Phytotherapy in treatment of Parkinson’s disease: a review

Figures & data

Figure 1. Factors that contribute to oxidative stress and ultimately neuronal cell death in PD.

Table 1. Plant active ingredients effective on Parkinson’s disease.

Name compound	Used model	Concentration	Effects	Chemical structures	References
Astragaloside IV	Cultures of primary nigral cells (PNCs)	50, 100 and 200 µM	1. Increased the level of TH and nitrite oxide synthase (NOS) immune reactivities 2. Protect dopaminergic neurons degeneration 3. Promoted neurite outgrowth and increased TH and NOS immune reactive of dopaminergic neurons		Chan et al. (2009)
Berberine	1. 6-OHDA induced cytotoxicity in PC12 cells 2. Unilateral 6-OHDA-lesioned rats	5, 10 and 30 µM	1. Depleted tyrosine hydroxylase-immuno positive cells in the substantia nigra 2. Decreased dopamine and norepinephrine levels in striatal regions		Kwon et al. (2010)
Baicalein	6-OHDA induced in vitro and in vivo	0.5, 5 μg/mL	1. Ameliorate SH-SY5Y cell apoptosis 2. Promote neurite outgrowth of PC12 cell 3. Attenuate muscle tremor 4. Increase tyrosine hydroxylase (TH)-positive neurons		Mu et al. (2009)
Caffeic acid phenethyl ester	In vitro (cerebellar granule neurons)	10 µm	1. Modulate the Ca^2+-induced release of cyctochrome c 2. Inhibit caspase-3 activation 3. Blocks cell death		Noelker et al. (2005)
Carnosic acid	Rat induced by 6-OHDA	20 mg/kg	1. Improved the locomotor activity 2. Reduced the apomorphine-caused rotation 3. Reduced lipid peroxidation 4. GSH reduction 5. Increased the protein expression of c-glutamate-cysteine ligase catalytic subunit, superoxide dismutase, and glutathione reductase 6. Reduction of the Bcl-2/Bax ratio 7. Induction of caspase 3 cleavage 8. Induction of poly (ADP ribose) polymerase (PARP) cleavage		Wu et al. (2015)
Curcumin	Rat induced by 6-OHDA	80 mg/kg pretreatment	1. Decreased MDA, 2. Increased glutathione, GPx, glutathione reductase, SOD, catalase, tyrosine hydroxylase and D2 receptor binding in brain tissue		Khuwaja et al. (2011)
Gallic acid	Rat induced by 6-OHDA	50, 100 and 200 mg/kg	1. Increased the passive avoidance memory 2. Increased total thiol in brain tissue 3. Increased GPx 4. Decreased MDA levels in brain tissue		Mansouri et al. (2013)
Ellagic acid	Rat induced by 6-OHDA	50 mg/kg	1. Increased of stride-length 2. Decreased the contralateral rotations 3. Decreased TNF-α and IL-1β levels in brain tissue		Farbood et al. (2015)
Ginsenoside Rg1	(6-OHDA) induced neurotoxicity in human neuroblastoma SK-N-SH cells	0.01 µM	1. Increased survival 2. Rescue occurred on cell viability 3. Restore the up-regulation of Bax and down-regulation of Bcl-2 mRNA and protein expression 4. Attenuate 6-OHDA-induced apoptosis		Gao et al. (2009)
Quercetin	Rat induced by 6- OHDA	50 mg/kg	1. Increased dopamine 2. Decreased protein carbonyl content		Haleagrahara et al. (2013)
Desferrioxamine	Rat induced by 6-OHDA	50 mg/kg	1. Decreased protein carbonyl content 2. Increased dopamine, GSH and SOD levels		Haleagrahara et al. (2013)
Thymoquinone	Rat induced by 6- OHDA	5, 10 mg/kg	1. Improved turning behaviour 2. Decreased MDA levels 3. Increased activity of superoxide dismutase 4. Prevented loss of SNC (substantia nigra pars compacta) neurons		Sedaghat et al. (2014)
Tripchlorolide	(MPTP)-lesioned C57BL/6 mice	1 µg/kg	1. Increased level of dopamine in the substantia nigra and striatum		Hong et al. (2007)
Sulforaphane	mice induced by 6-OHDA	5 mg/kg	1. Improved motor coordination 2. Blocking DNA fragmentation and caspase-3 activation 3. Increased glutathione levels		Morroni et al. (2013)

Table 2. Medicinal plants effective on Parkinson’s disease.

