Figure - available from: Parkinson’s Disease
This content is subject to copyright. Terms and conditions apply.
Effect of M. communis on the fibrillation of α-Syn. (a) The kinetic of α-Syn fibrillation in the absence (●) and the presence of 1% of M. communis (▵) monitored by ThT fluorescence. The continuous lines represent fits to (1). (b)–(e) AFM images and (f)-(g) far-UV CD spectra of α-Syn incubated without or with M. communis (1% v/v). (b), (c), and (f) are for α-Syn incubated without M. communis; (d), (e), and (g) are for samples incubated with M. communis. (▲) is considered for 7 h and (□) for 24 h incubation. (○) is reflected for fresh monomer protein. The concentration of α-Syn was 70 μM.
Source publication
α
-Synuclein (
α
-Syn) fibrillation links with Parkinson’s disease (PD) and several related syndromes. It is believed that exposure to the factors which promote fibrillation may induce and progress such neurodegenerative diseases (NDs). Herein, the effects of some wildly used essential oils including
Myrtus communis
(
M. communis
) on
α
-Syn fibril...
Citations
... Various Ayurvedic medicines and remedies have been operated for the treatment of several diseases in humans (Mukherjee et al., 2017), including indigestion, common cold, chronic diarrhea, blood sugar, blood pressure (Ganguly, 2010), and especially age-related neurological disorders (Kannappan et al., 2011;Singh et al., 2011;Sedaghat et al., 2014;Pathak-Gandhi and Vaidya, 2017;Abulfadl et al., 2018). (Ganguly, 2010) and have been proven to impose great efficacy with regard to age-related neurological disorders (Youdim and Joseph, 2001;Adams et al., 2007;Chonpathompikunlert et al., 2010;Mani et al., 2013;Rasool et al., 2014;Morshedi et al., 2015;Prabha and Anusha, 2015;Morshedi and Nasouti, 2016;Nemati et al., 2018;Keshavarzi et al., 2019;Mima et al., 2020;Hannan et al., 2021;Zeng et al., 2021). Therefore, this review aims to summarize the data on the neuroprotective effect of these common Indian spices on age-related neurological diseases ( Figure 1). ...
Aging is described as an advanced time-related collection of changes that may negatively affect with the risk of several diseases or death. Aging is a main factor of several age-related neurological disorders, including neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease, and dementia), stroke, neuroinflammation, neurotoxicity, brain tumors, oxidative stress, and reactive oxygen species (ROS). Currently available medications for age-related neurological disorders may lead to several side effects, such as headache, diarrhea, nausea, gastrointestinal (GI) diseases, dyskinesia, and hallucinosis. These days, studies on plant efficacy in traditional medicine are being conducted because herbal medicine is affordable, safe, and culturally acceptable and easily accessible. The Indian traditional medicine system called Ayurveda uses several herbs and medicinal plants to treat various disorders including neurological disorders. This review aims to summarize the data on the neuroprotective potential of the following common Indian spices widely used in Ayurveda: cumin ( Cuminum cyminum (L.), Apiaceae), black cumin ( Nigella sativa (L.), Ranunculaceae), black pepper ( Piper nigrum (L.), Piperaceae), curry leaf tree ( Murraya koenigii (L.), Spreng Rutaceae), fenugreek ( Trigonella foenum-graecum (L.), Fabaceae), fennel ( Foeniculum vulgare Mill, Apiaceae), cardamom ( Elettaria cardamomum (L.) Maton, Zingiberaceae), cloves ( Syzygium aromaticum (L.) Merr. & L.M.Perry, Myrtaceae), and coriander ( Coriandrum sativum (L.), Apiaceae) in age-related neurological disorders.
