Dr. Weeks’ Comment: Parkinson’s disease, like all neurological illnesses (MS, ALS, seizures etc.) is a disease of your fatty acids. Your nerves are fatty acids and when they are contaminated and inflamed they misfire.
This tragic illness, where good people lose control of their neurological function, is treatable by optimizing the diet and “changing your oil” (like you would in your car). Good oil in flushes bad oil out and since the nerves are mostly oil, you need an internal shampoo. Stopping eating the rancid, toxic commercial vegetable oils (soy, canola and corn in most junk food) and scrubbing clean your neuronal cell membranes from the glyphosate (RoundUp™) is step one. Get your level of glyphosate tested here.
But remember: Parkinson’s disease is fundamentally an inflammatory illness. So wouldn’t it be great were there an anti-inflammatory high quality oil?
And there is such an oil.
We recommend a synergistic blend of the three most powerful anti-inflammatory seed oils: black cumin seed, black raspberry seed and Chardonnay grape seed. “
Below we share the research on just one of that trio: the black cumin seed. Take a read and then get that internal shampoo!
RESEARCH ARTICLES FROM PUBMED
Biochemistry (Mosc). 2020 Feb;85(2):167-176.
Thymoquinone as a Potential Neuroprotector in Acute and Chronic Forms of Cerebral Pathology
N K Isaev 1 2, N S Chetverikov 2, E V Stelmashook 3, E E Genrikhs 3, L G Khaspekov 4, S N Illarioshkin 3
Thymoquinone is one of the main active components of the essential oil from black cumin (Nigella sativa) seeds. Thymoquinone exhibits a wide range of pharmacological activities, including neuroprotective action demonstrated in the models of brain ischemia/reperfusion, Alzheimer’s and Parkinson’s diseases, and traumatic brain injury. The neuroprotective effect of thymoquinone is mediated via inhibition of lipid peroxidation, downregulation of proinflammatory cytokines, maintenance of mitochondrial membrane potential, and prevention of apoptosis through inhibition of caspases-3, -8, and -9. Thymoquinone-based mitochondria-targeted antioxidants are accumulated in the mitochondria and exhibit neuroprotective properties in nanomolar concentrations. Thymoquinone reduces the negative effects of acute and chronic forms of brain pathologies. The mechanisms of the pharmacological action of thymoquinone and its chemical derivatives require more comprehensive studying. In this paper, we formulated the prospects of application of thymoquinone and thymoquinone-based drugs in the therapy of neurodegenerative diseases.
CNS Neurol Disord Drug Targets2018;17(6):412-420.
A Review on Possible Therapeutic Effect of Nigella sativa and Thymoquinone in Neurodegenerative Diseases
Saeed Samarghandian 1, Tahereh Farkhondeh 2, Fariborz Samini 3
Background & objective: Medicinal plants have attracted great attention in the recent years and is increasingly applied instead of the chemical drugs. Several documents showed that herbal medicine traditionally and clinically applied in the cure and prevention of several diseases. In the recent years, different medicinal plants and their main components have been chosen in neurological therapy. The less toxic effects, availability, and lower price of medicinal plants versus synthetic substances make them as excellent and simple selection in the treatment of nervous diseases. Nigella sativa (N. Sativa) L. (Ranunculaceae), well recognized as black cumin, has been utilized as a medicinal plant that has a strong traditional background. Thymoquinone (TQ) is one of the main active components of the volatile oil of N. sativa seeds and most effects and actions of N. Sativa are mainly related to TQ. The several pharmacological properties of N. sativa and TQ have been found, for example; anti-tumor, anti-microbial, anti-histaminic, immunomodulatory, anti-inflammatory, and anti-oxidant effects. Many reviews have investigated this valuable plant and its components, but none of them focused on their neuroprotective effects. Therefore, the aim of the present review was to show comprehensive and neuropharmacological properties of N. sativa and TQ. In this review, various studies on scientific databases regarding the effects of N. sativa and TQ in neurological diseases have been introduced. Studies on the neuroprotective effects of N. sativa and TQ which were published between1979 and 2018, were searched using various databases. The results of these studies showed that N. sativa and TQ have the protective effects against neurodegenerative diseases, including; Alzheimer, depression, encephalomyelitis, epilepsy, ischemia, Parkinson, and traumatic brain injury have been discussed in the cell lines and experimental animal models.Although there are many studies indicating the beneficial actions of this plant in the nervous system, the number of research projects relating to the human reports is rare.
