Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics
Abstract
:1. Introduction
2. Methods
3. Results and Discussion
3.1. Plants Secondary Metabolites: A Brief Overview
3.1.1. Background
3.1.2. Ethnopharmacological Relevance of Natural Compounds for NDDs
3.2. Pharmacological Activities of Plants Secondary Metabolites on Neurodegenerative Disorders (NDDs): in vitro and in vivo Studies.
3.2.1. Preventing Protein Misfolding and Aggregation
3.2.2. Antioxidant Activity
3.2.3. Anti-inflammatory Activity
3.2.4. Antiapoptotic and Neurotrophic Activities
3.2.5. Acetylcholinesterase Inhibition Activity
3.2.6. Monoamine Oxidase Inhibitors (MAOs)
3.2.7. Antithrombotic Activity
4. Future Perspectives
Author Contributions
Acknowledgments
Conflicts of Interest
References
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Compound/Type | Natural Source | Experimental Model | Effects/Mechanisms of action | Ref |
---|---|---|---|---|
Acacetin/flavanoid | Chrysanthemi indici, Calamintha, Linaria spp | In vitro model of PD | ↓6-hydroxydopamine-induced cell death ↓caspase-3, ↓caspase-9, ↓PARP and cytochrome c ↑Bcl-2/Bax, ↓ROS, ↓phosphorylation of JNK, ↓p38, ↓ERK1/2 MAPK | [69] |
Aegeline/alkaloid-amide | Aegle marmelos | In vitro yeast model of PD | Prevented α-synuclein-induced apoptosis, ↓ROS | [58] |
Andrographolide/diterpene lactone | Andrographis paniculata | In vitro model of PD | ↓PAF-induced platelet aggregation, ↓collagen-stimulated platelet activation, ↑TXA2, ↑phosphorylation of PKC, MAPK and AKT ↑eNOS, ↑NO, ↑eNOS-NO/cyclic GMP pathways, ↓PI3K/Akt/p38 MAPK ↓ PLC-γ2/PKC | [104] |
Apigenin/flavanoid | common constituent in plants | In vitro induced neurogenesis In vivo mouse model of AD | ↓inflammatory cytokines, ↓cortical hyperexcitation ↓Aβ burden, ↓oxidative stress, ↑ERK/CREB/BDNF pathway ↓β-amyloid neurotoxicity, ↑mitochondrion protection | [44,92] [109] |
Asiatic acid/triterpene | Centella asiatica | In vitro model of PD In vivo mouse model of PD | ↓apoptosis, ↓ROS ↑ERK, ↑PI3K/Akt/mTOR/GSK-3β pathways, ↓MAPK/P38, ↓JNK, ↓ERK, ↓dopamine depletion, ↑NTFs | [110] [70] |
Baicalein/flavanoid | Scutellaria baicalensis | Molecular docking simulation In vivo model of PD | ↓MAO-A, ↓Aβ ↓brain hypoxia, ↓H2O2, ↓iNOS, ↓NF-κB, ↓NO, ↓TNF-α, ↓oxidative stress, ↓mitochondrial dysfunction, ↑JNK, ↓TNF-α, ↓IL-6, ↓NF-κB, ↓MAPK, ↓dopaminergic neuron loss, ↓LDH, ↓NO, ↓glutamate | [111] [45] |
Berberine/alkaloid | Berberis genus | In vitro model of AD In vivo rodent model of AD | ↓AChE, ↓MAO-B, ↓BACE1, ↑IκB-α, ↑Akt,↑p38 kinase ERK1/2 ↓NF-κB, ↓TNF-α,↓IL-6 production, ↓MCP-1, ↓COX 2,↓iNOS ↓Aβ plaque, ↓ CTF-α, ↓CTF-β (which reflects α- and β-secretase processing of APP) | [112] [101] [49] |
Borneol/terpene derivative | common constituent in plants | Ex vivo rat blood | ↑PT, ↑TT, ↓thrombosis in veins | [108] |
Carvacrol/monoterpenoid phenol | Cyperus rotundus | In vitro MAO A and MAO B | ↓antiplatelet aggregation | [105] |
Chrysin/flavanoid | Hypericum afrum, Cytisus villosus | Molecular docking simulation | ↓MOA-A | [99] |
Crocin/carotenoid | Gardenia jasminoides Crocus sativus | In vivo mouse model of AD In vivo rat model of AD | ↓oxidative stress, ↑SOD, ↓MDA ↓AChE, ↑ACh activity ↓neuroinflammation, ↓TNF-α, ↓PGE, ↓iNOS, ↓COX2 ↓Tau hyperphosphorylation | [68] [56] |
