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
Abstract
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 PD yet 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.
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Review CNS Neurol Disord Drug Targets. 2018;17(6):412-420.doi: 10.2174/1871527317666180702101455.
A Review on Possible Therapeutic Effect of Nigella sativa and Thymoquinone in Neurodegenerative Diseases
Saeed Samarghandian 1, Tahereh Farkhondeh 2, Fariborz Samini 3
Abstract
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 between 1979 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.
Conclusion: Therefore, better designed clinical trials in humans are needed to confirm these effects.
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Review Biochemistry (Mosc). 2020 Feb;85(2):167-176. doi: 10.1134/S0006297920020042.
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
Abstract
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.
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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 7Affiliations expand
- PMID: 27752803
- DOI: 10.1007/s11064-016-2073-z
Abstract
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.
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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 2Affiliations expand
- PMID: 29759145
- PMCID: PMC5967628
- DOI: 10.1016/j.jneuroim.2018.04.018
Free PMC article
Abstract
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). …
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.