J Neuroimmunol. 2015 Sep 15;286:5-12.
doi: 10.1016/j.jneuroim.2015.06.011. Epub 2015 Jun 27.
Anti-inflammatory effects of thymoquinone in activated BV-2 microglial cells
Equar Taka 1, Elizabeth A Mazzio 1, Carl B Goodman 1, Natalie Redmon 1, Hernan Flores-Rozas 1, Renee Reams 1, Selina Darling-Reed 1, Karam F A Soliman 2
Thymoquinone (TQ), the main pharmacological active ingredient within the black cumin seed (Nigella sativa) is believed to be responsible for the therapeutic effects on chronic inflammatory conditions such as arthritis, asthma and neurodegeneration. In this study, we evaluated the potential anti-inflammatory role of TQ in lipopolysaccharide (LPS)-stimulated BV-2 murine microglia cells. The results obtained indicate that TQ was effective in reducing NO2(-) with an IC50 of 5.04μM, relative to selective iNOS inhibitor LNIL-l-N6-(1-iminoethyl)lysine (IC50 4.09μM). TQ mediated reduction in NO2(-) was found to parallel the decline of iNOS protein expression as confirmed by immunocytochemistry. In addition, we evaluated the anti-inflammatory effects of TQ on ninety-six (96) cytokines using a RayBio AAM-CYT-3 and 4 cytokine antibody protein array. Data obtained establish a baseline protein expression profile characteristic of resting BV-2 cells in the order of osteopontin>MIP-1alpha>MIP-1g>IGF-1 and MCP-I. In the presence of LPS [1ug/ml], activated BV-2 cells produced a sharp rise in specific pro-inflammatory cytokines/chemokine’s IL-6, IL-12p40/70, CCL12 /MCP-5, CCL2/MCP-1, and G-CSF which were attenuated by the addition of TQ (10μM). The TQ mediated attenuation of MCP-5, MCP-1 and IL-6 protein in supernatants from activated BV-2 cells were corroborated by independent ELISA. Moreover, the data obtained from the RT(2) PCR demonstrated a similar pattern where the LPS mediated elevation of mRNA for IL-6, CCL12/MCP-5, CCL2/MCP-1 were significantly attenuated by TQ (10μM). Also, in this study, consistent data were obtained for both protein antibody array densitometry and ELISA assays. In addition, TQ was found to reduce LPS mediated elevation in gene expression of Cxcl10 and a number of other cytokines in the panel. These findings demonstrate the significant anti-inflammatory properties of TQ in LPS activated microglial cells. Therefore, the obtained results might indicate the usefulness of TQ in delaying the onset of inflammation-mediated neurodegenerative disorders involving activated microglia cells.
Neurochem Res. 2016 Dec;41(12):3386-3398.
doi: 10.1007/s11064-016-2073-z. Epub 2016 Oct 18.
Nigella sativa Oil Reduces Extrapyramidal Symptoms (EPS)-Like Behavior in Haloperidol-Treated Rats
Tafheem Malik 1 2 3, Sheema Hasan 4, Shahid Pervez 4, Tasneem Fatima 5, Darakhshan Jabeen Haleem 6 7
The symptoms of Parkinsonism and oral dyskinesia have been showing to be induced by neuroleptics that significantly affect its clinical use. In this study, we investigate whether Nigella sativa-oil (NS) (black cumin seeds)-a traditional medicine used for the seizure treatment in eastern country-may reduce the haloperidol (HAL)-induced extrapyramidal symptoms (EPS)-like behavior in rats. After combine treatment with HAL (1 mg/kg) on NS (0.2 ml/rat), rats displayed a significant decreased EPS-like behavior including movement disorders and oral dyskinesia as compared to controls. Immunohistochemical analysis indicates that NS reduced astrogliosis in caudate and accumbens nuclei. These results suggest that NS may consider as an adjunct to antipsychotics to reduce the EPS-like side effect.
