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Preventive Effect of a Polyphenol-Rich Extract from Geranium sanguineum L. on Hepatic Drug Metabolism in Influenza Infected Mice

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Faculty of Medicine, Medical University of Sofia, 1431 Sofia, Bulgaria
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Institute of Neurobiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
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Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
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Faculty of Physics, Sofia University “St. Kliment Ohridski”, 1164 Sofia, Bulgaria
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Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Bonino-Pulejo, 98123 Messina, Italy
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Department of Biomedicine and Biotechnology, University of Catania, 95124 Catania CT, Italy
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Institute of Molecular Biology “Roumen Tsanev”, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
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Authors to whom correspondence should be addressed.
Sci. Pharm. 2020, 88(4), 45; https://doi.org/10.3390/scipharm88040045
Received: 28 August 2020 / Revised: 29 September 2020 / Accepted: 2 October 2020 / Published: 12 October 2020
The decreased hepatic drug metabolism (predominately first phase) is one of the essential reasons for numerous side effects and for increased drug toxicity during influenza virus infection (IVI). The present study aims to investigate some mechanisms of the preventive effect of a standardized polyphenol complex from the medicinal plant Geranium sanguineum L. (PPhC) (10 mg/kg nasally). A verified experimental model of IVI A/Aichi/2/68 (H3N2) (4.5 lg LD50) in male ICR (Institute of Cancer Research, USA) mice was used. Changes in hepatic monooxygenase activities as well as nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome C reductase activity and cytochtome P450 content were studied on days 2, 6, 9, 21 of the infection together with thiobarbituric acid reactive substances in the liver supernatant. Our data clearly demonstrates that IVI affects all components of the electronic chain of cytochrome P-450. N-demethylases and hydroxylases as well as the activity of cytochrome C reductase and cytochtome P-450 content were decreased in the course of the virus infection. This implies that free radicals play an important role not only in the pathogenesis of IVI, but also in the modulation of the hepatic monooxygenase activity. This is also consistent with the established polyphenol complex PPhC from the medicinal plant Geranium sanguineum L. preventive effect against increased thiobarbituric acid reactive substances (TBARS)-levels. PPhC restored most of the monooxygenase activities that were inhibited in IVI animals, even over the control levels, probably via multiple mechanisms that may entail antioxidant activity and selective antiviral and protein-binding effects. In contrast to infected animals, in healthy mice, PPhC showed moderate reversible inhibitory effect on hepatic monooxygenase activities. View Full-Text
Keywords: cytochrome P450 monooxygenases; antioxidants; polyphenols; Geranium sanguineum L.; influenza virus infection cytochrome P450 monooxygenases; antioxidants; polyphenols; Geranium sanguineum L.; influenza virus infection
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Abarova, S.; Tancheva, L.; Nikolov, R.; Serkedjieva, J.; Pavlova, E.; Bramanti, A.; Nicoletti, F.; Tzvetkov, N.T. Preventive Effect of a Polyphenol-Rich Extract from Geranium sanguineum L. on Hepatic Drug Metabolism in Influenza Infected Mice. Sci. Pharm. 2020, 88, 45.

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