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. 2020 Jul 1;11(2):224–232. doi: 10.34172/apb.2021.026

Effects of Medicinal Plants and Flavonoids on Parkinson’s Disease: A Review on Basic and Clinical Evidences

Mohammad Reza Khazdair 1, Majid Kianmehr 2, Akbar Anaeigoudari 3,*
PMCID: PMC8046395  PMID: 33880344

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder which is characterized by typical symptoms including gradual progressive muscle rigidity, tremor and loss of motor skills. Although there is no definitive cure for PD, the extract of some medicinal plants and their ingredients have been suggested to relieve its symptoms and to prevent disability in patients. This review is focused on therapeutic effects of some medicinal plants and their ingredients on PD. The findings presented in this review were collected from experimental and clinical studies in databases including PubMed, Web of Science and Google Scholar until the end of May 2019. The keywords "neurotoxicity " or "Parkinson’s disease" or "neuroprotective" and "Medicinal plants" and "Flavonoids" were searched. Based on the results of animal and clinical studies, the extract of medicinal plants and their components which are discussed in this review have neuro-protective effects against PD. These protective properties mainly are mediated through inhibition of dopamine metabolizing enzymes, reduction oxidant markers, increase of antioxidant agents and suppression of neuro-inflammation.

Keywords: Parkinson's disease, Neurotoxicity, Medicinal plants, Flavonoids

Introduction

Parkinson’s disease (PD) is considered as the most common neuronal destructive disease after Alzheimer’s disease (AD).1 This neurodegenerative disorder results from progressive damage in dopamine secreting cells in substantia nigra.2 Oxidative stress and neuro-inflammation have been recognized as key causes in dopaminergic neurons death in varous forms of PD.3 Researchers have been suggested that overload of reactive oxygen species (ROS) followed by brain ischemia can cause neurotoxicity resulting in PD.4 In addition, the contribution of nuclear factor κB (NF-κB), an effective key factor in expression of pro-inflammatory cytokines, to neuronal death in PD has been understood.5,6 The harmful impact of inflammatory mediators including tumor necrosis factors-α, interlukin (IL)-1β and IL-6, oxygen free radicals and inducible nitric oxide synthase on dopaminergic cells in substantia nigra pars compacta has been also ducumented.7,8 The drugs used for the cure of PD such as levodopa (L-dopa) and monoamine oxidase B (MAOB) inhibitors and dopamine agonists mdulate the brain dopamine content or trigger intracellular signalings through activating the dopamine receptors.9 Anticholinergic drugs have been also suggested to have anti-parkisonian effects.10 These medications have benefucial effects on rgidity and tremor in PD patients.11 In addition, antioxidant and anti-inflammatory agents have been shown to play a vital role in survival of neurons and alleviation of PD syptomes.12,13 Recently, the strong neuro-protective effect of medicinal plants extracts and phytochemicals in reduction of PD signs due to anti-oxidant and anti-inflammatory properties has been heighlited in various studies.14-16 Phytochemicals such as thymoquinone (TQ), crocin, curcumin and polyphenols have been shown to have cosidarable protective effects on nervous system via moulation oxidative stress and inflammatory responses.17-20 Therefore, the present review was aimed to investigate the therapeutic effects of medicinal plants and ingredients on PD.

Methods

The data narrated in our review were assembled from databases PubMed, Web of Science and Google Scholar until the end of May 2019. Data consist of animal and clinical researches. Letter to the editors and non-English language articles were not considered.

Mucuna pruriens

Mucuna pruriens from the Fabaceae family has been used in Indian traditional medicine for curing diseases such as PD (see Figure 1).21 One of the principal constitutes of this plant is L-dopa.22 The administration of food endocarp of M. pruriens seeds (5 g/kg) combined with carbidopa (50 mg/kg) had better effect than L-dopa in the test of free contralateral rotation induced by 6-hydroxydopamine (6-OHDA) in mice.23 M. pruriens seeds extract (400 mg/kg) also applied a significant anti-Parkinson effect in rats.24 Treatment with M. pruriens powder (2.5 or 5 g/kg/d) remarkably elevated the endogenous level of L-dopa, dopamine, norepinephrine and serotonin in the substantia nigra in 6-OHDA-induced PD rat model.25

Figure 1.

Figure 1

Mucuna pruriens.

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The HP-200 is a commercial preparation derived from M. pruriens in Ayurveda which has been proponed to have anti-Parkinson effects. The impact of M. pruriens endocarp in form of HP-200 (2.5, 5 or 10 g/kg/d) on the content of monoaminergic neurotransmitters in the different areas of the rats’ brain such as substantia nigra, striatum, cortex and hippocampus was pursued. Based on the results, this form of M. pruriens noticeably elevated the dopamine concentration in brain cortex of rats. Data also showed that this drug did not affect the concentration of L-dopa, dopamine, serotonin and norepinephrine in the nigrostriatal pathway of rats. These findings emphasizes that the anti-Parkinson properties of M. pruriens endocarp may be mediated via phytochemicals other than L-dopa or it likely can amplify the L-dopa effects.26

The clinical and pharmacokinetics effect of L-dopa followed by two doses of M. pruriens seeds powder (15 and 30 g) was assessed and compared with single doses of standard L-dopa/carbidopa (LD/CD) (200/50 mg) in PD patients. The results revealed that 30 g of M. pruriens seeds powder formulation possesses a marked quantity of L-dopa. This property was accompanied with the decreased duration without change of dyskinesia intensity in L-dopa response with respect to standard dose of this drug. These results suggest that this important and natural resource of L-dopa can possess helpful effects on L-dopa preparation in long lasting management of PD patients.27 Oral administration of M. pruriens powdered seeds (15 to 40 g) showed symptomatic control with the 4.5 to 5.5% of L-dopa in 33 patients with PD in a clinical trial.28 In the case report, carbidopa significantly led to the betterment of motor activities in a 48-year-old Parkinson woman when it was added to M. pruriens. This finding confirms that usage of a dopa-decarboxylase inhibitor to M. pruriens can be helpful for management of PD patients who are not interested to begin L-dopa.29 The protective effects of M. pruriens on PD have been presented in Table 1.

Table 1. The protective effect of Mucuna pruriens on PD .

