Therapeutic Potential of Baicalein in Alzheimer’s Disease and Parkinson’s Disease

Li, Yanwei; Zhao, Jinying; Hölscher, Christian

doi:10.1007/s40263-017-0451-y

Cited by 82 publications

(47 citation statements)

References 144 publications

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“…As the disease progresses, the effect of glutamate inhibition on the rate of degeneration increases. Baicalein, a Chinese medicine extracted from the root of Scutellaria baicalensis Georgi was able the show neuroprotective properties; this drug diminishes excitotoxicity by inhibiting the release of glutamate and antagonizing NMDA receptors (Lee et al, 2003;Li et al, 2017); it also diminishes excitotoxicity-induced by glucose-deprivation (Lee et al, 2003). Our modeling studies suggest that the selective glutamate inhibitors would show neuroprotective effect all through the course of the disease and strikingly even in advanced stages of disease progression.…”

Section: Glutamate Inhibition Therapymentioning

confidence: 76%

A computational model of loss of dopaminergic cells in Parkinson’s disease due to glutamate-induced excitotoxicity

Muddapu

Mandali

Chakravarthy

et al. 2018

Preprint

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Parkinson's disease (PD) is a neurodegenerative disease associated with progressive and inexorable loss of dopaminergic cells in Substantia Nigra pars compacta (SNc). A full understanding of the underlying pathogenesis of this cell loss is unavailable, though a number of mechanisms have been indicated in the literature. A couple of these mechanisms, however, show potential for the development of radical and promising PD therapeutics. One of these mechanisms is the peculiar metabolic vulnerability of SNc cells by virtue of their excessive energy demands; the other is the excitotoxicity caused by excessive glutamate release onto SNc by an overactive Subthalamic Nucleus (STN). To investigate the latter hypothesis computationally, we developed a spiking neuron network model of the SNc-STN-GPe system. In the model, prolonged stimulation of SNc cells by an overactive STN leads to an increase in a 'stress' variable; when the stress in a SNc neuron exceeds a stress threshold the neuron dies. The model shows that the interaction between SNc and STN involves a positive feedback due to which, an initial loss of SNc cells that crosses a threshold causes a runaway effect that leads to an inexorable loss of SNc cells, strongly resembling the process of neurodegeneration. The model further suggests a link between the two aforementioned PD mechanisms: metabolic vulnerability and glutamate excitotoxicity. Our simulation results show that the excitotoxic cause of SNc cell loss in PD might be initiated by weak excitotoxicity mediated by energy deficit, followed by strong excitotoxicity, mediated by a disinhibited STN. A variety of conventional therapies are simulated in the model to test their efficacy in slowing down or arresting SNc cell loss. Among the current therapeutics,

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Section: Glutamate Inhibition Therapymentioning

confidence: 76%

A computational model of loss of dopaminergic cells in Parkinson’s disease due to glutamate-induced excitotoxicity

Muddapu

Mandali

Chakravarthy

et al. 2018

Preprint

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“…The fascinating effects of this baicalein-enriched F5 on GBM cell inhibitory could be due to the its major capacities to inhibit complexes of cyclins to regulate the cell cycle [26], to induce apoptosis by activating caspase-9/-3 [27] and to inhibit tumor invasion and metastasis by reducing the expression of matrix metalloproteinase-2/-9 (MMP-2/-9) [28]. In addition, the ability of baicalein to cross the blood-brain barrier (BBB) [29,30] and distribute over a wide range of brain area after the intravenous or oral administration [31,32] has significantly supported its therapeutic potential for brain and central nervous system (CNS) diseases, including the brain cancer as discussed in this study. However, further detailed studies regarding the mechanism of baicalein-enriched F5 permeability to BBB and its inhibitory effects on cancerous brain cells are imperative to confirm the efficacy of this compound for treatment in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Baicalein-Enriched Fraction Extracted from Oroxylum indicum (L.) Benth. ex Kurz Leaves Exerts Antioxidant and Inhibitory Effects Against Glioblastoma Multiforme

et al. 2019

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Glioblastoma multiforme (GBM) is the most malignant subtype of primary brain cancer. To date, standard clinical treatment for GBM is limited in effectiveness and could impose additional side effects. Recently, numerous bioactive compounds isolated from natural plants appear to have beneficial anti-cancer properties. Here, the GBM inhibitory effect of baicalein, a bioactive flavonoid extracted from Oroxylum indicum (L.) Benth. ex Kurz, was evaluated. Firstly, three solvents were used to extract the baicalein. We found that the binary extraction system, using a combination of petroleum ether and methanol (PM), yielded the highest amount of baicalein (15%) compared to the mono extraction system using methanol (13%) or aqueous (0.04%) only. In order to further enhance the baicalein yield in PM crude extract, it was subjected to an enrichment fractionation procedure, which successfully increased the baicalein by nearly two-fold from the initial crude extract (15%) to the enriched fraction 5 (F5) (29%). The enriched F5 not only showed significantly higher (~2.5-fold) antioxidant properties as compared to the crude extract, it was also found to significantly suppress GBM cell proliferation ~2.5-fold better than the crude extract. In conclusion, this study successfully optimized an extraction procedure for increased yield of baicalein metabolite from O. indicum leaves and enhanced its therapeutic potential for GBM treatment.

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“…Many authors especially emphasize the polyphenols baicalein and curcumin as inhibitors of α-synuclein fibrillation. For baicalein, the therapeutic effects in Alzheimer’s and Parkinson’s diseases [ 164 ] and the ability to inhibit aggregation of both PrP [ 165 ] and α-synuclein [ 166 ] have been demonstrated. This compound inhibits amyloid aggregation of α-synuclein in vitro [ 167 ] and in vivo in mouse and rat models [ 166 , 168 ].…”

Section: Hydroxycinnamic Acid Derivatives Modulating the Pathologimentioning

confidence: 99%

Natural and Synthetic Derivatives of Hydroxycinnamic Acid Modulating the Pathological Transformation of Amyloidogenic Proteins

et al. 2020

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This review presents the main properties of hydroxycinnamic acid (HCA) derivatives and their potential application as agents for the prevention and treatment of neurodegenerative diseases. It is partially focused on the successful use of these compounds as inhibitors of amyloidogenic transformation of proteins. Firstly, the prerequisites for the emergence of interest in HCA derivatives, including natural compounds, are described. A separate section is devoted to synthesis and properties of HCA derivatives. Then, the results of molecular modeling of HCA derivatives with prion protein as well as with α-synuclein fibrils are summarized, followed by detailed analysis of the experiments on the effect of natural and synthetic HCA derivatives, as well as structurally similar phenylacetic and benzoic acid derivatives, on the pathological transformation of prion protein and α-synuclein. The ability of HCA derivatives to prevent amyloid transformation of some amyloidogenic proteins, and their presence not only in food products but also as natural metabolites in human blood and tissues, makes them promising for the prevention and treatment of neurodegenerative diseases of amyloid nature.

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Therapeutic Potential of Baicalein in Alzheimer’s Disease and Parkinson’s Disease

Cited by 82 publications

References 144 publications

A computational model of loss of dopaminergic cells in Parkinson’s disease due to glutamate-induced excitotoxicity

A computational model of loss of dopaminergic cells in Parkinson’s disease due to glutamate-induced excitotoxicity

Baicalein-Enriched Fraction Extracted from Oroxylum indicum (L.) Benth. ex Kurz Leaves Exerts Antioxidant and Inhibitory Effects Against Glioblastoma Multiforme

Natural and Synthetic Derivatives of Hydroxycinnamic Acid Modulating the Pathological Transformation of Amyloidogenic Proteins

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