Table 1.
Summary of nutraceuticals in PD
| Nutraceuticals | Compound | Proposed mechanism of action | Evidence on potential neuroprotective effects | References | ||
|---|---|---|---|---|---|---|
| Clinical trials | In vivo | In vitro | ||||
| Vitamin B complex | Vitamin supplement | Regulate levels of homocysteine Optimize mitochondrial function |
PD patients treated with l-Dopa and vitamin B showed a reduction in homocysteine levels compared to without vitamin B. | Protect against MPTP-induced SNpc dopaminergic neuronal loss and striatal DA depletion in mice | Miller et al. (2003), Lamberti et al. (2005), Yokoyama et al. (2010), Anderson et al. (2008), Mukherjee et al. (1997) | |
| Vitamin C and E | Antioxidant vitamin supplements | Vitamin C: Free radical scavenger in the cytosol Vitamin E: Lipid-soluble antioxidant to prevent lipid peroxidation in membranes |
Conflicting reports | Fahn (1991), Martin et al. (2002), Parkinson Study Group (1993), Olanow (2003), Zhang et al. (2002), Etminan et al. (2005) | ||
| Vitamin D | Vitamin supplement | Upregulate GDNF levels (promote outgrowth of dopaminergic axons) Increase glutathione levels Calcium homoeostasis Anti-apoptotic Immunomodulatory effects Reduce nitric oxide synthase Regulate dopamine levels |
Higher vitamin D serum levels, significantly lower risk of developing PD later in life | Attenuate 6-OHDA-induced and MPP+-induced neurotoxicity in rodent model Vitamin D receptor knockout mice developed motor defect |
Wang et al. (2001), Knekt et al. (2010), Kirik et al. (2001), Garcion et al. (2002), Evatt et al. (2008) | |
| Coenzyme Q10 (CoQ10) | Fat-soluble and vitamin-like quinone found abundantly in liver and the brain | Maintain proper transfer of electrons in the electron transport chain of mitochondria and ATP production Potent antioxidant that can reduce oxidized form of alpha-tocopherol to prevent lipid peroxidation |
Conflicting reports | Attenuate MPTP-induced neurotoxicity in rodent model | Beal et al. (1998), Cleren et al. (2008), Shults et al. (2002), Muller et al. (2003), Shults (2005) | |
| Creatine | Nitrogenous organic acid | Phosphorylated by creatine kinase to form phosphocreatine, an energy reserve in the brain and skeletal muscles Phosphocreatine is a key player in the maintenance of ATP levels, which in turn are important in synaptic activity and skeletal muscle functions |
Creatine treatment improved mood and reduced the dosages required for dopamine replacement therapy | Reduce loss of dopaminergic neurons in MPTP mouse model | Matthews et al. (1999), Bender et al. (2006) | |
| Fish oil | Polyunsaturated fatty acids (n-3 PUFA) | Important modulators for dopaminergic neurons in the basal ganglia Antidepressant effects mediated by an increase in serotonergic neurotransmission |
Reduce dopamine loss and prevent formation of DOPAC in MPTP-induced parkinsonism in mice Calon F et al. (2007) |
Denny Joseph and Muralidhara (2015), de Lau et al. (2005), Chen et al. (2003), Bousquet et al. (2008), Garcia-Arencibia et al. (2009) | ||
| Mucunapruriens, Mucunasanjappae | Natural sources of l-Dopa—plants belonging to Mucuna genus family | Consists of significant amounts of NADH and CoQ10 NADH: increases dopamine levels via upregulation of TH), counteracts the inhibition of mitochondrial complex 1 activity) and protects neurons against DNA damage caused by free radicals produced during the interaction between l-Dopa and divalent copper ions |
Patients prescribed with mucuna seed powder extract showed significant improvements with better tolerability compared to l-Dopa treatment alone Importantly, in the mucuna-treated patients, severe dyskinesia or peripheral dopaminergic neuronal damage was observed |
Protects against 6-OHDA toxicity in rodent model | Vaidya et al. (1978), Nagashayana et al. (2000), HP-200 in Parkinson’s Disease Study Group (1995), Manyam et al. (2004), Tharakan et al. (2007), Spencer et al. (1994), Patil et al. (2015), Hussian and Manyam (1997), Katzenschlager et al. (2004) | |
| EGCG in green tea | Polyphenolic compounds | Passes BBB Iron chelation Free radical scavenger Antioxidant Regulation of PKC Modulation of ROS–NO pathway AMPK activation |
Prospective cohort study of Singapore Chinese Health Study showed no relationship between green tea consumption and PD risk | Protects against 6-OHDA- and MPTP-induced parkinsonism in mice | Protects against 6-OHDA-induced toxicity in PC12 cells Protects against TNF-α and hydrogen peroxide-induced apoptosis in rat mesencephalic cells |
