Flavonoids and Their Biological Activities in Inflammation and Cancer

Flavonoids are a diverse group of polyphenolic compounds ubiquitously present in fruits, vegetables, tea and wine. Structurally defined by a C6–C3–C6 skeleton, they encompass subclasses such as flavones, flavonols, flavanones and anthocyanidins. Their capacity to scavenge reactive oxygen species underlies potent antioxidant activity, while regulation of transcription factors and kinases—including NF-κB and the JAK-STAT pathway—accounts for pronounced anti-inflammatory effects. In inflammatory settings, flavonoids attenuate the release of cytokines such as interleukin-1β and tumour necrosis factor-α, inhibit pro-inflammatory enzymes (cyclooxygenase-2, lipoxygenase) and modulate macrophage activation. In oncology, they exert chemopreventive and therapeutic actions via cell-cycle arrest, induction of apoptosis, inhibition of angiogenesis and reversal of multidrug resistance. Bioavailability is influenced by glycosylation and metabolic conjugation, while structural features—especially the number and position of hydroxyl substituents—dictate potency. With mounting epidemiological and mechanistic evidence, flavonoids hold promise as adjuvant agents in chronic inflammatory disorders and cancer prevention, bridging nutraceutical and pharmaceutical development on a global scale.

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Recent in vitro studies employing two- and three-dimensional macrophage models have refined our understanding of trihydroxyflavone derivatives. Comparison of 6,3′,4′- and 7,3′,4′-trihydroxyflavone revealed that positional variation of hydroxyl groups alters both reactive oxygen species scavenging and suppression of nitric oxide and cytokine production, with implications for targeted design of anti-inflammatory agents. Transcriptomic analyses highlighted involvement of IL-17, TNF and JAK-STAT pathways.

Investigations into flavonols and flavones such as quercetin, isoquercetin, kaempferol, myricetin, luteolin and apigenin have elucidated dual anti-inflammatory and antibacterial properties. Structural mapping of ortho-dihydroxy motifs in ring B correlates with enzyme inhibition (cyclooxygenase-2, lipoxygenase) and synergistic action alongside antibiotics, suggesting potential adjuvant use against resistant pathogens while tempering inflammation.

Studies on trihydroxyflavones across human cancer cell lines (lung A549, breast MCF-7, brain U87) have demonstrated anticancer efficacy at low micromolar concentrations. Although a moderate correlation between antioxidant potency and anti-proliferative activity was observed, the presence of ortho-dihydroxy groups and overall substitution pattern emerged as key determinants of cytotoxic selectivity, informing structure-activity relationships for chemopreventive flavonoid development.

Flavonoids and Their Biological Activities in Inflammation and Cancer publication trend

The graph below shows the total number of articles in flavonoids and their biological activities in inflammation and cancer across all publications each year (not limited to Nature Index journals).

Technical terms

Flavonoid: A polyphenolic plant metabolite with a characteristic C6–C3–C6 backbone involved in antioxidant and signalling modulation.

Reactive oxygen species (ROS): Highly reactive oxygen-containing molecules that can induce oxidative stress and influence cell signalling.

NF-κB: A transcription factor central to the regulation of genes involved in inflammation and immune responses.

JAK-STAT pathway: A signal transduction cascade in which Janus kinases activate STAT proteins to modulate gene expression linked to inflammation and proliferation.

Apoptosis: Programmed cell death critical for eliminating damaged or malignant cells.

Angiogenesis: Formation of new blood vessels, a process exploited by tumours to secure nutrients and facilitate growth.

References

1. Antioxidant and Anti-Inflammatory Effects of 6,3’,4´- and 7,3´,4´-Trihydroxyflavone on 2D and 3D RAW264.7 Models. Antioxidants (2023).
2. Flavonols and Flavones as Potential anti‐Inflammatory, Antioxidant, and Antibacterial Compounds. Oxidative Medicine and Cellular Longevity (2022).
3. Relationship between Antioxidant and Anticancer Activity of Trihydroxyflavones. Molecules (2017).