Phytother Res. 2009 May;23(5):696-700.
Thymoquinone protects dopaminergic neurons against MPP+ and rotenone
Khaled Radad 1, Rudolf Moldzio, Mokhtar Taha, Wolf-Dieter Rausch
Thymoquinone is the main active constituent of Nigella sativa seeds with antioxidant and antiinflammatory properties. In the present study, primary dopaminergic cultures from mouse mesencephala were used to investigate the neuroprotective effects of thymoquinone against MPP(+) and rotenone toxicities.MPP(+) (10 microm on day 10 in vitro (i.v.) for 48 h) significantly decreased the number of THir by 40% compared with untreated control cultures. Rotenone at both short (20 nm on day 10 i.v. for 48 h) and long-term (1 nm on day 6 i.v. for 6 consecutive days) toxicities reduced the number of THir neurons by 33% and 24%, respectively. Treatment of cultures with thymoquinone (0.01, 0.1, 1, 10 microm on day 8 i.v. for 4 days) rescued about 25% of THir neurons at concentrations of 0.1 microm and 1 microm against MPP(+)-induced cell death. Against rotenone, thymoquinone afforded significant protection in both short- and long-term models. In short-term rotenone toxicity, thymoquinone (from days 8-12 i.v.) saved about 65%, 74% and 79% of THir neurons at concentrations of 0.01, 0.1 and 1 microm, respectively, compared with cell loss induced by rotenone. In long-term rotenone toxicity, concomitant treatment of cultures with thymoquinone significantly rescued about 83-100% of THir neurons compared with rotenone-treated cultures. In conclusion,the current study presents for the first time the potential of thymoquinone to protect primary dopaminergic neurons against MPP(+) and rotenone relevant to Parkinson’s disease.
Neurosci Lett. 2014 Jun 6;570:126-31.
doi: 10.1016/j.neulet.2013.09.049. Epub 2013 Sep 27.
Thymoquinone protects cultured hippocampal and human induced pluripotent stem cells-derived neurons against α-synuclein-induced synapse damage
A H Alhebshi 1, A Odawara 1, M Gotoh 1, I Suzuki 2
The seeds of Nigella sativa are used worldwide to treat various diseases and ailments. Thymoquinone (TQ) that is present in the essential oil of these seeds mediates most of the plant’s diverse therapeutic effects. The present study aimed to determine whether TQ protects against α-synuclein (αSN)-induced synaptic toxicity in rat hippocampal and human induced pluripotent stem cell (hiPSC)-derived neurons. Here, we report that αSN decreased the level of synaptophysin, a protein used as an indicator of synaptic density, in cultured hippocampal and hiPSC-derived neurons. However, simultaneous treatment with αSN and TQ protected neurons against αSN-induced synapse damage, as revealed by immunostaining. Moreover, administration of TQ efficiently induced protection in these cells against αSN-induced inhibition of synaptic vesicle recycling in hippocampal and hiPSC-derived neurons as well as against mutated P123H β-synuclein (βSN) in hippocampal neurons, as revealed by experiments using the fluorescent dye FM1-43. Using a multielectrode array, we further demonstrated that the treatment of hiPSC-derived neurons with αSN induced a reduction in spontaneous firing activity, and cotreatment with αSN and TQ partially reversed this loss. These results suggest that TQ protects cultured rat primary hippocampal and hiPSC-derived neurons against αSN-induced synaptic toxicity and could be a promising therapeutic agent for patients with Parkinson’s disease and dementia with Lewy bodies.
