Identification of Proteomic Markers for Monitoring Direct Toxic Liver Injury (DTLI): Profiling Hepatoprotective Effects of Plant Polyphenols

Brzhozovskiy, Alexander G.; Semenov, Savva D.; Yurova, Maria N.; Semenov, Alexander L.; Bugrova, Anna E.; Zakharova, Natalia V.; Indeykina, Maria I.; Kharina, Daria A.; Kovaleva, Oxana A.; Zherebker, Alexander Y.; Fedoros, Elena I.; Kononikhin, Alexey S.; Nikolaev, Evgeny N.

doi:10.3390/ijms27146148

This is an early access version, the complete PDF, HTML, and XML versions will be available soon.

Open AccessArticle

Identification of Proteomic Markers for Monitoring Direct Toxic Liver Injury (DTLI): Profiling Hepatoprotective Effects of Plant Polyphenols

by

Alexander G. Brzhozovskiy

^1,2,

Savva D. Semenov

^1,3,

Maria N. Yurova

^1,4

,

Alexander L. Semenov

⁴,

Anna E. Bugrova

^1,5

,

Natalia V. Zakharova

⁵

,

Maria I. Indeykina

^1,5

,

Daria A. Kharina

¹,

Oxana A. Kovaleva

¹

,

Alexander Y. Zherebker

¹

,

Elena I. Fedoros

⁴

,

Alexey S. Kononikhin

^1,*

and

Evgeny N. Nikolaev

^1,*

¹

The Center for Bio- and Medical Technologies, 121205 Moscow, Russia

²

Centre for Applied Translational Genomics (CATG), Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU), Dubai Health, P.O. Box 50505, Dubai 50505, United Arab Emirates

³

Moscow Center for Advanced Studies, 123592 Moscow, Russia

⁴

N.N. Petrov National Medical Research Center of Oncology, 197758 Saint Petersburg, Russia

⁵

Emanuel Institute of Biochemical Physics, Russian Academy of Science, 119991 Moscow, Russia

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2026, 27(14), 6148; https://doi.org/10.3390/ijms27146148

Submission received: 18 May 2026 / Revised: 26 June 2026 / Accepted: 3 July 2026 / Published: 9 July 2026

Download Versions Notes

Abstract

The aim of this study was to examine the hepatoprotective activity of multicomponent mixtures of natural origin in the BALB/C mouse model (n = 59), with acute direct toxic liver injury (DTLI) induced by the administration of streptozotocin (STZ) (100 mg/kg) in combination with a high-fat and high-fructose diet (HFFD). The hepatoprotective activity of activated hydrolytic lignin (Bp-Cx-1), methanolic fraction of Bp-Cx-1 (Bp-Cx-M) and isoflavones from kudzu Pueraria lobata roots (IFL) were evaluated on molecular level using mass spectrometry (MS)-based omics technologies. Untargeted label-free DIA quantitation resulted in 7214 protein groups identification (FDR 1%) after filtering across 40 liver tissue extracts. All treatment groups were closer to the control samples on the liver proteomic landscape compared to the untreated DTLI group, with the best results shown for the Bp-Cx-M and IFL groups. In order to identify differences between specific groups, we applied the post hoc Dunn’s test and used Hedges’ g as the effect size metric, revealing 64 proteins that tended to return to their normal level after treatment. In-depth proteomic liver tissue analysis enabled us not only to reveal the main pathways such as inflammation and oxidative stress, which are in a good agreement with DTLI and non-alcoholic liver disease pathophysiology, but also to evaluate hepatoprotective activity of multicomponent mixtures of natural origin containing polyphenols and mostly associated with protein metabolism (e.g., PSMD7, HCFC1) and deubiquitination pathways (e.g., UCHL3). It is worth noting that the Bp-Cx-1 isolated methanol fraction (Bp-Cx-M) demonstrated a pronounced increased hepatoprotective activity compared to the parent material due to the enrichment with active components such as polyphenols. Consistent with the proteomic findings of restored ubiquitin–proteasome function, assessment by comet assay revealed that treatments with Bp-Cx-M and IFL significantly reduced DNA damage by 50% compared to the untreated DTLI group. The developed MS-based multi-omics approach may be implemented for the robust and high-throughput screening method during assessment of new hepatoprotective agents of synthetic or natural origin.

Keywords: polyphenols; hepatoprotection; mass spectrometry; biomarkers; mice

Share and Cite

MDPI and ACS Style

Brzhozovskiy, A.G.; Semenov, S.D.; Yurova, M.N.; Semenov, A.L.; Bugrova, A.E.; Zakharova, N.V.; Indeykina, M.I.; Kharina, D.A.; Kovaleva, O.A.; Zherebker, A.Y.; et al. Identification of Proteomic Markers for Monitoring Direct Toxic Liver Injury (DTLI): Profiling Hepatoprotective Effects of Plant Polyphenols. Int. J. Mol. Sci. 2026, 27, 6148. https://doi.org/10.3390/ijms27146148

AMA Style

Brzhozovskiy AG, Semenov SD, Yurova MN, Semenov AL, Bugrova AE, Zakharova NV, Indeykina MI, Kharina DA, Kovaleva OA, Zherebker AY, et al. Identification of Proteomic Markers for Monitoring Direct Toxic Liver Injury (DTLI): Profiling Hepatoprotective Effects of Plant Polyphenols. International Journal of Molecular Sciences. 2026; 27(14):6148. https://doi.org/10.3390/ijms27146148

Chicago/Turabian Style

Brzhozovskiy, Alexander G., Savva D. Semenov, Maria N. Yurova, Alexander L. Semenov, Anna E. Bugrova, Natalia V. Zakharova, Maria I. Indeykina, Daria A. Kharina, Oxana A. Kovaleva, Alexander Y. Zherebker, and et al. 2026. "Identification of Proteomic Markers for Monitoring Direct Toxic Liver Injury (DTLI): Profiling Hepatoprotective Effects of Plant Polyphenols" International Journal of Molecular Sciences 27, no. 14: 6148. https://doi.org/10.3390/ijms27146148

APA Style

Brzhozovskiy, A. G., Semenov, S. D., Yurova, M. N., Semenov, A. L., Bugrova, A. E., Zakharova, N. V., Indeykina, M. I., Kharina, D. A., Kovaleva, O. A., Zherebker, A. Y., Fedoros, E. I., Kononikhin, A. S., & Nikolaev, E. N. (2026). Identification of Proteomic Markers for Monitoring Direct Toxic Liver Injury (DTLI): Profiling Hepatoprotective Effects of Plant Polyphenols. International Journal of Molecular Sciences, 27(14), 6148. https://doi.org/10.3390/ijms27146148

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Identification of Proteomic Markers for Monitoring Direct Toxic Liver Injury (DTLI): Profiling Hepatoprotective Effects of Plant Polyphenols

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI