Possible Effects and Mechanisms of Dietary Natural Products and Nutrients on Depression and Anxiety: A Narrative Review
Abstract
:1. Introduction
2. Depression
2.1. Epidemiological Studies
2.2. Experimental Studies
2.2.1. Anti-Inflammatory Effect
2.2.2. Antioxidant Effect
2.2.3. Modulating the Production of Monoamine Neurotransmitters
2.2.4. Promoting the Production of Neurotrophins
2.2.5. Inhibition of the HPA Axis Hyperactivity
2.2.6. Modulation of Microbiota–Gut–Brain Axis
2.2.7. Other Mechanisms
Name | Study Type | Model | Dose | Effects and Mechanisms | Ref. |
---|---|---|---|---|---|
Animal Foods | |||||
Fish oil | In Vivo | Lupus-prone MRL/lpr mice | 728 mg/kg | Increased BDNF and synaptic protein Enhanced Nrf2-mediated antioxidant defenses; | [52] |
Plant Foods | |||||
Geum japonicum | In Vivo | ICR mice | 30, 100, 300 mg/kg | Exerted neuroprotective effects Upregulated expression of BDNF in hippocampus; | [60] |
In Vitro | SH-SY5Y cells | 0, 50, 100 μg/mL | Decreased CORT-induced neurotoxicity; | ||
Royal jelly | In Vivo | CUMS mice | 4.5 g/kg | Attenuated CUMS-induced depression Inhibited the biosynthesis of CORT; | [68] |
Purple cauliflower | In Vivo | CUMS mice | 50, 100, 200 mg/kg | Improved depressive symptoms Increased content of monoamine neurotransmitter Suppressed activity of MAO Upregulated BDNF, TrkB; | [19] |
Semen sojae praeparatum | In Vivo | CUMS rats | 0.97 g/kg | Exerted antidepressant effect Upregulated Ruminococcaceae_UCG-008 Regulated the 5-HT, NE, GABA, BDNF content | [89] |
Deoiled sunflower seeds | In Vivo | CUMS mice | NA | Ameliorated depression-like behaviors Upregulated dopamine, 5-HT, acetylcholine, NE, BDNF; | [54] |
Bifidobacteria-fermented red ginseng | In Vivo | C57BL/6 mice | 10, 25, 50 mg/kg | Exerted protective effects against Escherichia coli-induced depression Enhanced the abundance of Bacteroidetes Reduced the abundance of Proteobacteria Upregulated expression of BDNF; | [84] |
Navel orange essential oil | In Vivo | Kunming mice | 0.5, 1, 2% | Exerted anti-depressive effects Increased serotonin and dopamine levels in brain; | [56] |
Garlic essential oil | In Vivo | CUMS rats | 25, 50 mg/kg | Exerted anti-depressive effect Upregulated hippocampal BDNF, CREB, protein kinase B; | [59] |
Beverages | |||||
Grewia asiatica berry juice | In Vivo | SD male rats | Free access to 5%, 10%, 20%, 30% dilutions | Decreased oxidative damage Increased SOD and GPx levels Modulated the cholinergic system Decreased acetylcholinesterase and MDA levels; | [50] |
Maqui berry | In Vivo | Male balb/c mice | 25, 50, 100 mg/kg | Ameliorated post-stroke depression Upregulated expression level of GSH Enhanced activities of SOD, CAT; | [51] |
Adzuki bean sprout fermented milk | In Vivo | C57BL/6 mice | 0.1, 0.2, 0.4 mL/mouse | decreased depressive symptoms Upregulated the expression levels of 5-HT, NE, dopamine; | [57] |
Probiotics | |||||
Bifidobacterium E41 and M2CF22M7 | In Vivo | C57BL/6J mice | 1 × 109 CFU/mouse | Suppressed depression-like behaviors Improved the gut microbial dysbiosis Enhanced 5-HT and BDNF; | [79] |
