Plant-based foods, such as fruits, contain natural active principles, ranging from primary metabolites (nutritive factors, vitamins, and minerals) to secondary metabolites (phytochemicals). These bioactive principles play significant roles in mitigating several chronic diseases. Some epidemiological studies have identified antioxidant-rich secondary metabolites, such as flavonoids and anthocyanin, for their anti-inflammatory, antiproliferative, and ameliorative roles in neurological disorders. Generally, natural polyphenols express their neuroprotective capacity by relying on their mechanism ability to cross the blood-brain barrier to scavenge the pathological concentrations of reactive oxygen and nitrogen species. Equally, polyphenols modulate a series of mediating cell-signaling pathways of pathological diseases.
Neurodegenerative diseases essentially relate to any pathological condition that primarily affects the neuron [ 10]. They affect the central nervous and are typified by the regression and progressive decline of neurological functioning and cognitive deficit [ 11 ], which results in major conditions, such as Alzheimer’s, Parkinson’s, and dementia [ 12, 13 ]. This challenge is particularly devastating in aging populations, with Alzheimer’s disease affecting about 40 million people globally [14,15 ]. Exposure to multiple factors (environmental and genetic) contributes to the onset of neurodegenerative diseases. Neurotoxic metal pollutants, such as mercury, lead, cadmium, and arsenic, have been identified with Alzheimer’s and Parkinson’s disease, oxidative stress, neuronal death, mitochondrial dysfunction, modulation of metal homeostasis, and aggregation of α-synuclein proteins [16 –18 ]. A schematic description of the aforementioned is depicted in Figure 1. It is even more concerning that these environmental factors can cause damage to the neurologic system via epigenetic mechanisms and then trigger neurodegenerative disease in later years [18,19 ]. Neurodegeneration consists of a series of pathways that have been closely linked to its inflammatory process and, in particular, the pro-inflammatory cytokines implicated in the pathogenesis of functional and neurologic impairment [20].
Figure 1. Schematic representation of neurodegenerative diseases, their pathology, and target proteins.
The burden of neurological disorders and conditions has necessitated reliable data to enhance effective health planning approaches. Epidemiological data for neuro conditions, particularly Parkinson’s, dementia, and amyotrophic lateral sclerosis, have been reported in the last two decades [21 –25 ]. Frontotemporal dementia is typically identified in middle age, with reports of about 13% occurrence in people below the age of 50 [26 ]. Furthermore, Ref. [26] a systematic analysis of a demographics-based study was carried out and estimated about 2–31 frontotemporal dementia incidences per 100,000 people in Europe and developed countries of Asia and North America [ 26 ]. An average occurrence of Multiple System Atrophy (MSA) (3 per 100,000 people), average onset age (54–61 years), and demographic prevalence in Europe and North America have been reported in various studies [27–29].
3. Fruits in Neurodegenerative Prevention/Management
The brain is especially a centrally significant organ of the nervous system which requires a healthy diet, with fruits potentially offering a wide range of rich nutrient supplies [30]. Fruits represent a major dietary component across Western and Asian demographics. They have been reported to have positive synergy with and relation to chronic disease management [31– 34 ]. Examples of these common fruits include Malus domestic, Persea americana, Musa sinensis, Citrus limon, Musa paradisiaca, Pyrus communis, Citrus sinensis, Fragaria ananassa, and Ananas comosus (Figure 2).
Figure 2. Commonly consumed fruits with bioactive capacities; including Banana and Plantain.
Date palm fruits (Phoenix dactylifera) have been reported in studies for their potential biological capacity in nephroprotective, hepatoprotective, and anticancer activity [35–37]. Recently, the inhibitory effect of avocado juice against trypsin aggregation has been reported: a formation process associated with several neurological diseases [38]. Similarly, other reports identified the beneficial role of berries (blackberry and blueberry) with regard to the obstruction of the central nervous system and cognitive deficit [39,40]. The cactus pear (Opuntia ficus-indica) fruit has also been reported to have the biological capacity to modulate neuron excitation in a distributive manner across sectors of the brain [41]. Over time, a host of bioactive molecules cutting across nutritive and antinutritive factors, vitamins, minerals, and secondary metabolites have been screened, evaluated, and elucidated in several species and varieties of banana and plantain fruits, as shown in Table 1.