Curcumin/carotenoid | Curcuma longa | In vivo Dania rerio (zebrafish) model of NDD In vivo mouse model of stroke in vivo mice model of PD | Neuroprotective,↓tonic-clonic seizures ↓oxidative stress ↑GSH in cortex and hippocampus ↓infarct volumes, ↑M2 polarization of microglia/macrophages, ↓Aβ aggregation, ↓NF-κB, ↓α-synuclein oligomerization | [113] [76] [86] [50,114] |
Decursin/pyranocoumarin | Angelica gigas, Scutellaria baicalensis | In vitro model of PD | ↓MOA-A | [111] |
Epigallocatechin gallate/catechin | Camellia sinensis | In vivo rat model of AD rat model of PD | ↓Aβ fibrillogenesis, ↓oxidative stress, ↓AchE ↓α-synuclein aggregation | [18,51] |
Genistein/flavanoid | Glycine max | Molecular docking simulation In vitro model of AD | ↓MAO ↓inflammation, ↓NF-κB ↓Aβ toxicity, ↑apoptosis | [99] [44] |
Ginsenoside Rd/triterpene glycosides | Panax ginseng | In vivo rodent model of stroke | ↓excitotoxicity, ↓Ca2+ influx, ↑ GLT-1, ↓ ROS | [73] |
Ginsenoside Rg1/triterpene glycosides | Panax notoginseng | In vitro cell model of AD | ↓β- and γ-secretases, ↓NO, ↓ROS, ↓lipid peroxidation, ↓IL-1,↓IL-8, ↓TNF-α, ↓Aβ plaque, ↓caspase-9, ↓caspase-3 | [49] |
Hesperidin/flavanoid | Valeriana officinalis | Molecular docking simulation In vivo rat model of AD | ↓ BACE1 ↓oxidative stress, ↓Aβ fibril formation | [109] [46,55] |
Isoquercitrin/flavonoid | Common in plants | In vivo rat model of AD | ↓BACE1, ↓γ-secretase, ↓Aβ fibrillogenesis, ↓caspase-3, ↓caspase-9, ↓apoptosis, ↓amyloid plaque, ↓tau hyperphosphorylation | [46] |
Kolaviron/bioflavanoid complex | Garcinia kola | In vivo rat model of stroke | ↓MPO, ↓necrotic cell death, Preserved Na/K/ATPase activity | [87] |
Linalool/monoterpene | Lavandula spp. Rosmarinus officinalis Melissa officinalis Cymbopogon citratus | In vivo mouse model of AD In vitro cell model of ND | Anti-inflammatory ↓p38, ↓MAPK, ↓Nos2, ↓COX2, ↓IL-1β↓ Aβ in the hippocampus ↓tauopathy, inhibition of T-type Ca2+ channels | [54] [115] |
Luteolin/flavanoid | Common constituent in plants | In vivo mouse model of ND In vivo animal model of stroke | ↑GSH, ↓oxidative stress, ↓MDA, ↑Nrf2, antioxidant/anti-inflammatory ↑Nrf-2 dependent transcription of HO-1 neuroprotective against cerebral I/R injury | [77] [116] [82] |
Morin/flavanoid | Common constituent in plants | In vivo rat models of AD | ↓BACE1, ↓γ-secretase, ↓Aβ fibrillogenesis ↓apoptosis, ↑caspase-3, ↑caspase-9 ↓amyloid plaque, ↓tau hyperphosphorylation | [46] |
Myricetin/flavanoid | Common constituent in plants | Molecular docking simulation | ↓MAO | [99] |
Naringenin/flavanoid | Citrus paradise Citrus sinensis | In vitro models of AD | ↓inflammatory cytokines, ↓NF-κB signalling, ↑Nrf2/ARE signaling ↓NO | [71] |
Naringin/flavanoid | Citrus spp. | In vivo rat model of AD In vivo rodent model of PD | ↓AChE, ↓cognitive deficit, ↓GFAP, ↑neurotrophic factors | [92] [48] |
Narirutin/flavanoid | Citrus spp. | In vitro | ↓BACE1 ↓Aβ aggregation | [47] |
Nootkatone/sesquiterpene | Cyperus rotundus | In vitro MAOA and MAOB | ↓platelet aggregation | [105] |
Quercetin/flavanoid | Tea, citrus | Molecular docking simulation In vivo mouse model of AD In vivo rodent model of PD | ↓MAO, ↓PKC-ε ↓oxidative stress by ERK1/2 phosphorylation, p38MAPK dephosphorylation, ↓TNF-α, ↓IL-6, ↓GFAP, ↓MDA, ↑glutathione peroxidase, ↑AMPK activity ↓apoptosis, ↓GSK3β, ↓tau phosphorylation, ↓ROS, ↓Aβ aggregation ↓ BACE1, ↑NF-κB, ↓ROS, improved 6-OHDA-induced tremors | [99] [116] [48] [40] [57] |