Prevotella histicola | In Vivo | C57 BL/6 mice | 1 × 109 CFU/mouse | Protective effect against estrogen deficiency-induced depression Downregulated VCAM, MCP-1, IL-6, IL-8, TNF-α Increased the abundance of Akkermansia and Lactobacillus; | [44] |
Lacticaseibacillus paracasei NK112 | In Vivo | C57 BL/6J mice | NA | Exerted protective effects against Escherichia coli-induced depression Decreased IL-1α, IL-6, TNF-α Inhibited the activity of NF-κB; | [45] |
Lactobacillus casei | In Vivo | CUMS rats | NA | Mitigated depressive symptoms Reversed the structure change of gut microbiota Regulated BDNF/TrkB signaling; | [78] |
Lactobacillus casei | In Vivo | Pregnant rats | 8 × 108 CFU/kg | Exerted anti-depressive effects Changed the composition of gut microbiota Increased expression level of BDNF Suppressed BDNF–MAPK pathway | [77] |
Lactobacillus gasseri NK109 | IN VIVO | Mice | 1 × 108, 1 × 109 CFU/mouse | Improved Escherichia coli K1-induced depression Decreased the expression level of IL-1α Regulated gut microbiota; | [81] |
Lactobacillus kefiranofaciens ZW3 | In Vivo | CUMS mice | 1 × 107, 1 × 108, 1 × 109 CFU/mouse | Improved the symptoms of depression Regulated the gut microbiota composition Ameliorated constipation; | [80] |
Lactobacillus helveticus strain MCC1848 | In Vivo | C57BL/6J mice | 1 × 1011 CFU/mouse | Ameliorated depressive symptoms Improved the alteration of gene expression in nervous system development and signal transduction; | [90] |
Nutrients | |||||
SCFAs | In Vivo | High fructose-fed mice | NA | Decreased depression-like behaviors Inhibited microglia activation Reduced blood–brain barrier damage; | [94] |
n-3 PUFA | In Vivo | Wistar rats | 0 en% of n-3 PUFA, 1 en% of n-3 PUFA | Ameliorated post-menopausal depression Increased brainstem serotonin level Increased serotonin-1A receptor, BDNF, CREB, miRNA-155, GR Downregulated IL-6, IL-1β, TNF-α, prostaglandin E-2, CORT, ACTH, CRF, miRNA-218; | [42] |
n-3 PUFA | In Vivo | Wistar rats | 0 en% of n-3 PUFA, 1 en% of n-3 PUFA | Regulated the HPA axis Reduced circulating levels of ACTH and CORT Downregulated expression of CRF; | [67] |
EGCG | In Vivo | CUMS rats | 50 mg/kg | Exerted anti-depressive effects Reduced IL-6 and NO Decreased caspase-3 and caspase-9; | [46] |
EGCG | In Vivo | CUMS rats | 50 mg/kg | Improved depression-like behaviors Reduced serotonin in the colon Increased serotonin in the hippocampus; | [55] |
EPA-PL | In Vivo | ICR mice | NA | Ameliorated depressive symptoms Suppressed HPA axis hyperactivity; | [65] |
Sesamin | In Vivo | CUMS mice | 50 mg/kg | Improved depressive symptoms Increased BDNF, NT-3; | [61] |
Resveratrol | In Vivo | Wistar-Kyoto male rats | 40 mg/kg | alleviated depression-like behaviors increased BDNF, NT3; | [63] |
Dietary fiber | In Vivo | C57BL/6J mice | NA | Increased the expression levels of NE, 5-HT Inhibited neuroinflammation Promoted formation of short-chain fatty acids and reconstruction of gut microbiome; | [82] |