Doses used Model of study Effects Ref.
5 g/kg + carbidopa Mice Improvement in the test of free contralateral rotation induced by 6‐OHDA compared with L-dopa 23
400 mg/kg, Rat Significant anti-Parkinson effect 24
2.5 or 5 g/kg/d Rat Restoration of endogenous neurotransmitters such as, L-dopa, dopamine, norepinephrine and serotonin content in the substantia nigra 25
2.5, 5 or 10 g/kg/d of Endocarp form of HP-200 Rat Elevation of the dopamine concentration in brain cortex. 26
30 g Human Induction of marked quantity of L-dopa accompanied with the decreased duration without change of dyskinesia intensity in L-dopa response with respect to standard dose of this drug 27
15 to 40 g Human Symptomatic control with the 4.5% to 5.5% of L-dopa 28
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Vicia faba L.

Vicia faba which is known as broad beans, horse beans, or field beans is used as food for many years in the Mediterranean area, India, Pakistan, and China (Figure 2). The seeds of this rich natural source of L-dopa are full of proteins, carbohydrates, fiber, and vitamins.30 In a report, the usage of V. faba in remedy of PD patients resulted in ameliorating motor activity. This effect was comparable with treatment by L-dopa (125 mg) plus carbidopa (12 5 mg). It was indicated that the severity of dyskinesia in V. faba-treated three patients was similar to those of treated by L-dopa. In addition, plasma content of L-dopa significantly was high after V. faba ingestion in PD patients.31 In another study, administration of V. faba (250 g cooked) after 12 hours off medication in healthy volunteers (n=5) and PD patients (n=6) improved the clinical signs and enhanced the plasma content of L-dopa.32 Single dose of V. faba mixture (200 g) plus carbidopa in six PD patients showed the increased duration of motor response to V. faba compared with L-dopa medication. The prolonged motor response to V. faba corresponded to a much higher plasma concentration of L-dopa.33 These scientific documents exhibit that the consumption of V. faba can lead to a considerable enhancement in plasma concentration of L-dopa along with improvement in motor proficiency in PD patients. The protective effects of V. faba on PD were summarized in Table 2.

Figure 2.

Figure 2

Vicia faba L.

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Table 2. The protective effects of V. faba on PD .

Doses used Model of study Effects Ref.
250 g cooked Human Improvement of the clinical signs in PD patients and enhancement of plasma level of L-dopa 32
200 g + carbidopa Increase in duration of motor response along with enhancement in plasma concentration of L-dopa 333
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Nigella sativa L.

Nigella sativa is one of plant species of Ranunculaceae family which is flourished in the most part of world (Figure 3). The seeds ofthis medicinal plant are added as a food additive and spice to Persian foods including bread, pickle and salads.34 Ethanolic extracts of N. sativa (200 and 400 mg/kg) remarkably attenuated catalepsy in rats group extract compared to those of treated by chlorpromazine (CPZ) (3 mg/kg i.p.). N. sativa extracts also significantly decremented the amount of lipid peroxidation and level of nitrite and augmented glutathione vis-à-vis CPZ-treated group.35

Figure 3.

Figure 3

Nigella sativa L.

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The protective effects of N. sativa and its effective ingredient, TQ, on central nervous system (CNS) disorders such as neurotoxicity, epilepsy, PD and AD have been reviewed.36,37 N. sativa and TQ have been also documented to possess the anti-inflammatory, anti-oxidant, anti-cancer, anti-genotoxic and hepato-protective effects.38-40 It has been also reported that N. sativa oil can protect nervous system against Aβ-caused neurotoxicity through antioxidant effect in primary cerebellar neurons in rats41 as well as its effect on learning and memory.42 Oral administration of N. sativa hydroalcoholic seeds extract (100 and 200 mg/kg) has been reported to improve perphenazine-induced muscle rigidity score in mice, while in animals treated with 50 mg/kg of this plant extract had no any significant effect on this parameter compared to control group.43

Administration of N. sativa capsules (500 mg) twice daily for 9 weeks in 40 healthy volunteers increased attention, cognition and memory with respect to the placebo (500 mg) capsules-treated group.44 Similarly, in the other clinical study the effects of N. sativa capsules (500 mg) on healthy adolescent 14 - 17 years old (n=48) once daily for one month were evaluated. All healthy adolescent were managed for mood, cognition and anxiety with the relative tests in the start and the end of the study. N. sativa capsules (500 mg) decreased anxiety, stabilized mood and modulated cognition at the end of study.45 Therapeutic effect of TQ on behavioral, cellular changes and oxidative stress biomarkers in 6-OHDA-induced Parkinson’s rat model was assessed. Pretreatment with TQ (5 and 10 mg/kg) reduced the level of malondialdehyde (MDA) and prevented the loss of substantia nigra pars compact neurons.46 The neuro-protective effects of TQ against 1-methyl-4-phenylpyridinium (MPP+) and rotenone caused-toxicity in cell culture of dopaminergic cells of mouse mesencephalic were also investigated.Treatment withTQ (0.1 and 1 μM) saved about 25% of dopaminergic cultures (THir neurons) against MPP+-induced cell death. Furthermore, TQ (0.1, 1 and 10 μM) in a dose-dependent manner protected the THir neurons respectively 65%, 74% and 79% against rotenone-induced toxicity.47 The results of other study suggested that TQ had neuro-protective potential and could exert as a promising therapeutic agent to reduce the risk of developing of AD and other neurodegenerative disorders of the CNS such as PD.48

Carvacrol (CARis a monoterpenic phenol which is found in many aromatic plants such as N. sativa. Anti-inflammatory and antioxidant effects of carvacrol have been showed previously.49,50

In a study, CAR (40 mg/kg) induced a considerable neuro-protective effect against the unilateral 6-OHDA-caused Parkinson model in male mice. This protective effect was associated with down-regulation of caspase -3.51 Intrapretoneal adminstration of CAR (12.5 or 25 mg/kg) in a reserpine (RES)-triggered rat model of PD could prevent the increase in catalepsy behavior and number of vacuous chewing movements, but could not revert the decreased locomotor activity in open field test. Furthermore, CAR impeded the decrease in tyrosine hydroxylase (TH) immunostaining induced by RES in the substantia nigra pars compact and dorsal striatum.52

Pretreatment with CAR (10 mg/kg/d) also attenuated the neurotoxicity effect of 6-OHDA in hemi-Parkinson rat model. In this study, CAR significantly decreased the levels of MDA and nitrite content and enhanced catalase activity in midbrain. These results indicated that protective effect of CAR probably was mediated through ameliorating oxidative stress.53 Administration of CAR (25, 50 and 100 mg/kg, ip) for 6 weeks in 6-OHDA- lesioned rat model of PD ameliorated memory deficits. The results showed that CAR did not affect the rotation and hyperalgesia in lesioned rats. Based on results, CAR in mentioned doses also could not restore the decreased level of total thiol in the striatum of animals treated with 6-OHD.54 The protective effect of N. sativa and its components on PD were shown in Table 3.