Plant	Used model	Concentration	Effects	References
Tinospora cordifolia	Rat induced by 6-OHDA	200, 400 mg/kg	1. Increased the dopamine levels 2. Decreased iron asymmetry ratio 3. Decreased MDA levels 4. Increased mitochondrial complex I activity 5. Improved locomotor activity	Kosaraju et al. (2014)
Sesame seed oil (SO)	Mice induced by 6-OHDA	SO mix diet	1. Increased glutathione reductase (GR), glutathione-S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT) and content of glutathione (GSH) and thiobarbituric acid reactive substance (TBARS) 2. Inhibit the activation of Nox2 and Cox2 3. Restored MnSOD expression	Ahmad S et al. (2012)
Carthamus tinctorius L.	(MPTP)-lesioned rat	70, 35 mg/kg	1. Improve behavioural performances 2. Suppression of α-synuclein overexpression or aggregation 3. Suppression of reactive astrogliosis	Ren et al. (2016)
Chaenomeles speciosa	In vitro and in vivo assays, Chinese hamster ovary (CHO) cells, rat induced by 6-OHDA (MPTP)-lesioned mice	250, 500, 1000 mg/kg	1. Increased tyrosine hydroxylase-positive neurons in the substantia nigra 2. Increased D8 cell viability 3. Time-dependently reduced abnormal turns in apomorphine-induced rotational turning	Zhao et al. (2008)
Portulaca oleracea	Rat induced by 6-OHDA	200, 400 mg/kg	1. Increase in crossings and rearing in open field test	Martins et al. (2016)
Paeonia suffruticosa	(MPTP)-lesioned mice	25, 50 mg/kg	1. Increased movement distance in the open field test 2. Increased total striatal dopamine 3. Attenuated the loss of dopaminergic neurons 4. Reversed down regulation Akt and the mitochondrial OXPHOS subunits	Kim et al. (2014)
Mucuna pruriens	Rat induced by 6-OHDA	40, 80, 120 mg/kg	1. Reduced risk for drug-induced dyskinesias 2. Increased nigrostriatal catecholamine content	Lieu et al. (2010)
Hyoscyamus niger seeds	Unilateral intrastriatal injection of rotenone in rat	125, 250, 500 mg/kg	1. Attenuated motor disabilities 2. Increased level of GSH content and GPX, SOD and CAT activities	Khatri and Juvekar (2015)
Hibiscus asper leaves	Rat induced by 6-OHDA	50, 100 mg/kg	1. Increased SOD, GPX and CAT activities, total GSH content 2. Reduced MDA level	Hritcu et al. (2011)
Gynostemma pentaphyllum	Rat induced by 6-OHDA	10, 30 mg/kg	1. Recovered the levels of dopamine, 3,4 dihydroxyphenylacetic acid, homovanillic acid and norepinephrine in striatum 2. Ameliorated the loss of TH-immunopositive neurons in substantia nigra	Choi et al. (2010)
Ginkgo biloba	Rat induced by 6-OHDA	50, 100, 150 mg/kg	1. Decreased rotation 2. Improved locomotor activity and muscular coordination 3. Increased GSH content 4. Decreased generation of TBARS 5. Increased SOD, CAT activities 6. Increase in the number of dopaminergic D2 receptors in striatum	Ahmad M et al. (2005)
Fructus Alpiniaoxyphylla	Zebrafish and PC12 cell models	20% solution	1. Restored dopaminergic (DA) neuron degeneration 2. Attenuated a deficit of locomotor activity 3. Increased the viability of 6-OHDA-treated PC12 cells 4. Attenuating cellular apoptosis	Zhang et al. (2012)
Delphinium denudatum	Rat induced by 6-OHDA	200, 400, 600 mg/kg	1. Decreased MDA levels 2. Increased GSH content 3. Increased SOD, CAT activities 4. Increased levels of dopamine	Ahmad M et al. (2006)
Bacopa monniera Linn	Rat induced by 6-OHDA	20, 40 mg/kg	1. Decreased MDA levels 2. Increased GSH content 3. Increased SOD, CAT activities	Shobana et al. 2012
Althaea officinalis L.	Rat induced by 6-OHDA	10 mg/kg	1. Attenuated rotational behaviour 2. Decreased MDA levels	Rezaei and Alirezaei (2014)
Albizia adianthifolia	Rat induced by 6-OHDA	150, 300 mg/kg	1. Improved working memory and reference memory 2. Attenuated the contralateral rotational asymmetry	Beppe et al. (2014)
Valeriana officinalis	Rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells	0.049, 0.098 and 0.195 mg/mL	1. Increase in cell viability	de Oliveria et al. (2009)
Black tea	Rat induced by 6-OHDA	1.5%	1. Recovery in d-amphetamine induced circling behaviour and spontaneous locomotor activity 2. Recovery indopamine (DA)-D2 receptor binding, striatal DA and 3-4-dihydroxy phenyl acetic acid (DOPAC) level 3. Decreased MDA levels 4. Increased GSH content 5. Increased SOD and CAT activities 6. Increased TH protein level and TH mRNA expression in substantianigra	Chaturvedi et al. (2006)
Panax ginseng	Rat received β-sitosterol β-D-glucoside	100 mg/kg/d	1. Reduced dopaminergic cell loss, microgliosis, and accumulation of α-synuclein aggregates	Van Kampen et al. (2014)
Safflower	Mouse induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-	35, 70 mg/kg/d	1. Reversed the decreased protein expression of tyrosine hydroxylase, dopamine transporter and DJ-1 2. Increased dopamine levels 3. Decreased acetylcholine levels	Ablat et al. (2016)
Hypericum perforatum	Rat induced by 6-OHDA	200 mg/kg/d	1. Attenuated apomorphine-induced rotational behaviour, 2. Decreased the latency to initiate and the total time on the narrow beam task 3. Decreased MDA levels 4. Increased catalase activity	Kiasalari et al. (2016)
Oxalis corniculata l.	C57 male mice MPTP administration	250, 500 mg/kg	1. Decreased SOD activity 2. Increased catalase activity	Aruna et al. (2016)

