Platanosides, a potential botanical drug combination, decrease liver injury caused by acetaminophen overdose in mice
Document Type
Article
Publication Date
7-22-2022
Abstract
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.
Keywords
Nitric-oxide synthase, Mitochondrial permeability transition, Induced hepatotoxicity, Oxidative stress, Platanus-orientalis, Benzoquinone imine, Protein nitration, n-acetylcysteine, Active-site, Toxicity
Divisions
CHEMISTRY
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)
Publication Title
Journal of Natural Products
Volume
85
Issue
7
Publisher
American Chemical Society
Publisher Location
1155 16TH ST, NW, WASHINGTON, DC 20036 USA