... Interestingly, another polyphenol, Cuminaldehyde, isolated from Iranian cumin, was found to be superior to Baicalein. It inhibited α-syn fibrillation [394] and blocked protein assembly into β-structural fibrils by the interaction with its amine and aldehyde groups with α-syn [395]. In the same line of evidence, one of the most popular catechins, (−)-Epigallocatechin 3-gallate (EGCG), a flavanol compound predominantly present in green tea, inhibited α-syn aggregation and fibrillation in a concentration-dependent manner [396]. ...
Mon projet de thèse s’inscrit dans l’étude des synucléinopathies, une famille de maladies neurodégénératives. Les trois principales synucléinopathies sont la maladie de Parkinson, l’atrophie multisystématisée et la démence à corps de Lewy. Ces maladies sont caractérisées par une perte de neurones dans des régions cérébrales spécifiques et la présence d’inclusions intra-cytoplasmiques positives pour l’α-synucléine dans les neurones (Corps de Lewy) ou dans les oligodendrocytes (Inclusions gliales cytoplasmiques). Les causes d’induction de ces maladies restent encore inconnues et les traitements curatifs sont inexistants. L’objectif de mon travail de thèse visait à étudier les mécanismes neurodégénératifs et de potentielles cibles thérapeutiques dans le contexte des synucléinopathies. Je me suis tout d’abord intéressée aux mécanismes impliqués dans la transmission de l’α-synucléine issue de patients atteints de l’atrophie multisystématisée. Ce travail nous a permis de développer un potentiel nouveau modèle de l’atrophie multisystématisée chez la souris et le primate non-humain, par la transmission de l’α-synucléine dans le cerveau. Dans un deuxième temps, nous nous sommes intéressés à des cibles thérapeutiques éventuelles pour la maladie de Parkinson dans un même modèle animal de la pathologie. Nous avons pu vérifier l’efficacité et la pertinence de trois différentes stratégies ciblant plusieurs mécanismes affectés dans la maladie de Parkinson dans le but d’induire une protection des neurones dopaminergiques de la substance noire des souris. Nous avons pu démontrer une dérégulation des niveaux de zinc au cours de la pathologie qui a suscité l’intérêt de cibler son homéostasie dans le cerveau à travers une molécule chélatrice du zinc. Ensuite, la surexpression d’un facteur de transcription impliqué dans la survie des neurones dopaminergiques ainsi que dans le stress oxydatif et le protéasome a montré son intérêt comme cible thérapeutique de la maladie de Parkinson. Enfin, une molécule anti-agrégative a aussi démontré sa capacité à induire une neuroprotection. En résumé, ces travaux montrent d’abord l’importance de l’α-synucléine dans la mise en place et la progression des synucléinopathies, mais aussi la nécessité de cibler d’autres mécanismes dérégulés dans ces pathologies pour proposer des nouvelles stratégies thérapeutiques.
... Another important aspect that is usually associated with studies on PD is on α-Syn fibrillation. It is presumed that protein structural modifications resulting in amyloid fibril formation progresses towards neurodegenerative disorders [140]. However, the exact factors of α-Syn actions of misfolding and aggregation in the brain are still scarce. ...
... In addition, it should also be noted that preventive measures against α-Syn fibrillation are yet to be available; hence, the acceleration of the fibrillation process via certain factors should be avoided. Among some of the common factors are metal ions, small molecules, nanoparticles, and, particularly, toxins that could intensify the aggregation process [140,[230][231][232][233]. The next two in vitro studies were performed by the same research team, where they highlighted the effects of 15 various Iranian EOs against α-Syn fibrillation [140,141]. ...
... In addition, it should also be noted that preventive measures against α-Syn fibrillation are yet to be available; hence, the acceleration of the fibrillation process via certain factors should be avoided. Among some of the common factors are metal ions, small molecules, nanoparticles, and, particularly, toxins that could intensify the aggregation process [140,[230][231][232][233]. The next two in vitro studies were performed by the same research team, where they highlighted the effects of 15 various Iranian EOs against α-Syn fibrillation [140,141]. ...