Table 3. The protective effect of N. sativa and its components on neurotoxicity andParkinson's disease .

Plants /component Dose Model of study Effects Ref.
Nigella sativa 200 and 400 mg/kg Rat Attenuation of catalepsy, reduction of the amount of lipid peroxidation and nitrite level, augmentation of glutathione content 35
100 and 200 mg/kg Mice Improvement of perphenazine-induced muscle rigidity score 43
500 mg/kg Human Enhancement of attention, memory and cognition 44
500 mg/kg Human Decrease of anxiety, stabilization of mood and modulation of cognition 45
TQ 5 and 10 mg/kg Rat Reduction of MDA level and prevention of the loss of substantia nigra pars compact neurons 46
0.1 and 1 μM THir neurons Protection of dopaminergic cultures against MPP+ and rotenone-induced cell death. 47
Carvacrol 40 mg/kg mice down-regulation of caspase -3 51
12.5 or 25 mg/kg Rat Prevention of increase in catalepsy behavior and number of vacuous chewing movement and mitigation of HT in RES-triggered rat model of PD in the substantia nigra pars compact and dorsal striatum 52
10 mg/kg/d Rat Attenuation of neurotoxicity, decrement of MDA and nitrit and enhancment of catalase activity in 6- OHDA-caused hemi-Parkinson rat model 53
25, 50 and 100 mg/kg Rat Amelioration of memory deficits 6-OHDA- lesioned rat model of PD 54
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Crocus sativus L.

Crocus sativus or saffron from the Iridaceae family was cultivated in many countries including Iran, Turkey, Afghanistan and Spain (Figure 4).55 C. sativus and its constituents are used to treat cognitive disorders and some neural disorders. This herb is also used as smooth muscle relaxant agents in Iranian traditional medicine.56-58 Saffron and its components have been suggested to have useful effects in neurodegenerative disorders in animal studies.59 The protective effect of C. sativus on dopaminergic cells in the substantia nigra pars compact and retina in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced acute PD was studied. Administration of C. sativus (0.01% w/v) in drinking water saved dopaminergic cells of the substantia nigra pars compact and retina from MPTP-induced injury in mice.59

Figure 4.

Figure 4

Crocus sativus L.

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Formation and accumulation of toxic amyloid structures can result in induction of neurodegenerative disorders including PD and AD. Crocin and safranal, two main components of C. sativus, have been reported to inhibit fibrillation of apo-α-lactalbumin causing neuronal damage under amyloidogenic conditions.60 Treatment with C. sativus (50 mg/kg) has been also shown to prevent the development of PD in lead (Pb)-induced damage in nervous system. This effect was associated with the increase of TH level in various brain areas including substantia nigra compacta, locus coeruleus, dorsal striatum and medial forebrain bundle of mice.61

The oral administration of crocin (30 mg/kg) on MPTP-stimulated Parkinson model in male BALB/c mice after 15 days treatment resulted in the increment of staying time on the wire in the hanging test. Treatment with crocin also improved MPTP-induced cell death in the substantia nigra compacta of mice.62 Intraperitoneal administration of crocin (30 and 60 mg/kg/d) could also diminish the thiobarbituric acid reactive substance and nitrite levels in the hippocampus after 6 weeks in 6-OHDA model of PD in rats.63 Intraperitoneal injection of C. sativus-extracted crocetin (25, 50 and 75 µg/kg) has been also indicate to have neuro-protective effects in Parkinsonism rat model caused by 6-OHDA. In this study, the enhanced level of antioxidant indicators and dopamine content was reported.64 Crocetin also has been shown to rescue substantia nigra compacta against thiobarbituric acid when it was intraperitoneally infused.65 The Results of research studies indicated that crocin derived from C. sativus (10 µM) protects the PC12 cells against MPP+–caused injury and can improve cytotoxicity related to endoplasmic reticulum.66 The protective effects of C. sativus and crocin on neurotoxicity and PD has been condensed in Table 4.

Table 4. The protective effects of C. sativus and crocin on neurotoxicity and Parkinson's disease .

Plants /Component Doses Model of study Effects Ref.
C. sativus 0.01% w/v Mice Protection of dopaminergic cells in the substantia nigra pars compact and retina against MPTP-induced injury 59
50 mg/kg Mice Prevention of the development of PD in Lead Pb -induced damage in nervous system, increase of TH level in various brain areas including substantia nigra compacta, locus coeruleus, dorsal striatum and medial forebrain bundle 61
Crocin 30 mg/kg Mice Increment of staying time on the wire in the hanging test and prevention of cell death in the substantia nigra compacta in MPTP-stimulated Parkinson model 62
30 and 60 mg/kg/d Rat Decrease of thiobarbituric acid reactive substance and nitrite level in the hippocampus after 6 weeks in 6-OHDA model of PD 63
25, 50 and 75µg/kg Rat Enhanced level of antioxidant indicators and dopamine content in Parkinsonism model caused by 6-OHDA 64
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Curcuma longa

