholar 

  25. Xu J-L, Liu Z-F, Zhang X-W, Liu H-L, Wang Y. Microbial oligosaccharides with biomedical applications. Mar Drugs. 2021;19(6):350.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Triantis V, Bode L, van Neerven RJJ. Immunological effects of human milk oligosaccharides. Front Pediatr. 2018;6:190.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mannino MH, Zhu Z, Xiao H, Bai Q, Wakefield MR, Fang Y. The paradoxical role of IL-10 in immunity and cancer. Cancer Lett. 2015;367(2):103–7.

    Article  CAS  PubMed  Google Scholar 

  28. Oft M. Immune regulation and cytotoxic T cell activation of IL-10 agonists — preclinical and clinical experience. Semin Immunol. 2019;44:101325.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Oft M. IL-10: master switch from tumor-promoting inflammation to antitumor immunity. Cancer Immunol Res. 2014;2(3):194–9.

    Article  CAS  PubMed  Google Scholar 

  30. Li B, Alli R, Vogel P, Geiger TL. IL-10 modulates DSS-induced colitis through a macrophage-ROS-NO axis. Mucosal Immunol. 2014;7(4):869–78.

    Article  CAS  PubMed  Google Scholar 

  31. Silawal S, Willauschus M, Schulze-Tanzil G, Gögele C, Geßlein M, Schwarz S. IL-10 could play a role in the interrelation between diabetes mellitus and osteoarthritis. Int J Mol Sci. 2019;20(3):768.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shamskhou EA, Kratochvil MJ, Orcholski ME, et al. Hydrogel-based delivery of Il-10 improves treatment of bleomycin-induced lung fibrosis in mice. Biomaterials. 2019;203:52–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Mazer M, Unsinger J, Drewry A, et al. IL-10 has differential effects on the innate and adaptive immune systems of septic patients. J Immunol. 2019;203(8):2088–99.

    Article  CAS  PubMed  Google Scholar 

  34. Mollazadeh H, Cicero AFG, Blesso CN, Pirro M, Majeed M, Sahebkar A. Immune modulation by curcumin: the role of interleukin-10. Crit Rev Food Sci Nutr. 2019;59(1):89–101.

    Article  CAS  PubMed  Google Scholar 

  35. Xu Y, Li Y, Liu X, et al. SPIONs enhances IL-10-producing macrophages to relieve sepsis via Cav1-Notch1/HES1-mediated autophagy. Int J Nanomed. 2019;14:6779–97.

    Article  CAS  Google Scholar 

  36. Park HJ, Lee SJ, Cho J, et al. Tamarixetin exhibits anti-inflammatory activity and prevents bacterial sepsis by increasing IL-10 production. J Nat Prod. 2018;81(6):1435–43.

    Article  CAS  PubMed  Google Scholar 

  37. Li J, Huang L, Yu L-T, et al. Feruloylated oligosaccharides alleviate central nervous inflammation in mice following spinal cord contusion. J Agric Food Chem. 2020;68(52):15490–500.

    Article  CAS  PubMed  Google Scholar 

  38. Fang H-Y, Chen Y-K, Chen H-H, Lin S-Y, Fang Y-T. Immunomodulatory effects of feruloylated oligosaccharides from rice bran. Food Chem. 2012;134(2):836–40.

    Article  CAS  PubMed  Google Scholar 

  39. Yu Q, Liao M, Sun C, et al. LBO-EMSC hydrogel serves a dual function in spinal cord injury restoration the PI3K-Akt-mTOR pathway. ACS Appl Mater Interfaces. 2021;13(41):48365–77.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Wentao Shi for his technical assistance and Ziyue Liu for collecting samples. We appreciated for the guidance provided from Ethics Committee in Jiangsu university in the animal experiments.

Funding

This work was financially supported by the Natural Science Foundation of Jiangsu Province (BK20220529). Experiments were conducted at School of Medicine in Jiangsu University.

Author information

Authors and Affiliations

Authors

Contributions

Zhe Wang: investigation, supervision, formal analysis, methodology, writing — original draft. Xingxing Zhang: formal analysis, methodology, writing — original draft. Deming Lv: resources, writing — review and editing. Sucheng Cao: methodology, validation. Guang Yang: writing — review and editing, formal analysis. Zhijian Zhang: conceptualization, project administration, funding acquisition, supervision. Qingtong Yu: conceptualization, methodology, writing — review and editing, investigation, funding acquisition.

Corresponding authors

Correspondence to Zhijian Zhang or Qingtong Yu.

Ethics declarations

Ethics approval

All procedures performed in studies were in accordance with the ethical standards of the institutional and/or national research committee.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Conflict of interest

The authors declare no competing interests.

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

Wang, Z., Zhang, X., Lv, D.m. et al. Fructus lycii oligosaccharide alleviates acute liver injury via PI3K/Akt/mTOR pathway. Immunol Res 72, 271–283 (2024). https://doi.org/10.1007/s12026-023-09431-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12026-023-09431-y

Keywords

Navigation