Dietary pectins | In Vivo | BALB/c mice | 50 mg/kg | Suppressed depression-like behaviors Increased the levels of IL-6, IFN-γ Downregulated the protein level of STAT3; | [95] |
Coniferyl ferulate | In Vivo | C57BL/6 SPF mice | 50 mg/kg | Exerted protective effect Improved the reconstruction of gut microbiome Downregulated the expression levels of IL-6, IL-1β, TNF-α; | [88] |
Coniferyl ferulate | In Vitro | PC12 cells | 0.2, 2, 20 μmol/L | Exerted anti-depressive effect Decreased the production of ROS Suppressed mitochondrial apoptotic pathways; | [96] |
Nicotinamide riboside | In Vivo | C57BL/6J mice | 400 mg/kg | Changed the composition of gut microbiota Decreased inflammation-related cytokines Increased BDNF levels; | [86] |
Soy isoflavones | In Vivo | CUMS rats | 40, 80, 160 mg/kg | Improved depressive symptoms Enhanced the diversity of gut microbiota Upregulated monoamine neurotransmitter levels; | [87] |
Curcumin | In Vivo | Wistar male rats | 40 mg/kg | Attenuated depression-like behaviors Suppressed excessive synaptic loss Improved synaptic function; | [92] |
Lycopene | In Vitro | SH-SY5Y cells | 1~10 μM | Alleviated oxidative damage Reduced 8-OHdG, MDA, and protein carbonyls expressions Inhibited PERK signaling pathway; | [48] |
Chlorogenic acid | In Vivo | Wistar rats | 500 mg/kg | Had anti-depressive effects Increased Burkholderiales, Bifidobacterium Reduced Desulfovibrionales, Desulfovibrio; | [83] |
Apple phenolic | In Vivo | Kunming mice | 200 ppm in normal saline | Improved lead acetate-induced depression-like behaviors Attenuated neuroinflammation and neuronal apoptosis Regulated miR-22-3p/SIRT1 signaling pathway; | [39] |
Alkaloids | In Vivo | C57BL/6N mice | 200 mg/kg | Mitigated LPS-induced depressive symptoms Inhibited neuroinflammation Repressed BDNF-mediated endoplasmic reticulum stress Increased autophagy; | [91] |
In Vitro | BV2 cells | 50 μg/mL | Inhibited pro-inflammatory mediators and NO production; | ||
Aponin compounds | In Vivo | CMS rats | 240 mg/kg | Exerted anti-depressive effect Inhibited the hyperactivation of HPA axis Improved the synthesis and transport processes of neurotransmitters; | [66] |
Saccharina japonica ethanol extract | In Vivo | C57BL/6 mice | 1, 2, 4 g/kg | Decreased the depression-like behaviors Increased activity of superoxide dismutase Increased anti-inflammatory cytokines Downregulated NF-κB, NOD-like receptor 3, TLR-4; | [43] |
2.3. Clinical Trials
3. Anxiety
3.1. Epidemiological Studies
3.2. Experimental Studies
3.2.1. Anti-Inflammatory Effect
3.2.2. Antioxidant Effect
3.2.3. Modulation of Gut Microbiota
3.2.4. Regulation of Production of Neuroactive Substances
3.2.5. Other Mechanisms
Name | Study Type | Model | Dose | Effects and Mechanisms | Ref. |
---|---|---|---|---|---|
Animal foods | |||||
Honey | In Vivo | Wistar rats | 0.26, 0.31, 0.36 g/kg | Had protective effects against anxiety Decreased TNF-α, IL-6; | [20] |
Plant foods | |||||
Saffron | In Vivo | Rats | 30, 60 mg/kg | Exerted anxiolytic effect Downregulated serum cortisol level Upregulated BDNF in hippocampal; | [128] |
