Oleander attenuates hepatic inflammation in a TLR4-independent manner and by favorable modulation of hepatocellular global metabolome that supports cytoprotection

Dey, P and Tewari, N and Dutta, S and Newman, RA and Chaudhuri, TK (2024) Oleander attenuates hepatic inflammation in a TLR4-independent manner and by favorable modulation of hepatocellular global metabolome that supports cytoprotection. In: Journal of Ethnopharmacology, 323 .

PDF jou_eth_323_2024.pdf - Published Version Restricted to Registered users only Download (6MB) | Request a copy

Abstract

Ethnopharmacological relevance: Nerium oleander is used to treat liver-associated chronic metabolic diseases in traditional medicinal systems across the globe. The hepatoprotective effects of oleander are mentioned in Indian and Chinese traditional medicinal literature. Aim of the study: The present study aimed to investigate the cellular mechanisms behind the hepatoprotective effects of a non-toxic dose of oleander (NO). Materials and methods: The hepatoprotective effects of NO were tested against lipopolysaccharide (LPS)-treated HepG2 cells. Oxidative stress response was studied using cellular enzymatic assays, and gene expression was analyzed using qRT-PCR. HepG2 cells were pretreated with TAK-242 (pharmacological inhibitor of TLR4) to decipher the anti-inflammatory mechanisms of NO. Cell-free metabolites were analyzed using GCMS and were subjected to pathway enrichment analysis. Results: NO reduced systemic inflammation, serum lipid peroxidation byproducts, and glucose without affecting serum transaminase levels and hepatic histopathological features. NO attenuated the inflammation-induced loss of antioxidant enzyme activities and mRNA expressions of toll-like receptor-4 (TLR4)/nuclear factor κβ (NFκβ)-dependent inflammatory genes. In TAK-242 pretreated cells, LPS was unable to induce inflammatory and oxidative responses. However, NO treatment in TAK-242 pretreated cells with LPS stimulation further reduced the signs of inflammation and improved hepatoprotective activities. A comparative analysis of the intracellular global metabolome from HepG2 cells with and without NO treatment indicated NO-mediated favorable modulation of intracellular metabolic pathways that support cytoprotective activities. Conclusion: NO protects HepG2 cells from LPS-induced oxidative and inflammatory injury. The hepatoprotective effects of NO are mediated by a TLR4-independent process and through a favorable modulation of the intracellular global metabolome that supports cytoprotection. © 2024

Item Type:	Journal Article
Publication:	Journal of Ethnopharmacology
Publisher:	Elsevier Ireland Ltd
Additional Information:	The copyright for this article belongs to Elsevier Ireland Ltd.
Keywords:	alanine aminotransferase; antiinflammatory agent; catalase; glucose; glutathione; immunoglobulin enhancer binding protein; lipopolysaccharide; malonaldehyde; Nerium oleander extract; peroxidase; resatorvid; toll like receptor 4, alanine aminotransferase blood level; albino mouse; aminotransferase blood level; animal cell; animal experiment; animal model; animal tissue; antiinflammatory activity; antioxidant activity; Article; cell protection; controlled study; cytotoxicity; drug isolation; drug megadose; enzymatic assay; enzyme activity; enzyme blood level; gene expression; glucose blood level; Hep-G2 cell line; hepatitis; histopathology; human; human cell; lipid blood level; lipid peroxidation; lipopolysaccharide-induced inflammation; liver protection; low drug dose; metabolome; mouse; mRNA expression level; Nerium oleander; nonhuman; oxidative stress; pathway enrichment analysis; real time reverse transcription polymerase chain reaction
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	01 Mar 2024 06:12
Last Modified:	01 Mar 2024 06:12
URI:	https://eprints.iisc.ac.in/id/eprint/83875

Actions (login required)

View Item