Despite the improvements in life expectancy, neurodegenerative conditions have arguably become the most dreaded maladies of older people. The neuroprotective and anti-ageing potentials of essential oils (EOs) are widely evaluated around the globe. The objective of this review is to analyse the effectiveness of EOs as neuroprotective remedies among the four common age-related neurodegenerative diseases. The literature was extracted from three databases (PubMed, Web of Science and Google Scholar) between the years of 2010 to 2020 using the medical subject heading (MeSH) terms “essential oil”, crossed with “Alzheimer’s disease (AD)”, “Huntington’s disease (HD)”, “Parkinson’s disease (PD)” or “amyotrophic lateral sclerosis (ALS)”. Eighty three percent (83%) of the studies were focused on AD, while another 12% focused on PD. No classifiable study was recorded on HD or ALS. EO from Salvia officinalis has been recorded as one of the most effective acetylcholinesterase and butyrylcholinesterase inhibitors. However, only Cinnamomum sp. has been assessed for its effectiveness in both AD and PD. Our review provided useful evidence on EOs as potential neuroprotective remedies for age-related neurodegenerative diseases.
... Therefore, differentiated SH-SY5Y cells have been used as appropriate in vitro cell model to study the mechanism of rotenone neurotoxicity. SH-SY5Y cells were grown in 12-well plates to a density of 4Â10 4 cells/well and then treated with RA dissolved in DMEM-F12 (2% FBS) to a final concentration of 10 μM, incubated for eight days (the medium was replaced every two days) [41]. ...
Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders with no precise etiology. Multiple lines of evidence support that environmental factors, either neurotoxins or neuroinflammation, can induce Parkinsonism. In this study, we purified an active compound, neobaicalein (Skullcapflavone II), from the roots of Scutellaria pinnatifida (S. pinnatifida). Neobaicalein not only had protective impacts on rotenone-induced neurotoxicity but in glial cultures, it dampened the inflammatory response when stimulated with lipopolysaccharide (LPS). Neobaicalein had high antioxidant activity without any obvious toxicity. In addition, it could raise the cell viability, decrease early apoptosis, reduce the generation of reactive oxygen species (ROS), and keep the neurite's length normal in the treated SH-SY5Y cells. Pathway enrichment analysis (PEA) and target prediction provided insights into the PD related genes, protein-protein interaction (PPI) network, and the key proteins enriched in the signaling pathways.
Furthermore, docking simulation (DS) on the proteins of the PD-PPI network revealed that neobaicalein might interact with the key proteins involved in PD pathology, including MAPK14, MAPK8, and CASP3. It also blocks the destructive processes, such as cell death, inflammation, and oxidative stress pathways. Our results demonstrate that neobaicalein alleviates pathological effects of factors related to PD, and may provide new insight into PD therapy.
... Moreover, novel strategies like encapsulation (e.g., β-cyclodextrin) have been reported and are also available in several reviews for increased efficacy, stability, and release of EO/components of EO (Kfoury et al. 2019). A recent study directs the attention toward involvement of EO from Myrtus communis in leading α-synuclein toward formation of fibrils, which ultimately contributes to the progression of Parkinson's and related symptoms (Morshedi and Nasouti 2016). Study revealed that α-synuclein treated with M. communis EO caused significant induction of α-synuclein for crossed β-sheet formation in comparison with the untreated α-synuclein. ...
... The study further states the relatively high PD incidence in the Zoroastrian community using this plant in their religious activities. Also, the study suggests for the inclusion of fibril formation test in clinical trials for efficacy of various EO against different neurological disorders considering the impact EO has on the α-synuclein fibrillation (Morshedi and Nasouti 2016). The report highlights the importance of such tests on EO to improve the care and prevention methods being followed in neurological disorders, which are still difficult to treat and/or cure. ...