Bergamot essential oil | In Vivo | SD rats | 200 mg/kg | Improved anxiety Decreased IL-1β, IL-6, TNF-α Enhanced the activity of GPx, CAT, SOD; | [111] |
Red pomegranate fruit extract-based formula | In Vivo | C57BL/6J mice | 2.0, 1.5, 1.0 mg/g | Exerted anxiolytic effect Increased 5-HT in hippocampus Suppressed indoleamine-2,3-dioxygenase Improved tryptophan hydroxylase Reduced NF-κ B, TNF-α, IL-6, IL-1β, IFN-γ, MDA Promoted the activities of NOS, SOD and CAT; | [113] |
Beverages | |||||
Low-dose alcohol | In Vivo | C57BL/6 mice | 0.8 g/kg | Decreased anxiety-like behaviors Upregulated adiponectin Activated Nrf2 signaling pathway; | [117] |
Breadfruit pulp | In Vivo | Zebrafish | NA | Exerted anxiolytic effect Regulated the serotoninergic system | [126] |
Probiotics | |||||
Lactobacillus sakei | In Vivo | Mice | OK67: 2 × 108, 1 × 109, 2 × 109 CFU/mouse PK16: 1 × 109, 5 × 109 CFU/mouse | Mitigated anxiety-like behaviors Inhibited the population of Proteobacteria Decreased fecal lipopolysaccharide levels Inhibited NF-κB Increased AMPK; | [121] |
Lactococcus lactis WHH2078 | In Vivo | CUMS mice | 1 × 109 CFU/mouse | Decreased serum CORT Increased 5-HT, BDNF Restored abundances of Firmicutes and Bacteroidetes; | [120] |
Escherichia coli Nissle 1917 | In Vivo | C57BL/6 mice | 0.5 × 1010, 1 × 1010 CFU/mouse | Attenuated anxiety-like behaviors Inhibited the pathologic gut–brain circuit; | [122] |
Weissella paramesenteroides WpK4 | In Vivo | C57BL/6 mice | 1 × 108 CFU/mouse | Mitigated anxiety-related behaviors Decreased gut permeability Regulation of gut–brain axis; | [124] |
Pediococcus acidilactici CCFM6432 | In Vivo | C57BL/6 mice | 5 × 109 CFU/mouse | Attenuated anxiety-like behaviors Improved the gut microbial composition Inhibited hyperactivity of HPA axis Upregulated phosphorylated CREB; | [123] |
Nutrients | |||||
Caffeine and caffeic acid | In Vivo | Swiss albino mice | Caffeine: 15 mg/kg Caffeine + caffeic acid: 10 mg/kg + 5 mg/kg | Attenuated anxiety-like behaviors Decreased inflammatory markers levels; | [110] |
Sesamol | In Vivo | C57BL/6J mice | 100 mg/kg | Reduced anxiety-like behaviors Decreased neuroinflammatory responses Inhibition of TLR-4/NF-κB pathway Stimulated Nrf2 signaling pathway Increased BDNF, NE, 5-HT Repaired synaptic impairments Regulated BDNF/TrkB/CREB signaling pathway; | [109] |
Curcumin | In Vivo | Rats | 0.1, 0.5% | Low doses: exerted anxiolytic effect, improved the synaptic plasticity, enhanced neural circuits High doses: reversed anxiolytic effect, induced neuroinflammation; | [131] |
Curcumin | In Vivo | Swiss albino mice | 20, 40, 80, 160 mg/kg | Ameliorated anxiety-like behaviors Promoted the production of neuronal cells Suppressed neuroinflammation; | [135] |
n-3 PUFA | In Vivo | Wistar rats | 500 mg/kg | Attenuated obesity-induced anxiety Exerted anti-inflammatory effect Decreased IL-6, TNF-α; | [112] |
Blumea lacera leaf methanol extract | In Vivo | Swiss albino mice | 200, 400 mg/kg | Mitigated anxiety-like behaviors Suppressed ROS formation; | [116] |
