Platanosides, a potential botanical drug combination, decrease liver injury caused by acetaminophen overdose in mice

Samuvel, Devadoss J. and Nguyen, Nga T. and Jaeschke, Hartmut and Lemasters, John J. and Wang, Xiaojuan and Choo, Yeun Mun and Hamann, Mark T. and Zhong, Zhi (2022) Platanosides, a potential botanical drug combination, decrease liver injury caused by acetaminophen overdose in mice. Journal of Natural Products, 85 (7). pp. 1779-1788. ISSN 0163-3864, DOI

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ABSTRACT: Oxidative stress plays an important role in acetaminophen (APAP)-induced hepatotoxicity. Platanosides (PTSs) isolated from the American sycamore tree (Platanus occidentalis) represent a potential new four-molecule botanical drug class of antibiotics active against drug-resistant infectious disease. Preliminary studies have suggested that PTSs are safe and well tolerated and have antioxidant properties. The potential utility of PTSs in decreasing APAP hepatotoxicity in mice in addition to an assessment of their potential with APAP for the control of infectious diseases along with pain and pyrexia associated with a bacterial infection was investigated. On PTS treatment in mice, serum alanine aminotransferase (ALT) release, hepatic centrilobular necrosis, and 4-hydroxynonenal (4-HNE) were markedly decreased. In addition, inducible nitric oxide synthase (iNOS) expression and c-JunN-terminal kinase (JNK) activation decreased when mice overdosed with APAP were treated with PTSs. Computational studies suggested that PTSs may act as JNK-1/2 and Keap1-Nrf2 inhibitors and that the isomeric mixture could provide greater efficacy than the individual molecules. Overall, PTSs represent promising botanical drugs for hepatoprotection and drug-resistant bacterial infections and are effective in protecting against APAP-related hepatotoxicity, which decreases liver necrosis and inflammation, iNOS expression, and oxidative and nitrative stresses, possibly by preventing persistent JNK activation.

Item Type: Article
Funders: United States Department of Health & Human Services National Institutes of Health (NIH) - USA (Grant No: P30 DK123704, P30 DK123704, AA025379, P30 CA138313 & S10 OD018113)
Uncontrolled Keywords: Nitric-oxide synthase; Mitochondrial permeability transition; Induced hepatotoxicity; Oxidative stress; Platanus-orientalis; Benzoquinone imine; Protein nitration; n-acetylcysteine; Active-site; Toxicity
Subjects: Q Science > QD Chemistry
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 08 Nov 2023 02:26
Last Modified: 08 Nov 2023 02:26

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