Table 1.

Effect of natural products for PD.

Origin of Extraction	Mechanism	Cell or Animal Model	Inducer	Mode of Action and Target Signal	Site of Action (Figure 1)	Ref.
Duzhong Fang	Inflammation	C57bl/6 mice	MPTP	↓ locomotor dysfunction, inflammation, Iba1, microglia reactivity state ↑ striatal dopamine content, dopaminergic neurons, TH	3	[128]
KOK	Inflammation	C57BL/6 mice	MPTP ML385	↓ neurological dysfunction and motor impairments, the loss of dopaminergic neurons and fibers, Iba1, the upregulation of inflammatory mediators (IL-6, TNF-α, COX-2, and iNOS), neurotoxicity (microglial activation and inflammatory response ↓), BBB disruption markers (PECAM-1 and GFAP), neurotoxicity and inflammation (phosphorylated forms of ERK, JNK, and p38 & IκB and NF-κB ↓), ROS, MAPKs and NF-κB signaling pathways ↑ Nrf2 signaling (decreases the expression levels of Keap1 (a repressor protein that binds to Nrf2), and increases the expression levels of Nrf2 transcription factor, Nrf2 targeting genes HO-1 and NQO-1)	3	[130]
DBYW	Mitochondrial dysfunction	Rat PC-12 cells	pDJ-1 transfection MPP+	↓ DJ-1, mitochondrial dysfunction ↑ mitochondrial mass, total ATP content, the Akt phosphorylation	2	[132]
BvPLA2	Inflammation	Human A53T α-Syn Transgenic mice	A53T Transgenes	↓ motor dysfunction, α-Syn, the activation and numbers of microglia, and the ratio of M1/M2	3	[135]
Hesperetin	Inflammation	Wistar rats	6-OHDA	↓ astrogliosis (GFAP ↓), apoptosis (nigral DNA fragmentation ↓), the loss of SNC dopaminergic neurons ↑ striatal catalase activity and GSH content, Bcl2	3	[136]
Paeonol	Inflammation	C57BL/6 mice	MPTP	↓ motor dysfunction, oxidative stress (the activity levels of SOD, CAT, and GSH ↑), neuroinflammation(the number of Iba1-positive and IL-1β-positive cells ↓), ↑ TH-positive neurons, BDNF, dopaminergic neurons protection	3	[138]
Gastrodin	Mitochondrial dysfunction	Drosophila melanogaster	PINK1 gene mutant	↓ the loss of dopaminergic neurons, the onset of Parkinson-like phenotypes ↑ lifespan, climbing ability, resistance to oxidative stress, enzyme activities of superoxide dismutase (SOD) and catalase (CAT), the expression of anti-oxidative genes	2	[140]
Trehalose	Lysosomal Disorders	Human A53T α-Syn Transgenic mice	A53T Transgenes	↓ α-Synuclein-Induced Behavioral Impairment, α-Synuclein Accumulation ↑ DA Neuronal Survival, protection against the reduction of TH protein expression, autophagosome formation, LC3-II levels	1	[143]
BSJDF	Lysosomal Disorders	Pheochromocytoma12 (PC12)	MPP+ (MPTP)	improved cell survival in the PC12 cell PD model activated the autophagic process in PC12 cells. increased expression of Atg12 and LC3 proteins and upregulated Atg12 mRNA.	1	[146]
NRD	inflammation	Wistar rats	Rotenone	↑ level of superoxide dismutase, catalase, and glutathione ↓ level of malondialdehyde inhibited the release of proinflammatory cytokines and inflammatory mediators prevented ROT-induced glial cell activation and the loss of dopaminergic neurons and nerve fibers attenuated rotenone-induced dopaminergic neurodegeneration.	3	[148]
Vanillic acid	Mitochondrial dysfunction	Sprague Dawley rats	Rotenone	↓ Weight gain, Catalepsy, Rearing TBARS level (at 25 mg/kg and 50 mg/kg) SAG(superoxide anion generation) ↑ behaviour, CAT	2	[149]
Vanillin	Inflammation	Male Wistar rats	6-OHDA	↓ apomorphine-induced rotations, free radical release, expression of pro-inflammatory cytokines, lipid peroxidation ↑ striatal dopamine content, glutathione and superoxide dismutase enzyme protection of dopaminergic neurons	3	[151]