Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer’s Disease: A Narrative Review
Abstract
:1. Introduction
2. Literature Searching Strategy
3. Ferulic Acid: General Aspects
3.1. Natural Occurrence
3.2. Chemical Features
4. Pharmacology of Ferulic Acid
4.1. Pharmacological Activities and Mechanisms of Action
4.1.1. Anti-Inflammatory Properties
4.1.2. Antioxidant Properties
4.2. Pharmacokinetic Properties
5. Ferulic Acid and Alzheimer’s Disease (AD)
5.1. In Vitro Studies
5.2. In Vivo Studies
5.3. Clinical Trials
6. Ferulic Acid as a Possible Strategy to Fight Type 3 Diabetes
7. Safety Profile
8. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Source | mg of FA/100 g of Product | Reference | |
---|---|---|---|
Barley extract | 1358–2293 a | [31] | |
Barley—whole grain flour | 25–34 b | [31] | |
Corn—refined bran | 2610–3300 a | [31] | |
Corn—dehulled kernels | 174 a | [31] | |
Corn flour | 38 a | [31] | |
Millet grits | 26 a | [26] | |
Oat bran | 33 a | [31] | |
Whole oat | 25–35 a | [31] | |
Cereals | Rice—endosperm cell wall | 910 a | [31] |
Rye bran | 280 a | [31] | |
Rye—whole grain flour | 86 a | [31] | |
Rye grain | 90–117 b | [27] | |
Wheat—soft and hard bran | 1351–1456 a | [31] | |
Wheat—fine bran | 530–540 a | [31] | |
Wheat bran | 300 a | [26] | |
Whole wheat flour | 89 a | [31] | |
Barley—whole grain flour | 25–34 b | [31] | |
Avocado | 1.1 a | [26] | |
Broccoli | 4.1 a | [26] | |
Carrot | 1.5 a | [26] | |
Cauliflower | 0.35 a | [26] | |
Eggplant | 7.3–35 a | [31] | |
Garlic | 0.63 a | [26] | |
Peanut | 8.7 a | [26] | |
Red cabbage | 6.3 a | [26] | |
Vegetables and Fruits | Soybean | 12 a | [26] |
Spinach | 7.4 a | [31] | |
Tomato | 0.29–6 a | [31] | |
White cabbage | 0.27 a | [26] | |
Banana | 5.4 a | [26] | |
Blueberry fruits | 290–1697 a | [20] | |
Grapefruit | 11.6 a | [26] | |
Mandarin | 9.24 a | [26] | |
Chokeberries | 0.01–2.8 a | [32] | |
Orange | 0.3 a | [26] | |
Plum | 1.47 a | [26] | |
Strawberry | 12.17 a | [26] | |
Apple juice | 0.1 a | [26] | |
Beer | 0.95 a | [26] | |
Beverages | Black tea | 0.16 a | [26] |
Coffee | 9.1 a | [26] | |
Orange juice | 4.7 a | [26] |
Species | Family Name | Source | mg of FA/g of Product | Reference |
---|---|---|---|---|
Angelica sinensis (Oliv.) Diels | Umbelliferae | roots | 0.049–1.502 a | [38] |
Angelica sinensis (Oliv.) Diels | Umbelliferae | roots b | 0.018–0.035 | [39] |
Ferula assa-foetida L. | Umbelliferae | leaves c | 4.62 | [35] |
Ferula assa-foetida L. | Umbelliferae | gum c | 3.72 | [35] |
Hyssopus officinalis L. | Lamiaceae | herb | 0.45 d | [41] |
Lavandula angustifolia Mill. | Lamiaceae | flowers b | 1.31 | [42] |
Lavandula angustifolia Mill. | Lamiaceae | flowers | 0.1 d | [41] |
Lavandula x intermedia Emeric ex Loisel | Lamiaceae | flowers b | 0.11 | [42] |
Mentha x piperita L. | Lamiaceae | leaves b | 0.5 | [42] |
Micromeria graeca L. | Lamiaceae | aerial parts b | 0.27 | [42] |
Micromeria Juliana (L.) Benth. ex Rchb. | Lamiaceae | aerial parts b | 0.28 | [42] |
Micromeria thymifolia (Scop.) Fritsch | Lamiaceae | aerial parts b | 0.93 | [42] |
Origanum majorana L. | Lamiaceae | herb | 0.05 d | [41] |
Rosmarinus officinalis L. | Lamiaceae | leaves | 0.05 d | [41] |