Chan WS, Durairajan SSK, Lu JH, Wang Y, Xie LX, Kum WF, Koo I, Yung KK, Li M. 2009. Neuroprotective effects of astragaloside IV in 6-hydroxydopamine-treated primary nigral cell culture. Neurochem Int. 6:414–422.

 Web of Science ®Google Scholar

Kwon IH, Choi HS, Shin KS, Lee BK, Lee CK, Hwang BY, Lim SC, Lee MK. 2010. Effects of berberine on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and a rat model of Parkinson’s disease. Neurosci Lett. 1:29–33.

 Web of Science ®Google Scholar

Mu X, He G, Cheng Y, Li X, Xu B, Du G. 2009. Baicalein exerts neuroprotective effects in 6-hydroxydopamine-induced experimental parkinsonism in vivo and in vitro. Pharmacol Biochem Behav. 4:642–648.

 Web of Science ®Google Scholar

Noelker C, Bacher M, Gocke P, Wei X, Klockgether T, Du Y, Dodel R. 2005. The flavanoide caffeic acid phenethyl ester blocks 6-hydroxydopamine-induced neurotoxicity. Neurosci Lett. 1:39–43.

 Web of Science ®Google Scholar

Wu CR, Tsai CW, Chang SW, Lin CY, Huang LC, Tsai CW. 2015. Carnosic acid protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinson’s disease: involvement of antioxidative enzymes induction. Che-Biol Interact. 225:40–46.

 PubMed Web of Science ®Google Scholar

Khuwaja G, Khan MM, Ishrat T, Ahmad A, Raza SS, Ashafaq M, Javed H, Khan MB, Khan A, Vaibhav K, et al. 2011. Neuroprotective effects of curcumin on 6-hydroxydopamine-induced Parkinsonism in rats: behavioral, neurochemical and immunohistochemical studies. Brain Res. 1368:254–263.

 PubMed Web of Science ®Google Scholar

Mansouri MT, Farbood Y, Sameri MJ, Sarkaki A, Naghizadeh B, Rafeirad M. 2013. Neuroprotective effects of oral gallic acid against oxidative stress induced by 6-hydroxydopamine in rats. Food Chem. 2:1028–1033.

 Web of Science ®Google Scholar

Farbood Y, Sarkaki A, Dolatshahi M, Mansouri SMT, Khodadadi A. 2015. Ellagic acid protects the brain against 6-hydroxydopamine induced neuroinflammation in a rat model of Parkinson’s disease. Basic Clin Neurosci. 2:83.

