Abstract:
Treatment of liver injury induced by various toxicants represents a serious clinical challenge. Here, we utilized
the ability of natural agents to inhibit microsomal lipid peroxidation (LPO) as the in-vitro screening paradigm for
selecting efficacious tissue-protective combinations of cooperatively acting medicinal plants. Based on screening
of 70 water-ethanol extracts obtained from different parts of 65 plants we prepared a highly active phytocomposition
(PC-1) containing oregano (Origanum vulgare), wild thyme (Thymus serpyllum) and coltsfoot
(Tussilago farfara) aerial parts, valerian (Valeriana officinalis) leaves and little-leaf linden (Tilia cordata) flowers.
PC-1 extract exhibited the strongest anti-PLO and antihemolytic effects in vitro compared to those of the individual
plants and other compositions tested. Using luciferase reporter assay and Western blotting in HepG2
human hepatocellular carcinoma cells, we found that PC-1 extract activated the Nrf2/antioxidant response
element signaling pathway more effectively than the extracts of other phytocompositions. Importantly, oral
administration of PC-1 extract (100–200 mg/kg) markedly ameliorated liver injury in rats acutely or chronically
intoxicated by carbon tetrachloride. This was evidenced by improved liver histology, blood chemistry parameters,
and microsomal LPO status and superoxide dismutase activity. In addition, treatment with PC-1 extract
salvaged the osmotic resistance of erythrocytes in carbon tetrachloride-intoxicated rats. Collectively, these data
support the strategy of in-vitro plant selection for developing efficacious tissue-protective phytocompositions.
