AUTHOR=Singh Babita , Pandey Shivani , Rumman Mohammad , Kumar Shashank , Kushwaha Prem Prakash , Verma Rajesh , Mahdi Abbas Ali 

TITLE=Neuroprotective and Neurorescue Mode of Action of Bacopa monnieri (L.) Wettst in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson’s Disease: An In Silico and In Vivo Study

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.616413

DOI=10.3389/fphar.2021.616413

ISSN=1663-9812

ABSTRACT=<p><bold>Ethnopharmacological Relevance:</bold> Parkinson’s disease (PD) is characterized by progressive death of dopaminergic neurons. The presently used medicines only tackle the symptoms of PD, but none makes a dent on the processes that underpin the disease’s development. Herbal medicines have attracted considerable attention in recent years. <italic>Bacopa monnieri</italic> (L.) <italic>Wettst</italic> (Brahmi) has been used in Indian Ayurvedic medicine to enhance memory and intelligence. Herein, we assessed the neuroprotective role of <italic>Bacopa monnieri</italic> (L.) <italic>Wettst</italic> on Parkinson’s disease.</p><p><bold>Aim of the Study:</bold><italic>Bacopa monnieri</italic> (L.) <italic>Wettst</italic>, a medicinal herb, is widely used as a brain tonic. We investigated the neuroprotective and neurorescue properties of <italic>Bacopa monnieri</italic> (L.) <italic>Wettst</italic> extract (BME) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mice model of PD.</p><p><bold>Materials and Methods:</bold> The mice model of MPTP-induced PD is used in the study. In the neuroprotective (BME + MPTP) and neurorescue (MPTP + BME) experiments, the animals were administered 40 mg/kg body weight BME orally before and after MPTP administration, respectively. Effect of BME treatment was evaluated by accessing neurobehavioral parameters and levels of dopamine, glutathione, lipid peroxide, and nitrites. An <italic>in silico</italic> study was performed using AutoDock Tools 1.5.6 (ADT).</p><p><bold>Results:</bold> A significant recovery in behavioral parameters, dopamine level, glutathione level, lipid peroxides, and nitrite level was observed in BME-treated mice. Treatment with BME before or after MPTP administration has a protective effect on dopaminergic neurons, as evidenced by a significant decrease in GFAP immunostaining and expression of inducible nitric oxide synthase (iNOS) in the substantia nigra region; however, the degree of improvement was more prominent in mice receiving BME treatment before MPTP administration. Moreover, the <italic>in silico</italic> study revealed that the constituents of BM, including bacosides, bacopasides, and bacosaponins, can inactivate the enzyme monoamine oxidase B, thus preventing the breakdown of MPTP to MPP+.</p><p><bold>Conclusion:</bold> Our results showed that BME exerts both neuroprotective and neurorescue effects against MPTP-induced degeneration of the nigrostriatal dopaminergic neurons. Moreover, BME may slow down the disease progression and delay the onset of neurodegeneration in PD.</p>