Ng, Guan, et al. (2012), Pan et al. (2003), Mandel et al. (2006), Levites et al. (2001), Mandel et al. (2004), Guo et al. (2007), Tan et al. (2008), Xu et al. (2015) |
| Curcuminoids in curry | Polyphenolic flavonoid that constitutes approximately 4 % of turmeric | Antioxidant Restoring glutathione levels (protect neurons against protein oxidation and preserving mitochondrial complex 1 activity) Anti-inflammatory (inhibits LPS-induced morphological changes of microglia and reduces LPS-induced production of pro-inflammatory factors and their gene expressions) |
Protect neurons against protein oxidation and preserve mitochondrial complex I activity Reduce 6-OHDA-induced neurotoxicity in rodent models Significantly reversed MPTP-induced depletion of DA and DOPAC in mice |
Protect neurons against protein oxidation and preserve mitochondrial complex I activity Reduce 6-OHDA-induced neurotoxicity in MES 23.5 cells by modulating NF-κB translocation Prevent MPTP-induced neurotoxicity in SH-SY5Y cells and PC12 cells by targeting the JNK, the Bcl-2 mitochondria and the ROS–iNOS pathways |
Jagatha et al. (2008), Zbarsky et al. (2005), Wang et al. (2009a), Yang et al. (2008), Yu et al. (2010), Chen et al. (2006), Rajeswari and Sabesan (2008), Wang et al. (2010), Pandey et al. (2008) | |
| Baicalein | Flavonoid extracted from the root of Scutellariabaicalensis, a traditional Chinese herb commonly known as Huang Qin | Antioxidant Anti-inflammatory Inhibit fibrillization of alpha-synuclein |
Rescues MPTP- and 6-OHDA-induced neurotoxicity in rodent models | Attenuate mitochondrial depolarization and proteasome inhibition in PC12 cells induced by familial alpha-synuclein mutation (E46K). | van Leyen et al. (2006), Chen et al. (2008), Cheng et al. (2008), Mu et al. (2009), Waxman et al. (2010), Jiang et al. (2010) | |
| Resveratrol | A phytoalexin found in plants such as grapes, peanuts, berries and pines | Inhibition of NADPH oxidase and suppression of IL1-a and TNF-α triggered by LPS Modulate levels of BAX and Bcl-2 in vitro Stimulation of SIRT1 in SK-N-BE cells Free radical scavenger |
Attenuate MPTP-, 6-OHDA- and LPS-induced toxicity in rodent models | Protect dopaminergic neurons against toxicity induced by LPS, DA or MPTP | Zhang et al. (2010), Bournival et al. (2009), Lee et al. (2007), Lu et al. (2008), Khan et al. (2010), Bureau et al. (2008), Albani et al. (2009), Pallas et al. (2009), Pallas et al. (2008) | |
| Oxyresveratrol | Heartwood or fruit of Artocarpusheterophyllus, Artocarpuslakoocha, Actocarpusgomezianus and Actocarpusdadah
Wood or fruit of mulberry trees Fruit of Melaleucaleucadendron Rhizomes of Smilacischinae Egyptian herb Schoenocaulonofficinale |
Anti-inflammatory effects, particularly those isolated from Artocarpusheterophyllus, Artocarpusdadahor mulberry wood Free radical scavenger (penetrates neurons easily) Upregulate SIRT1 |
Protect against 6-OHDA-induced toxicity in SH-SY5Y cells by reducing the release of lactate dehydrogenase and caspase-3-specific activity | Fang et al. (2008), Su et al. 2002), Chao et al. (2008) | ||
| Ginsenoside | Ginsenosides, a phytoestrogen, are a class of molecules extracted from several species of ginseng | Regulate several pathways (P13K/AKT, ERK, JNK, ROS-NFkB, IGF-1 receptor signalling pathways and oestrogen receptor pathway) Maintain glutathione levels Anti-apoptotic (Attenuate JNK signalling) Prevent elevation of iron levels by regulating the expression of iron transport proteins |
Attenuate MPTP-, 6-OHDA- and rotenone-induced toxicity in rodent models | Chen et al. (2005), Wang et al. (2009b), Xu et al. (2009), Leppa and Bohmann (1999) | ||
| Genistein | A phytoestrogen found mainly in soy and peanuts | Binds to oestrogen receptor β and upregulates anti-oxidative and anti-apoptotic genes Antioxidant (Increase the levels of malondialdehyde, superoxide dismutase, and monoamine oxidase) Anti-apoptotic (Tyrosine kinase inhibitor, attenuate activation of PKC) |
Attenuate 6-OHDA-induced toxicity in rodents | Attenuate hydrogen peroxide-induced cell death in N27 cells | Kaul et al. (2005), Baluchnejadmojarad et al. (2009) | |
| Holy Basil (Ocimum sanctum) | A leaf extract from a plant known as Tulsi, which is found throughout India | Anti-microbial Anti-stress Anti-diabetic Hepatoprotective Anti-inflammatory Neuroprotective Cardioprotective |
