**3. Mechanisms of antioxidative action of vegetable phytochemicals**

Generally, the protective effect of vegetables has been credited to their antioxidant components. Antioxidants prolong the onset of free radical generation due to their capacity to supply hydrogen atoms or chelate metals implicated in ROS formation [18]. The mode of operation by which antioxidants negate the influence of free radicals involves various mechanisms among which is the termination of the free radicals [32] and post-modification of resultant bioactive compounds during metabolism [33].

Cells can respond to the effect of antioxidant phytochemicals by interacting with receptors and enzymes involved in signal transduction, or through modification of gene expressions that may affect the redox status of the cell and subsequent induction of series of redox-dependent reactions [34]. Reference [34] also presented an evolving evidence that phytochemicals like flavonoids may participate in the modulation of intracellular signalling cascades. Intracellular signalling pathways serve as major avenues of connection between the plasma membrane and regulatory targets in various intracellular compartments [35]. This signalling process also leads to the activation of protein kinases by phosphorylation, and then affects the activity of transcription factors that regulates gene expression [36]. Ruiz et al. [37] showed that the signalling cascades enable the cells to regulate processes such as growth, proliferation, and apoptosis. Phytochemicals can modulate effects in cells through selective actions on different components of the signalling cascades.

One of the mechanisms utilised by carotenoids is inhibition of the oxidation initiated by singlet oxygen. Flavonoids possess antioxidant, anti-inflammatory, antimutagenic and anti-carcinogenic properties. Apigenin is a flavone found in parsley and celery. It prevents inflammation by hampering the production of proinflammatory cytokines and cyclooxygenase 2 (COX-2) expression through the inhibition of nuclear factor-*κ*B (NF-*κ*B) (**Figure 3**), phosphoinositide-3-kinase (PI3K/Akt) and activating transcription factor-3/cyclic adenosine monophosphate (ATF/cyclic AMP) responsive element signalling pathways [38]. Kaempferol, a flavonol present in broccoli suppresses the inflammatory activities of inducible nitric oxide synthase (iNOS) and COX-2 by blocking signal transducer and activator of transcription 1 (STAT-1), NF-*κ*B, and activator protein 1 (AP-1) signalling pathways as observed in activated macrophages and human endothelial cells [39]. Quercetin, known to be present in green leafy vegetables, onions and broccoli, exerts its potent antioxidant and anti-inflammatory activities by inhibiting the expression of pro-inflammatory cytokines [40] and suppressing (tumour necrosis factor) TNF-induced NF-*κ*B (**Figure 3**) [41]. Furthermore, it can also regulate lipid profile thereby reducing glycaemia through the inhibition of 11β-hydroxysteroid dehydrogenase type 1 [42].

Lycopene, a carotenoid present in tomatoes, diminishes inflammatory response by reducing the gene expressions of iNOS and COX-2 [43] as well as IL-12 production. This is achieved by obstructing mitogen-activated protein kinase (MAPK) signalling and the activation of NF-*κ*B [44]. Moreover, *β*-carotene in green-coloured leafy vegetables prevents the genetic expressions of LPS-induced iNOS, COX-2, and TNF-α by reducing phosphorylation and degradation of I-kappa B-related protein (I*κ*BR) and nuclear translocation of NF-*κ*B in macrophages [45]. Lutein, known for its yellow pigmentation in leafy vegetables such as spinach was discovered to have

**Figure 3.** *Mechanism of inhibition of inflammation and oxidative stress by phytochemicals in vegetables.*

the ability to repress LPS- and hydrogen peroxide-induced pro-inflammatory gene expression by diminishing the activities of PI3K and NF-*κ*B inducing kinase (NIK) and phosphorylation of Akt [46].