 Google Scholar

Gao QG, Chen WF, Xie JX, Wong MS. 2009. Ginsenoside Rg1 protects against 6‐OHDA‐induced neurotoxicity in neuroblastoma SK‐N‐SH cells via IGF‐I receptor and estrogen receptor pathways. J Neurochem. 5:1338–1347.

 Web of Science ®Google Scholar

Haleagrahara N, Siew CJ, Ponnusamy K. 2013. Effect of quercetin and desferrioxamine on 6-hydroxydopamine (6-OHDA) induced neurotoxicity in striatum of rats. J Toxicol Sci. 1:25–33.

 Web of Science ®Google Scholar

Sedaghat R, Roghani M, Khalili M. 2014. Neuroprotective effect of thymoquinone, the Nigella sativa bioactive compound, in 6-hydroxydopamine-induced hemi-Parkinsonian rat model. Iran J Pharm Res. 1:227.

 Google Scholar

Hong Z, Wang G, Gu J, Pan J, Bai L, Zhang S, Chen SD. 2007. Tripchlorolide protects against MPTP‐induced neurotoxicity in C57BL/6 mice. Eur J Neurosci. 6:1500–1508.

 Web of Science ®Google Scholar

Morroni F, Tarozzi A, Sita G, Bolondi C, Zolezzi Moraga JM, Cantelli-Forti G, Hrelia P. 2013. Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson’s disease. Neurotoxicol. 36:63–71.

 PubMed Web of Science ®Google Scholar

Kosaraju J, Chinni S, Roy PD, Kannan E, Antony AS, Kumar MS. 2014. Neuroprotective effect of Tinospora cordifolia ethanol extract on 6-hydroxy dopamine induced Parkinsonism. Indian J Pharmacol. 2:176.

 Web of Science ®Google Scholar

Ahmad S, Khan MB, Hoda MN, Bhatia K, Haque R, Fazili IS, Jamal A, Khan JS, Katare DP. 2012. Neuroprotective effect of sesame seed oil in 6-hydroxydopamine induced neurotoxicity in mice model: cellular, biochemical and neurochemical evidence. Neurochem Res. 3:516–526.

 Web of Science ®Google Scholar

Ren R, Shi C, Cao J, Sun Y, Zhao X, Guo Y, Wang C, Lei H, Jiang H, Ablat N, et al. 2016. Neuroprotective effects of a standardized flavonoid extract of safflower against neurotoxin-induced cellular and animal models of Parkinson’s disease. Sci Rep. 6:221–235.

 Web of Science ®Google Scholar

Zhao G, Jiang Z-H, Zheng X-w, Zang S-Y, Guo L-H. 2008. Dopamine transporter inhibitory and antiparkinsonian effect of common flowering quince extract. Pharmacol Biochem Behav. 90:363–371.

 PubMed Web of Science ®Google Scholar

Martins WB, Rodrigues SA, Silva HK, Dantas CG, Junior W, Cardoso JC, Filho LX, Gomes MZ. 2016. Neuroprotective effect of Portulaca oleracea extracts against 6-hydroxydopamine-induced lesion of dopaminergic neurons. Acad Bras Cienc. 3:150–439.

 Google Scholar

Kim HG, Park G, Piao Y, Kang MS, Pak YK, Hong SP, Oh MS. 2014. Effects of the root bark of Paeonia suffruticosa on mitochondria-mediated neuroprotection in an MPTP-induced model of Parkinson’s disease. Food Chem Toxicol. 65:293–300.

 PubMed Web of Science ®Google Scholar

Lieu CA, Kunselman AR, Manyam BV, Venkiteswaran K, Subramanian T. 2010. A water extract of Mucuna pruriens provides long-term amelioration of parkinsonism with reduced risk for dyskinesias. Parkinsonism Relat Disord. 7:458–465.

 Web of Science ®Google Scholar

Khatri DK, Juvekar AR. 2015. Propensity of Hyoscyamus niger seeds methanolic extract to allay stereotaxically rotenone-induced Parkinson’s disease symptoms in rats. Orient Pharm Expe Med. 4:327–339.

 Google Scholar

Hritcu L, Foyet HS, Stefan M, Mihasan M, Asongalem AE, Kamtchouing P. 2011. Neuroprotective effect of the methanolic extract of Hibiscus asper leaves in 6-hydroxydopamine-lesioned rat model of Parkinson’s disease. J Ethnopharmacol. 137:585–591.