Salvia officinalis L. | Lamiaceae | leaves b | 0.77 | [42] |
Salvia officinalis L. | Lamiaceae | leaves | 0.05 d | [41] |
Salvia miltiorrhiza B. | Lamiaceae | roots e | 8.32 a | [43] |
Teucrium arduini L. | Lamiaceae | aerial parts b | 0.97 | [42] |
Teucrium chamaedrys L. | Lamiaceae | aerial parts b | 1.37 | [42] |
Teucrium montanum L. | Lamiaceae | aerial parts b | 1.70 | [42] |
Teucrium polium L. | Lamiaceae | aerial parts b | 1.38 | [42] |
Thymus vulgaris L. | Lamiaceae | aerial parts b | 0.49 | [42] |
Study | Animal Models and Species (Number, Sex, Age) | Administration | Outcome | ||
---|---|---|---|---|---|
Behavioral Change | Neuropathological Change | Biochemical Change | |||
Yan et al., 2001 [95] | i.c.v. injection of Aβ1–42 ICR mice (10, M, 4 weeks) | 0.002%, 0.004%, and 0.006% (w/v) Free drinking 1, 2, 3, or 4 weeks | ↑ memory | ↓ Hippocampus GFAP and IL-1β immunoreactivities | ↑ Cortex Acetylcholine level but not statistically significant |
Kim et al., 2004 [96] | i.c.v. injection of Aβ1–42 ICR mice (6, M, 4 weeks) | 0.006% (w/v) Free drinking 4 weeks | NA | ↓ microglial activation | ↓ IFN-γ |
Cho et al., 2005 [97] | i.c.v. injection of Aβ1–42 ICR mice (6, M, 4 weeks) | 0.006% (w/v) Free drinking 4 weeks | NA | ↓ astrocytes activation | ↓ hippocampal oxidative stress |
Jin et al., 2005 [98] | i.c.v. injection of Aβ25–35 Sprague Dawley rats (7 weeks) | 50, 100 or 250 mg/kg ig 3 weeks | NA | ↓ astrocytes activation | ↓ IL-1β and FasL ↓ p-p38 MAPK and caspase-3 ↑ ERK-1/2 and Akt/PKB activation |
Jin et al., 2006 [99] | i.c.v. injection of Aβ1–40 Sprague Dawley rats (8 weeks) | 100 or 200 mg/kg ig 3 weeks | NA | ↑ hippocampal CA1 pyramidal neurons | ↓ p-MKK3/MKK6, p-p-38 MAPK ↑ p-MAPKAPK-2, p-Hsp27, PARP ↓ IL-1β ↓ caspase-9, -3 and -7 activation |
Kim et al., 2007 [100] | i.p. injection of TMT ICR mice (8, M) | 0.002% or 0.005% (w/v) Free drinking 28 days | ↓ memory impairment | NA | ↑ ChAT activity |
Mamiya et al., 2008 [101] | i.c.v. injection of BSO ICR mice (10/15, M, 25 weeks) | 0.5, 1, or 5 mg/kg sc 6 days | ↑ recognition memory ↑ short-term memory | ↓ protein oxidation ↓ carbonyl protein levels in forebrains | NA |
Jin et al., 2008 [102] | Aged Sprague Dawley rats (M, 21 months) | 100 or 200 mg/kg in food 4 weeks | NA | ↓ microglia and astrocytes activation in cortex and hippocampus Better arrangement of hippocampal CA1 pyramidal neurons | ↓ IL-1β, p-MKK4, p-JNK, p-c-Jun ↑ p-ERK-1/2, p-MEK 1/2 ↓ caspase -3 and -7 activation |
Hamaguchi et al., 2009 [103] | Mice double mutation K670N-M671L Tg2576 mice (10, F, 5 months) | 0.5% in food 10 months | NA | ↓ Aβ deposits | NA |
Beibei et al., 2011 [104] | Injected KA into hippocampus CA1 region KM mice (10, M and F, 6 weeks) | 20, 40 and 80 mg/kg ig 30 days | ↑ learning and cognitive skills | ↓ GFAP in hippocampal CA1 region | NA |
Yan et al., 2013 [105] | APP/PS1 mice (5, F, 6 months) | 5.3 and 16 mg/kg/d Free drinking 6 months | ↑ memory | ↓ Aβ1–42 and Aβ1–40 levels | ↓ Il-1β |
Mori et al., 2013 [106] | PSAPP C57BL/6J mice (12, M and F, 6 months) | 30 mg/kg ig 6 months | ↓ behavioral impairment | ↓ Aβ deposits ↓ neuroinflammation and oxidative stress ↓ microglial and astroglial activation | ↑ Iba1 ↓ TNF-a, IL-1β, Sod1, catalase, Gpx1 ↓ GFAP |