Curcuma longa, turmeric, is widely grown and cultivated as spice in the south-east Asian countries (Figure 5).67 This medicinal plant possesses natural polyphenol and non-flavonoid modulating oxidative damage of nervous system68 and other body organs69,70 C. longa has been also realized to have several pharmacological effects including anti-inflammatory and anti-cancer.71 In a study, the aqueousextractof C. longa (560 mg/kg) significantly could inhibit the activity of dopamine metabolizing enzyme, monoamine oxidase A (MAOA), in the brain of mice.72 The C. longa extract (0.001, 0.01, 0.05, 0.1, 0.2 and 0.4 mg/mL) also ameliorated salsolinol-induced toxicity in human neuroblastoma cells (SH-SY5Y cells), reduced mitochondria-derived ROS and down-regulated caspase 3 activity.73 It has been reported that water soluble extract of curcumin (50-200 mg/kg p.o.) increased serotonin and dopamine level in the brain tissues and dose 50 mg/kg of it enhanced the antidepressant-like effect of classical antidepressants drugs in mice.74 Curcumin (5, 10 and 20 mg/kg) increased the content of monoaminergic neurotransmitters including norepinephrine and dopamine in hippocampal tissue. Furthermore, curcumin obviously up-regulated the expression of derived neurotrophic factor (BDNF), TrkB, and phosphatidylinositide 3-kinases (PI3K) in hippocampal tissue.75,76 Administration of curcumin at doses 50, 100 and 200 mg/kg improved cognitive deficits and mitochondrial dysfunction in mice.77 Intraperitoneal injection of curcumin (50 and 100 mg/kg,) improved neurological deficits and increased the number of NeuN-labeled neurons in the ischemia reperfusion in rats.78,79 Immunohistochemistry results showed that curcumin (0.1, 1 and 10 µM) inhibited p-IRE1α, p-PERK and NLRP3 expression in hippocampus CA1 region of rtas.80 Li et al also suggested that curcumin exerts protective effects on rats brain against cerebral ischemia- reperfusion injury through increasing neuron survival, reducing inflammatory cytokine production and activating JAK2/STAT3 signaling pathway.81 It has been documented that curcumin (5 and 10 μM) restored malic impact of OxyHb on livability of primary cortical cells and decreased their apoptosis.82 Wang et al reported that curcumin (10 μm) significantly inhibited 6-OHDA-induced NFκB transcription in the MES23.5 cells and inhibited ROS intracellular accumulation.83 Curcumin has been also reported to improve nitric oxide (NO)-mediated degeneration in PC12 cells.84 Curcumin (500nM) also could inhibit the MAOB activity with both the competitive and noncompetitive inhibition. This effect of curcumin was comparable with the effect of selegiline as a MAOB inhibitor.85 According to these results, curcumin can be considered as a possible cause for inhibiting MAOB and be used in the treatment of PD and other neurological disorders. Oral administration of curcumin (100 mg/kg) ameliorated muscular strength in rotenone-induced motor deficits in rats. Treatment with curcumin also drastically increased the falling time of rats from inverted screen compared to treated group with rotenone. Curcumin also significantly improved stride length of forelimb, hind limb; hind base and paw overlapping in rats. Curcumin pretreatment significantly attenuated the decreasing effect of rotenone on function of dopaminergic system in striatum via increasing the level of dopamine and dihydroxyphenylacetic acid. In addition, the glutathione levels of treated rats with curcumin significantly increased with respect to those of rotenone group.86 The protective effects of C. longa and curcumin on PD were compacted in Table 5.

Figure 5.

Figure 5

Curcuma longa.

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Table 5. The protective effects of C. longa and curcumin on neurotoxicity and PD .

Plants /Component Doses Model of study Effects Ref.
C. longa 560 mg/kg Mice Inhibition of the activity of dopamine metabolizing enzyme, MAOA in the brain 72
0.001-0.4 mg/ml SH-SY5Y cells Amelioration of salsolinol-induced toxicity, reduction of mitochondria-derived ROS and down-regulation of caspase 3 activity 73
Curcumin 50-200 mg/kg Mice Increase of serotonin and dopamine levels in the brain tissues and enhancement of the antidepressant-like effect of classical antidepressants drugs 74
5, 10 and 20 mg/kg Rat Increase of monoaminergic neurotransmitters content and up-regulation of derived neurotrophic factor BDNF , TrkB, and phosphatidylinositide 3-kinases PI3K expression in hippocampal tissue 75,76
50, 100, 200 mg/kg Mice Improvement of cognitive deficits and mitochondrial dysfunction 77
50 and 100 mg/kg Rat Improvement of neurological deficits and increase the number of NeuN-labeled neurons in the ischemia reperfusion 78.79
0.1, 1 and 10 µM Rat Inhibition of p-IRE1α, p-PERK and NLRP3 expression in hippocampus CA1 region 80
5 and 10 μM Cortical neurons Improvement of cell viability and decreased neuronal apoptosis 82
10 μm MES23.5 cells inhibition of 6-OHDA-induced NFκB transcription and ROS intracellular accumulation 83
500nM Rat Inhibition of the MAOB activity with both the competitive and noncompetitive 85
100 mg/kg Rat amelioration of muscular strength, increase of falling time, improvement of stride length of forelimb, hind limb; hind base and paw overlapping in rotenone-induced motor deficits. Attenuation of the decreasing effect of rotenone on glutathione level and function of dopaminergic system in striatum via increasing the level of dopamine and dihydroxyphenylacetic acid. 86
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Conclusion

Our review narrates an overview of therapeutic properties of medicinal plants and their ingredients on PD. The experimental and clinical data emphasize that neuro-protective effect of medicinal plants including M. pruriens, V. faba, N. sativa and C. sativus mainly are mediated via reduction of oxidative stress and neuro-inflammation resulting in the induction of PD. In addition, a part of anti-Parkinson properties of these plants can be attributed to the inhibition of MAOs and to modulate the content of neurotransmitters such as dopamine, norepinephrine and serotonin in the substantia nigra.

Ethical Issues

Not applicable.

Conflict of Interest

The authors declare that there is no conflict of interest regarding the publication of this paper.

