Table 3.

The phytochemicals showed neuroprotective effects in the in vivo models of Parkinson's disease by targeting α-synuclein.

Phytochemicals (Plant name, family)	In vivo animal model	Effects and mechanisms observed	References
Apigenin (Flavone found in fruits and vegetables)	Unilateral stereotaxic intranigral infusion of ROT-induced PD in rats	■ Improves behavioral, biochemical and mitochondrial enzymes ■ Attenuates pro-inflammatory cytokines release and NF-κB expression ■ Inhibits neurotrophic factors and α-syn aggregation ■ Enhances TH and dopamine D2 receptor expression	Anusha et al., 2017
Acteoside (Cistanche deserticola or Cistanche tubulosa, Orobanchaceae)	Rotenone-induced PD in rats	■ Inhibits α-syn, caspase-3 activity and microtubule-associated protein 2 (MAP2) downregulation ■ Binds and inhibits caspase-3 in silico and showed neuroprotection	Yuan et al., 2016
Acacetin (O-methylated flavone from Asteraceae)	Caenorhabditis elegans model system	■ Improves lifespan, survival, stress resistance ■ Enhances antioxidant and stress resistance genes ■ Inhibits α-syn aggregation and age pigment lipofuscin	Asthana et al., 2016
Acetylcorynoline (Corydalis bungeana Turcz, Papaveraceae)	Transgenic C. elegans (OW13) expressing human α-syn, GFP in dopaminergic neurons and 6-OHDA-induced PD	■ Decreases 6-OHDA-induced DA neuron degeneration ■ Prevents α-syn aggregation and recovers lipid content ■ Restores food-sensing behavior in 6-OHDA-treated animals ■ Suppresses apoptosis by decreasing egl-1 expression ■ Increases rpn5 expression that enhances the activity of proteasomes	Fu et al., 2014a
Apocyanin (Picrorhiza kurroa Royle ex Benth, Plantains)	Lipolysaccharide-injection in substantia niagra-induced PD in rats	■ Ameliorates proinflammatory cytokines, improves behavior ■ Inhibits NADPH oxidase, caspase 3, 9 and TUNEL positivity ■ Inhibits α-syn deposition and prevents dopaminergic neurons	Sharma et al., 2016
Acetylcorynoline (Corydalis bungeana, Papaveraceae)	Caenorhabditis elegans strain (BZ555) expresses the green fluorescent protein in dopaminergic neurons, and a transgenic strain (OW13) express h α-syn in muscle cells PD model	■ Appears safe and devoid of adverse effect in animals ■ Decreases dopaminergic degeneration in BZ555 strain ■ Prevents α-syn aggregation and recovers lipid contents ■ Restores food-sensing behavior, and dopamine levels ■ Prolongs life-span in 6-OH-treated N2 strain ■ Decreases egl-1 expression to suppress apoptosis pathways ■ Increases rpn5 expression to enhance proteasomes activity	Fu et al., 2014a
Baicalein (Flavonoid from Scutellaria baicalensis, Lamiaceae)	Intranigral infusion of MPP+ in rat brain	■ Attenuates α-syn aggregation ■ Inhibits inflammasome activation and cathepsin B production ■ Inhibits apoptosis (caspases 9 and 12, and autophagy (LC3-II)	Hung et al., 2016
n-Butylidenephthalide (Angelica sinensis, Apiaceae)	Caenorhabditis elegans express green fluorescent protein in neurons, BZ555 and a transgenic expresses human α-syn (OW13)	■ Attenuates dopaminergic degeneration and prolongs life-span ■ Reduces α-syn accumulation ■ Restores dopamine, lipid content and food-sensing behavior ■ Blocks egl-1 expression that inhibits apoptosis ■ Enhances rpn-6 expression to increase proteasomes activity	Fu et al., 2014b
Curcumin (Curcuma longa, Zingiberaceae)	Interaction of curcumin and α-syn in genetic synucleinopathy of α-syn-GFP mouse line overexpresses α-syn	■ Chronic and acute curcumin treatment improves gait impairments and increases phosphorylated forms of α-syn at cortical presynaptic terminals in α-syn-GFP line ■ Increases phosphorylated α-syn in terminals without affecting α-syn aggregation	Spinelli et al., 2015
Alginate-curcumin nanocomposite	Supplemented with diet to Drosophila melangoster	■ Delays climbing disability in flies ■ Reduces oxidative stress and apoptosis in the brain of PD flies	Siddique et al., 2013b
α-Linolenic acid	Caenorhabditis elegans wild type N2 and transgenic (UA44) exposed to 6-OHDA	■ Improves locomotion, pharyngeal pumping, and lifespan ■ Shows a visibly significant reduction in neuronal degeneration ■ Increases GFP expression within in neurons	Shashikumar et al., 2015
