*2.2.4 Human trials*

*Bioethics in Medicine and Society*

other experimental models.

*2.2.3 Mice/rat/rodents*

greater control over dosage and ease of administering substances to large numbers of animals. Furthermore, larval behaviors can be exploited in assays to test the effects of the treatment. Being a vertebrate, the central nervous system of larval zebra fish expressions an extremely homologous to humans. Therefore, toxicology studies performed on larval zebra fish can be very helpful in deciding the putative targets in humans [50]. Thus *Danio rerio* commonly known as zebrafish is a charming popular animal model for treatments in neuropharmacology and pharmacogenetics. Both the adult and larval zebrafish are presently studied to increase the understanding of central nervous system's function and dysfunction [51]. There are various studied reports by Gerlai et al. on the latent learning, behavior, and memory alteration of adult zebrafish [51–55]*.* Apart from fish, there are several

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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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 Parkinson's disease [61, 62].