References

  • 1.Cardoso BR, Roberts BR, Bush AI, Hare DJ. Selenium, selenoproteins and neurodegenerative diseases. Metallomics. 2015;7(8):1213–28. doi: 10.1039/c5mt00075k. [DOI] [PubMed] [Google Scholar]
  • 2.Maggio R, Riva M, Vaglini F, Fornai F, Molteni R, Armogida M. et al. Nicotine prevents experimental parkinsonism in rodents and induces striatal increase of neurotrophic factors. J Neurochem. 1998;71(6):2439–46. doi: 10.1046/j.1471-4159.1998.71062439.x. [DOI] [PubMed] [Google Scholar]
  • 3.Trist BG, Hare DJ, Double KL. Oxidative stress in the aging substantia nigra and the etiology of Parkinson’s disease. Aging Cell. 2019;18(6):e13031. doi: 10.1111/acel.13031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Siesjö BK, Memezawa H, Smith ML. Neurocytotoxicity: pharmacological implications. Fundam Clin Pharmacol. 1991;5(9):755–67. doi: 10.1111/j.1472-8206.1991.tb00765.x. [DOI] [PubMed] [Google Scholar]
  • 5.Qu M. The neuroprotective effect of steroid receptor coactivator-interacting protein (SIP) in astrocyte model of 1-methyl-4-phenylpyridinium (MPP⁺)-induced Parkinson’s disease. Med Sci Monit. 2019;25:5776–84. doi: 10.12659/msm.912106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140(6):918–34. doi: 10.1016/j.cell.2010.02.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Javed H, Azimullah S, Meeran MFN, Ansari SA, Ojha S. Neuroprotective effects of thymol, a dietary monoterpene against dopaminergic neurodegeneration in rotenone-induced rat model of Parkinson’s disease. Int J Mol Sci. 2019;20(7) doi: 10.3390/ijms20071538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Hirsch EC, Breidert T, Rousselet E, Hunot S, Hartmann A, Michel PP. The role of glial reaction and inflammation in Parkinson’s disease. Ann N Y Acad Sci. 2003;991:214–28. doi: 10.1111/j.1749-6632.2003.tb07478.x. [DOI] [PubMed] [Google Scholar]
  • 9.Sybertz E, Krainc D. Development of targeted therapies for Parkinson’s disease and related synucleinopathies. J Lipid Res. 2014;55(10):1996–2003. doi: 10.1194/jlr.R047381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Kostelnik A, Cegan A, Pohanka M. Anti-Parkinson drug biperiden inhibits enzyme acetylcholinesterase. Biomed Res Int. 2017;2017:2532764. doi: 10.1155/2017/2532764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Yuan H, Zhang ZW, Liang LW, Shen Q, Wang XD, Ren SM. et al. Treatment strategies for Parkinson’s disease. Neurosci Bull. 2010;26(1):66–76. doi: 10.1007/s12264-010-0302-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Giri B, Belanger K, Seamon M, Bradley E, Purohit S, Chong R. et al. Niacin ameliorates neuro-inflammation in Parkinson’s disease via GPR109A. Int J Mol Sci. 2019;20(18):4559. doi: 10.3390/ijms20184559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Schirinzi T, Martella G, Imbriani P, Di Lazzaro G, Franco D, Colona VL. et al. Dietary vitamin E as a protective factor for Parkinson’s disease: clinical and experimental evidence. Front Neurol. 2019;10:148. doi: 10.3389/fneur.2019.00148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Javed H, Nagoor Meeran MF, Azimullah S, Adem A, Sadek B, Ojha SK. Plant extracts and phytochemicals targeting α-synuclein aggregation in Parkinson’s disease models. Front Pharmacol. 2018;9:1555. doi: 10.3389/fphar.2018.01555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Amro MS, Teoh SL, Norzana AG, Srijit D. The potential role of herbal products in the treatment of Parkinson’s disease. Clin Ter. 2018;169(1):e23–e33. doi: 10.7417/t.2018.2050. [DOI] [PubMed] [Google Scholar]
  • 16.Morgan LA, Grundmann O. Preclinical and potential applications of common western herbal supplements as complementary treatment in Parkinson’s disease. J Diet Suppl. 2017;14(4):453–66. doi: 10.1080/19390211.2016.1263710. [DOI] [PubMed] [Google Scholar]
  • 17.Dos Santos-Neto LL, de Vilhena Toledo MA, Medeiros-Souza P, de Souza GA. The use of herbal medicine in Alzheimer’s disease-a systematic review. Evid Based Complement Alternat Med. 2006;3(4):441–5. doi: 10.1093/ecam/nel071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Suk K. Suk KRegulation of neuroinflammation by herbal medicine and its implications for neurodegenerative diseasesA focus on traditional medicines and flavonoids. Neurosignals. 2005;14(1-2):23–33. doi: 10.1159/000085383. [DOI] [PubMed] [Google Scholar]
  • 19.Khazdair MR, Anaeigoudari A, Hashemzehi M, Mohebbati R. Neuroprotective potency of some spice herbs, a literature review. J Tradit Complement Med. 2019;9(2):98–105. doi: 10.1016/j.jtcme.2018.01.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Baghcheghi Y, Hosseini M, Beheshti F, Salmani H, Anaeigoudari A. Thymoquinone reverses learning and memory impairments and brain tissue oxidative damage in hypothyroid juvenile rats. Arq Neuropsiquiatr. 2018;76(1):32–40. doi: 10.1590/0004-282x20170182. [DOI] [PubMed] [Google Scholar]
  • 21.Lampariello LR, Cortelazzo A, Guerranti R, Sticozzi C, Valacchi G. The magic velvet bean of Mucuna pruriens. J Tradit Complement Med. 2012;2(4):331–9. doi: 10.1016/s2225-4110(16)30119-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Prakash D, Niranjan A, Tewari SK. Some nutritional properties of the seeds of three Mucuna species. Int J Food Sci Nutr. 2001;52(1):79–82. doi: 10.1080/09637480020027264. [DOI] [PubMed] [Google Scholar]