Active Molecules (Nutritive Factors and Secondary Metabolites) | Active Molecule Constituents in Banana and Plantain Fruit Components (Pulp and Peel) |
Neuromechanism-Related Protein/Gene Targets |
---|---|---|
Tannin![]() |
|
|
Phenolic acid![]() |
|
|
Quercetin![]() |
|
|
Rutin![]() |
|
|
Carbohydrates![]() |
|
|
Lipids![]() |
|
|
Magnesium![]() |
|
|
Zinc![]() |
|
|
Copper![]() |
|
|
Alkaloid![]() |
|
|
Saponin![]() |
|
|
Phytate (Phytic acid)![]() |
|
|
Vitamins B![]() |
|
|
Anthocyanin![]() |
|
|
Vitamin E (Tocopherol)![]() |
|
|
Selenium![]() |
|
|
Phytosterol![]() |
|
|
Terpenoids![]() |
|
|
Glycosides![]() |
|
|
Anthraquinone![]() |
|
|
Arginine![]() |
|
|
β-carotene![]() |
|
|
Lycopene![]() |
|
|
Vitamin C (ascorbic)![]() |
|
Table 2: Other neuroprotective-related bioactivity mechanisms of key bioactive compounds. |
Bioactive Compounds |
---|
Bioactive Compounds |
Biological mechanisms of action related to neuroactivity |
Bioactive Compounds |
Biological mechanisms of action related to neuroactivity |
|
Inhibition of apoptosis-related damage to DNA [230]. | ||||
Biological Mechanisms of Action Related to Neuroactivity | Bioactive Compounds | Biological Mechanisms of Action Related to Neuroactivity |
---|
TANNINS
|
-Condensed tannins and Hydrolysable tannins Antioxidant (free-radical scavenging) (metal chelation) (pro-oxidative enzyme inhibition) (endogenous antioxidant system interaction) (inhibition of xanthine oxidase-induced Lipid peroxidation) [208,209]. -Procyanidins Antioxidant enzyme gene expression in cells [210]. -Ellagitannins (geranin, corilagin, furosin) Anti-inflammatory mechanisms such as depletion of apoptotic cells [208]. |
ANTHOCYANIN |
Delphinidin Cyanidin Anti-inflammatory, anti-Alzheimer, antitumor, Antioxidative properties by depleting the expression of cytokine markers [211]. |
|
QUERCETIN |
-Oxygen radical scavenging, metal chelation, and attenuation of nitric oxide synthase [212]. -Expressive mechanism of paraoxonase 2 for neuroprotection in neurons and brain cells [213-215]. -Anti-inflammatory mechanism via inflammatory gene repression (blocking) [216]. -Regulation of apoptosis and inhibition of cleaving enzyme (BACE 1) [217,218]. -Impairment of chemokines and cytokines [219]. -Quercetin-3-O-diglucoside-7-O-glucoside Anti-inflammatory, antioxidant effects, and lipoxygenase inhibitory effects [220]. |
MYRICETIN |
Kaempferol Antitumor, anti-inflammation, and antioxidant properties are exercised via an antiproliferative mechanism in cells, attenuation mechanism against inflammation, and tumor growth factors [221,124]. |
|
ALKALOIDS |
Vincristine Antineuroblastoma property exerted via the mechanisms truncating the glutathione metabolism [222]. Tetrandrine Anti-inflammatory and anti-tumor activities are linked to the calcium-channel blocking mechanism [223]. Skimmianine Anti-inflammatory property via the inhibition of nitric oxide production [224]. |
CATECHIN |
-Anti-inflammation, anti-oxidative stress mechanism via modulation of -tyrosine kinase receptor [225]. -Modulation of signal transduction pathways to protect cell proliferation, inflammation, and metastasis [226]. |