Essential oils (EO), produced from isoprenoid pathways are a blend of hydrocarbons and its oxygenated derivatives, which possess many biological properties. EO are conventionally used in medications, and also for sanitary, cosmetic, fragrance, essence, preservatives, and food additives. In pharmaceutical applications, they are used as antimicrobial (viricidal, fungicidal, bactericidal), antiseptic, anti-parasitical, insecticidal, pesticidal, and herbicidal agents. Owing to the complexity and stability (singly or combinations) exhibited by EO, they have crossed the conventional boundaries, and are now explored for their efficacy against neurological disorders. EO are reported to exhibit antioxidant, anti-inflammatory, neuroprotective, anxiolytic, anticonvulsant or antiepileptic, memory enhancing, anticholinesterase, cognitive and mood effects, antidepressant, neuropathic, antinociceptive, anti-psychosis, anti-Parkinson’s, antimigraine, anti-meningitis, anti-dementia, and anti-Alzheimer’s properties. This has favored the use of EO in the prevention and cure of neurological disorders. Moreover, the mode of action of EO for these arrays of biological properties is identified, and several unknowns are being investigated. With the advent of modern technologies and methodologies, EO from many aromatic and medicinal plants are now isolated, characterized, and explored against many neurological disorders, and some have succeeded to reach the phases of clinical trials. Furthermore, EO pose negligible side effects, and are permeable to blood–brain barrier. Efforts are in progress to further increase their stability, release, and potency against neurological disorders. Thus, in this chapter, an updated summary of EO explored against some common neurological disorders along with their possible mode of action has been presented.
... Interestingly, another polyphenol, Cuminaldehyde, isolated from Iranian cumin, was found to be superior to Baicalein. It inhibited αsyn fibrillation [394] and blocked protein assembly into β-structural fibrils by the interaction with its amine and aldehyde groups with α-syn [395]. In the same line of evidence, one of the most popular catechins, (−)-Epigallocatechin 3-gallate (EGCG), a flavanol compound predominantly present in green tea, inhibited α-syn aggregation and fibrillation in a concentration-dependent manner [396]. ...
Parkinson’s Disease (PD) is characterized both by the loss of dopaminergic neurons in the substantia nigra and the presence of cytoplasmic inclusions called Lewy Bodies. These Lewy Bodies contain the aggregated α-synuclein (α-syn) protein, which has been shown to be able to propagate from cell to cell and throughout different regions in the brain. Due to its central role in the pathology and the lack of a curative treatment for PD, an increasing number of studies have aimed at targeting this protein for therapeutics. Here, we reviewed and discussed the many different approaches that have been studied to inhibit α-syn accumulation via direct and indirect targeting. These analyses have led to the generation of multiple clinical trials that are either completed or currently active. These clinical trials and the current preclinical studies must still face obstacles ahead, but give hope of finding a therapy for PD with time.
... The majority of plant extracts used in traditional medicines are based on long-established knowledge of their health benefits, time tested safety due to ancient use, and potential therapeutic effects. However, some plants are not as beneficial as documented or are detrimental; the essential oil from Myrtus communis, which is popular in the Zoroastrian community for aroma (Morshedi and Nasouti, 2016), increases α-syn fibrillation and enhances α-syn toxicity in human neuroblastoma cells (Morshedi and Nasouti, 2016). This study suggests that essential oils used in aromatherapy should be investigated for their potential neurotoxicity or neurodegenerative ability. ...
... The majority of plant extracts used in traditional medicines are based on long-established knowledge of their health benefits, time tested safety due to ancient use, and potential therapeutic effects. However, some plants are not as beneficial as documented or are detrimental; the essential oil from Myrtus communis, which is popular in the Zoroastrian community for aroma (Morshedi and Nasouti, 2016), increases α-syn fibrillation and enhances α-syn toxicity in human neuroblastoma cells (Morshedi and Nasouti, 2016). This study suggests that essential oils used in aromatherapy should be investigated for their potential neurotoxicity or neurodegenerative ability. ...
