Page 163 - EJMO-9-1

Eurasian Journal of Medicine and
Oncology
Potential of flavonoids against glioblastoma

inflammatory, and anti-cancer activities, and these isolated Future directions for this research should include
compounds share structural similarities with neoflavones, detailed mechanistic studies to fully understand the
which have estrogen-like activity and potential cancer cell pathways through which these flavonoids exert their effects
proliferation inhibition. The cytotoxic activity observed on glioblastoma cells. In vivo studies and combinational
35
aligns with the established molecular mechanisms of therapies using these compounds with conventional
flavonoids in inducing apoptosis and disrupting critical chemotherapeutic agents may reveal synergistic effects and
signaling pathways in cancer cells. address potential challenges like drug resistance.
Furthermore, several phenolic constituents from 5. Conclusion
P. chinensis, such as quercetin, gallic acid, and arbutin
derivatives, have demonstrated robust anti-cancer This comprehensive investigation into the anti-cancer
36
properties, supporting the hypothesis that this plant’s potential of P. chinensis highlights its significant therapeutic
diverse chemical profile may contribute synergistically to efficacy against glioblastoma cells. The flavonoids isolated
its biological activities. These observations are consistent from its methanolic extract demonstrated potent, dose-
with earlier studies on other Pistacia species, such as dependent cytotoxicity, and in silico analyses confirmed
Pistacia lentiscus and Pistacia atlantica, which have their drug-like properties, with Compound 1 emerging as
demonstrated anti-cancer effects against various cell lines, particularly promising. These findings establish a strong
thereby expanding the scientific understanding of this basis for developing novel plant-based chemotherapeutic
genus’s therapeutic scope. 37-40 agents. Despite this promise, several challenges must be
addressed to advance these compounds toward clinical
Comparative analysis with other plant-derived application. Limited BBB permeability may restrict their
flavonoids and phenolic compounds suggests that the therapeutic reach to glioblastoma tissues, while potential
flavonoids from P. chinensis exhibit either comparable off-target effects necessitate careful toxicity profiling to
or superior cytotoxicity against glioblastoma cells. This ensure safety. In addition, chemical modifications may
implies that these compounds might exert their anti-cancer be required to enhance their bioavailability and clinical
effects through mechanisms involving the induction of efficacy. Future research should focus on overcoming these
apoptosis, cell cycle arrest, and interference with tumor- limitations through advanced delivery systems, in vivo
promoting signaling pathways. 41,42 studies, and exploring these flavonoids in combination
The study also incorporated in silico analysis, revealing therapies. This work underscores the potential of P.
significant binding affinities of Compound 1 (-10.319 chinensis as a valuable source of innovative cancer
kcal/mol) and Compound 2 (-10.458 kcal/mol) toward treatments and offers a roadmap for their development
the mTOR (PDB ID: 5OQ4) and AKT1 (PDB ID: 3O96) into clinically viable therapeutics.
proteins, respectively. These interactions underscore their Acknowledgments
potential as mTOR/AKT pathway inhibitors, aligning
with the observed effects of other natural compounds, None.
like luteolin, in glioblastoma inhibition. 43,44 In addition,
absorption, distribution, metabolism, excretion, and Funding
toxicity (ADMET) profiling indicated favorable drug- None.
like characteristics for both compounds, with high
gastrointestinal absorption and moderate bioavailability Conflict of interest
despite limited blood–brain barrier (BBB) permeability. Marcello Iriti is an Editorial Board Member of this
This limitation might be mitigated through conjugation journal but was not in any way involved in the editorial
with BBB-crossing inhibitors, enhancing their clinical and peer-review process conducted for this paper, directly
applicability. or indirectly. Separately, other authors declared that they
Quantum chemical analysis through DFT further have no known competing financial interests or personal
supported the molecular stability and reactivity of these relationships that could have influenced the work reported
flavonoids, particularly Compound 1, which exhibited in this paper.
superior electronic properties conducive to strong protein- Author contributions
ligand interactions. These results resonate with existing
studies employing DFT calculations to elucidate the Conceptualization: Abdur Rauf, Soonmin Ho, Muhammad
molecular characteristics of natural compounds, suggesting Umer Khan
promising lead candidates for anti-cancer therapy. 45-48 Data curation: Zuneera Akram, Omar S. Bahattab

Volume 9 Issue 1 (2025) 155 doi: 10.36922/ejmo.5768