LC/ESI-MS/MS phytochemical profiling and apoptotic effect of Haloxylon scoparium leaf extract on hepatocellular carcinoma

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Ghareeb M.A.; Bakchiche B.; Aouiffat Y.; Aboushousha T.; Marzouk M.; Okasha H.

Journal: Scientific Reports

Publisher: Nature Research

Publication Date: 23 October 2025

Volume / Issue: Volume 15 / Issue 1

Article No.: 37154

ISSN: 20452322

DOI: 10.1038/s41598-025-21041-2

Scopus: View on Scopus

PubMed: 41131348

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Ghareeb M.A., Medicinal Chemistry Department, Theodor Bilharz Research Institute, P.O. 30, Kornaish El-Nile, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Bakchiche B., Laboratory of Biological and Agricultural Sciences (LBAS), Amar Telidji University, Laghouat, 03000, Algeria, Research Unit of Medicinal Plant (RUMP) Attached to Center of Biotechnology (CRBt, 3000, Constantine), Laghouat, 03000, Algeria; Aouiffat Y., Laboratory of Biological and Agricultural Sciences (LBAS), Amar Telidji University, Laghouat, 03000, Algeria, Research Unit of Medicinal Plant (RUMP) Attached to Center of Biotechnology (CRBt, 3000, Constantine), Laghouat, 03000, Algeria; Aboushousha T., Department of Pathology, Theodor Bilharz Research Institute, P.O. Box 30, Kornaish El Nile, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Marzouk M., Chemistry of Tanning Materials and Leather Technology Department, Chemical Industries Research Institute, National Research Centre, 33 El-Bohouth St. (Former El-Tahrir St.), Dokki, Cairo, 12622, Egypt; Okasha H., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, P.O. Box 30, Kornaish El Nile, Warrak El-Hadar, Imbaba, Giza, 12411, Egypt

Abstract

Haloxylon scoparium, a plant native to Moroccan Sahara, was investigated for its potential anticancer activity against hepatocellular carcinoma (HCC). The study aimed to evaluate the effects of its methanolic extract on HCC and to conduct detailed chemical analysis using LC-ESI-MS/MS. In vitro cytotoxicity was assessed using HepG2 liver cancer cell line. In vivo experiments involved inducing HCC in mice with diethylnitrosamine (DEN). The study monitored inflammatory (TNF-α), apoptotic (BAX, Caspase-3, Caspase-8), and oncogenic markers (AFP, Bcl-2) through blood and liver tissue analysis. Liver histopathology was also performed to evaluate tissue-level changes. Mice survival rates were 83.33% in the DEN group and 91.67% in the DEN/H. scoparium group. Liver function markers (TBILR, ALP, AST) significantly decreased in the treatment group. TNF-α levels, elevated in DEN-only mice, were notably reduced after treatment. Oncogenic markers showed significant elevation in the DEN group but were decreased in the treatment group, whereas apoptotic markers were significantly elevated after treatment. Histopathology revealed more preserved liver architecture and scattered apoptotic foci in treated mice. Phytochemical profiling identified 27 compounds, including organic acids, phenolic acid derivatives, and flavonoids by LC/ESI-MS/MS. Molecular docking using AutoDock MGLTools 1.5.7 showed strong binding affinities of quercetin and isorhamnetin glycosides with cancer-related proteins (BCL-2, BAX, Caspases, AFP, TNF-α), supporting experimental results. 3D interaction models and box plots confirmed the stability and specificity of ligand–protein interactions. The study concludes that H. scoparium extract demonstrates promising multi-target anticancer potential and may serve as a valuable candidate for pharmaceutical development. © The Author(s) 2025.

Keywords

Good health and well-being; Haloxylon scoparium; Hepatocellular carcinoma; In silico study; LC/ESI-MS/MS; Polyphenols; TNF-α; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Hepatocellular; Chromatography, Liquid; Hep G2 Cells; Humans; Liver Neoplasms; Male; Mice; Molecular Docking Simulation; Phytochemicals; Plant Extracts; Plant Leaves; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; antineoplastic agent; phytochemical; plant extract; animal; chemistry; drug effect; drug therapy; electrospray mass spectrometry; Hep-G2 cell line; human; liquid chromatography; liver cell carcinoma; liver tumor; metabolism; molecular docking; mouse; pathology; plant leaf

Citation Information

Scopus Citations: 3

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