**2. Treatment strategies of Parkinson's disease**

#### **2.1 Neuroprotective potential of** *Mucuna*

Parkinson's disease (PD) was initially discovered by Dr. James Parkinson in 1817; it is a chronic neurological disorder triggered by a progressive loss of dopaminergic neurons present in the nigrostriatal part of the brain and found to be common in U.S [12]. In 1970, only few effective drugs were available for treatment of the PD but there is no such therapy yet that completely treats PD. Only thing we can do is to stop the progression of Parkinson's disease or delay the of PD by replacement of dopaminergic neuron or by mimicking the neuron by using substituent. Management of PD is mainly divided into two categories: first involves improving symptomatic treatment of motor and non-motor types of symptoms and second will be addressing potential causes of PD. Firstly in 1978 Vaidya et al., published the report that PD can be treated by *Mucuna* extract, a natural source of levodopa having better activity than the synthetic version of levodopa drug [13]. Similar studies were reported in 1990 and 1994 by Kempster et al. and Rabey et al. [14, 15]. L-DOPA is a precursor of dopamine (**Figure 1**), norepinephrine (noradrenaline),

**Figure 1.** *Synthesis pathway of L-DOPA, dopamine and further metabolites.*

and epinephrine (adrenaline), together known as catecholamines. The dopamine produced cannot cross the blood–brain barrier but L-DOPA can. Outside the brain, L-DOPA can directly be converted to 3-O-methyldopa (3-OMD) by catechol-Omethyl transferase (COM T) and then further to vanillactic acid (VLA), which leads to primary same side effect. To avoid this conversion, standard clinical practices use DOPA decarboxylase inhibitor such as carbidopa or benserazide and often a catechol-O-methyl transferase (COMT) inhibitor [16–18]. L-DOPA present in *Mucuna* plant (anti-Parkinson's drug) [19–21] helps to produce dopamine. Along with L-DOPA, the reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by *Mucuna* are stress-producing free radicals playing a great role in the physiological functioning of the body [21–30]. The content of antioxidant compounds using different solvents in different species of *Mucuna,* the concentration of antioxidants and other phytochemicals are extremely different. Ethanolic extract of *Mucuna* seed shows good antioxidant activity due to high phenolic content as compared to methanol, water, and acetone [31]. Some reports also conclude that water is as universal solvent, which shows the significant quantity of phenolic, flavonoids, and strong antioxidants which have the ability to scavenge free radicals using different assays. LCMS (liquid chromatography mass spectrophotometry) report of four different species **Table 1** shows that there are various components like phenolic flavonoids and bioactive compounds present in the *Mucuna* that are responsible for the production of reactive species [32]. Along with L-DOPA and antioxidants, other secondary metabolites like phenolics, flavonoids, vitamins, enzymes, and protein also have a cumulative effect in the management of PD. Few reports on *Mucuna* show correlation between L-DOPA, protein, and carbohydrates. The use of plants for the treatment of PD is more beneficial than chemically manufactured L-dopa due to its high potential required in the levo and dextro form purification. It is also studied that various compounds present in *Mucuna* are responsible for the antimicrobial action, which can be utilized in dealing with various infectious diseases and ulcers [31, 32, 44]. Experiments on various plant pathogens suggest that methanolic extract of *Mucuna pruriens* seeds showed the highest antimicrobial activity [45]. A similar type of study done by Pujari et al. also determined that methanol extracts of *Mucuna pruriens* seeds were found to have the best inhibiting activity among all scrutinized pathogens as compared to ethanol and acetone solvents. But alcoholic extract of *Mucuna pruriens* (L.) leaves has significant antioxidant and antibacterial


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*Parkinsonism and Potential of Mucuna Beans DOI: http://dx.doi.org/10.5772/intechopen.92855*

activity [45]. Dopaminergic agonists or dopamine replacement therapy is a common and most effective way to cure PD. It decreases the signs of disease by sustaining the level of dopamine; however, it cannot regenerate or halt the degeneration. It only replaces or mimics dopamine by inhibiting its breakdown. Apomorphine, bromocriptine, pergolide, piribedil, pramipexole, and ropinirole are some dopaminergic agonists mainly used to heal the PD. All these bioactive compounds present in the *Mucuna* species have cumulative effect in the treatment of PD. *Mucuna pruriens* is a species from the Fabaceae family and Faboideae subfamily. *M. pruriens* is an annual twinning plant in bushes, hedges, and one of the popular medicinal plants indigenous to tropical countries like India [42]. It is useful in relieving inflammation, delirium, neuropathy, cephalalgia, and general debility, nephropathy, dysmenorrhea, amenorrhea, ulcers, constipation, elephantiasis, consumption, helminthiasis, fever, and dropsy. The trichomes of pods contain serotonin and mucunain. The trichomes are used as anthelmintic. Seeds contain glutathione, gallic acid, levodopa (4-3, 4-dihydroxy phenylalanine), lecithin, prurenine, prurenidine,

glycosides, nicotine, minerals, and dark brown viscous oil [42].

climbing behavior compared to flies that consumed L-DOPA.

Natural products are valuable sources of bioactive compounds that can be exploited for novel therapeutic potential in PD pathogenesis. There are number of publications reported till now dealing with experiments on hundreds of compounds from various plant species for their different activity in curing the Parkinson's disease [46]. However, rapid screening of plant-derived natural products and characterization of bioactive compounds is a challenging job. This problem was combated by using *Drosophila melanogaster* and zebrafish as experimental models at initial stages then followed by studies on various experimental models like, *C. elegans,* mice/rat, and also cell lines (e.g., murine BV-2 microglia and human SH-SY5Y neuroblastoma cells). Few verdicts using different models are listed underneath.

*Drosophila melanogaster*, universally familiar as the fruit fly, have turned up as an outstanding model for human neurodegenerative diseases, comprising PD. Due to their high degree of conserved molecular pathways with mammalian models, Drosophila PD models serve to be an inexpensive solution to pilot stages of target validation in the drug discovery pipeline. Fruit fly acts as a screening platform to evaluate the therapeutic potential of phytochemicals from natural extracts against PD [47]. *Drosophila melanogaster* is a persuasive tool to explore molecular facets and physiopathology of Parkinson's disease (PD) [48]*.* There are studies that compare the effects of L-DOPA vs. MP extract using a Drosophila model of autosomal recessive PD in which flies carried a mutation in the PTEN-induced putative kinase 1 (PINK-1) gene [49]. Their observations illustrates that *Drosophila* fed on MP had a significantly extended lifespan, showed a restored olfactory response and improved

Owing to its large number of favorable properties, Zebra fish has been used widely as experimental animal for various diseases. Zebra fish are inexpensive, easy to conserve, develop rapidly, and breed in large quantities. Larval zebra fish are also extensively used in toxicity screens since they have a permeable skin through which substances added in the rearing medium are effortlessly taken up. This permits for

**2.2 Experimental models studied for PD**

*2.2.1* Drosophila melanogaster

*2.2.2 Zebra fish (*Danio rerio*)*