|
TERPENOIDS Paeoniflorin, Triptolidenol, Tripterine, Triptonide, Gindenoside, Oleanoic acid |
Anti-inflammatory activity via interleukin-6 inhibition [227]. Anti-nociceptive, antioxidant and anti-inflammatory properties [228]. |
RUTIN |
-Anti-apoptotic mechanism against cell death [112] -Depletion of pro-inflammatory cytokine expression [229]. |
|
LIPID Omega-3 DHA |
Anti-inflammatory properties, Cell survival promotors [230]. |
Neuroprotectin D1 Lipid |
TANNINS |
(free-radical scavenging) (metal chelation) (pro-oxidative enzyme inhibition) (endogenous antioxidant system interaction) (inhibition of xanthine oxidase-induced Lipid peroxidation) [208,209]. |
ANTHOCYANIN | Delphinidin Cyanidin Anti-inflammatory, anti-Alzheimer, antitumor, and antioxidative properties by depleting the expression of cytokine markers [211]. |
Anti-inflammatory mechanisms, such as depletion of apoptotic cells [208]. |
|||
QUERCETIN |
|
MYRICETIN | Kaempferol Antitumor, anti-inflammation, and antioxidant properties are exercised via an antiproliferative mechanism in cells, attenuation mechanism against inflammation, and tumor growth factors [124,221]. |
|
|||
ALKALOIDS | Vincristine Antineuroblastoma property exerted via the mechanisms truncating the glutathione metabolism [222]. Tetrandrine Anti-inflammatory and antitumor activities are linked to the calcium-channel blocking mechanism [223]. Skimmianine Anti-inflammatory property via the inhibition of nitric oxide production [224]. |
CATECHIN |
|
TERPENOIDS Paeoniflorin, Triptolidenol, Tripterine, Triptonide, Gindenoside, Oleanoic Acid |
Anti-inflammatory activity via interleukin-6 inhibition [227]. Anti-nociceptive, antioxidant and anti-inflammatory properties [228]. | RUTIN |
|
LIPID Omega-3 DHA |
Anti-inflammatory properties, Cell survival promotors [230]. |
Neuroprotectin D1 Lipid | Inhibition of apoptosis-related damage to DNA [230]. |
| |||
| |||
| |||
| |||
| |||
| |||
| |||
| |||
|
|
||
β-cryptoxanthin![]() |
|
||
β-sitosterol![]() |
|
|
|
Sesamin![]() |
- M. sapientum/M. acuminata peel extracts (methanol) [119]. |
|
|
Myricetin![]() |
|
|
|
Catechin![]() |
|
Table 1. Compendium of active molecules in Banana and Plantain |
fruits. |
|
Active Molecules (Nutritive factors and Secondary metabolites) |
Banana and Plantain fruit compartmental constitution |
Neuromechanism-related protein/gene targets |
Tannin |
- M. paradisiaca peel (unripe) (5.39±0.02 mg/g) [42] - M. paradisiaca peel (ripe) (4.24±0.01 mg/g) [42] - M. paradisiaca peel (over-ripe) (2.84±0.03 mg/g) [42]. - M. paradisiaca fruit (2.30±0.215%) [43]. - M. paradisiaca peel extract (aqueous) (14.69±0.34 mg/g) [44] - M. paradisiaca peel extract (80% ethanol) (17.66±0.34 mg/g) [44] - M. paradisiaca peel extract (80% methanol) (24.21±0.17 mg/g) [44] - M. paradisiaca peel extract (80% acetone) (15.90±0.28 mg/g) [44] - M. paradisiaca peel flour (30.98±1.01 mgGAE/g) [45] - Cavendish banana peel (5.60±0.02 mg/g) [46] - Red banana peel (5.75±0.03 mg/g) [46] - White banana peel (5.00±0.37 mg/g) [46] - M. paradisiaca raw pulp (7.05±1.00 µgEC/mg) [47] |
-GFAP [48] -PGC-1α/Nrf-2/Ho-1 [49]. |