  • 23.Singh SK, Yadav D, Lal RK, Gupta MM, Dhawan SS. Inducing mutations through γ-irradiation in seeds of Mucuna pruriens for developing high L-DOPA-yielding genotypes. Int J Radiat Biol. 2017;93(4):426–32. doi: 10.1080/09553002.2016.1254832. [DOI] [PubMed] [Google Scholar]
  • 24.Lieu CA, Kunselman AR, Manyam BV, Venkiteswaran K, Subramanian T. A water extract of Mucuna pruriens provides long-term amelioration of parkinsonism with reduced risk for dyskinesias. Parkinsonism Relat Disord. 2010;16(7):458–65. doi: 10.1016/j.parkreldis.2010.04.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Manyam BV, Dhanasekaran M, Hare TA. Neuroprotective effects of the antiparkinson drug Mucuna pruriens. Phytother Res. 2004;18(9):706–12. doi: 10.1002/ptr.1514. [DOI] [PubMed] [Google Scholar]
  • 26.Manyam BV, Dhanasekaran M, Hare TA. Effect of antiparkinson drug HP-200 (Mucuna pruriens) on the central monoaminergic neurotransmitters. Phytother Res. 2004;18(2):97–101. doi: 10.1002/ptr.1407. [DOI] [PubMed] [Google Scholar]
  • 27.Katzenschlager R, Evans A, Manson A, Patsalos PN, Ratnaraj N, Watt H. et al. Mucuna pruriens in Parkinson’s disease: a double blind clinical and pharmacological study. J Neurol Neurosurg Psychiatry. 2004;75(12):1672–7. doi: 10.1136/jnnp.2003.028761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Vaidya AB, Rajagopalan TG, Mankodi NA, Antarkar DS, Tathed PS, Purohit AV. et al. Treatment of Parkinson’s disease with the cowhage plant-Mucuna pruriens Bak. Neurol India. 1978;26(4):171–6. [PubMed] [Google Scholar]
  • 29.Radder DLM, Tiel Groenestege AT, Boers I, Muilwijk EW, Bloem BR. Mucuna pruriens combined with carbidopa in Parkinson’s disease: a case report. J Parkinsons Dis. 2019;9(2):437–9. doi: 10.3233/jpd-181500. [DOI] [PubMed] [Google Scholar]
  • 30.Macarulla MT, Medina C, De Diego MA, Chávarri M, Zulet MA, Martínez JA. et al. Effects of the whole seed and a protein isolate of faba bean (Vicia faba) on the cholesterol metabolism of hypercholesterolaemic rats. Br J Nutr. 2001;85(5):607–14. doi: 10.1079/bjn2000330. [DOI] [PubMed] [Google Scholar]
  • 31.Rabey JM, Vered Y, Shabtai H, Graff E, Korczyn AD. Improvement of parkinsonian features correlate with high plasma levodopa values after broad bean (Vicia faba) consumption. J Neurol Neurosurg Psychiatry. 1992;55(8):725–7. doi: 10.1136/jnnp.55.8.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Rabey JM, Vered Y, Shabtai H, Graff E, Harsat A, Korczyn AD. Broad bean (Vicia faba) consumption and Parkinson’s disease. Adv Neurol. 1993;60:681–4. [PubMed] [Google Scholar]
  • 33.Kempster PA, Bogetic Z, Secombei JW, Martin HD, Balazs ND, Wahlqvist ML. Motor effects of broad beans (Vicia faba) in Parkinson’s disease: single dose studies. Asia Pac J Clin Nutr. 1993;2(2):85–9. [PubMed] [Google Scholar]
  • 34.Hajhashemi V, Ghannadi A, Jafarabadi H. Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug. Phytother Res. 2004;18(3):195–9. doi: 10.1002/ptr.1390. [DOI] [PubMed] [Google Scholar]
  • 35.Sandhu KS, Rana AC. Evaluation of anti Parkinson’s activity of Nigella sativa (kalonji) seeds in chlorpromazine induced experimental animal model. Int J Pharm Pharm Sci. 2013;5(3):884–8. [Google Scholar]
  • 36.Khazdair MR. The protective effects of Nigella sativa and its constituents on induced neurotoxicity. J Toxicol. 2015;2015:841823. doi: 10.1155/2015/841823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Beheshti F, Khazaei M, Hosseini M. Neuropharmacological effects of Nigella sativa. Avicenna J Phytomed. 2016;6(1):104–16. [PMC free article] [PubMed] [Google Scholar]
  • 38.Samarghandian S, Farkhondeh T, Samini F. A review on possible therapeutic effect of Nigella sativa and thymoquinone in neurodegenerative diseases. CNS Neurol Disord Drug Targets. 2018;17(6):412–20. doi: 10.2174/1871527317666180702101455. [DOI] [PubMed] [Google Scholar]
  • 39.Su X, Ren Y, Yu N, Kong L, Kang J. Thymoquinone inhibits inflammation, neoangiogenesis and vascular remodeling in asthma mice. Int Immunopharmacol. 2016;38:70–80. doi: 10.1016/j.intimp.2016.05.018. [DOI] [PubMed] [Google Scholar]
  • 40.Mohebbatia R, Khazdair MR, Karimi S, Abbasnezhad A. Hepatoprotective effects of combination hydroalcoholic extracts of Nigella sativa and Curcuma longa on adriamycin-induced oxidative stress in rat. J Rep Pharm Sci. 2017;6(2):93–102. [Google Scholar]
  • 41.Ismail N, Ismail M, Latiff LA, Mazlan M, Mariod AA. Black cumin seed (Nigella sativa Linn) oil and its fractions protect against beta amyloid peptide-induced toxicity in primary cerebellar granule neurons. J Food Lipids. 2008;15(4):519–33. doi: 10.1111/j.1745-4522.2008.00137.x. [DOI] [Google Scholar]
  • 42.Sahak MK, Kabir N, Abbas G, Draman S, Hashim NH, Hasan Adli DS. The role of Nigella sativa and its active constituents in learning and memory. Evid Based Complement Alternat Med. 2016;2016:6075679. doi: 10.1155/2016/6075679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Hadipour Jahromy M, Jalili M, Jamshidi Mohajer A, Kamali Poor F, Mansoori Dara S. Effects of Nigella sativa seed extract on perphenzine-induced muscle rigidity in male mice. World J Neurosci. 2014;4(4):313–8. doi: 10.4236/wjns.2014.44035. [DOI] [Google Scholar]
  • 44.Bin Sayeed MS, Asaduzzaman M, Morshed H, Hossain MM, Kadir MF, Rahman MR. The effect of Nigella sativa Linn seed on memory, attention and cognition in healthy human volunteers. J Ethnopharmacol. 2013;148(3):780–6. doi: 10.1016/j.jep.2013.05.004. [DOI] [PubMed] [Google Scholar]
