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In PD, decreased striatal dopamine occurred following selective neurodegeneration of dopaminergic neurons of the substantia nigra par compacta SNc and impairment of several basal ganglia functions. However, the sensitivity of dopaminergic neurons also conferred to intrinsic and excitotoxic insult and does not rely on absence of dopamine metabolism.

Parkinson’s Disease

There are two characteristic features of dopaminergic neurons which makes them especially more susceptible to excitotoxic challenge. First dopamine neurons show a prolonged axonal branch, which offer extensive neurotransmitter release sites. Enhanced mitochondrial impairment is observed in the axons of dopaminergic neurons and this is one of the reasons to show elevated susceptibility. Second, dopamine neurons act as autonomous pacemakers and display spontaneous activity. All these processes are required to complete the requirements of bioenergetics and to prevent the unnecessary activation of ATP-sensitive potassium channels that may inhibit the spontaneous activity of neurons.

Nigral dopaminergic neurons and different brain nuclei neurons involved in sensorimotor integration are capable with mechanisms that maintain to rapidly implement a correct strategy upon environmental stress.

Parkinson’s Disease

As a result, for this adaptive ability is the vulnerability of the system to environmental toxins, age, and genetic mutations or that can increase the reactive oxygen species production which ca warrant the proteostasis, DNA damages, especially in mitochondria. Impairment in mitochondria ultimately leads to cause impaired mitophagy and also compromised.

In the recent years, a growing effort has been taken in the development of innovative neuroprotective molecules of natural origin with high efficacy and low side effects to prevent neuronal deaths [ 10 , 19 ]. Several studies have been attempted to examine the effects of extracted components from different plants on neurotoxicity. Among the numerous compounds from plants, flavonoids are the utmost effective components with a broader range of pharmacological and health-promoting properties [ 20 , 21 ]. To date, almost different flavonoid compounds have been discovered and are classified into various subgroups, including flavonols, flavones, flavanols, flavanones, isoflavones, etc.

Numerous vegetables and fruits, flavonoid compounds are the major classes of natural polyphenols. The consumption of flavonoid-rich fruits and vegetables significantly reduces the risk of many diseases in humans [ 23 , 24 ]. Baicalein 5,6,7-trihydroxyflavone; C 15 H 10 O 5 is an important flavonoid compound mainly isolated from the roots of S. Earlier studies clearly showed that baicalein has various pharmacological properties such as antioxidant, anti-inflammatory, antidiabetic, anticancer, antiulcerative colitis, antithrombotic, antiviral, eye protective, cardioprotective, neuroprotective, and hepatoprotective properties [ 25 ].

It also possesses anticonvulsive, anxiolytic, and mild sedative actions [ 26 ]. Earlier, some authors clearly reviewed the anticancer, anti-inflammatory, cardioprotective properties, ocular disorders, and mitochondrial function [ 34 , 35 , 36 , 37 ]. Baicalein halts PD progression by reducing oxidative stress, inhibiting excitotoxicity, inhibiting aggregation of disease-specific amyloid proteins, and stimulating neurogenesis and antiapoptosis as well as anti-inflammatory properties. However, scientific literature review on the neuroprotective effects of baicalein is still missing.

PD develops with the aggregation of disease-specific proteins in amyloid nature. It is well known that polyphenols, including baicalein or other flavonoids, are readily oxidized to quinones by oxygen because of their reductive nature, although quinones are readily reactive with the side-chain amino groups of proteins. The BBB is an important network that plays a key role in maintaining homeostasis of the central nervous system, and its disturbance is prominently recognized for many neuronal disorders [ 27 ].

The BBB is made up of microvessel endothelial cells, in the arrangement of basement membrane, pericytes, neurons, and astrocytes. The BBB brings a hard barrier between the blood and brain parenchyma cells. However, several transport systems help to ease the channel of selective constituents across the BBB. The deprived oral bioavailability and aqueous solubility are the major drawback for the pharmaceutical formulations and clinical practice of baicalein.