Chamomile decoction | In Vivo | Wistar rats | 100 mg/kg | Ameliorated high fat diet-induced anxiety Suppressed lipoperoxidation Promoted antioxidant enzymes activities Inhibited AChE, BChE; | [118] |
Goat milk fat | In Vivo | Wistar rats | NA | Palliated anxiety-like behaviors Decreased MDA Increased GSH; | [114] |
Tangeretin | In Vivo | Rats | 100, 200 mg/kg | Decreased anxiety-like behaviors Activated Nrf2; | [115] |
Panaxynol | In Vivo | CUMS mice | 1.0 mg/kg | Improved CUMS-induced anxiety symptoms Suppressed the HPA axis hyperfunction Increased the release of 5-HT Promoted synaptic plasticity; | [127] |
L-theanine | In Vivo | WKY rats | 0.4 mg/kg | Attenuated anxiety-related behaviors Decreased glutamate levels Increased methionine levels Improved hippocampal activity; | [129] |
Queen bee acid | In Vivo | SD rats | 12, 24 mg/kg | Decreased anxiety-like behaviors Promoted the growth of neurons; | [130] |
3.3. Clinical Trials
4. Conclusions and Perspectives
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Name | Study Type | Participants | Dose | Effects | Ref. |
---|---|---|---|---|---|
Animal Foods | |||||
Fish | Cross-sectional study | 9183 Korean adults 19 ≤ age ≤ 64 | 4 times/week vs. <1 time/week | Associated with a lower risk of depression Total: OR, 0.52; 95% CI, 0.37–0.74 Men: OR, 0.64; 95% CI, 0.30–1.37 Women: OR, 0.44; 95% CI, 0.29–0.67; | [31] |
Fatty fish | Cross-sectional study | 6587 participants | Second, third, fourth quintiles vs. the lowest quintiles | U-shaped relationship with depression (OR, 0.77; 95% CI, 0.63–0.94) (OR, 0.71; 95% CI, 0.58–0.87) (OR, 0.78; 95% CI, 0.64–0.96); | [32] |
Plant foods | |||||
Legume and nut | Cross-sectional study | 3172 participants 18 ≤ age ≤ 55 | The highest vs. the lowest quartile | No association with depression Men: OR, 0.96; 95% CI, 0.54–1.71 Women: OR, 0.98; 95% CI, 0.65–1.48; | [35] |
Walnut | Cross-sectional study | 26,656 participants | Daily walnut consumption vs. no nut consumption | Protective effect on depression Total: OR, 0.67; 95% CI, 0.48–0.93 Men: OR, 0.72; 95% CI, 0.41–1.27 Women: OR, 0.62; 95% CI, 0.46–0.84; | [30] |
Seaweed and mushroom fiber | Cross-sectional study | 2960 adults 19 ≤ age ≤ 64 | Seaweed fiber: ≥1.02 g/day vs. <0.31 g/day Mushroom fiber: ≥0.14 g/day vs. <0.03 g/day | Inversely associated with depressive symptoms Seaweed fiber: OR, 0.38; 95% CI, 0.20–0.72 Mushroom fiber: OR, 0.18; 95% CI, 0.01–0.37; | [29] |
Beverages | |||||
Green tea | Cross-sectional study | 9576 Korean adults age ≥ 19 | ≥3 cups/week vs. none or <1 cup/week | Decreased the prevalence of depression (OR, 0.79; 95% CI, 0.63–0.99); | [25] |
Tea | Cohort study | 3177 participants age ≥ 55 | ≥3 cups/day vs. none or <1 cup/day | Associated with a lower risk of depression (OR, 0.32; 95% CI, 0.12–0.84); | [24] |
Coffee | Cohort study | 14,413 university graduates | ≥4 cups/day vs. <1 cup/day | Associated with a lower risk of depression (HR, 0.37; 95% CI, 0.15–0.95); | [33] |
Soft drink | Cross-sectional study | 8085 college students | >25 g sugar/day from soft drinks vs. none | Associated with a higher risk of depression (Mean difference, 0.22; 95% CI, 0.15–0.29); | [36] |
