An Updated Review of the Anticancer Mechanisms and Therapeutic Potential of Naringenin.

The revolution in the 21st century has witnessed the development of the industrial and healthcare systems. Human health and well-being are still global challenges despite this modernization and advancement. Cancer is extensively affecting people, demanding special attention and an effective dietary approach. Bioactive compound-based natural therapies are a significant strategy to reduce the cancer burden. Naringenin, a bioactive compound widely distributed in the citrus family and is known for several health-promoting properties, including anticancer activity. The current review highlights the anticancer potential of Naringenin by exploring recent studies through various databases like Google Scholar, PubMed, ScienceDirect, and Web of Science. The analyses revealed that Naringenin can inhibit cell proliferation and oncogenesis through different molecular mechanisms and signaling pathways like apoptosis induction, cell cycle arrest, and modulation of P13K/AKT/mTOR, TGF-β1/Smad3, NF-κB, TLR4, and MAPK pathways. Moreover, it can inhibit inflammatory markers (IL-6, TNF-α, and IL-1β), downregulate oncogenes (Ras, HER2, MYC, and BCR/ABL1), and upregulate tumor suppressor genes (TSGs) such as TP53, PTEN, and BRCA1 and BRCA2 expression. Combining Naringenin with other bioactive compounds, chemotherapy drugs, and nanoformulations is a novel way to enhance its anticancer activity. However, poor bioavailability, stability, and lack of clinical trials and in silico studies hinder its therapeutic potential. Therefore, advanced techniques to enhance its stability and clinical trials regarding anticancer potential are required to validate its promising efficacy. The current review focuses on Naringenin's bioavailability, antioxidant, and anticancer potential through possible mechanisms.