Curr Mol Pharmacol. 2021 Jan 5.
doi: 10.2174/1874467214666210105140944. Online ahead of print.
The mechanistic role of thymoquinone in Parkinson’s disease: focus on neuroprotection in pre-clinical studies
Mohammad Najim Uddin 1, Mohammad Injamul Hoq 2, Israt Jahan 1, Shafayet Ahmed Siddiqui 3, Chayan Dhar Clinton 4, Mohammed Ibrahim 5, Mohammad Safiqul Islam 3, Md Jakaria 6
Thymoquinone (TQ) is one of the leading phytochemicals, which is abundantly found in Nigella sativa L. seeds. TQ exhibited various biological effects such as antioxidant, anti-inflammatory, antimicrobial, and anti-tumoral in several pre-clinical studies.Parkinson’s disease (PD) is a long-term neurodegenerative disease with movement difficulties, and the common feature of neurodegeneration in PD patients is caused by dopaminergic neural damage in the substantia nigra pars compacta. The neuroprotective activity of TQ has been studied in various neurological disorders. TQ-mediated neuroprotection against PDyet to be reported in a single frame; therefore, this review is intended to narrate the potentiality of TQ in the therapy of PD. TQ has been shown to protect against neurotoxins via amelioration of neuroinflammation, oxidative stress, apoptosis, thereby protects neurodegeneration in PD models. TQ could be an emerging therapeutic intervention in PD management, but mechanistic studies have been remained to be investigated to clarify its neuroprotective role.
J Neuroimmunol. 2018 Jul 15;320:87-97.
doi: 10.1016/j.jneuroim.2018.04.018. Epub 2018 May 4.
Thymoquinone increases the expression of neuroprotective proteins while decreasing the expression of pro-inflammatory cytokines and the gene expression NFκB pathway signaling targets in LPS/IFNγ -activated BV-2 microglia cells
Makini K Cobourne-Duval 1, Equar Taka 1, Patricia Mendonca 1, Karam F A Soliman 2
Neuroinflammation and microglial activation are pathological markers of a number of central nervous system (CNS) diseases. Chronic activation of microglia induces the release of excessive amounts of reactive oxygen species (ROS) and pro-inflammatory cytokines. Additionally, chronic microglial activation has been implicated in several neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Thymoquinone (TQ) has been identified as one of the major active components of the natural product Nigella sativa seed oil. TQ has been shown to exhibit anti-inflammatory, anti-oxidative, and neuroprotective effects. In this study, lipopolysaccharide (LPS) and interferon gamma (IFNγ) activated BV-2 microglial cells were treated with TQ (12.5 μM for 24 h). We performed quantitative proteomic analysis using Orbitrap/Q-Exactive Proteomic LC-MS/MS (Liquid chromatography-mass spectrometry) to globally assess changes in protein expression between the treatment groups. Furthermore, we evaluated the ability of TQ to suppress the inflammatory response using ELISArray™ for Inflammatory Cytokines. We also assessed TQ’s effect on the gene expression of NFκB signaling targets by profiling 84 key genes via real-time reverse transcription (RT2) PCR array. Our results indicated that TQ treatment of LPS/IFNγ-activated microglial cells significantly increased the expression of 4 antioxidant, neuroprotective proteins: glutaredoxin-3 (21 fold; p < 0.001), biliverdin reductase A (15 fold; p < 0.0001), 3-mercaptopyruvate sulfurtransferase (11 fold; p < 0.01), and mitochondrial lon protease (>8 fold; p < 0.001) compared to the untreated, activated cells. Furthermore, TQ treatment significantly (P < 0.0001) reduced the expression of inflammatory cytokines, IL-2 = 38%, IL-4 = 19%, IL-6 = 83%, IL-10 = 237%, and IL-17a = 29%, in the activated microglia compared to the untreated, activated which expression levels were significantly elevated compared to the control microglia: IL-2 = 127%, IL-4 = 151%, IL-6 = 670%, IL-10 = 133%, IL-17a = 127%. Upon assessing the gene expression of NFκB signaling targets, this study also demonstrated that TQ treatment of activated microglia resulted in >7 fold down-regulation of several NFκB signaling