 PubMed Web of Science ®Google Scholar

Choi HS, Park MS, Kim SH, Hwang BY, Lee CK, Lee MK. 2010. Neuroprotective effects of herbal ethanol extracts from Gynostemma pentaphyllum in the 6-hydroxydopamine-lesioned rat model of Parkinson’s disease. Molecules. 4:2814–2824.

 Web of Science ®Google Scholar

Ahmad M, Saleem S, Ahmad AS, Yousuf S, Ansari MA, Khan MB, Ishrat T, Chaturvedi RK, Agrawal AK, Islam F. 2005. Ginkgo biloba affords dose‐dependent protection against 6‐hydroxydopamine‐induced parkinsonism in rats: neurobehavioural, neurochemical and immunohistochemical evidences. J Neurochem. 1:94–104.

 Web of Science ®Google Scholar

Zhang ZJ, Cheang LC, Wang MW, Li GH, Chu IK, Lin ZX. 2012. Ethanolic extract of fructus Alpinia oxyphylla protects against 6-hydroxydopamine-induced damage of PC12 cells in vitro and dopaminergic neurons in zebrafish. Cell Mol Neurobiol. 1:27–40.

 Web of Science ®Google Scholar

Ahmad M, Yousuf S, Khan MB, Ahmad AS, Saleem S, Hoda MN, Islam F. 2006. Protective effects of ethanolic extract of Delphinium denudatum in a rat model of Parkinson’s disease. Hum Exp Toxicol. 7:361–368.

 Web of Science ®Google Scholar

Shobana C, Kumar RR, Sumathi T. 2012. Alcoholic extract of Bacopa monniera Linn. protects against 6-hydroxydopamine-induced changes in behavioral and biochemical aspects: a pilot study. Cell Mol Neurobiol. 7:1099–1112.

 Web of Science ®Google Scholar

Rezaei M, Alirezaei M. 2014. Protective effects of Althaea officinalis L. extract in 6-hydroxydopamine-induced hemi-Parkinsonism model: behavioral, biochemical and histochemical evidence. J Physiol Sci. 3:171–176.

 Web of Science ®Google Scholar

Beppe GJ, Dongmo AB, Foyet HS, Tsabang N, Olteanu Z, Cioanca O, Hancianu M, Dimo T, Hritcu L. 2014. Memory-enhancing activities of the aqueous extract of Albizia adianthifolia leaves in the 6-hydroxydopamine-lesion rodent model of Parkinson’s disease. BMC Complement Altern Med. 14:142.

 PubMed Web of Science ®Google Scholar

de Oliveria DM, Barreto G, De Andrade DVG, Saraceno E, Aon-Bertolino L, Capani F, Dos Santos El Bachá R, Giraldez LD. 2009. Cytoprotective effect of Valeriana officinalis extract on an in vitro experimental model of Parkinson disease. Neurochem Res. 2:215–220.

 Web of Science ®Google Scholar

Chaturvedi R, Shukla S, Seth K, Chauhan S, Sinha C, Shukla Y, Agrawal AK. 2006. Neuroprotective and neurorescue effect of black tea extract in 6-hydroxydopamine-lesioned rat model of Parkinson’s disease. Neurobiol Dis. 2:421–434.

 Web of Science ®Google Scholar

Van Kampen JM, Baranowski DB, Shaw CA, Kay DG. 2014. Panax ginseng is neuroprotective in a novel progressive model of Parkinson’s disease. Exp Gerontol. 50:95–105.

 PubMed Web of Science ®Google Scholar

Ablat N, Lv D, Ren R, Xiaokaiti Y, Ma X, Zhao X, Sun Y, Lei H, Xu J, Ma Y, et al. 2016. Neuroprotective effects of a standardized flavonoid extract from safflower against a rotenone-induced rat model of Parkinson’s disease. Molecules. 21:1107.

 PubMed Web of Science ®Google Scholar

Kiasalari Z, Baluchnejadmojarad T, Roghani M. 2016. Hypericum perforatum hydroalcoholic extract mitigates motor dysfunction and is neuroprotective in intrastriatal 6-Hydroxydopamine rat model of Parkinson's disease. Cell Mol Neurobiol. 36:521–530.

 PubMed Web of Science ®Google Scholar

Aruna K, Rajeswari PDR, Sankar SR. 2016. The effects of Oxalis corniculata L. extract against MPTP induced oxidative stress in mouse model of Parkinson’s disease. J Pharm Sci Res. 8:1136.

 Google Scholar