Open Access

ARTICLE

Ketogenic diet with oxyresveratrol and zinc inhibits glioblastoma and restores memory function and motor coordination

by TANVI VIJAY GUJARAN^1,#, VIGNESH BALAJI EASWARAN^1,#, RUNALI SANKHE¹, PUGAZHANDHI BAKTHAVATCHALAM^2,3, HERMAN SUNIL DSOUZA⁴, K. SREEDHARA RANGANATH PAI^1,*

1 Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, India
2 Division of Anatomy, Department of Basic Medical Science, Manipal Academy of Higher Education, Manipal, 576104, India
3 Department of Anatomy and Physiology, American University of Antigua, University Park, Antigua, W1451, West Indies
4 Department of Radiation Biology and Toxicology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, 576104, India

* Corresponding Author: K. SREEDHARA RANGANATH PAI. Email:
# These authors contributed equally to this work

Oncology Research 2025, 33(2), 381-395. https://doi.org/10.32604/or.2024.049538

Received 10 January 2024; Accepted 13 June 2024; Issue published 16 January 2025

Abstract

Background: To date, there is no effective cure for the highly malignant brain tumor glioblastoma (GBM). GBM is the most common, aggressive central nervous system tumor (CNS). It commonly originates in glial cells such as microglia, oligodendroglia, astrocytes, or subpopulations of cancer stem cells (CSCs). Glucose plays an important role in the, which energy metabolism of normal and cancer cells, but cancer cells exhibit an increased demand for glucose is required for their differentiation and proliferation. The main aim of this study is to explore the anti-cancer efficacy of the ketogenic diet against GBM. Also, this research focuses on the identification of the catalytic action of zinc in epigenetic modulators such as oxyresveratrol and ensures the combinatorial effect in the treatment of GBM. Method: In this study, we have evaluated various parameters to understand the therapeutic efficacy of the treatment groups through in vivo experiments against aggressive brain tumors. Intracerebroventricular experiments were performed to induce the tumor in the animals and estimate the tumor burden and proliferative index. Followed by the Morris water maze, an open field test, and rota rod was performed to evaluate the memory and motor coordination. To understand the glucose, and ketone level modification before and after treatment, the level of glucose and ketone was analyzed. Moreover, the zinc level is assessed using flame atomic absorption spectroscopy. Results: The results suggested that the ketogenic diet has an anti-cancer efficacy against C6-induced GBM cell lines. Also, it exerts a synergistic effect with the epigenetic modulator, oxyresveratrol, and zinc against GBM cell lines. Moreover, the treatment groups improved memory and motor coordination and modified the glucose and ketone levels to reduce the tumor burden and Ki-67 proliferative index. Conclusion: This study revealed the therapeutic effect of the ketogenic diet along with its combination such as oxyresveratrol and zinc against the C6-induced GBM in the Wistar rats. Also, it improved memory and motor coordination and reduced tumor growth. It also modified the glucose and ketone levels in the tumor-induced animal and supported to diminish the tumor burden.

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