Squamosamide (N-[2-(4-Hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl) acrylamide) (Annona glabra, Annonaceae)	6-OHDA-induced PD in rats	■ Improves motor dysfunction and behavior ■ Enhances dopamine level and TH activity ■ Decreases α-syn expression mediated by the Akt/mTOR pathway ■ Reduces RTP801 expression, a protein in the pathogenesis of PD	Bao et al., 2012
Geraniol (Monoterpene from rose oil, palmarosa oil, and citronella oil)	MPTP-induced PD in C57BL/6 mice	■ Reduces α-syn aggregation in dose dependent manner ■ Improves nigral dopamine, TH and dopamineric terminals in striatum ■ Improves neuromuscular disability and Lewy body aggregation	Rekha et al., 2013
Irisflorentin (Belamcanda chinensis L. DC., Iridaceae)	Transgenic or 6-hydroxydopamine-induced PD in Caenorhabditis elegans	■ Prevents α-syn accumulation ■ Improves dopaminergic neurons, food-sensing, and life-span ■ Promotes rpn-3 expression to enhance the activity of proteasomes ■ Down-regulates egl-1 expression to block apoptosis pathways	Chen et al., 2015a
Lycopene (Red grapes, peanuts)	Rotenone-induced PD in mouse	■ Increases the TH content and decreases α-syn and LC3-B positive neurons	Liu et al., 2013
N-2-(4-hydroxy-phenyl)-ethyl]-2-(2, 5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide) (FLZ, a novel synthetic derivative of squamosamide from a Chinese herb)	Chronic PD mouse model induced by MPTP combined with probenecid (MPTP/p) and subacute PD models	■ Improves motor behavior and dopaminergic neuronal function ■ Elevates dopaminergic neurons, dopamine level, and TH activity ■ Decreases α-syn phosphorylation, nitration, and aggregation ■ Decreases interaction between α-syn and TH, which eventually improved dopaminergic neuronal function ■ Activates Akt/mTOR phosphorylation signaling pathway	Bao et al., 2015
Salidroside (Phenylpropanoid glycoside from Rhodiola rosea L., Crassulaceae)	MPTP/MPP(+) models of Parkinson's disease and 6-OHDA and overexpresssion of WT/A30P-α-syn in SH-SY5Y cells.	■ Protects dopaminergic neurons and regulates apoptotic proteins caspase-3,6 and 9, cyt-c and Smac release and Bcl-2/Bax ■ Reduces α-syn aggregation ■ Protects cells and cell viability mainly through recovering the 20S proteasome activity ■ Decreases pSer129-α-syn and promotes the clearance of α-syn	Wang et al., 2015b, Li et al., 2018
Shatavarin IV (Steroidal glucosides, syn: asparinin B in roots of Asparagus racemosus, Asparagaceae)	Caenorhabditis elegans model of PD	■ Improves antioxidant and stress defense genes ■ Raises dopamine levels, inhibits lipids ■ Inhibits α-syn aggregation involving ubiquitin proteasomal system	Smita et al., 2017
2,3,5,4′-tetrahydroxy stilbene-2-O-β-D-glucoside (Polygonum multiflori, Polygonaceae)	APPV717I transgenic mice expressing α-syn in the hippocampus	■ Prevents α-syn overexpression at an early and late stage in the hippocampus ■ Inhibits production of dimer and tetramer of α-syn protein ■ Reverses the increased expression of α-syn	Zhang et al., 2013
2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (Polygonum multiflori, Polygonaceae)	Memory and movement functions and its mechanisms related to synapses and α-syn in aged mice	■ Inhibits α-syn aggregation and α-syn levels in the hippocampus ■ Improves memory, movement and protects synaptic ultrastructure ■ Enhances synaptophysin, phosphorylated synapsin I and post-synaptic density protein 95 (PSD95) and calcium/calmodulin-dependent protein kinase II (p-CaMKII) expression	Shen et al., 2015
10-O-trans-p-Coumaroylcatalpol (Premna integrifolia syn: Premna serratifolia, Verbenaceae)	Transgenic Caenorhabditis elegans model of PD expressing α-syn	■ Inhibits α-syn aggregation ■ Extends life span, stress resistance and reduces oxidative stress ■ Enhances longevity promoting transcription factors	Shukla et al., 2012
Withanolide A (Steroidal lactone from Withania somnifera L. Dunal, Solanaceae)	Transgenic Drosophila melanogaster model	■ Improves lifespan and delays age-associated physiological changes ■ Inhibits α-syn aggregation and modulation of acetylcholine.	Akhoon et al., 2016