Tags

Type your tag names separated by a space and hit enter

The integrated use of in silico methods for the hepatotoxicity potential of Piper methysticum.
Food Chem Toxicol. 2020 Nov; 145:111663.FC

Abstract

Herbal products as supplements and therapeutic intervention have been used for centuries. However, their toxicities are not completely evaluated and the mechanisms are not clearly understood. Dried rhizome of the plant kava (Piper methysticum) is used for its anxiolytic, and sedative effects. The drug is also known for its hepatotoxicity potential. Major constituents of the plant were identified as kavalactones, alkaloids and chalcones in previous studies. Kava hepatotoxicity mechanism and the constituent that causes the toxicity have been debated for decades. In this paper, we illustrated the use of computational tools for the hepatotoxicity of kava constituents. The proposed mechanisms and major constituents that are most probably responsible for the toxicity have been scrutinized. According to the experimental and prediction results, the kava constituents play a substantial role in hepatotoxicity by some means or other via glutathione depletion, CYP inhibition, reactive metabolite formation, mitochondrial toxicity and cyclooxygenase activity. Some of the constituents, which have not been tested yet, were predicted to involve mitochondrial membrane potential, caspase-3 stimulation, and AhR activity. Since Nrf2 activation could be favorable for prevention of hepatotoxicity, we also suggest that these compounds should undergo testing given that they were predicted not to be activating Nrf2. Among the major constituents, alkaloids appear to be the least studied and the least toxic group in general. The outcomes of the study could help to appreciate the mechanisms and to prioritize the kava constituents for further testing.

Authors+Show Affiliations

Yeditepe University, Faculty of Pharmacy, Department of Toxicology, 34755, Atasehir, Istanbul, Turkey.Yeditepe University, Faculty of Pharmacy, Department of Pharmacognosy, 34755, Atasehir, Istanbul, Turkey.Yeditepe University, Faculty of Pharmacy, Department of Toxicology, 34755, Atasehir, Istanbul, Turkey. Electronic address: ahmet.aydin@yeditepe.edu.tr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32827561

Citation

Tugcu, Gulcin, et al. "The Integrated Use of in Silico Methods for the Hepatotoxicity Potential of Piper Methysticum." Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, vol. 145, 2020, p. 111663.
Tugcu G, Kırmızıbekmez H, Aydın A. The integrated use of in silico methods for the hepatotoxicity potential of Piper methysticum. Food Chem Toxicol. 2020;145:111663.
Tugcu, G., Kırmızıbekmez, H., & Aydın, A. (2020). The integrated use of in silico methods for the hepatotoxicity potential of Piper methysticum. Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, 145, 111663. https://doi.org/10.1016/j.fct.2020.111663
Tugcu G, Kırmızıbekmez H, Aydın A. The Integrated Use of in Silico Methods for the Hepatotoxicity Potential of Piper Methysticum. Food Chem Toxicol. 2020;145:111663. PubMed PMID: 32827561.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The integrated use of in silico methods for the hepatotoxicity potential of Piper methysticum. AU - Tugcu,Gulcin, AU - Kırmızıbekmez,Hasan, AU - Aydın,Ahmet, Y1 - 2020/08/20/ PY - 2020/02/05/received PY - 2020/06/27/revised PY - 2020/07/30/accepted PY - 2020/8/23/pubmed PY - 2021/5/11/medline PY - 2020/8/23/entrez KW - DILI KW - Hepatotoxicity KW - Kava KW - Piper methysticum KW - Tox21 KW - Toxicity prediction SP - 111663 EP - 111663 JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JO - Food Chem Toxicol VL - 145 N2 - Herbal products as supplements and therapeutic intervention have been used for centuries. However, their toxicities are not completely evaluated and the mechanisms are not clearly understood. Dried rhizome of the plant kava (Piper methysticum) is used for its anxiolytic, and sedative effects. The drug is also known for its hepatotoxicity potential. Major constituents of the plant were identified as kavalactones, alkaloids and chalcones in previous studies. Kava hepatotoxicity mechanism and the constituent that causes the toxicity have been debated for decades. In this paper, we illustrated the use of computational tools for the hepatotoxicity of kava constituents. The proposed mechanisms and major constituents that are most probably responsible for the toxicity have been scrutinized. According to the experimental and prediction results, the kava constituents play a substantial role in hepatotoxicity by some means or other via glutathione depletion, CYP inhibition, reactive metabolite formation, mitochondrial toxicity and cyclooxygenase activity. Some of the constituents, which have not been tested yet, were predicted to involve mitochondrial membrane potential, caspase-3 stimulation, and AhR activity. Since Nrf2 activation could be favorable for prevention of hepatotoxicity, we also suggest that these compounds should undergo testing given that they were predicted not to be activating Nrf2. Among the major constituents, alkaloids appear to be the least studied and the least toxic group in general. The outcomes of the study could help to appreciate the mechanisms and to prioritize the kava constituents for further testing. SN - 1873-6351 UR - https://www.unboundmedicine.com/medline/citation/32827561/The_integrated_use_of_in_silico_methods_for_the_hepatotoxicity_potential_of_Piper_methysticum_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-6915(20)30553-6 DB - PRIME DP - Unbound Medicine ER -