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Hepatoprotective Activity of Nature-Derived Polyphenols Studied by Mass Spectrometry Based Multi-OMICS Approach
Alexander G Brzhozovskiy1, Savva D Semenov1,2, Alexander Y Zherebker1
1Project Center of Omics Technologies and Advanced Mass Spectrometry, 121205 Moscow, Russia.
Abstract:
The aim of this study was to examine the hepatoprotective activity of multicomponent mixtures of natural origin in the BALB/C mouse model, with subacute liver failure (SALF) induced by the administration of toxin carbon tetrachloride (CCl4). The hepatoprotective activity of activated hydrolytic lignin (BP-Cx-1), humic acid peloids (HA), and isoflavones from kudzu Pueraria lobata roots (IFL) was evaluated using mass spectrometry (MS)-based omics technologies. Our MS-based approach revealed new insights into the molecular mechanisms of the hepatoprotective activity of multicomponent mixtures of natural origin. Significant differences were observed in the proteome and metabolome profiles of the urine and liver of BALB/c mice with SALF between a control group with CCl4 administration, intact controls, and groups receiving potential hepatoprotectors of natural origin (BP-Cx-1, HA, IFL). Proteomic and metabolomics analyses demonstrated that among the hepatoprotectors, IFL possessed the highest hepatoprotective potential, which correlated well with the relative effectiveness of the drugs recorded during in vitro studies. These results correlate with the relative effectiveness of the drugs recorded in previous in vitro and in vivo studies. The leading IFL activity may be attributed to a higher content of active polyphenolic components compared to heterogeneous HA and BP-Cx-1. Enrichment with active components by fractionation is a direction that can be explored for developing hepatoprotective agents based on natural complex polyphenols.
Insights
Isoflavones from kudzu roots (IFL) show the strongest liver-protective effects against carbon tetrachloride (CCl4)-induced liver injury in mice. This natural compound demonstrated significant hepatoprotective potential in omics-based studies.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Subacute liver failure (SALF) poses a significant health challenge.
- Natural compounds are explored for potential hepatoprotective properties.
- Carbon tetrachloride (CCl4) is a common toxin used to induce liver injury in experimental models.
Purpose of the Study:
- To evaluate the hepatoprotective activity of natural multicomponent mixtures: activated hydrolytic lignin (BP-Cx-1), humic acid peloids (HA), and isoflavones from kudzu (IFL).
- To investigate the molecular mechanisms underlying the hepatoprotective effects using mass spectrometry (MS)-based omics technologies.
- To compare the efficacy of different natural hepatoprotectors in a BALB/C mouse model of SALF.
Main Methods:
- Induction of subacute liver failure (SALF) in BALB/C mice using carbon tetrachloride (CCl4).
- Administration of natural compounds: activated hydrolytic lignin (BP-Cx-1), humic acid peloids (HA), and isoflavones from kudzu (IFL).
- Analysis of proteome and metabolome profiles in urine and liver tissues using MS-based omics technologies.
Main Results:
- Significant differences in proteomic and metabolomic profiles were observed between control and treatment groups.
- Isoflavones from kudzu (IFL) exhibited the highest hepatoprotective potential among the tested natural compounds.
- The efficacy of IFL correlated with its higher content of active polyphenolic components and previous in vitro/in vivo findings.
Conclusions:
- Isoflavones from kudzu (IFL) demonstrate significant hepatoprotective activity in a mouse model of CCl4-induced liver injury.
- MS-based omics technologies provide valuable insights into the molecular mechanisms of natural hepatoprotectors.
- Fractionation and enrichment of active components from natural sources represent a promising strategy for developing novel hepatoprotective agents.