Tsai et al., 2015 [107] | i.c.v. injection of Aβ1–40 SD rats (10–12, M, 9 weeks) | 50 and 100 mg/kg ig 2 weeks | ↓ cognitive function impairment ↑ improve memory | NA | ↑ GSH, SOD ↓ Zn-SOD and AChE Activity |
Kikugawa et al., 2016 [89] | i.c.v. injection of Aβ25–35 C57BL/6 J mice (6, M, 6 weeks) | 0.1 µmol/g/day po 42 days | ↑ contextual freezing response impairment | ↑ neurons survival | NA |
Mori et al., 2017 [108] | APP/PS1 C57BL/6J mice (8, M and F, 12 months) | 30 mg/kg ig 3 months | ↑ memory | ↓ Aβ deposits ↓ astrocytosis, microgliosis, synaptotoxicity ↓ neuroinflammation and oxidative stress | ↓ sAPP-α/holo-APP and β-oligomers ↑ ADAM10 and ↓ BACE1 ↑ synaptophysin ↓ TNF-α, IL-1β, SOD1, GPx1 |
Yue et al., 2017 [109] | APP/PS1 C57BL/6 mice (10, 5 weeks) | 20, 40, 100 mg/kg ig 7 days | NA | ↓ apoptosis and oxidative stress | ↑ Bcl-2 and ↓ Bax, p-JNK, p-C-Jun, Caspase3 ↓ MDA and ↑ SOD |
Rui et al., 2018 [110] | Injected KA into hippocampus CA1 region KM mice (M and F, 6 weeks) | 20, 40, and 80 mg/kg 30 days | N/A | ↓ positive GFAP cells in cerebral cortical glial cells | ↓ IL-1β, IL-6, and TNF-α |
Zafeer et al., 2019 [111] | ICV-STZ Wistar rats (6, M, 2 months) | 100 mg/kg po 21 days | ↓ spatial memory and learning loss | ↓ oxidative stress ↓ mitochondrial damage | ↓ ROS ↑ Drp-1, PGC1-α ↓ Mfn2, BAX, Cytochrome-C, LPO, and DNA fragmentation |
Mori et al., 2019 [112] | APP/PS1 mice (8, M and F, 12 months) | 30 mg/kg ig 3 months | ↑ memory | ↓ Aβ deposits ↓ astrocytosis and microgliosis ↓ neuroinflammation and oxidative stress ↓ synaptotoxicity | ↓ amyloidogenic APP cleavage ↓ ADAM10 and BACE1 ↓ GFAP and Iba1 ↓ TNF-α and IL-1β, ↓ SOD1 and GPx1 ↑ synaptophysin |
Qian et al., 2019 [113] | Injecting Aβ1–42 into the lateral ventricle KM mice (10, M, 6 weeks) | 0.1 and 0.4 g/kg ig | ↑ spatial positioning memory | ↓ morphological changes ↓ Aβ generation | ↓ Drp1, CnAα, CnAβ, and BACE1 ↓ Tau and pS396 protein |
Wang et al., 2021 [114] | APP/PS1 mice (6 months) | 20 mg/kg/day Free drinking 30 days | ↑ spatial memory | ↑ capillary density and diameter ↑ whole-brain blood vessels ↓ Aβ plaque deposits ↓ area of aggregative microglial cells ↓ ET1- mediated vasoconstriction and prevention of CBF reduction | ↓ BACE1 |
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Di Giacomo, S.; Percaccio, E.; Gullì, M.; Romano, A.; Vitalone, A.; Mazzanti, G.; Gaetani, S.; Di Sotto, A. Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer’s Disease: A Narrative Review. Nutrients 2022, 14, 3709. https://doi.org/10.3390/nu14183709
Di Giacomo S, Percaccio E, Gullì M, Romano A, Vitalone A, Mazzanti G, Gaetani S, Di Sotto A. Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer’s Disease: A Narrative Review. Nutrients. 2022; 14(18):3709. https://doi.org/10.3390/nu14183709
Chicago/Turabian StyleDi Giacomo, Silvia, Ester Percaccio, Marco Gullì, Adele Romano, Annabella Vitalone, Gabriela Mazzanti, Silvana Gaetani, and Antonella Di Sotto. 2022. "Recent Advances in the Neuroprotective Properties of Ferulic Acid in Alzheimer’s Disease: A Narrative Review" Nutrients 14, no. 18: 3709. https://doi.org/10.3390/nu14183709