Delay loss of climbing ability and reduce the oxidative stress in brain of the Drosophila PD model | Siddique et al. (2014) | ||
| Nucleoprotein | Extracted from salmon soft roe and consists mainly of a mixture of DNA nucleotide and protamine | ROS scavenger Reduce accumulation of lipofuscin-like substances in the brain, which is often related to Lewy body formation |
Prevent locomotor impairment and dopaminergic neuronal degeneration in MPTP-induced toxicity mice model | Kiriyama et al. (2015) | ||
| Nordihydroguaiaretic acid (NDGA) | Polyphenol extracted from compound of creosote bush (Larrea tridentate) | Antioxidant Anti-genotoxic Anti-neoplastic Antiviral Anti-inflammatory Inhibit the accumulation of alpha-synuclein (hallmark of PD) |
Delay the loss of climbing ability in Drosophila PD model | Siddique et al. (2012) | ||
| Quercetin (Q) | Natural flavonoid found in fruits and vegetables such as onion, broccoli and apple | Antioxidant Anti-inflammatory Anti-cancer |
Protect against chronic rotenone toxicity and dopaminergic neuronal loss in 6-OHDA rat models of PD | Haleagrahara et al. (2011), Denny Joseph and Muralidhara (2015) | ||
| Magnesium | Dietary supplement | DA uptake Vesicular storage and transport Alter Ca2+-mediated neurotoxicity Activate CuZn-SOD, thereby attenuating formation of ONOO–, involved with α-synuclein aggregation |
Philippu et al. (1975), Safar et al. (2010), Lin et al. (2002), Johnson (2001) | |||
| Caffeine | Psychoactive CNS stimulant found in coffee | Regulate expression of genes involved in oxidative stress (cytochrome c oxidase subunits, enolase alpha, NADH dehydrogenase, aldehyde dehydrogenase) Regulate expression of ubiquitin–proteasome pathway-related genes (ubiquitin-conjugating enzyme, protease 26S subunit, ubiquitin B and C) Cell-cycle regulation |
Risk of suffering PD decreases as consumption of coffee increases | Protect against 6-OHDA- and MPTP-induced dopaminergic neuronal loss in mice | Gongora-Alfaro (2010), Singh et al. (2010) | |
| Eucalyptus Oil | Eucalyptus citriodora leaf extract | Antioxidant | Delay of the loss of climbing ability in Drosophila PD model | Siddique et al. (2013) | ||
| Ginkobiloba extract (EGb 761) | Ginkobiloba leaves containing flavonoids and terpenoids | Antioxidant Anti-inflammatory Anti-apoptotic |
Pretreatment with EGb 761 decreases lipid peroxidation and improves locomotor activity in 6-OHDA rat model In a MPTP rat model, EGb 761 prevents dopaminergic neurotoxicity, decreases SOD activity, decreases oxidative stress and apoptosis induced by MPP+ |
EGb 761 provide neuroprotection against paraquat-induced apoptosis of PC12 cells | Kim et al. (2004), Kang et al. (2007), Rojas et al. (2012), Ahmad et al. (2005), Yang et al. (2001) | |
| Shengmai San (SMS) and LingGuiZhuGanTang (LGZGT) | Traditional Chinese Medicine SMS comprise of three crude drug components, Radix Ginseng (Panax ginseng) (Araliaceae), Radix Ophiopogonis (Ophiopogonjaponicus) (Liliaceae) and FructusSchisandrae (Schisandrachinensis) (Schisandraceae) LGZGT comprise of four crude drug components, Cinnamon twig (Cinnamomum cassia Presl.) (Lauraceae), Atractylodisrhizoma (AtractylodesmacrocephalaKoidz.) (Compositae), Glycyrrhizae radix (GlycyrrhizauralensisFisch.) (Leguminosae) and one fungi Hoelen (Poriacocos (Schw.) (Wolf Polyporaceae) |
Antioxidant | Protects against MPTP-induced dopaminergic neuronal loss in mice | Giridharan et al. (2011) | ||
| Swallow root (Decalepishamiltonii) | Extract from plant species swallow root | Antioxidant | Improved climbing ability and circadian rhythm of locomotor activity of transgenic alpha-synuclein Drosophila PD model and resulted in an associated reduction in levels of ROS and lipid peroxidation and enhancement in the activities of catalase and superoxide dismutase | Jahromi et al. (2015) | ||
| TianmaGouteng Yin (TGY) | Traditional Chinese Medicine | Unclear | Improved survival rates and locomotor function of rotenone-intoxicated Drosophila PD model Reduced levels of alpha-synuclein and prevented degeneration of dopaminergic neurons in alpha-synuclein transgenic Drosophila Protects rotenone-induced dopaminergic neuronal loss in mice |
Alleviated apoptotic cell death in human dopaminergic neuroblastoma SH-SY5Y cell line treated with rotenone | Liu et al. (2015) | |