... It prevented α-syn fibrillation even in the presence of seeds with negligible disaggregating effect on the preformed fibrils of α-syn. Interestingly, it was found to be superior to baicalein, a known inhibitor of α-syn fibrillation and blocked protein assembly into β-structural fibrils that were attributed to interaction with amine and aldehyde groups in the chemical structure (Morshedi and Nasouti, 2016). ...
Alzheimer’s disease (AD) and dementia are disorders of the aging population and becoming major health care burden worldwide due to unavailability of complete therapy. AD is the most frequent cause of dementia among 60% to 80% patients and has effected 45 million people globally which is estimated to triple by 2050 (Alzheimer’s, 2015). AD is a progressive, neurodegenerative disorder, characterized by behavioral turbulence, cognitive dysfunctions, imperfection in routine life activities, thus putting a huge socioeconomic burden on the health care system ( Ahmad et al., 2015; Ali et al., 2017; Ayaz et al., 2017b). Among the pathophysiological hallmarks of the disease are
the deficiency of vital neurotransmitter acetylcholine (ACh), deposition of amyloid plaques (Aβ), highly phosphorylated tau proteins, and imbalance in gluatamatergic system ( Ayaz et al., 2017a; Khalil et al., 2018 ; Ovais et al., 2018a). Only five drugs are linically approved for use, among which tacrine, galantamine, donepezil, and rivastigmine are cholinesterase inhibitors whereas the fifth one memantine is glutamatergic system modulator (Ayaz et al., 2015 ; Kamal et al., 2015). These drugs have limited efficacy and are associated with side effects like tacrine is hepatotoxic (Watkins et al., 1994). Currently, results from clinical trials performed in mild to moderate AD dementia have
directed researchers to find more effective yet safe alternatives from natural sources (Yiannopoulou and Papageorgiou, 2013 ; Cummings et al., 2014 ; Ovais et al., 2018b).
... The majority of plant extracts used in traditional medicines are based on long-established knowledge of their health benefits, time tested safety due to ancient use, and potential therapeutic effects. However, some plants are not as beneficial as documented or are detrimental; the essential oil from Myrtus communis, which is popular in the Zoroastrian community for aroma (Morshedi and Nasouti, 2016), increases α-syn fibrillation and enhances α-syn toxicity in human neuroblastoma cells (Morshedi and Nasouti, 2016). This study suggests that essential oils used in aromatherapy should be investigated for their potential neurotoxicity or neurodegenerative ability. ...
... The majority of plant extracts used in traditional medicines are based on long-established knowledge of their health benefits, time tested safety due to ancient use, and potential therapeutic effects. However, some plants are not as beneficial as documented or are detrimental; the essential oil from Myrtus communis, which is popular in the Zoroastrian community for aroma (Morshedi and Nasouti, 2016), increases α-syn fibrillation and enhances α-syn toxicity in human neuroblastoma cells (Morshedi and Nasouti, 2016). This study suggests that essential oils used in aromatherapy should be investigated for their potential neurotoxicity or neurodegenerative ability. ...
... It prevented α-syn fibrillation even in the presence of seeds with negligible disaggregating effect on the preformed fibrils of α-syn. Interestingly, it was found to be superior to baicalein, a known inhibitor of α-syn fibrillation and blocked protein assembly into β-structural fibrils that were attributed to interaction with amine and aldehyde groups in the chemical structure (Morshedi and Nasouti, 2016). ...