  • 45.Bin Sayeed MS, Shams T, Fahim Hossain S, Rahman MR, Mostofa A, Fahim Kadir M. et al. Nigella sativa L seeds modulate mood, anxiety and cognition in healthy adolescent males. J Ethnopharmacol. 2014;152(1):156–62. doi: 10.1016/j.jep.2013.12.050. [DOI] [PubMed] [Google Scholar]
  • 46.Sedaghat R, Roghani M, Khalili M. Neuroprotective effect of thymoquinone, the nigella sativa bioactive compound, in 6-hydroxydopamine-induced hemi-parkinsonian rat model. Iran J Pharm Res. 2014;13(1):227–34. [PMC free article] [PubMed] [Google Scholar]
  • 47.Radad K, Moldzio R, Taha M, Rausch WD. Thymoquinone protects dopaminergic neurons against MPP+ and rotenone. Phytother Res. 2009;23(5):696–700. doi: 10.1002/ptr.2708. [DOI] [PubMed] [Google Scholar]
  • 48.Alhibshi AH, Odawara A, Suzuki I. Neuroprotective efficacy of thymoquinone against amyloid beta-induced neurotoxicity in human induced pluripotent stem cell-derived cholinergic neurons. Biochem Biophys Rep. 2019;17:122–6. doi: 10.1016/j.bbrep.2018.12.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Khazdair MR, Ghorani V, Alavinezhad A, Boskabady MH. Pharmacological effects of Zataria multiflora Boiss L and its constituents focus on their anti-inflammatory, antioxidant, and immunomodulatory effects. Fundam Clin Pharmacol. 2018;32(1):26–50. doi: 10.1111/fcp.12331. [DOI] [PubMed] [Google Scholar]
  • 50.Khazdair MR, Alavinezhad A, Boskabady MH. Carvacrol ameliorates haematological parameters, oxidant/antioxidant biomarkers and pulmonary function tests in patients with sulphur mustard-induced lung disorders: a randomized double-blind clinical trial. J Clin Pharm Ther. 2018;43(5):664–74. doi: 10.1111/jcpt.12684. [DOI] [PubMed] [Google Scholar]
  • 51.Dati LM, Ulrich H, Real CC, Feng ZP, Sun HS, Britto LR. Carvacrol promotes neuroprotection in the mouse hemiparkinsonian model. Neuroscience. 2017;356:176–81. doi: 10.1016/j.neuroscience.2017.05.013. [DOI] [PubMed] [Google Scholar]
  • 52.Lins L, Souza MF, Bispo JMM, Gois AM, Melo TCS, Andrade RAS. et al. Carvacrol prevents impairments in motor and neurochemical parameters in a model of progressive parkinsonism induced by reserpine. Brain Res Bull. 2018;139:9–15. doi: 10.1016/j.brainresbull.2018.01.017. [DOI] [PubMed] [Google Scholar]
  • 53.Baluchnejadmojarad t, Hassanshahi J, Roghani M, mansouri M, Raoufi S. Protective effect of carvacrol in 6-hydroxydopamine hemi-parkinsonian rat model. J Basic Clin Pathophysiol. 2014;2(2):29–34. [Google Scholar]
  • 54.Haddadi H, Rajaei Z, Alaei H, Shahidani S. Chronic treatment with carvacrol improves passive avoidance memory in a rat model of Parkinson’s disease. Arq Neuropsiquiatr. 2018;76(2):71–7. doi: 10.1590/0004-282x20170193. [DOI] [PubMed] [Google Scholar]
  • 55.Ghaffari S, Roshanravan N. Saffron; an updated review on biological properties with special focus on cardiovascular effects. Biomed Pharmacother. 2019;109:21–7. doi: 10.1016/j.biopha.2018.10.031. [DOI] [PubMed] [Google Scholar]
  • 56.Khazdair MR, Boskabady MH, Hosseini M, Rezaee R, Tsatsakis AM. The effects of Crocus sativus (saffron) and its constituents on nervous system: a review. Avicenna J Phytomed. 2015;5(5):376–91. [PMC free article] [PubMed] [Google Scholar]
  • 57.Hosseinzadeh H, Motamedshariaty V, Hadizadeh F. Antidepressant effect of keamperol, a constituent of saffron (Crocus sativus) petal, in mice and rats. Pharmacologyonline. 2007;2:367–70. [Google Scholar]
  • 58.Mokhtari-Zaer A, Khazdair MR, Boskabady MH. Smooth muscle relaxant activity of Crocus sativus (saffron) and its constituents: possible mechanisms. Avicenna J Phytomed. 2015;5(5):365–75. [PMC free article] [PubMed] [Google Scholar]
  • 59.Purushothuman S, Nandasena C, Peoples CL, El Massri N, Johnstone DM, Mitrofanis J. et al. Saffron pre-treatment offers neuroprotection to Nigral and retinal dopaminergic cells of MPTP-Treated mice. J Parkinsons Dis. 2013;3(1):77–83. doi: 10.3233/jpd-130173. [DOI] [PubMed] [Google Scholar]
  • 60.Ebrahim-Habibi MB, Amininasab M, Ebrahim-Habibi A, Sabbaghian M, Nemat-Gorgani M. Fibrillation of alpha-lactalbumin: effect of crocin and safranal, two natural small molecules from Crocus sativus. Biopolymers. 2010;93(10):854–65. doi: 10.1002/bip.21477. [DOI] [PubMed] [Google Scholar]
  • 61.Tamegart L, Abbaoui A, Makbal R, Zroudi M, Bouizgarne B, Bouyatas MM. et al. Crocus sativus restores dopaminergic and noradrenergic damages induced by lead in Meriones shawi: a possible link with Parkinson’s disease. Acta Histochem. 2019;121(2):171–81. doi: 10.1016/j.acthis.2018.12.003. [DOI] [PubMed] [Google Scholar]
  • 62.Haeri P, Mohammadipour A, Heidari Z, Ebrahimzadeh-Bideskan A. Neuroprotective effect of crocin on substantia nigra in MPTP-induced Parkinson’s disease model of mice. Anat Sci Int. 2019;94(1):119–27. doi: 10.1007/s12565-018-0457-7. [DOI] [PubMed] [Google Scholar]
  • 63.Rajaei Z, Hosseini M, Alaei H. Effects of crocin on brain oxidative damage and aversive memory in a 6-OHDA model of Parkinson’s disease. Arq Neuropsiquiatr. 2016;74(9):723–9. doi: 10.1590/0004-282x20160131. [DOI] [PubMed] [Google Scholar]
  • 64.Ahmad AS, Ansari MA, Ahmad M, Saleem S, Yousuf S, Hoda MN. et al. Neuroprotection by crocetin in a hemi-parkinsonian rat model. Pharmacol Biochem Behav. 2005;81(4):805–13. doi: 10.1016/j.pbb.2005.06.007. [DOI] [PubMed] [Google Scholar]
