*2.2.3 Mice/rat/rodents*

Many clinical trials have been done on herbal extract and their isolated compound, which has opened a new scenario in the area of PD. The models of PD are induced by different chemical compounds like 6-OHDA, rotenone, and MPTP based on the aim of the experiment. Singh et al. investigated the effect of ethanolic extract of *Mucuna pruriens* (Mp) on the reduction of oxidative stress level, nitric oxide (NO), and subsequent influence on lipid peroxidation in paraquat (PQ ) induced Parkinsonian mouse model. MTTP-induced Parkinson mouse models were also studied by them for the reduction of estrogen by *Mucuna pruriens* [26, 55, 56]. Yadav et al. demonstrated that Mp seed extract reduces oxidative stress in nigrostriatal tissue and improves neurobehavioral activity and the expression of tyrosine hydroxylase (TH) in SN and striatum of the brain in PQ-intoxicated mice [56]. Apoptotic pathways of dopaminergic neurons in the PQ mouse model were also found to be inhibited by the neuroprotective activity of *Mucuna pruriens* [57]. Experiments also reveal that the *Mucuna pruriens* has a resilient anti-inflammatory property that diminishes the neuroinflammation by plummeting inducible nitric oxide synthase expression in Parkinsonian mice model. Symptomatic and neuroprotective efficacy in rodent model of Parkinson's disease using *Mucuna pruriens* seed extract were studied by Kasture and Pontis [58]. Significance of *M. pruriens* in sperm parameters and sexual behavior of streptozotocin-induced diabetic male rat were studied by Sekar Suresh et al. [59]. Earlier efforts exhibited the capability of *Mucuna pruriens* seeds extract to induce contralateral turning behavior in the 6-hydroxydopamine (6-OHDA)-lesion persuaded rat model of PD [60]. Likewise, the potential of *Mucuna* seed powder extract significantly improved activity of brain mitochondrial complex-I without disturbing total monoamine oxidase activity *in vitro* [61]. *Mucuna pruriens* also has the potential to amend immune components like tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interferon-λ (IFN-λ), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), and interleukin-2 (IL-2) in the central nervous system, thereby, averting the progression of dopaminergic neurons degeneration, in PD [62]. Moreover *M. pruriens* was also assessed for levodopa pharmacokinetics by Sarrafchi et al., in a double-blinded clinical and pharmacological study. They observed that administration of *M. pruriens* at doses of 2.5, 5.0, or 10.0 g/kg/day for 52 weeks significantly increased the dopamine content of the cortex in animal model of PD. Therefore, they concluded that *M. pruriens* seed powder with natural source of levodopa probably has benefits over conventional levodopa preparations in treatment of PD due to its longer action and speedy onset without increase in adverse effect [63]. Thus, *M. pruriens* would seem to be a remarkable commercially viable alternative to standard L-dopa [64]. Likewise, an improvement in motor

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

*2.2.4 Human trials*

Parkinson's disease [61, 62].

**2.3 Other drugs and their effects**

exhibiting anti-apoptotic effect [68–70].

skills and dyskinesia analogous to those induced by equivalent doses of L-DOPA was also found to be induced by *M. pruriens* preparations in rat and macaque monkey models of PD [61]. Therefore, all these studies strongly advocate the use

Copious studies have scrutinized the effect of MP in PD patients. The bioavailability of L-DOPA in the central nervous system is about one-fifth when pooled with carbidopa or benserazide due to nonexistence of DOPA decarboxylase inhibitor (DDCI) in *Mucuna* [61–65]*.* Even then, the first report in 1978 revealed that 23 PD patients were treated with MP with similar effect and better tolerance than L-DOPA/benserazide. This study was followed by an open study where 60 PD patients in Hoehn and Yahr stage I–IV were treated with MP preparations for over 12 weeks, which led to momentous headways in both UPDRS score and the Hoehn and Yahr stage. This captivated the attention on the registration of *Mucuna* preparation (Zandopa™) as a treatment for PD in India [61]. Cilia et al. executed a crossover study (*N* = 14) on PD patients in an advanced stage with motor fluctuations and peak-of-dose dyskinesia. The observations indicated better motor improvement on *Mucuna* powder consumption in comparison to the effect imparted by intake of an equivalent dose of L-DOPA/benserazide [66]. Innumerable experiments are still under investigation by several assemblages of researchers from all over the world to understand the PD progression and come up with innovative strategies to treat

Gargantuan improvement has been done to treat the PD for over half-century.

There are various studies proving that the dopamine agonist or levodopa has stronger symptomatic benefits as the MAOB inhibitor; however, there was no evidence of direct comparison between them [71–74]. Older people provide more rapid onset improvement than younger patients. Dopamine agonist is more prominent in younger people with dyskinesia and older people with orthostatic hypotension and CNS effects (hallucinations). Pharmacokinetic studies revel that COMT inhibitors

Diverse individuals from different places have come up with different treatments. Miscellaneous categories of drugs are being used apart from levodopa. Yet to date there are no complete cure strategies for PD. But some symptomatic palliative treatments are being implemented to slow down the disease progression. There are various enzymes used in the management of PD. Enzymes monoamine oxidase-B (MAO-B) and catechol-o-methyl-transferase (COMT) are normally involved in metabolism of dopamine. Therefore, few inhibitors of the two enzymes (MAO-B and COMT) have been extensively studied. Inhibitors like selegiline, rasagiline, tolcapone, and entacapone are being used for the disease modification in PD from previous few years. N-propargyl-methamphetamine is known as selegiline, which is an irreversible inhibitor of MAO-B. Action of selegiline was studied in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinsonism in monkeys [67]. It was used at concentration of 10 mg/ day, but they found that it loses its selectivity at higher concentrations of dosage [67]. Various other reports show the neuroprotective potential of selegiline but there is no such report proving that selegiline has "disease-modification" effects [68–70]. The *in vitro* and *in vivo* experimental Parkinsonian models indicate that rasagiline (N-propargyl-1-(R)-aminoindan) acted as irreversible MAOB inhibitor

of *Mucuna pruriens*: a treasurable herbal plant for treatment of PD.

skills and dyskinesia analogous to those induced by equivalent doses of L-DOPA was also found to be induced by *M. pruriens* preparations in rat and macaque monkey models of PD [61]. Therefore, all these studies strongly advocate the use of *Mucuna pruriens*: a treasurable herbal plant for treatment of PD.