Sugar-sweetened drink | Cohort study | 15,546 Spanish university graduates | The highest vs. the lowest quartile | No association with depression (HR, 1.12; 95% CI, 0.90–1.41); | [37] |
Nutrients | |||||
Carbohydrate | Two-sample Mendelian randomization analysis | 268,922 samples | NA | A causal relationship with a lower risk of depression (OR, 0.42; 95% CI, 0.28–0.62); | [34] |
Dietary fiber | Cross-sectional study | 459 hypertensive patients | 10.5–15.4 g/day vs. ≥15.4 g/day | Associated with a higher incidence of depression (OR, 2.641; 95% CI, 1.050–6.640); | [26] |
Selenium | Cross-sectional study | 736 Brazilian farmers 18 ≤ age ≤ 59 | ≥95.26 μg/day vs. ≤66.66 μg/day | Decreased the risk of depression (OR, 0.461; 95% CI, 0.236–0.901); | [27] |
Name | Study Type | Participants | Dose | Effects | Ref. |
---|---|---|---|---|---|
Plant foods | |||||
Legume and nut | Cross-sectional study | 3172 participants 18 ≤ age ≤ 55 | The highest vs. the lowest quartile | Protective effect on anxiety in men Men: OR, 0.34; 95% CI, 0.14–0.82 Women: OR, 1.06; 95% CI, 0.63–1.77; | [35] |
Beverages | |||||
Soft drinks | Cross-sectional study | 8085 college students | >25 g sugar/day from soft drinks vs. none | Associated with a higher risk of anxiety (Mean difference, 0.11; 95% CI, 0.04–0.18); | [36] |
Nutrients | |||||
Dietary fiber | Cross-sectional study | 459 hypertensive patients | <8.1 g/day vs. ≥15.4 g/day | Associated with a higher incidence of depression (OR, 2.757; 95% CI, 1.035–7.346); | [26] |
n-3 fatty acids | Cross-sectional study | 12,268 adults | The highest vs. the lowest quintile | Inversely associated with anxiety EPA: OR, 0.82; 95% CI, 0.69–0.98 DHA: OR, 0.83; 95% CI, 0.69–0.98 DPA: OR, 0.82; 95% CI, 0.69–0.98; | [107] |
Branched-chain amino acids | Cross-sectional study | 3175 Iranian adults 18 ≤ age ≤ 55 | The highest vs. the lowest tertile | Associated with a lower risk of anxiety (OR, 0.66; 95% CI, 0.47–0.91); | [105] |
Vitamin B6 | Cross-sectional study | 3362 adults | The lowest vs. the highest tertile | Associated with a higher risk of anxiety (OR, 2.30; 95% CI, 1.19–4.46); | [106] |
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Wu, S.-X.; Li, J.; Zhou, D.-D.; Xiong, R.-G.; Huang, S.-Y.; Saimaiti, A.; Shang, A.; Li, H.-B. Possible Effects and Mechanisms of Dietary Natural Products and Nutrients on Depression and Anxiety: A Narrative Review. Antioxidants 2022, 11, 2132. https://doi.org/10.3390/antiox11112132
Wu S-X, Li J, Zhou D-D, Xiong R-G, Huang S-Y, Saimaiti A, Shang A, Li H-B. Possible Effects and Mechanisms of Dietary Natural Products and Nutrients on Depression and Anxiety: A Narrative Review. Antioxidants. 2022; 11(11):2132. https://doi.org/10.3390/antiox11112132
Chicago/Turabian StyleWu, Si-Xia, Jiahui Li, Dan-Dan Zhou, Ruo-Gu Xiong, Si-Yu Huang, Adila Saimaiti, Ao Shang, and Hua-Bin Li. 2022. "Possible Effects and Mechanisms of Dietary Natural Products and Nutrients on Depression and Anxiety: A Narrative Review" Antioxidants 11, no. 11: 2132. https://doi.org/10.3390/antiox11112132