Phenolic acid |
- Banana pulp (76.3 mgGAE/g) [50] - M. acuminata pulp (methanol extract) (778 mgQE/g) [51] - M. acuminata peel (methanol extract) (1168 mgQE/g) [51] - M. acuminata pulp (ethanol extract) (950 mgQE/g [51] - M. acuminata peel (ethanol extract) (897 mgQE/g) [51]. - M. paradisiaca pulp (methanol extract) (936 mgQE/g) [51] - M. paradisiaca peel (methanol extract) (1346 mgQE/g) [51] M. paradisiaca pulp (ethanol extract) (950 mgQE/g) [51] - M. paradisiaca peel (ethanol extract) (952 mgQE/g) [51] - Banana pulp extracts (150.13 to 386.22 mgGAE/100g) [52] - M. paradisiaca pulp extract (166.90 ± 0.96 to 341.00 ± 34.6 mg GAE/g) [53] - M. acuminata (75.01 to 685.57 mgGAE/g) [54] - M. sinensis pulp (43.83 ± 1.13 to 119.05 ± 5.80 mgGAE/g) [55] - M. sinensis peel (47.68 ± 2.14 to 157.19 ± 4.76 mgGAE/g) [55] - M. paradisiaca pulp (17.41 ± 0.17 to 114.80 ± 1.49 mgGAE/g) [55] - M. paradisiaca peel (75.14 ± 0.55 to 136.87 ± 5.69 mgGAE/g) [55] - M. acuminata pulp (42.85±0.80 to 523.60±9.05 mgGAE/100g) [56] - M. acuminata peel (150.48±16.17 to 199.61±14.68 mgGAE/ 100g) [56]. |
|
Quercetin |
- Banana fruit (292 µg/100g) [57]. |
- BDNF-TrkB-PI3K/Akt [58] - Bax/Bcl2 and Caspase-3 [59]. |
Rutin |
- Dessert banana (Gros Michel var.) (494.43 ± 153.71 µg/g) [60]. |
- Aβ, interleukin IL-1 [61,62] - TNF-α and IL-1β [63] - poly ADP-ribosyl polymerase, glutathione reductase, glutathione peroxidase [63] - Caspase-3 and Prion protein peptide (Prp) [64] - Interleukin-8, Cyclooxygenase-2, NF-kB and GFAP [65,66]. - p38 MAPK [67] |
Carbohydrates |
- M. paradisiaca pulp (18.8 to 78.5 g/100g) [68] - M. paradisiaca peel (68.0 ± 0.3 g/100g) [69] - Musa spp. (16.72 to 35.24 g/100g) [70] - Banana fruit (21.70 to 41.33 g/100g) [71] |
- p-JNK and p-ERK [72] -TrKA receptor, ERK1/2, MPTP [73]. |
Lipids |
- M. paradisiaca (0.9 ± 0.1 g/100g) [69] - M. paradisiaca (0.33 ± 0.34 g/100g) [74] - |
|
Magnesium |
- M. paradisiaca peel (27.0±0.08 to 76.0±0.55 mg/g) [42] - M. paradisiaca peel flour (14.5±0.0 mg/100g) [69] - Banana peel (62.5 ± 0.01 mg/100g) [75] - Plantain peel (64.12 ± 0.04 mg/100g) [75] - M. paradisiaca pulp (29.00 ± 34.30 mg/kg) [76] - M. paradisiaca peel (34.50 ± 34.80 mg/kg) [76] - M. paradisiaca peel (324.50±0.15 to 394.93±0.11 mg/100g) [77]. |
N- methyl-D-aspartate [78] |
Zinc |
- Plantain (Musa ABB) and Cooking banana (Musa AAB) (0.2 ± 0.0 to 0.4 ± 0.0 mg/100g) [79] - M. paradisiaca pulp (1.00 to 13.35 mg/kg) [76] - M. paradisiaca peel (3.10 to 3.70 mg/kg) [76] - M. paradisiaca peel (26.96 ± 0.02 to 39.02 ± 0.01 mg/100g) [77]. |
- Caspase [80] - Maltose binding protein (MBP) [81]. |
Copper |
- Banana peel (2.55 ± 0.01 mg/100g) [75] - Plantain peel (5.82 ± 0.03 mg/100g) [75] - M. paradisiaca peel (3.29 ± 0.00 to 3.42 ± 0.01 mg/100g) [77] |
|
Alkaloid |
- M. sapientum fruit (0.251 ± 0.003 to 0.778 ± 0.006%) [43] - M. paradisiaca fruit (0.187 ± 0.001 to 1.027 ± 0.003%) [43] - M. acuminata fruit (0.083 ± 0.001 to 0.860 ± 0.005%) [43]. |
- Aβ peptide [82] - BDNF, MAP2, GAP43, PSD-95, KLK 8 [83,84] |
Saponin |