α-Synuclein (α-syn) is a presynaptic protein that regulates the release of neurotransmitters from synaptic vesicles in the brain. α-Syn aggregates, including Lewy bodies, are features of both sporadic and familial forms of Parkinson's disease (PD). These aggregates undergo several key stages of fibrillation, oligomerization, and aggregation. Therapeutic benefits of drugs decline with disease progression and offer only symptomatic treatment. Novel therapeutic strategies are required which can either prevent or delay the progression of the disease. The link between α-syn and the etiopathogenesis and progression of PD are well-established in the literature. Studies indicate that α-syn is an important therapeutic target and inhibition of α-syn aggregation, oligomerization, and fibrillation are an important disease modification strategy. However, recent studies have shown that plant extracts and phytochemicals have neuroprotective effects on α-syn oligomerization and fibrillation by targeting different key stages of its formation. Although many reviews on the antioxidant-mediated, neuroprotective effect of plant extracts and phytochemicals on PD symptoms have been well-highlighted, the antioxidant mechanisms show limited success for translation to clinical studies. The identification of specific plant extracts and phytochemicals that target α-syn aggregation will provide selective molecules to develop new drugs for PD. The present review provides an overview of plant extracts and phytochemicals that target α-syn in PD and summarizes the observed effects and the underlying mechanisms. Furthermore, we provide a synopsis of current experimental models and techniques used to evaluate plant extracts and phytochemicals. Plant extracts and phytochemicals were found to inhibit the aggregation or fibril formation of oligomers. These also appear to direct α-syn oligomer formation into its unstructured form or promote non-toxic pathways and suggested to be valuable drug candidates for PD and related synucleinopathy. Current evidences from in vitro studies require confirmation in the in vivo studies. Further studies are needed to ascertain their potential effects and safety in preclinical studies for pharmaceutical/nutritional development of these phytochemicals or dietary inclusion of the plant extracts in PD treatment.
... DOPG vesicles containing calcein at self-quenching concentrations (70 mM) were prepared as described 32 . Briefly, 5 mg/mL DOPG and 70 mM of calcein were dissolved in 1 mL PBS, subjected to 10 times freezing in liquid nitrogen and thawing at 50 °C, extruded 21 times through a 100 nm filter and purified on a PD-10 desalting column (GE Healthcare). ...
The protein α-synuclein (αSN) aggregates to form fibrils in neuronal cells of Parkinson's patients. Here we report on the effect of neutral (zwitterionic) nanoliposomes (NLPs), supplemented with cholesterol (NLP-Chol) and decorated with PEG (NLP-Chol-PEG), on αSN aggregation and neurotoxicity. Both NLPs retard αSN fibrillization in a concentration-independent fashion. They do so largely by increasing lag time (formation of fibrillization nuclei) rather than elongation (extension of existing nuclei). Interactions between neutral NLPs and αSN may locate to the N-terminus of the protein. This interaction can even perturb the interaction of αSN with negatively charged NLPs which induces an α-helical structure in αSN. This interaction was found to occur throughout the fibrillization process. Both NLP-Chol and NLP-Chol-PEG were shown to be biocompatible in vitro, and to reduce αSN neurotoxicity and reactive oxygen species (ROS) levels with no influence on intracellular calcium in neuronal cells, emphasizing a prospective role for NLPs in reducing αSN pathogenicity in vivo as well as utility as a vehicle for drug delivery.
... Additional investigation suggested that cuminaldehyde impaired β-structural assembly of alpha synuclein fibrils, thereby inhibiting its fibrillation [23]. On the contrary, inhibitory effects of cuminaldehyde on alpha synuclein fibrillation was weakened by essential oil of Myrtus communis [27], indicating that essential oils from natural sources are not always beneficial. ...
Cuminaldehyde is one of major constituents identified in the essential oil of a number of commonly used spices such as green cumin (Cuminum Cyminum L.) which has been traditionally used for the treatment of dyspepsia, diarrhea, abdominal colic and Jaundice. Cumin essential oil has multiple pharmacological actions including antioxidant, antidiabetic, anti-inflammatory, antibacterial and anticancer effects. Therefore, a great deal of attention has been given to investigate the role of cuminaldehyde in mediating cumin's multiple therapeutic benefits. This short review highlights the most significant recently reported findings which unravel the extent to which cuminaldehyde contributes to the therapeutic effects of its producing herbs. Apart from its non-medical effects as natural bio-fumigant, cuminaldehyde is a promising potential drug candidate against various diseases.