  • 65.José Bagur M, Alonso Salinas GL, Jiménez-Monreal AM, Chaouqi S, Llorens S, Martínez-Tomé M. et al. Saffron: an old medicinal plant and a potential novel functional food. Molecules. 2017;23(1):30. doi: 10.3390/molecules23010030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Zhang GF, Zhang Y, Zhao G. Crocin protects PC12 cells against MPP(+)-induced injury through inhibition of mitochondrial dysfunction and ER stress. Neurochem Int. 2015;89:101–10. doi: 10.1016/j.neuint.2015.07.011. [DOI] [PubMed] [Google Scholar]
  • 67.Karlowicz-Bodalska K, Han S, Freier J, Smolenski M, Bodalska A. Curcuma longa as medicinal herb in the treatment of diabetic complications. Acta Pol Pharm. 2017;74(2):605–10. [PubMed] [Google Scholar]
  • 68.Mohebbati R, Khazdair MR, Hedayati M. Neuroprotective effects of medicinal plants and their constituents on different induced neurotoxicity methods: a review. J Rep Pharm Sci. 2017;6(1):34–50. [Google Scholar]
  • 69.Mohebbati R, Shafei MN, Soukhtanloo M, Mohammadian Roshan N, Khajavi Rad A, Anaeigoudari A. et al. Adriamycin-induced oxidative stress is prevented by mixed hydro-alcoholic extract of Nigella sativa and Curcuma longa in rat kidney. Avicenna J Phytomed. 2016;6(1):86–94. [PMC free article] [PubMed] [Google Scholar]
  • 70.Mohebbati R, Anaeigoudari A, Khazdair MR. The effects of Curcuma longa and curcumin on reproductive systems. Endocr Regul. 2017;51(4):220–8. doi: 10.1515/enr-2017-0024. [DOI] [PubMed] [Google Scholar]
  • 71.Atlan M, Neman J. Targeted transdermal delivery of curcumin for breast cancer prevention. Int J Environ Res Public Health. 2019;16(24):4949. doi: 10.3390/ijerph16244949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72.Yu ZF, Kong LD, Chen Y. Antidepressant activity of aqueous extracts of Curcuma longa in mice. J Ethnopharmacol. 2002;83(1-2):161–5. doi: 10.1016/s0378-8741(02)00211-8. [DOI] [PubMed] [Google Scholar]
  • 73.Ma XW, Guo RY. Dose-dependent effect of Curcuma longa for the treatment of Parkinson’s disease. Exp Ther Med. 2017;13(5):1799–805. doi: 10.3892/etm.2017.4225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.Kulkarni SK, Akula KK, Deshpande J. Evaluation of antidepressant-like activity of novel water-soluble curcumin formulations and St John’s wort in behavioral paradigms of despair. Pharmacology. 2012;89(1-2):83–90. doi: 10.1159/000335660. [DOI] [PubMed] [Google Scholar]
  • 75.Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS. et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem. 2005;280(7):5892–901. doi: 10.1074/jbc.M404751200. [DOI] [PubMed] [Google Scholar]
  • 76.Yang J, Song S, Li J, Liang T. Neuroprotective effect of curcumin on hippocampal injury in 6-OHDA-induced Parkinson’s disease rat. Pathol Res Pract. 2014;210(6):357–62. doi: 10.1016/j.prp.2014.02.005. [DOI] [PubMed] [Google Scholar]
  • 77.Khatri DK, Juvekar AR. Neuroprotective effect of curcumin as evinced by abrogation of rotenone-induced motor deficits, oxidative and mitochondrial dysfunctions in mouse model of Parkinson’s disease. Pharmacol Biochem Behav. 2016;150-151:39–47. doi: 10.1016/j.pbb.2016.09.002. [DOI] [PubMed] [Google Scholar]
  • 78.Liu L, Zhang W, Wang L, Li Y, Tan B, Lu X. et al. Curcumin prevents cerebral ischemia reperfusion injury via increase of mitochondrial biogenesis. Neurochem Res. 2014;39(7):1322–31. doi: 10.1007/s11064-014-1315-1. [DOI] [PubMed] [Google Scholar]
  • 79.Tu XK, Yang WZ, Chen JP, Chen Y, Ouyang LQ, Xu YC. et al. Curcumin inhibits TLR2/4-NF-κB signaling pathway and attenuates brain damage in permanent focal cerebral ischemia in rats. Inflammation. 2014;37(5):1544–51. doi: 10.1007/s10753-014-9881-6. [DOI] [PubMed] [Google Scholar]
  • 80.Li Y, Li J, Li S, Li Y, Wang X, Liu B. et al. Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK. Toxicol Appl Pharmacol. 2015;286(1):53–63. doi: 10.1016/j.taap.2015.03.010. [DOI] [PubMed] [Google Scholar]
  • 81.Li L, Li H, Li M. Curcumin protects against cerebral ischemia-reperfusion injury by activating JAK2/STAT3 signaling pathway in rats. Int J Clin Exp Med. 2015;8(9):14985–91. [PMC free article] [PubMed] [Google Scholar]
  • 82.Li X, Zhao L, Yue L, Liu H, Yang X, Wang X. et al. Evidence for the protective effects of curcumin against oxyhemoglobin-induced injury in rat cortical neurons. Brain Res Bull. 2016;120:34–40. doi: 10.1016/j.brainresbull.2015.11.006. [DOI] [PubMed] [Google Scholar]
  • 83.Wang J, Du XX, Jiang H, Xie JX. Curcumin attenuates 6-hydroxydopamine-induced cytotoxicity by anti-oxidation and nuclear factor-kappa B modulation in MES235 cells. Biochem Pharmacol. 2009;78(2):178–83. doi: 10.1016/j.bcp.2009.03.031. [DOI] [PubMed] [Google Scholar]
  • 84.Chen J, Tang XQ, Zhi JL, Cui Y, Yu HM, Tang EH. et al. Curcumin protects PC12 cells against 1-methyl-4-phenylpyridinium ion-induced apoptosis by bcl-2-mitochondria-ROS-iNOS pathway. Apoptosis. 2006;11(6):943–53. doi: 10.1007/s10495-006-6715-5. [DOI] [PubMed] [Google Scholar]
  • 85.Khatri DK, Juvekar AR. Kinetics of inhibition of monoamine oxidase using curcumin and ellagic acid. Pharmacogn Mag. 2016;12(Suppl 2):S116–20. doi: 10.4103/0973-1296.182168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.Madiha S, Batool Z, Tabassum S, Liaquat L, Sadir S, Perveen T. et al. Therapeutic effects of Curcuma longa against rotenone-induced gross motor skill deficits in rats. Pak J Zool. 2018;50(4):1245–56. doi: 10.17582/journal.pjz/2018.50.4.1245.1256. [DOI] [Google Scholar]

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