Previous reports showed that baicalin and baicalein 6-O-sulfate are the metabolic product of baicalein in the blood [ 66 , 67 ]. Several studies have demonstrated that oral administration of baicalein endures widespread glucuronidation within the wall of intestine and liver in humans and rats [ 68 ]. Additionally, baicalein was found less absorbed by colon when compared to stomach and small intestine [ 69 ].

In another study, conducted on monkeys, it has been reported that the different doses of baicalein bioavailability range Baicalein has been shown a novel potential therapeutic agent for the treatment of neurological diseases. Therefore, clinical trials are essential for baicalein in order to confirm the potential therapeutic efficacy against neurodegenerative diseases. Two phase I clinical trials have been done based on chewable tablets of baicalein in Chinese healthy adult volunteers. Without any additional treatment, mild adverse effects were fixed. Blood pressure and electrocardiogram were found normal during the entire period of study.

No sign of toxicity observed in liver and kidney or any other serious adverse effects were not observed [ 74 ]. In , another study in Chinese subjects based on placebo-controlled, single-center, and double-blind parallel group investigated the pharmacokinetics, safety, and tolerability of baicalein following multiple-ascending-dose protocol [ 75 ]. High-performance liquid chromatography—tandem mass spectrometry methods were employed to assay the baicalein and its metabolite in urine, feces, and plasma samples.

On day 8, plasma samples are given steady-state concentration of analytes after repeated dosing.

The analytes concentration increased with increasing dose. The dose proportionality constant b for the area under the plasma concentration-time curves of baicalein and baicalin was 0. Phase I clinical trials of baicalein showed that oral administration is safe to humans. But additional studies of baicalein are needed in the patients of neurodegenerative diseases to strengthen its therapeutic importance.

This suggests baicalein to be considered as solid treatment tool for neurodegenerative diseases including PD. Importantly, baicalein is safe and sufficiently well tolerated by healthy volunteers as evidenced by two phase I clinical trials based on Chinese healthy adult volunteers [ 74 , 75 ].

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HJ wrote and revised the chapter; SO critically proofread the final version and provided the important inputs to prepare the final version of the chapter. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Help us write another book on this subject and reach those readers.

Structural connectivity-based topography of the human globus pallidus: Implications for therapeutic targeting in movement disorders. A Technical Note. Front Surg. Advances in Parkinson's Disease: Years Later. Front Neuroanat. Movement Disorders Sept Luk KC. Focal ultrasound strikes a new tune for targeted drug delivery.

Focus on Parkinson's Disease

Mov Disord Clin Pract. Magnetic resonance imaging-guided focused ultrasound thalamotomy in Parkinson tremor: Reoperation after benefit decay. Medical and surgical management of advanced Parkinson's disease. Is there a role for MR-guided focused ultrasound in Parkinson's disease?

Epub Feb Bretsztajn L, Gedroyc W. Brain-focussed ultrasound: what's the "FUS" all about? A review of current and emerging neurological applications. Br J Radiol. Lancet Neurol. Click here for additional references on focused ultrasound for Parkinson's. Meet the Experts Timeline of Focused Ultrasound. Symptoms and targets being assessed for treatment using focused ultrasound include: Parkinsonian tremor — target in the thalamus thalamotomy Parkinsonian dyskinesia — target in the globus pallidus pallidotomy or subthalamic nucleus Parkinsonian tremor or akinesia — target in the pallidothalamic tract At this time, focused ultrasound is only being assessed to treat one side of the brain, so it will affect tremor or dyskinesia unilaterally.

Advantages Focused ultrasound is non-invasive — no incisions, holes in the skull, electrodes in the brain — and therefore has reduced risk for infection and blood clots. Precise targeting minimizes damage to non-targeted healthy brain. It also does not involve the collateral damage to healthy tissue or the risk of infections associated with implanting a foreign body.