Anti-GBM effects of polyphenolic extract from Avicennia marina

Abstract

Ethnopharmacological relevance: Avicennia marina, (Forssk.) Vierh. the most common halo-tolerant plant, is rich in polyphenolic compounds such as phenols, flavonoids, saponins, alkaloids, and steroids. Avicennia marina exhibits significant therapeutic potential, including antioxidants, antiviral, immunosuppressive, and anticancer properties. Numerous halo-tolerant plant metabolites have been examined for their anti-cancer effects; nevertheless, their efficacy against Glioblastoma multiforme (GBM), an aggressive malignant neoplasm, remains poorly understood. Aim of the study: This study investigates the anticancer efficacy of Avicennia marina (AM) in GBM. The majority of GBM treatments are non-specific and provide limited survival benefits for people with GBM. This study aims to scientifically validate the traditional usage of AM by evaluating its cytotoxic effects and exploring its therapeutic potential. Materials and methods: To evaluate the cytotoxic effect of the purified polyphenols of AM against GBM cells, various in-vitro analysis was performed cytotoxicity assay, apoptosis assay, wound healing assay, caspase 3/7, Reactive oxygen species (ROS) generation and Mitogen-Activated Protein Kinase (MAPKinase) proteomic array. Gas chromatography–mass spectrometry (GC–MS) was performed to profile the secondary metabolites present in the phenolic fraction of AM. Results: The half maximum inhibitory concentration (IC50) of AM was 0.80 μg/mL for LN229 cells and 1.10 μg/mL for SNB19 cells, both of which are lower than the known chemotherapeutic drug, Temozolomide (TMZ). GC–MS examination of the isolated polyphenols identified 14 secondary metabolites. Furthermore, AM elevated intracellular reactive oxygen species and activated caspase 3/7 in both cell lines, triggering apoptosis and leads to GBM cell mortality. Furthermore, AM inhibits the migration of GBM cells over time, demonstrating its anti-metastatic efficacy. Additionally, investigation of the MAPK signaling pathway demonstrated the phosphorylation of critical proteins associated with the ERK, JNK, and p38 protein families. The upregulation of p70S6 kinase and the downregulation of Akt2, Akt3, p38α, and RSK1 indicate that AM could impact the protein synthesis pathway and cell cycle progression. Conclusion: The study indicates that polyphenols in Avicennia marina may serve as a promising candidate for the development of new anti-GBM pharmaceuticals.