targets genes, including interleukin 6 (IL6), complement factor B (CFB), chemokine (CC motif) ligand 3 (CXCL3), chemokine (CC) motif ligand 5 (CCL5) compared to the untreated, activated microglia. This modulation in gene expression counteracts the >10-fold upregulation of these same genes observed in the activated microglia compared to the controls. Our results show that TQ treatment of LPS/IFNγ-activated BV-2 microglial cells induce a significant increase in expression of neuroprotective proteins, a significant decrease in expression inflammatory cytokines, and a decrease in the expression of signaling target genes of the NFκB pathway. Our findings are the first to show that TQ treatment increased the expression of these neuroprotective proteins (biliverdin reductase-A, 3-mercaptopyruvate sulfurtransferase, glutaredoxin-3, and mitochondrial lon protease) in the activated BV-2 microglial cells. Additionally, our results indicate that TQ treatment decreased the activation of the NFκB signaling pathway, which plays a key role in neuroinflammation. In conclusion, our results demonstrate that TQ treatment reduces the inflammatory response and modulates the expression of specific proteins and genes and hence potentially reduce neuroinflammation and neurodegeneration driven by microglial activation.
Pharmacognosy Res. Jan-Mar 2017;9(1):12-20.
The Influence of Pluronic F68 and F127 Nanocarrier on Physicochemical Properties, In vitro Release, and Antiproliferative Activity of Thymoquinone Drug
Salwa Shaarani 1, Shahrul Sahul Hamid 2, Noor Haida Mohd Kaus 1
Background: This study reports on hydrophobic drug thymoquinone (TQ), an active compound found in the volatile oil of Nigella sativa that exhibits anticancer activities. Nanoformulation of this drug could potentially increase its bioavailability to specific target cells.
Objective: The aim of this study was to formulate TQ into polymer micelle, Pluronic F127 (5.0 wt %) and Pluronic F68 (0.1 wt %), as a drug carrier to enhance its solubility and instability in aqueous media.
Conclusion: This study suggests higher molecular weight Pluronic polymer micelles (F127) with hydrophilic-hydrophobic segments which could be used as a suitable candidate for sustainable delivery of TQ. However, comprehensive studies should be carried out to establish the suitability of Pluronic F127 as a carrier for other drugs with similar challenges as TQ.
Summary: There is a rising interest in integrating nanotechnology with medicine, creating a nanomedicine aiming for high efficiency and efficacy of disease diagnosis and treatment. In drug delivery, the term nanomedicine describes the nanometer-sized range (1-1000 nm) of a multi-component drug for disease treatments. As such, liposome-based nanoparticulate delivery vehicles have been approved by the Food and Drug Administration (FDA) for clinical applications. The main purpose of introducing nanoscale drug delivery is to improve the pharmacological and pharmacokinetic profiles of therapeutic molecules. Drug or therapeutic molecules can be either released through the cleavage of a covalent linkage between drug molecules and polymers (conjugation) or through the diffusion from a drug and polymer blended matrix (physical encapsulation). Polymers play an important role in the design of nanocarriers for therapeutic deliveries. In Asia, Nigella sativa seed oil has been used traditionally for its various medicinal benefits. One of its most potent compound which is thymoquinone has been intensively investigated for its anti-cancer effects in colorectal carcinoma, breast adenocarcinoma, osteosarcoma, ovarian carcinoma, myeloblastic leukemia, and pancreatic carcinoma. In addition, it is reported to show anti-inflammatory potential, antidiabetic, antihistaminic effects, as well as the ability to alleviate respiratory diseases, rheumatoid arthritis, multiple sclerosis, and Parkinson’s disease. This study aims to formulate and characterize different pluronic-based thymoquinone nanocarrier and investigate its effect against breast cancer cells