Resveratrol/stilbenoid | Vitis vinifera | In vivo rat model of PD In vivo rodent model of PD | ↓COX2, ↓TNF-α, ↓NF-κB, ↓β-amyloid plaques ↓TNF-α, ↓IL-6, ↑BDNF, ↑IL-10, ↓TNF-α, ↓NF-κB ↑ERK1-2/CREB, ↑BDNF, ↑GDNF, ↓NO, ↓iNOS, ↓Aβ in glial cells, ↑AMPL-SIRT-1 | [53] [40] |
Rutin/flavanoid | Abundant in Citrus fruits | In vitro In vitro In vivo rodent model of AD | ↓pro-inflammatory cytokines, ↓ROS Protected neurons against oxidative injury ↑SOD, ↑CAT, ↑GPx, ↓iNOS ↑MAPK, ↑apoptosis, ↑JNK, ↑p38 MAPK ↓ IL-1, ↓IL-6, ↑BDNP expression | [72] [92] [117] [92] |
Silibinin/flavanoid | Silybinisus laborinum | In vivo rat model of AD In vivo rat model of PD In vivo rat model of stroke | ↓AChE, ↓ROS ↓Aβ aggregation, ↓hypoxic/ischemic injury Protected neurons from H2O2-mediated oxidative stress ↓LC3-II, ↓Beclin-1 levels | [118] [57] [119] |
Sulforaphane/isothiocynate | Cruciferous vegetables | In vitro cell model of AD In vivo mouse model of AD | ↓IL-1β, ↓Aβ1-42-stimulated THP-1 macrophages Dephosphorylated STAT-1, ↑Nrf2 ↑neurogenesis, ↓aluminium load, ↓Aβ deposition ↑p75NTR, ↓Aβ burden | [74] [120] [93] |
Withanamides A and C/amido compounds | Withania somnifera | In vivo rat model of AD | ↓Aβ fibril formation | [44] |
Withanolide A/amido compound | Withania somnifera | In vivo rat model of AD | ↑axonal/dendritic regeneration exhibited neurotrophic activity | [89] |
Withanone | Withania somnifera | In vivo rat model of AD | Protect neurons and glial cells | [121] |
Wogonin/flavanoid | Suctellaria baicalensis | In vivo rat model of stroke | ↓synthesis of thrombin, ↓factor-Xa ↓APTT, ↓PT | [108] |
α-cyperone | Cyperus rotundus | In vivo rodent model of stroke | ↓platelet aggregation | [105] |
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Sharifi-Rad, M.; Lankatillake, C.; Dias, D.A.; Docea, A.O.; Mahomoodally, M.F.; Lobine, D.; Chazot, P.L.; Kurt, B.; Boyunegmez Tumer, T.; Catarina Moreira, A.; et al. Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics. J. Clin. Med. 2020, 9, 1061. https://doi.org/10.3390/jcm9041061
Sharifi-Rad M, Lankatillake C, Dias DA, Docea AO, Mahomoodally MF, Lobine D, Chazot PL, Kurt B, Boyunegmez Tumer T, Catarina Moreira A, et al. Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics. Journal of Clinical Medicine. 2020; 9(4):1061. https://doi.org/10.3390/jcm9041061
Chicago/Turabian StyleSharifi-Rad, Mehdi, Chintha Lankatillake, Daniel A. Dias, Anca Oana Docea, Mohamad Fawzi Mahomoodally, Devina Lobine, Paul L. Chazot, Begum Kurt, Tugba Boyunegmez Tumer, Ana Catarina Moreira, and et al. 2020. "Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics" Journal of Clinical Medicine 9, no. 4: 1061. https://doi.org/10.3390/jcm9041061
APA StyleSharifi-Rad, M., Lankatillake, C., Dias, D. A., Docea, A. O., Mahomoodally, M. F., Lobine, D., Chazot, P. L., Kurt, B., Boyunegmez Tumer, T., Catarina Moreira, A., Sharopov, F., Martorell, M., Martins, N., Cho, W. C., Calina, D., & Sharifi-Rad, J. (2020). Impact of Natural Compounds on Neurodegenerative Disorders: From Preclinical to Pharmacotherapeutics. Journal of Clinical Medicine, 9(4), 1061. https://doi.org/10.3390/jcm9041061