- M. paradisiaca peel (327 mg/100g) [85] - Banana fruit (11.6 mg/100g) [71] - M. sapientum fruit (0.145 ± 0.005 to 2.268 ± 0.003%) [43] - M. paradisiaca fruit (0.773 ± 0.003 to 0.973 ± 0.033%) [43] - M. sapientum peel (29.25 ± 0.11 mg/100g) [86] |
- p53 and p-p38 [87]. |
Phytate (Phytic acid) |
- Musa spp. (11.96 ± 1.05 to 24.15 ± 0.95 mg/100g) [88] - M. paradisiaca peel (9.064 ± 0.04 to 11.12 ± 0.05 mg/g) [42]. |
- Aβ peptide [89] |
Vitamins B |
- Musa ABB (0.002 to 0.032 mg/100g) [88] - M. sapientum pulp (0.06 ± 0.002 to 0.08 ± 0.001 mg/100g) [43] - M. paradisiaca pulp (0.07 ± 0.000 to 0.08 ± 0.001 mg/100g) [43] - M. acuminata pulp (0.07 ± 0.001 to 0.08 ± 0.002 mg/100g) [43] - M. sapientum (0.29 ± 0.008 to 0.32 ± 0.008 mg/100g) [43] - M. paradisiaca (0.24 ± 0.008 to 0.28 ± 0.118 mg/100g) [43] - M. acuminata (0.30 ± 0.008 to 0.35 ± 0.012 mg/100g) [43] - M. paradisiaca fruit (0.39 ± 0.02 mg/100g) [90]. |
|
Anthocyanin |
- M. paradisiaca peel (aqueous extract) [91]. |
- ASK1-JNK/p38 [92] - Interleukin-1β and TNF-α [93,94] |
Vitamin E (Tocopherol) |
- M. sapientum pulp (17.53 ± 1.18 µg/g) [95] - M. paradisiaca pulp (20.20 ± 1.99 µg/g) [95]. |
- ERβ-PI3K/Akt [96]. |
Selenium |
-Bananas (0.024 ± 0.0019 µg/g) [97] -Banana fruit (< 0.001 µg/g) [98] -Bananas (160 ± 1.33 µg/kg) [99] -Bananas (2.3 ± 0.20 µg/g) [100] |
- Aβ peptide [101] - N-acetylcysteine [102].
|
Phytosterol |
- Bananas (7.8 ± 6.9 mg/d) [103] |
- Acetylcholineaterase [104] - β- secretase [105]. |
Terpenoids |
- M. acuminata peel (0.21 ± 0.00 to 0.28 ± 0.01 mg/g) [46] -M. paradisiaca peel (1.83 ± 0.19 to 1.88 ± 0.24 g/100g) [106]. |
- Glutamate decarboxylase [107]. |
Glycosides |
- M. sapientum (0.261 ± 0.001 to 0.769 ± 0.002 mg/100g) [43] - M. paradisiaca (0.35 ± 0.001 to 0.602 ± 0.004 mg/100g) [43] - M. acuminata (0.498 ± 0.003 to 0.811 ± 0.004 mg/100g) [43].
|
- NF-kB and STAT 3 gene [108]. |
Anthraquinone |
- M. paradisiaca peel (aqueous extract) [91]. |
- NF-kB and TGF-β1 [109] - ERK/MMP-9 and NOX2 (gp91phox) [110]. |
Arginine |
- Sweet banana fruit pulp (57.0 mg/100g) [111]. |
- HIF-1α/LDHA [112] |
β-carotene |
- Banana fruit (68.0 µg/100g) [111] - Plantain fruit (390 -1035 µg/100g) [111] |
- Nrf2/Keap 1 [81] |
Lycopene |
- M. sapientum pulp (0.80 ± 0.01 µg/g) [95] - M. paradisiaca pulp (0.91 ± 0.00 µg/g) [95]. |
- NF-kB [113] - Tau protein and GSH-Px [114] |
β-cryptoxanthin |
- Banana (Musa sp.) peel (0.08 ± 1.28 µg/g) [115] |
|
β-sitosterol |
- Bananas (7.8 ± 6.9 mg/d) [103] - Banana (Musa sp.) peel extract (269-601 mg/kg) [116] |
- Aβ, β-secretase and γ-secretase [117,118] |
Sesamin |
- M. sapientum/ M. acuminata peel extracts (methanol) [119] |
- MAPK and COX-2 [120] - MMP-9 [121] - ERK1/2 and SIRT1 [122] |
Myricetin |
- Dessert banana peel (Grand Nain cultivar) (125.32 ± 17.18 to 172.28 ± 12.38 µg/g) [60] - Musa sp. (Banana fruit) (143 µg/100g) [123] |
- BDNF-Akt/GSK-3β/ MTOR and - P13K/Akt/MTORC1 [124] |
Catechin |
- M. Cavendish peel (1.34 ± 0.27% of 29.2 mgGAE/g) phenolic compounds [125] |
|
Vitamin C (ascorbic)
|
- M. paradisiaca peel (11.72 mg/100g) [85] - Dessert banana (Musa sp.) fruit pulp (4.5 to 12.7 mg/100g) [126] |
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