It is proved that consumption of a high amount of fruits, fruit juices, and other forms of plant based foods (such as vegetables and nuts) will reduce the risks of developing many life threatening chemo- and neuro-degenerative diseases such as cancer and cardiovascular diseases [
54]. The absence of undesirable side effects has promoted consumption significantly. The presence of natural bioactive phytochemicals such as phenolic, vitamins (e.g., vitamin E), and carotenoids is attributed to their potential antioxidant activity. Apart from scavenging ability against RONS, these antioxidants can protect against ROS-mediated oxidative damage by elevating cellular antioxidant capacity [
55]. Though there are many reports of fruit juices that were found to be potential candidates for the prevention of chemo- and neuro-degenerative diseases, the underlying mechanism of action is still unclear. As a result, studies have been conducted to unveil the mechanism of the Nrf2 pathway. A number of phenolic compounds abundantly present in fruit juices have been identified and these could modulate the Nrf2 pathway through translocation of Nrf2 into the nucleus, up-regulation of antioxidant enzymes, and reduction of RONS.
Citrus sinensis, also known as Washington Navel orange, is chemically rich in carotenoids with known antioxidant and anti-inflammatory activity, and cellular protective activity against oxidative stress [
56]. Carotenoids like lycopene, phytoene, and β-carotenes are abundantly found in their peel and pulp. A study carried out on pasteurized
C. sinensis orange juices extracted from pulp showed significantly increased reduction of ROS, up-regulation of antioxidant enzyme genes such as GST-4, SOD-4, GCS-1, and HSP-16-2, and resistivity against oxidative stress as a consequence of high carotenoid content [
56]. Anthocyanins are another class of natural phytochemicals called flavonoids, abundantly found in nature. Anthocyanins in pomegranate are responsible for the color of the fruit and its biological function is still not fully known [
57], although anthocyanins and hydrolysable tannins isolated from the juices of pomegranate significantly increased Nrf2 expression in nitrosodiethylamine-induced fibrotic rats [
58]. Meanwhile, another study showed that punicalagin isolated from pomegranate fruit juice increased Nrf2 nuclear translocation, up-regulated HO-1 gene expression and decreased the generation of RONS. As a result, stress-induced cell death and apoptosis of IEC-6 cells were significantly reduced [
59]. Chlorogenic acid, vanillic acid, syringic acid, trans-ferulic acid, protocatechuic acid, 4-coumaroylquinic acid, and
p-coumaric acid are some of the common phenolic acids abundantly found in fruits [
60]. These natural acids together with flavonoids catechins, epicatechins, and the epicatechin dimer procyanidin B2 showed strong antioxidant activity, because of their ability to activate Nrf2 translocation and strong up-regulation of HO-1, GPX2GSR, CAT, and NQO-1 antioxidant enzymes. Furthermore, it was reported that these phytochemicals identified in fruit juices like apple and blueberry provided protection against RONS-induced toxicity and were beneficial to endothelial cell activation and vascular functions [
61,
62]. Noni is a tropical tree native to Southeast Asia, Australia, and the South Pacific including Hawaii. Noni is used in traditional medicine for a diverse range of ailments. Its anti-cancer, anti-inflammatory, and antidiabetic properties were well known in folklore, but there was a lack of scientific evidence to support the claims [
63]. As a result, Chen et al. in 2018 tested different organic extracts of Noni juice against Nrf2 activity. They found that aqueous and chloroform extracts protect the cells from
tert-butyl hydroperoxide (TBHP)-induced cell damage and significantly decrease TBHP cytotoxicity, apoptosis, and RONS generation. Meanwhile, nuclear accumulation of Nrf2 and up-regulation of HO-1, CAT, and SOD-1 were also observed [
64]. This antioxidant and neuroprotection activity may be due to the presence of different types of phytochemicals in both fractions, such as high phenolic and flavonoid content in the chloroform fraction and rich polysaccharides content in the aqueous fraction [
64]. This study showed the neuroprotective activity of Noni extracts and their molecular mechanisms. In two studies carried out by Senger and Cao on Noni fruit juice, three alkyl catechols, namely 4-ethyl catechol, 4-methyl catechol, and 4-vinyl catechol [
47], and a coumarin compound scopoletin [
65] were identified as Nrf2 co-factors. These compounds significantly increased the nuclear translocation of Nrf2 and the up-regulation of the expression of HO-1 and NQO-1 genes [
47,
65]. Similarly, vegetable juices like broccoli, sprout, garlic, cabbage juices and betanin from beetroot juice activated Nrf2 translocation and up-regulation of a panel of antioxidant genes such as GSTP, GSTM, GSTT, NQO-1, HO-1, thioredoxin, thioredoxin reductase, and NAD(P)H:quinones [
66,
67,
68]. Phytochemicals present in fruit juices as Nrf2 activators (
Figure 5) are listed in
Table 2.